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WUSTL Neuroscience Publications Archive - June 2013

 Scopus weekly report:

June 27, 2013

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June 27, 2012

Documents

http://www.scopus.com/static/mail/images_R5/s.gifHarms, M.B.a c , Cady, J.a , Zaidman, C.a , Cooper, P.a , Bali, T.a , Allred, P.a , Cruchaga, C.b c , Baughn, M.d , Libby, R.T.e , Pestronk, A.a c , Goate, A.b c , Ravits, J.d , Baloh, R.H.f
Lack of C9ORF72 coding mutations supports a gain of function for repeat expansions in amyotrophic lateral sclerosis
(2013Neurobiology of Aging, 34 (9), pp. 2234.e13-e19. 

a Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
b Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
c Hope Center for Neurological Disorders, Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
d Department of Neurosciences, University of California San Diego, La Jolla, CA, United States
e Benaroya Research Institute, Seattle, WA, United States
f Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, United States


Abstract
Hexanucleotide repeat expansions in C9ORF72 are a common cause of familial and apparently sporadic amyotrophic lateral sclerosis (ALS) and frontal temporal dementia (FTD). The mechanism by which expansions cause neurodegeneration is unknown, but current evidence supports both loss-of-function and gain-of-function mechanisms. We used pooled next-generation sequencing of the C9ORF72 gene in 389 ALS patients to look for traditional loss-of-function mutations. Although rare variants were identified, none were likely to be pathogenic, suggesting that mutations other than the repeat expansion are not a common cause of ALS, and providing supportive evidence for a gain-of-function mechanism. We also show by repeat-primed PCR genotyping that the C9ORF72 expansion frequency varies by geographical region within the United States, with an unexpectedly high frequency in the Mid-West. Finally we also show evidence of somatic instability of the expansion size by Southern blot, with the largest expansions occurring in brain tissue. © 2013 Elsevier Inc.


Author Keywords
Amyotrophic lateral sclerosis;  C9ORF72;  C9ORF72 hexanucleotide repeat;  Genetics

Document Type: Article
Source: Scopus

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Malkoc, S.A.a , Hedgcock, W.b , Hoeffler, S.c
Between a rock and a hard place: The failure of the attraction effect among unattractive alternatives
(2013Journal of Consumer Psychology, 23 (3), pp. 317-329. 

a Washington University in St. Louis, St. Louis, MO, United States
b University of Iowa, Iowa City, IA, United States
c Vanderbilt University, Nashville, TN, United States


Abstract
Many important decisions that consumers face involve choosing between options that are unattractive or undesirable-the proverbial "lesser of two evils." Consumers, who face budget or geographical constraints, for example, end up with mostly undesirable consideration sets; yet a choice is necessary. We examine the role of option set desirability in the context of the well-established attraction effect. In five studies, we show that the attraction effect occurs in desirable domains but is eliminated when all the options are undesirable (Experiments 1-4). We further find that this asymmetric effect is consistent with a shift in decision makers' processing styles. Decision makers show more vigilant processing when making choices among undesirable (vs. desirable) domains (Experiments 3A and 3B), which results in an attenuated attraction effect (Experiment 4). Our results indicate that the attraction effect might not be as robust as generally thought and establishes (un)desirability as an important boundary condition. © 2012 Society for Consumer Psychology.


Author Keywords
(Un)desirability;  Attraction effect;  Context effects;  Decision making

Document Type: Article
Source: Scopus

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Larsen, D.P.a , Butler, A.C.b , Roediger Iii, H.L.c
Comparative effects of test-enhanced learning and self-explanation on long-term retention
(2013) Medical Education, 47 (7), pp. 674-682. Cited 1 time.

a Department of Neurology, Washington University in St. Louis School of Medicine, St. Louis, MO, United States
b Department of Pscyhology and Neuroscience, Duke Univeristy, Durham, NC, United States
c Department of Psychology, Washington University in St. Louis, St. Louis, MO, United States


Abstract
Context: Educators often encourage students to engage in active learning by generating explanations for the material being learned, a method called self-explanation. Studies have also demonstrated that repeated testing improves retention. However, no studies have directly compared the two learning methods. Methods: Forty-seven Year 1 medical students completed the study. All students participated in a teaching session that covered four clinical topics and was followed by four weekly learning sessions. In the learning sessions, students were randomised to perform one of four learning activities for each topic: testing with self-generated explanations (TE); testing without explanations (T); studying a review sheet with self-generated explanations (SE), and studying a review sheet without explanations (S). Students repeated the same activity for each topic in all four sessions. Six months later, they took a free-recall clinical application test on all four topics. Results: Repeated testing led to better long-term retention and application than repeatedly studying the material (p < 0.0001, η2 = 0.33). Repeated generation of self-explanations also improved long-term retention and application, but the effect was smaller (p < 0.0001, η2 = 0.08). When data were collapsed across topics, both testing conditions produced better final test performance than studying with self-explanation (TE = 40% > SE = 29% [p = 0.001, d = 0.70]; T = 36% > SE = 29% [p = 0.02, d = 0.48]). Studying with self-explanation led to better retention and application than studying without self-explanation (SE = 29% > S = 20%; p = 0.001, d = 0.68). Our analyses showed significant interaction by topic (p = 0.001, η2 = 0.06), indicating some variation in the effectiveness of the interventions among topics. Conclusions: Testing and generating self-explanations are both learning activities that can be used to produce superior long-term retention and application of knowledge, but testing is generally more effective than self-explanation alone. © 2013 John Wiley & Sons Ltd.


Document Type: Article
Source: Scopus

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Connolly, A.M.a b , Florence, J.M.a , Cradock, M.M.b , Malkus, E.C.a , Schierbecker, J.R.a , Siener, C.A.a , Wulf, C.O.a , Anand, P.a , Golumbek, P.T.a b , Zaidman, C.M.a b , Philip Miller, J.c , Lowes, L.P.d , Alfano, L.N.d , Viollet-Callendret, L.d , Flanigan, K.M.d , Mendell, J.R.d , McDonald, C.M.e , Goude, E.e , Johnson, L.e , Nicorici, A.e , Karachunski, P.I.f , Day, J.W.f , Dalton, J.C.f , Farber, J.M.f , Buser, K.K.f , Darras, B.T.g , Kang, P.B.g , Riley, S.O.g , Shriber, E.g , Parad, R.g , Bushby, K.h , Eagle, M.h
Motor and cognitive assessment of infants and young boys with Duchenne Muscular Dystrophy: Results from the Muscular Dystrophy Association DMD Clinical Research Network
(2013) Neuromuscular Disorders, 23 (7), pp. 529-539. 

a Department of Neurology, Washington University School of Medicine, Saint Louis, MO, United States
b Department of Pediatrics, Washington University School of Medicine, Saint Louis, MO, United States
c Division of Biostatistics, Washington University School of Medicine, Saint Louis, MO, United States
d Department of Pediatrics, Nationwide Children's Hospital, Ohio State University, Columbus, OH, United States
e Department Physical Medicine and Rehabilitation, University of California, Davis Medical Center, Sacramento, CA, United States
f Department of Neurology, University of Minnesota, Minneapolis, MN, United States
g Department of Neurology, Harvard University, Boston Children's Hospital, Boston, MA, United States
h Department of Neurology and Institute of Genetic Medicine, Newcastle upon Tyne, Newcastle, United Kingdom


Abstract
Therapeutic trials in Duchenne Muscular Dystrophy (DMD) exclude young boys because traditional outcome measures rely on cooperation. The Bayley III Scales of Infant and Toddler Development (Bayley III) have been validated in developing children and those with developmental disorders but have not been studied in DMD. Expanded Hammersmith Functional Motor Scale (HFMSE) and North Star Ambulatory Assessment (NSAA) may also be useful in this young DMD population. Clinical evaluators from the MDA-DMD Clinical Research Network were trained in these assessment tools. Infants and boys with DMD (. n=. 24; 1.9. ±. 0.7. years) were assessed. The mean Bayley III motor composite score was low (82.8. ±. 8; p≤. .0001) (normal. =. 100. ±. 15). Mean gross motor and fine motor function scaled scores were low (both p≤. .0001). The mean cognitive comprehensive (. p=. .0002), receptive language (. p≤. .0001), and expressive language (. p=. .0001) were also low compared to normal children. Age was negatively associated with Bayley III gross motor (. r=. -0.44; p=. .02) but not with fine motor, cognitive, or language scores. HFMSE (. n=. 23) showed a mean score of 31. ±. 13. NSAA (. n=. 18 boys; 2.2. ±. 0.4. years) showed a mean score of 12. ±. 5. Outcome assessments of young boys with DMD are feasible and in this multicenter study were best demonstrated using the Bayley III. © 2013 Elsevier B.V.


Author Keywords
Bayley III Scales of Infant and Toddler Development;  Duchenne Muscular Dystrophy;  Hammersmith Functional Motor Scale Extended;  Infant;  North Star Ambulatory Assessment

Document Type: Article
Source: Scopus

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Wolf, T.a b , Koster, J.a
Perceived recovery as a predictor of physical activity participation after mild stroke
(2013) Disability and Rehabilitation, 35 (14), pp. 1143-1148. 

a Program in Occupational Therapy, Washington University, School of Medicine, 4444 Forest Park Avenue, St. Louis, MO 63108, United States
b Department of Neurology, Washington University, School of Medicine, St. Louis, MO, United States


Abstract
Purpose: The purpose of this study was to identify what acute care variables and/or perceived recovery factors could predict decreased participation in physical activities post-mild stroke. Methods: Secondary analysis of persons with mild stroke. Participants were split into two groups based on the percentage of high-demand leisure (HDL) activities retained on the Activity Card Sort (ACS) at 6 months post-stroke. Demographic variables, measures from the acute care setting (National Institutes of Health Stroke Scale (NIHSS), premorbid Barthel Index, and Modified Rankin Scale), and a perceived recovery measure collected at 6 months post-stroke (Stroke Impact Scale (SIS)) were analyzed between groups using independent samples t-tests and logistic regression. Results: There were no significant differences between groups on any of the demographic or acute care setting measures. Logistic regression indicated that only the overall perceived recovery (p = 0.05) and strength domain scores (p = 0.01) of the SIS were statistically significant factors for determining the percent of retained HDL activities following mild stroke. Conclusions: Clinicians must consider the clients' own perceived recovery level and other more subjective factors in determining what barriers are limiting their physical activity participation after stroke. Implications for Rehabilitation Persons with mild stroke are significantly decreasing their participation in physical activities post-stroke. Common stroke measures from the acute care setting that are currently used in practice are not sensitive enough to predict the changes in physical activity after mild stroke. Perceived level of recovery/limitations should be considered by clinicians in determining what barriers are affecting clients' physical activity participation after stroke. © 2013 Informa UK, Ltd.


Author Keywords
Exercise;  Mild stroke;  Participation;  Perceived recovery;  Physical activity

Document Type: Article
Source: Scopus

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Kamio, Y.a , Inada, N.a , Moriwaki, A.a , Kuroda, M.a b , Koyama, T.a , Tsujii, H.a , Kawakubo, Y.b , Kuwabara, H.b , Tsuchiya, K.J.c , Uno, Y.d , Constantino, J.N.e
Quantitative autistic traits ascertained in a national survey of 22 529 Japanese schoolchildren
(2013) Acta Psychiatrica Scandinavica, 128 (1), pp. 45-53. 

a Department of Child and Adolescent Mental Health, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan
b Department of Child Neuropsychiatry, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
c Research Center for Child Mental Development, United Graduate School of Child Development, School of Medicine, Hamamatsu University, Hamamatsu, Japan
d Department of Psychiatry and Psychiatry for Parents and Children, Graduate School of Medicine, Nagoya University, Nagoya, Japan
e Departments of Psychiatry and Pediatrics, School of Medicine, Washington University, St. Louis, MO, United States


Abstract
Objective: Recent epidemiologic studies worldwide have documented a rise in prevalence rates for autism spectrum disorders (ASD). Broadening of diagnostic criteria for ASD may be a major contributor to the rise in prevalence, particularly if superimposed on an underlying continuous distribution of autistic traits. This study sought to determine the nature of the population distribution of autistic traits using a quantitative trait measure in a large national population sample of children. Method: The Japanese version of the Social Responsiveness Scale (SRS) was completed by parents on a nationally representative sample of 22 529 children, age 6-15. Results: Social Responsiveness Scale scores exhibited a skewed normal distribution in the Japanese population with a single-factor structure and no significant relation to IQ within the normal intellectual range. There was no evidence of a natural 'cutoff' that would differentiate populations of categorically affected children from unaffected children. Conclusion: This study provides evidence of the continuous nature of autistic symptoms measured by the SRS, a validated quantitative trait measure. The findings reveal how paradigms for diagnosis that rest on arbitrarily imposed categorical cutoffs can result in substantial variation in prevalence estimation, especially when measurements used for case assignment are not standardized for a given population. © 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


Author Keywords
Autism;  Classification;  Diagnosis;  Prevalence;  Questionnaire

Document Type: Article
Source: Scopus

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Tandon, R.a , Heckers, S.b , Bustillo, J.c , Barch, D.M.d e , Gaebel, W.f , Gur, R.E.g h , Malaspina, D.i j , Owen, M.J.k , Schultz, S.l , Tsuang, M.m n o , van Os, J.p q , Carpenter, W.r s
Catatonia in DSM-5
(2013) Schizophrenia Research, . Article in Press. 

a Department of Psychiatry, University of Florida Medical School, Gainesville, FL, USA
b Department of Psychiatry, Vanderbilt University, Nashville, TN, USA
c Department of Psychiatry, University of New Mexico, Albuquerque, NM, USA
d Department of Psychology, Washington University, St. Louis, MO, USA
e Department of Psychiatry and Radiology, Washington University, St. Louis, MO, USA
f Department of Psychiatry, Duesseldorf, Germany
g Department of Psychiatry, Perlman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
h Department of Neurology and Radiology, Perlman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
i Department of Psychiatry, New York University, New York, NY, USA
j Creedmoor Psychiatric Center, New York State Office of Mental Health, USA
k MRC Centre for Neuropsychiatric Genetics and Genomics and Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, Wales, United Kingdom
l Department of Psychiatry, University of Iowa School of Medicine, Iowa City, IA, USA
m Center for Behavioral Genomics, Department of Psychiatry and Institute of Genomic Medicine, University of California, San Diego, CA, USA
n Veterans Affairs San Diego Healthcare System, San Diego, CA, USA
o Harvard Institute of Psychiatric Epidemiology and Genetics, Harvard School of Public Health, Boston, MA, USA
p Maastricht University Medical Centre, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht, The Netherlands
q King's College London, King's Health Partners, Department of Psychosis Studies, Institute of Psychiatry, London, United Kingdom
r Department of Psychiatry, Maryland Psychiatric Research Center, Baltimore, MD, USA
s VISN 5 MIRECC < Veterans' Healthcare System, Baltimore, MD, USA


Abstract
Although catatonia has historically been associated with schizophrenia and is listed as a subtype of the disorder, it can occur in patients with a primary mood disorder and in association with neurological diseases and other general medical conditions. Consequently, catatonia secondary to a general medical condition was included as a new condition and catatonia was added as an episode specifier of major mood disorders in DSM-IV. Different sets of criteria are utilized to diagnose catatonia in schizophrenia and primary mood disorders versus neurological/medical conditions in DSM-IV, however, and catatonia is a codable subtype of schizophrenia but a specifier for major mood disorders without coding. In part because of this discrepant treatment across the DSM-IV manual, catatonia is frequently not recognized by clinicians. Additionally, catatonia is known to occur in several conditions other than schizophrenia, major mood disorders, or secondary to a general medical condition. Four changes are therefore made in the treatment of catatonia in DSM-5. A single set of criteria will be utilized to diagnose catatonia across the diagnostic manual and catatonia will be a specifier for both schizophrenia and major mood disorders. Additionally, catatonia will also be a specifier for other psychotic disorders, including schizoaffective disorder, schizophreniform disorder, brief psychotic disorder, and substance-induced psychotic disorder. A new residual category of catatonia not otherwise specified will be added to allow for the rapid diagnosis and specific treatment of catatonia in severely ill patients for whom the underlying diagnosis is not immediately available. These changes should improve the consistent recognition of catatonia across the range of psychiatric disorders and facilitate its specific treatment.


Author Keywords
Catatonia;  Classification;  Diagnosis;  DSM;  DSM-5;  Mood disorder;  Nosology;  Schizophrenia

Document Type: Article in Press
Source: Scopus

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Kaviani, H.a , Mirbaha, H.b , Pournaseh, M.c , Sagan, O.d
Can music lessons increase the performance of preschool children in IQ tests?
(2013) Cognitive Processing, pp. 1-8. Article in Press. 

a Department of Psychology, Faculty of Health and Social Sciences, University of Bedfordshire, Park Square, Luton, LU1 3JU, United Kingdom
b Department of Neurology, Washington University School of Medicine, St. Louis, 63110, United States
c Family Service Toronto, 540 Finch Ave., West Toronto, M2R 1N7, Canada
d Bishop Grosseteste University, Lincoln, LN1 3DY, United Kingdom


Abstract
The impact of music on human cognition has a distinguished history as a research topic in psychology. The focus of the present study was on investigating the effects of music instruction on the cognitive development of preschool children. From a sample of 154 preschool children of Tehran kindergartens, 60 children aged between 5 and 6 were randomly assigned to two groups, one receiving music lessons and the other (matched for sex, age and mother's educational level) not taking part in any music classes. Children were tested before the start of the course of music lessons and at its end with 4 subtests of the Tehran-Stanford-Binet Intelligence Scale (TSB). The experimental group participated in twelve 75-min weekly music lessons. Statistical analysis showed significant IQ increase in participants receiving music lessons, specifically on the TSB verbal reasoning and short-term memory subtests. The numerical and visual/abstract reasoning abilities did not differ for the two groups after lessons. These data support studies that found similar skills enhancements in preschool children, despite vast differences in the setting in which the instruction occurred. These findings appear to be consistent with some neuroimaging and neurological observations which are discussed in the paper. © 2013 Marta Olivetti Belardinelli and Springer-Verlag Berlin Heidelberg.


Author Keywords
Cognition;  Intelligence;  Music;  Preschool children;  Short-term memory

Document Type: Article in Press
Source: Scopus

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Tandon, R.a , Gaebel, W.b , Barch, D.M.c d e , Bustillo, J.f , Gur, R.E.g h i , Heckers, S.j , Malaspina, D.k l , Owen, M.J.m , Schultz, S.n , Tsuang, M.o p q , Van Os, J.r s , Carpenter, W.t u
Definition and description of schizophrenia in the DSM-5
(2013) Schizophrenia Research, . Article in Press. 

a Department of Psychiatry, University of Florida Medical School, Gainesville, FL, USA
b Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine University, Dusseldorf, Germany
c Department of Psychology, Washington University, St. Louis, MO, USA
d Department of Psychiatry, Washington University, St. Louis, MO, USA
e Department of Radiology, Washington University, St. Louis, MO, USA
f Department of Psychiatry, University of New Mexico, Albuquerque, NM, USA
g Department of Psychiatry, Perlman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
h Department of Neurology, Perlman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
i Department of Radiology, Perlman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
j Department of Psychiatry, Vanderbilt University, Nashville, TN, USA
k Department of Psychiatry, New York University, New York, NY, USA
l Creedmoor Psychiatric Center, New York State Office of Mental Health, USA
m MRC Centre for Neuropsychiatric Genetics and Genomics, Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, Wales, United Kingdom
n Department of Psychiatry, University of Iowa School of Medicine, Iowa City, IA, USA
o Center for Behavioral Genomics, Department of Psychiatry and Institute of Genomic Medicine, University of California, San Diego, CA, USA
p Veterans Affairs San Diego Healthcare System, San Diego, CA, USA
q Harvard Institute of Psychiatric Epidemiology and Genetics, Harvard School of Public Health, Boston, MA, USA
r Maastricht University Medical Centre, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht, The Netherlands
s King's College London, King's Health Partners, Department of Psychosis Studies, Institute of Psychiatry, London, United Kingdom
t Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD, USA
u VISN 5 MIRECC, Veterans' Healthcare System, Baltimore, MD, USA


Abstract
Although dementia praecox or schizophrenia has been considered a unique disease for over a century, its definitions and boundaries have changed over this period and its etiology and pathophysiology remain elusive. Despite changing definitions, DSM-IV schizophrenia is reliably diagnosed, has fair validity and conveys useful clinical information. Therefore, the essence of the broad DSM-IV definition of schizophrenia is retained in DSM-5. The clinical manifestations are extremely diverse, however, with this heterogeneity being poorly explained by the DSM-IV clinical subtypes and course specifiers. Additionally, the boundaries of schizophrenia are imprecisely demarcated from schizoaffective disorder and other diagnostic categories and its special emphasis on Schneiderian "first-rank" symptoms appears misplaced. Changes in the definition of schizophrenia in DSM-5 seek to address these shortcomings and incorporate the new information about the nature of the disorder accumulated over the past two decades. Specific changes in its definition include elimination of the classic subtypes, addition of unique psychopathological dimensions, clarification of cross-sectional and longitudinal course specifiers, elimination of special treatment of Schneiderian 'first-rank symptoms', better delineation of schizophrenia from schizoaffective disorder, and clarification of the relationship of schizophrenia to catatonia. These changes should improve diagnosis and characterization of individuals with schizophrenia and facilitate measurement-based treatment and concurrently provide a more useful platform for research that will elucidate its nature and permit a more precise future delineation of the 'schizophrenias'. © 2013 Elsevier B.V.


Author Keywords
Classification;  criteria;  Definition;  DSM;  DSM-5;  heterogeneity;  Nosology;  RDoC;  Schizophrenia;  Subtypes

Document Type: Article in Press
Source: Scopus

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Hutchison, R.M.a , Womelsdorf, T.b , Allen, E.A.c d , Bandettini, P.A.e , Calhoun, V.D.d f , Corbetta, M.g h , Della Penna, S.g , Duyn, J.H.i , Glover, G.H.j , Gonzalez-Castillo, J.e , Handwerker, D.A.e , Keilholz, S.k , Kiviniemi, V.l , Leopold, D.A.m , de Pasquale, F.g , Sporns, O.n , Walter, M.o p , Chang, C.i
Dynamic functional connectivity: Promise, issues, and interpretations
(2013) NeuroImage, . Article in Press. 

a Robarts Research Institute, Western University, London, Ontario, Canada
b Department of Biology, Centre for Vision Research, York University, Toronto, Ontario, Canada
c K.G. Jebsen Center for Research on Neuropsychiatric Disorders, University of Bergen, Norway
d The Mind Research Network, Albuquerque, NM, USA
e Section on Functional Imaging Methods, Laboratory of Brain and Cognition, National Institute of Mental Health, Bethesda, MD, USA
f Department of ECE, The University of New Mexico, Albuquerque, NM, USA
g Department of Neuroscience and Imaging and Institute for Advanced Biomedical Technologies, G. D'Annunzio University, Chieti, Italy
h Department of Radiology, Washington University, St. Louis, MO, USA
i Advanced MRI Section, Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA
j Department of Radiology, Stanford University, Stanford, CA, USA
k Department of Biomedical Engineering, Emory University/Georgia Institute of Technology, Atlanta, GA, USA
l Department of Diagnostic Radiology, Oulu University Hospital, Finland
m Section on Cognitive Neurophysiology and Imaging, Laboratory of Neuropsychology, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA
n Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, USA
o Clinical Affective Neuroimaging Laboratory, Otto-von-Guericke University, Magdeburg, Germany
p Leibniz Institute for Neurobiology, Center for Behavioral and Brain Sciences, Magdeburg, Germany


Abstract
The brain must dynamically integrate, coordinate, and respond to internal and external stimuli across multiple time scales. Non-invasive measurements of brain activity with fMRI have greatly advanced our understanding of the large-scale functional organization supporting these fundamental features of brain function. Conclusions from previous resting-state fMRI investigations were based upon static descriptions of functional connectivity (FC), and only recently studies have begun to capitalize on the wealth of information contained within the temporal features of spontaneous BOLD FC. Emerging evidence suggests that dynamic FC metrics may index changes in macroscopic neural activity patterns underlying critical aspects of cognition and behavior, though limitations with regard to analysis and interpretation remain. Here, we review recent findings, methodological considerations, neural and behavioral correlates, and future directions in the emerging field of dynamic FC investigations. © 2013 Elsevier Inc. All rights reserved.


Author Keywords
Dynamics;  Fluctuations;  Functional connectivity;  Functional MRI (fMRI);  Resting state;  Spontaneous activity

Document Type: Article in Press
Source: Scopus

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Ramos, E.a b , Bien-Willner, G.a c , Li, J.d , Hughes, A.a b , Giacalone, J.a b , Chasnoff, S.a b , Kulkarni, S.c , Parmacek, M.d , Cole, F.b , Druley, T.a b
Genetic variation in MKL2 and decreased downstream PCTAIRE1 expression in extreme, fatal primary human microcephaly
(2013) Clinical Genetics, . Article in Press. 

a Center for Genome Sciences and Systems Biology Washington University School of Medicine St. Louis, MO USA
b Department of Pediatrics
c Department of Pathology and Immunology Washington University School of Medicine St. Louis, MO USA
d Penn Cardiovascular Institute University of Pennsylvania School of Medicine Philadelphia, PA USA


Abstract
The genetic mechanisms driving normal brain development remain largely unknown. We performed genomic and immunohistochemical characterization of a novel, fatal human phenotype including extreme microcephaly with cerebral growth arrest at 14-18weeks gestation in three full sisters born to healthy, non-consanguineous parents. Analysis of index cases and parents included familial exome sequencing, karyotyping, and genome-wide single nucleotide polymorphism (SNP) array. From proband, control and unrelated microcephalic fetal cortical tissue, we compared gene expression of RNA and targeted immunohistochemistry. Each daughter was homozygous for a rare, non-synonymous, deleterious variant in the MKL2 gene and heterozygous for a private 185kb deletion on the paternal allele, upstream and in cis with his MKL2 variant allele, eliminating 24 CArG transcription factor binding sites and MIR4718. MKL1 was underexpressed in probands. Dysfunction of MKL2 and its transcriptional coactivation partner, serum response factor (SRF), was supported by a decrease in gene and protein expression of PCTAIRE1, a downstream target of MKL2:SRF heterodimer transcriptional activation, previously shown to result in severe microcephaly in murine models. While disruption of the MKL2:SRF axis has been associated with severe microcephaly and disordered brain development in multiple model systems, the role of this transcription factor complex has not been previously demonstrated in human brain development. © 2013 The Authors.


Author Keywords
CArG-box binding factor;  Exome;  Microcephaly;  MKL2;  SRF

Document Type: Article in Press
Source: Scopus

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Tu, T.-W.a d , Kim, J.H.b , Yin, F.Q.c , Jakeman, L.B.c , Song, S.-K.b
The impact of myelination on axon sparing and locomotor function recovery in spinal cord injury assessed using diffusion tensor imaging
(2013) NMR in Biomedicine, . Article in Press. 

a Department of Mechanical Engineering and Materials Science Washington University in St. Louis MO USA
b Department of Radiology Washington University in St. Louis MO USA
c Department of Physiology and Cell Biology and Center for Brain and Spinal Cord Repair Ohio State University Columbus, OH USA
d Radiology and Imaging Sciences, Clinical Center, National Institute of Health, Bethesda, MD, USA


Abstract
The dysmyelinated axons of shiverer mice exhibit impaired conduction characteristics, similar to early postnatal axons before myelination, whereas the patterns of neuronal activity and connectivity are relatively comparable with those of wild-type myelinated axons. This unique dysmyelination pattern is exploited in the present study to determine the role of compact myelin in the loss and recovery of function following traumatic spinal cord injury (SCI). We applied in vivo diffusion tensor imaging (DTI) and post-mortem immunohistochemistry analysis to examine changes in myelin and axonal integrity, and evaluated these changes in concert with the analysis of locomotor function from 1 to 4 weeks following a mid-thoracic contusion injury in homozygous shiverer and heterozygous littermate mice. The DTI biomarkers, axial and radial diffusivities, are noninvasive indicators of axon and myelin integrity in response to SCI of both myelinated and dysmyelinated spinal cord. We show that myelin is critical for normal hind limb function in open field locomotion. However, when the functional outcome is limited during chronic SCI, the extent of recovery is associated with residual axonal integrity and independent of the extent of intact myelin at the lesion epicenter. © 2013 John Wiley & Sons, Ltd.


Author Keywords
Diffusion tensor imaging;  Dysmyelination;  Myelin;  Spinal cord injury;  White matter

Document Type: Article in Press
Source: Scopus

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Klingstedt, T.a , Shirani, H.a , Åslund, K.O.A.a , Cairns, N.J.b , Sigurdson, C.J.c , Goedert, M.d , Nilsson, K.P.R.a
The Structural Basis for Optimal Performance of Oligothiophene-Based Fluorescent Amyloid Ligands: Conformational Flexibility is Essential for Spectral Assignment of a Diversity of Protein Aggregates
(2013) Chemistry - A European Journal, . Article in Press. 

a Department of Chemistry, Linköping University, 581 83 Linköping (Sweden)
b Department of Neurology, Alzheimer's Disease Research Center, Washington University, St. Louis, Missouri 63110 (USA)
c Department of Pathology, University of California, San Diego, La Jolla, California 92093-0612 (USA)
d MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH (UK)


Abstract
Protein misfolding diseases are characterized by deposition of protein aggregates, and optical ligands for molecular characterization of these disease-associated structures are important for understanding their potential role in the pathogenesis of the disease. Luminescent conjugated oligothiophenes (LCOs) have proven useful for optical identification of a broader subset of disease-associated protein aggregates than conventional ligands, such as thioflavinT and Congo red. Herein, the molecular requirements for achieving LCOs able to detect nonthioflavinophilic Aβ aggregates or non-congophilic prion aggregates, as well as spectrally discriminate Aβ and tau aggregates, were investigated. An anionic pentameric LCO was subjected to chemical engineering by: 1)replacing thiophene units with selenophene or phenylene moieties, or 2)alternating the anionic substituents along the thiophene backbone. In addition, two asymmetric tetrameric ligands were generated. Overall, the results from this study identified conformational freedom and extended conjugation of the conjugated backbone as crucial determinants for obtaining superior thiophene-based optical ligands for sensitive detection and spectral assignment of disease-associated protein aggregates. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Author Keywords
Alzheimer's disease;  Fluorescent probes;  Luminescent conjugated oligothiophenes;  Microscopy;  Protein folding

Document Type: Article in Press
Source: Scopus

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Leibel, S.a , Bloomberg, G.b
Attention-deficit/hyperactivity disorder stimulant medication reaction masquerading as chronic cough
(2013) Annals of Allergy, Asthma and Immunology, . Article in Press. 

a Department of Pediatric Allergy/Immunology, Washington University School of Medicine, St Louis, Missouri
b Department of Pediatrics, Washington University School of Medicine, St Louis, Missouri


Document Type: Article in Press
Source: Scopus

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Marquardt, L.M.a , Sakiyama-Elbert, S.E.a b
Engineering peripheral nerve repair
(2013) Current Opinion in Biotechnology, . Article in Press. 

a Department of Biomedical Engineering, Washington University, St. Louis, MO 63130, USA
b Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA


Abstract
Current approaches for treating peripheral nerve injury have resulted in promising, yet insufficient functional recovery compared to the clinical standard of care, autologous nerve grafts. In order to design a construct that can match the regenerative potential of the autograft, all facets of nerve tissue must be incorporated in a combinatorial therapy. Engineered biomaterial scaffolds in the future will have to promote enhanced regeneration and appropriate reinnervation by targeting the highly sensitive response of regenerating nerves to their surrounding microenvironment. © 2013 Elsevier Ltd. All rights reserved.


Document Type: Article in Press
Source: Scopus

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Smith, S.M.a , Beckmann, C.F.c , Andersson, J.a , Auerbach, E.J.b , Bijsterbosch, J.a , Douaud, G.a , Duff, E.a , Feinberg, D.A.d , Griffanti, L.a e , Harms, M.P.f , Kelly, M.a , Laumann, T.f , Miller, K.L.a , Moeller, S.b , Petersen, S.f , Power, J.f , Salimi-Khorshidi, G.a , Snyder, A.Z.f , Vu, A.T.b d , Woolrich, M.W.g , Xu, J.b h , Yacoub, E.b , Ugurbil, K.b , Van Essen, D.C.f , Glasser, M.F.f
Resting-state fMRI in the Human Connectome Project
(2013) NeuroImage, . Article in Press. 

a FMRIB (Oxford Centre for Functional MRI of the Brain), Oxford University, Oxford, UK
b Center for Magnetic Resonance Research, University of Minnesota Medical School, Minneapolis, MN, USA
c Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands and MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands
d Helen Wills Institute for Neuroscience, University of California, Berkeley, CA, USA
e Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milan, Italy and MR Laboratory, Fondazione Don Carlo Gnocchi ONLUS, Milan, Italy
f Washington University School of Medicine, Washington University, St. Louis, MO, USA
g OHBA (Oxford Centre for Human Brain Activity), Oxford University, Oxford, UK
h Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA


Abstract
Resting-state functional magnetic resonance imaging (rfMRI) allows one to study functional connectivity in the brain by acquiring fMRI data while subjects lie inactive in the MRI scanner, and taking advantage of the fact that functionally related brain regions spontaneously co-activate. rfMRI is one of the two primary data modalities being acquired for the Human Connectome Project (the other being diffusion MRI). A key objective is to generate a detailed in vivo mapping of functional connectivity in a large cohort of healthy adults (over 1000 subjects), and to make these datasets freely available for use by the neuroimaging community. In each subject we acquire a total of 1 h of whole-brain rfMRI data at 3 T, with a spatial resolution of 2 × 2 × 2 mm and a temporal resolution of 0.7 s, capitalizing on recent developments in slice-accelerated echo-planar imaging. We will also scan a subset of the cohort at higher field strength and resolution. In this paper we outline the work behind, and rationale for, decisions taken regarding the rfMRI data acquisition protocol and pre-processing pipelines, and present some initial results showing data quality and example functional connectivity analyses. © 2013 Elsevier Inc. All rights reserved.

Document Type: Article in Press
Source: Scopus

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Lichtenhan, J., Salt, A.
Amplitude modulation of audible sounds by non-audible sounds: Understanding the effects of wind turbine noise
(2013) Proceedings of Meetings on Acoustics, 19, art. no. 040064, 9 p. 

Washington University in St. Louis, St. Louis, MO 63110, United States


Abstract
Our research has suggested a number of mechanisms by which low-frequency noise could bother individuals living near wind turbines: causing endolymphatic hydrops, exciting subconscious pathways, and amplitude modulation of audible sounds. Here we focus on the latter mechanism, amplitude modulation. We measured single-auditory-nerve fiber responses to probe tones at their characteristic frequency in cats. A 50 Hz tone, which did not cause an increase in spontaneous firing rate (i.e., was not audible to the fiber when presented alone) was used to amplitude modulate responses to the probe tone. We found that as probe frequency decreased, a lower level of the low-frequency non-audible tone was needed to achieve criterion amplitude modulation. In other words, low-frequencies that are coded in the cochlear apex require less low-frequency sound pressure level to be amplitude modulated as compared to higher-frequencies that are coded in the cochlear base. This finding was validated, and extended to lower frequencies, by amplitude modulating gross measures of onset-synchronous (compound action potentials) and phase-synchronous (auditory nerve overlapped waveforms) in guinea pigs. Our results suggest that that infrasound generated by wind turbines may cause amplitude modulation of audible sounds, which is often the basis for complaints from those living near wind turbines. © 2013 Acoustical Society of America.

Document Type: Conference Paper
Source: Scopus

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Roediger III., H.L., DeSoto, K.A.
Confidence and memory: Assessing positive and negative correlations
(2013) Memory, . Article in Press. 

Department of Psychology, Washington University in St. Louis, MO, USA


Abstract
The capacity to learn and remember surely evolved to help animals solve problems in their quest to reproduce and survive. In humans we assume that metacognitive processes also evolved, so that we know when to trust what we remember (i.e., when we have high confidence in our memories) and when not to (when we have low confidence). However this latter feature has been questioned by researchers, with some finding a high correlation between confidence and accuracy in reports from memory and others finding little to no correlation. In two experiments we report a recognition memory paradigm that, using the same materials (categorised lists), permits the study of positive correlations, zero correlations, and negative correlations between confidence and accuracy within the same procedure. We had subjects study words from semantic categories with the five items most frequently produced in norms omitted from the list; later, subjects were given an old/new recognition test and made confidence ratings on their judgements. Although the correlation between confidence and accuracy for studied items was generally positive, the correlation for the five omitted items was negative in some methods of analysis. We pinpoint the similarity between lures and targets as creating inversions between confidence and accuracy in memory. We argue that, while confidence is generally a useful indicant of accuracy in reports from memory, in certain environmental circumstances even adaptive processes can foster illusions of memory. Thus understanding memory illusions is similar to understanding perceptual illusions: Processes that are usually adaptive can go awry under certain circumstances. © 2013 Copyright Taylor and Francis Group, LLC.


Author Keywords
Categorised lists;  Confidence;  Memory accuracy;  Metacognition;  Recognition memory

Document Type: Article in Press
Source: Scopus

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Peelle, J.E.
Cortical responses to degraded speech are modulated by linguistic predictions
(2013) Proceedings of Meetings on Acoustics, 19, art. no. 060108, 5 p. 

Department of Otolaryngology, Washington University in St. Louis, 660 South Euclid Ave, St. Louis, MO 63110, United States


Abstract
Our perceptual experience is formed by combining incoming sensory information with prior knowledge and expectation. When speech is not fully intelligible, non-acoustic information may be particularly important. Predictions about a degraded acoustic signal can be provided extrinsically (for example, by presenting a written cue) or intrinsically (if the speech is still partially intelligible). Here I review two studies in which the neural response to speech was measured using magnetoencephalography (MEG), with speech clarity parametrically manipulated using noise vocoding. In a study of isolated word processing, accurate predictions provided by written text enhanced subjective clarity and changed the response in early auditory processing regions of temporal cortex. In a separate study looking at connected speech, the phase of ongoing cortical oscillations was matched to that of the acoustic speech envelope in the range of the syllable rate (4-8 Hz). Critically, this phase-locking was enhanced in left temporal cortex when speech is intelligible. Both experiments thus highlight neural responses in brain regions associated with relatively low-level speech perception. Together these findings support the ability of linguistic information to provide predictions that shape auditory processing of spoken language, particularly when acoustic clarity is compromised. © 2013 Acoustical Society of America.


Document Type: Conference Paper
Source: Scopus

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Naismith, R.T.a , Xu, J.a , Klawiter, E.C.a , Lancia, S.a , Tutlam, N.T.a , Wagner, J.M.d , Qian, P.a , Trinkaus, K.b , Song, S.-K.c , Cross, A.H.a
Spinal cord tract diffusion tensor imaging reveals Disability substrate in demyelinating disease
(2013) Neurology, 80 (24), pp. 2201-2209. Cited 1 time.

a Department of Neurology, Washington University, St. Louis, MO, United States
b Department of Biostatistics, Washington University, St. Louis, MO, United States
c Department of Radiology, Washington University, St. Louis, MO, United States
d Department of Physical Therapy and Athletic Training, Saint Louis University, St. Louis, MO, United States


Abstract
Objective: This study assessed the tissue integrity of major cervical cord tracts by using diffusion tensor imaging (DTI) to determine the relationship with specific clinical functions carried by those tracts. Methods: This was a cross-sectional study of 37 patients with multiple sclerosis or neuromyelitis optica with remote cervical cord disease. Finger vibratory thresholds, 25-foot timed walk (25FTW), 9-hole peg test (9HPT), and Expanded Disability Status Scale were determined. DTI covered cervical regions C1 through C6 with 17 5-mm slices (0.9 x 0.9 mm in-plane resolution). Regions of interest included posterior columns (PCs) and lateral corticospinal tracts (CSTs). Hierarchical linear mixed-effect modeling included covariates of disease subtype (multiple sclerosis vs neuromyelitis optica), disease duration, and sex. Results: Vibration thresholds were associated with radial diffusivity (RD) and fractional anisotropy (FA) in the PCs (both p < 0.01), but not CSTs (RD, p = 0.29; FA, p = 0.14). RD and FA in PCs, and RD in CSTs were related to 9HPT (each p < 0.0001). 25FTW was associated with RD and FA in PCs (p < 0.0001) and RD in CSTs (p = 0.008). Expanded Disability Status Scale was related to RD and FA in PCs and CSTs (p < 0.0001). Moderate/severe impairments in 9HPT (p = 0.006) and 25FTW (p = 0.017) were more likely to show combined moderate/severe tissue injury within both PCs and CSTs by DTI. Conclusions: DTI can serve as an imaging biomarker of spinal cord tissue injury at the tract level. RD and FA demonstrate strong and consistent relationships with clinical outcomes, specific to the clinical modality. © 2013 American Academy of Neurology.


Document Type: Article
Source: Scopus

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Freeman, G.M.a , Krock, R.M.a , Aton, S.J.a , Thaben, P.b , Herzog, E.D.a
GABA networks destabilize genetic oscillations in the circadian pacemaker
(2013Neuron, 78 (5), pp. 799-806. 

a Department of Biology, Washington University, St. Louis, MO 63130, United States
b Institute for Theoretical Biology, Humboldt University, 10115 Berlin, Germany


Abstract
Systems of coupled oscillators abound in nature. How they establish stable phase relationships under diverse conditions is fundamentally important. The mammalian suprachiasmatic nucleus (SCN) is a self-sustained, synchronized network of circadian oscillators that coordinates daily rhythms in physiology and behavior. To elucidate the underlying topology and signaling mechanisms that modulate circadian synchrony, we discriminated the firing of hundreds of SCN neurons continuously over days. Using an analysis method to identify functional interactions between neurons based on changes in their firing, we characterized a GABAergic network comprised of fast, excitatory, and inhibitory connections that is both stable over days and changes in strength with time of day. By monitoring PERIOD2 protein expression, we provide the first evidence that these millisecond-level interactions actively oppose circadian synchrony and inject jitter into daily rhythms. These results provide a mechanism by which circadian oscillators can tune their phase relationships under different environmental conditions. © 2013 Elsevier Inc.

Document Type: Article
Source: Scopus

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Monsell, S.E.a , Mock, C.a , Roe, C.M.b , Ghoshal, N.b , Morris, J.C.b , Cairns, N.J.b , Kukull, W.a
Comparison of symptomatic and asymptomatic persons with Alzheimer disease neuropathology
(2013) Neurology, 80 (23), pp. 2121-2129. 

a National Alzheimer's Coordinating Center, University of Washington, Seattle, WA, United States
b Department of Neurology, Washington University, School of Medicine, St. Louis, MO, United States


Abstract
Objectives: We sought to identify demographic and clinical features that were associated with expression of symptoms in the presence of Alzheimer disease (AD) neuropathologic changes. Methods: We studied 82 asymptomatic (Clinical Dementia Rating global score = 0) and 824 symptomatic subjects (Clinical Dementia Rating score >0) with low to high AD neuropathologic changes at autopsy who were assessed at 1 of 34 National Institute on Aging-funded Alzheimer's Disease Centers. All subjects underwent a clinical examination within 1 year of death. Logistic regression was used to evaluate factors associated with the odds of being asymptomatic vs symptomatic. Results: Asymptomatic subjects tended to have low neurofibrillary tangle scores but a wide range of neuritic plaque frequencies. There were, however, a few asymptomatic subjects with very high tangle and neuritic plaque burden, as well as symptomatic subjects with few changes. In the multivariable model, asymptomatic subjects were older (odds ratio [OR] = 1.04; 95%confidence interval [CI] = 1.01-1.07), had lower clinical Hachinski Ischemic Score (OR = 0.82; 95%CI = 0.69-0.97), were less likely to have an APOE ε4 allele (OR = 0.36; 95% CI = 0.16-0.83), and had lower neurofibrillary tangle score (OR = 0.28; 95% CI = 0.17-0.45) compared with symptomatic subjects. Conclusions: Dissociating clinical symptoms from pathologic findings better allows for investigation of preclinical AD. Our results suggest that although the severity of the pathology, particularly neurofibrillary tangles, has a large role in determining the extent of symptoms, other factors, including age, APOE status, and comorbidities such as cerebrovascular disease also explain differences in clinical presentation. © 2013 American Academy of Neurology.

Document Type: Article
Source: Scopus

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Poldrack, R.A.a , Barch, D.M.b , Mitchell, J.P.c , Wager, T.D.d , Wagner, A.D.e , Devlin, J.T.f , Cumba, C.a , Koyejo, O.a , Milham, M.P.g
Towards open sharing of task-based fMRI data: The OpenfMRI project
(2013) Frontiers in Neuroinformatics, (JUNE), . 

a University of Texas at Austin, United States
b Washington University, St. Louis, United States
c Harvard University, United States
d University of Colorado, United States
e Stanford University, United Kingdom
f University College, London, United Kingdom
g Child Mind Institute, United States


Abstract
The large-scale sharing of task-based functional neuroimaging data has the potential to allow novel insights into the organization of mental function in the brain, but the eld of neuroimaging has lagged behind other areas of bioscience in the development of data sharing resources. This paper describes the OpenFMRI project (accessible online at http://www.openfmri.org), which aims to provide the neuroimaging community with a resource to support open sharing of task-based fMRI studies. We describe the motivation behind the project, focusing particularly on how this project addresses some of the well-known challenges to sharing of task-based fMRI data. Results from a preliminary analysis of the current database are presented, which demonstrate the ability to classify between task contrasts with high generalization accuracy across subjects, and the ability to identify individual subjects from their activation maps with moderately high accuracy. Clustering analyses show that the similarity relations between statistical maps have a somewhat orderly relation to the mental functions engaged by the relevant tasks. These results highlight the potential of the project to support large-scale multivariate analyses of the relation between mental processes and brain function. © 2013 Poldrack, Barch, Mitchell, Wager, Wagner, Devlin, Cumba, Koyejo and Milham.


Document Type: Article
Source: Scopus

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Wong, M.
A critical review of mTOR inhibitors and epilepsy: From basic science to clinical trials
(2013Expert Review of Neurotherapeutics, 13 (6), pp. 657-669. 

Department of Neurology, Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis, MO 63110, United States


Abstract
Present medications for epilepsy have substantial limitations, such as medical intractability in many patients and lack of antiepileptogenic properties to prevent epilepsy. Drugs with novel mechanisms of action are needed to overcome these limitations. The mTOR signaling pathway has emerged as a possible therapeutic target for epilepsy. Preliminary clinical trials suggest that mTOR inhibitors reduce seizures in tuberous sclerosis complex (TSC) patients with intractable epilepsy. Furthermore, mTOR inhibitors have antiepileptogenic properties in preventing epilepsy in animal models of TSC. Besides TSC, accumulating preclinical data suggest that mTOR inhibitors may have antiseizure or antiepileptogenic actions in other types of epilepsy, including infantile spasms, neonatal hypoxic seizures, absence epilepsy and acquired temporal lobe epilepsy following brain injury, but these effects depend on a number of conditions. Future clinical and basic research is needed to establish whether mTOR inhibitors are an effective treatment for epilepsy. © 2013 Expert Reviews Ltd.


Author Keywords
epilepsy;  epileptogenesis;  everolimus;  mTOR;  rapamycin;  seizures;  traumatic brain injury;  tuberous sclerosis

Document Type: Review
Source: Scopus

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Tosoni, A.a d e , Shulman, G.L.a , Pope, A.L.W.a , McAvoy, M.P.b , Corbetta, M.a b c d e
Distinct representations for shifts of spatial attention and changes of reward contingencies in the human brain
(2013) Cortex, 49 (6), pp. 1733-1749. Cited 1 time.

a Department of Neurology, Washington University School of Medicine, St. Louis, United States
b Department of Radiology, Washington University School of Medicine, St. Louis, United States
c Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, United States
d Department of Neuroscience and Imaging, Gabriele D'Annunzio University, Italy
e Institute for Advanced Biomedical Technologies, Gabriele D'Annunzio University Foundation, Italy


Abstract
Success in a dynamically changing world requires both rapid shifts of attention to the location of important objects and the detection of changes in motivational contingencies that may alter future behavior. Here we addressed the relationship between these two processes by measuring the blood-oxygenation-level-dependent (BOLD) signal during a visual search task in which the location and the color of a salient cue respectively indicated where a rewarded target would appear and the monetary gain (large or small) associated with its detection. While cues that either shifted or maintained attention were presented every 4 to 8. sec, the reward magnitude indicated by the cue changed roughly every 30. sec, allowing us to distinguish a change in expected reward magnitude from a maintained state of expected reward magnitude. Posterior cingulate cortex was modulated by cues signaling an increase in expected reward magnitude, but not by cues for shifting versus maintaining spatial attention. Dorsal fronto-parietal regions in precuneus and frontal eye field (FEF) also showed increased BOLD activity for changes in expected reward magnitude from low to high, but in addition showed large independent modulations for shifting versus maintaining attention. In particular, the differential activation for shifting versus maintaining attention was not affected by expected reward magnitude. These results indicate that BOLD activations for shifts of attention and increases in expected reward magnitude are largely separate. Finally, visual cortex showed sustained spatially selective signals that were significantly enhanced when greater reward magnitude was expected, but this reward-related modulation was not observed in spatially selective regions of dorsal fronto-parietal cortex. © 2012 Elsevier Ltd.


Author Keywords
Changes in expected reward magnitude;  Maintenance of attention at a location;  Shifts of spatial attention

Document Type: Article
Source: Scopus

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Ray Dorsey, E.a , George, B.P.c , Leff, B.b , Willis, A.W.d
The coming crisis: Obtaining care for the growing burden of neurodegenerative conditions
(2013Neurology, 80 (21), pp. 1989-1996. Cited 1 time.

a Department of Neurology, Johns Hopkins Medicine, Baltimore, MD, United States
b Department of Neurology and Medicine, Johns Hopkins Medicine, Baltimore, MD, United States
c University of Rochester, School of Medicine and Dentistry, Rochester, NY, United States
d Department of Neurology, Washington University, School of Medicine, St. Louis, MO, United States


Abstract
As the US population ages, the burden of neurodegenerative disorders, including Alzheimer disease and Parkinson disease, will increase substantially. However, many of these patients and their families currently do not receive neurologic care. For example, a recent study found that over 40% of Medicare beneficiaries with an incident Parkinson disease diagnosis did not receive neurologist care early after diagnosis and those who did not were more likely to fracture a hip, be placed in a nursing home, and die. While geography, age, race, and sex likely contribute to these observed disparities in care and outcomes, a large barrier may be Medicare's reimbursement policies, which value procedures over care. With further reductions in Medicare reimbursement constantly on the horizon, the devaluing of clinical care will likely continue. Rather than guaranteeing access to care, Medicare's reimbursement policies may increasingly be an impediment to care. © 2013 American Academy of Neurology.

Document Type: Article
Source: Scopus

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Benatar, M.a , Wuu, J.a , Fernandez, C.a , Weihl, C.C.b , Katzen, H.a , Steele, J.a , Oskarsson, B.c , Taylor, J.P.d
Motor neuron involvement in multisystem proteinopathy: Implications for ALS
(2013) Neurology, 80 (20), pp. 1874-1880. 

a Department of Neurology, University of Miami, Miami, FL, United States
b Department of Neurology, Washington University, St. Louis, MO, United States
c Department of Neurology, University of California Davis, Davis, United States
d Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, United States


Abstract
Objective: To explore the putative connection between inclusion body myopathy, Paget disease, frontotemporal dementia (IBMPFD) and motor neuron disease (MND). Methods: Clinical, genetic, and EMG characterization of 17 patients from 8 IBMPFD families. Results: Limb weakness was the most common clinical manifestation (present in 15 patients, median onset age 38 years, range 25-52), with unequivocal evidence of upper motor neuron dysfunction in 3. EMG, abnormal in all 17, was purely neurogenic in 4, purely myopathic in 6, and mixed neurogenic/myopathic in 7. Cognitive/behavioral impairment was detected in at least 8. Mutations in VCP (R155H, R159G, R155C) were identified in 6 families, and in hnRNPA2B1 (D290V) in another family. The genetic cause in the eighth family has not yet been identified. Conclusion: Mutations in at least 4 genes may cause IBMPFD, and its phenotypic spectrum extends beyond IBM, Paget disease, and frontotemporal dementia (FTD). Weakness, the most common and disabling manifestation, may be caused by muscle disease or MND. The acronym IBMPFD is, therefore, insufficient to describe disorders due to VCP mutations or other recently identified IBMPFD-associated genes. Instead, we favor the descriptor multisystem proteinopathy (MSP), which encompasses both the extended clinical phenotype and the previously described prominent pathologic feature of protein aggregation in affected tissues. The nomenclature MSP1, MSP2, and MSP3 may be used for VCP-, HNRNPA2B1-, and HNRNPAl-associated disease, respectively. Genetic defects in MSP implicate a range of biological mechanisms including RNA processing and protein homeostasis, both with potential relevance to the pathobiology of more common MNDs such as amyotrophic lateral sclerosis (ALS) and providing an additional link between ALS and FTD. © 2013 American Academy of Neurology.

Document Type: Article
Source: Scopus

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Ostendorf, A.P.a , McKinstry, R.C.b , Shimony, J.S.b , Gutmann, D.H.a
Teaching neuroimages: T2 hyperintensities in neurofibromatosis type 1
(2013) Neurology, 80 (20), pp. e215-e216. 

a Department of Neurology, Washington University, School of Medicine, St. Louis, MO, United States
b Mallinkrodt Institute of Radiology, Washington University, School of Medicine, St. Louis, MO, United States

Document Type: Note
Source: Scopus

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Roe, C.M.a c , Fagan, A.M.a b c , Grant, E.A.a j , Hassenstab, J.a d , Moulder, K.L.a c , Dreyfus, D.M.a d , Sutphen, C.L.c , Benzinger, T.L.S.a e i , Mintun, M.A.e k , Holtzman, D.M.a b c , Morris, J.C.a c f g h
Amyloid imaging and CSF biomarkers in predicting cognitive impairment up to 7.5 years later
(2013) Neurology, 80 (19), pp. 1784-1791. 

a Knight Alzheimer's Disease Research Center, Washington University, School of Medicine, St. Louis, MO, United States
b Hope Center for Neurological Disorders, Washington University, School of Medicine, St. Louis, MO, United States
c Department of Neurology, Washington University, School of Medicine, St. Louis, MO, United States
d Department of Psychology, Washington University, School of Medicine, St. Louis, MO, United States
e Department of Radiology, Washington University, School of Medicine, St. Louis, MO, United States
f Department of Pathology and Immunology, Washington University, School of Medicine, St. Louis, MO, United States
g Department of Physical Therapy, Washington University, School of Medicine, St. Louis, MO, United States
h Department of Occupational Therapy, Washington University, School of Medicine, St. Louis, MO, United States
i Department of Neurosurgery, Washington University, School of Medicine, St. Louis, MO, United States
j Division of Biostatistics, Washington University, School of Medicine, St. Louis, MO, United States
k Avid Radiopharmaceuticals, Philadelphia, PA, United States


Abstract
Objectives: We compared the ability of molecular biomarkers for Alzheimer disease (AD), including amyloid imaging and CSF biomarkers (Aβ 42, tau, ptau181, tau/Aβ42, ptau 181/Aβ42), to predict time to incident cognitive impairment among cognitively normal adults aged 45 to 88 years and followed for up to 7.5 years. Methods: Longitudinal data from Knight Alzheimer's Disease Research Center participants (N = 201) followed for a mean of 3.70 years (SD = 1.46 years) were used. Participants with amyloid imaging and CSF collection within 1 year of a clinical assessment indicating normal cognition were eligible. Cox proportional hazards models tested whether the individual biomarkers were related to time to incident cognitive impairment. "Expanded" models were developed using the biomarkers and participant demographic variables. The predictive values of the models were compared. Results: Abnormal levels of all biomarkers were associated with faster time to cognitive impairment, and some participants with abnormal biomarker levels remained cognitively normal for up to 6.6 years. No differences in predictive value were found between the individual biomarkers (p &gt; 0.074), nor did we find differences between the expanded biomarker models (p &gt; 0.312). Each expanded model better predicted incident cognitive impairment than the model containing the biomarker alone (p &lt; 0.005). Conclusions: Our results indicate that all AD biomarkers studied here predicted incident cognitive impairment, and support the hypothesis that biomarkers signal underlying AD pathology at least several years before the appearance of dementia symptoms. © 2013 American Academy of Neurology.

Document Type: Article
Source: Scopus

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Daniels, D.J.a , Vellimana, A.K.b , Zipfel, G.J.b , Lanzino, G.a
Intracranial hemorrhage from dural arteriovenous fistulas: Clinical features and outcome
(2013) Neurosurgical Focus, 34 (5), art. no. E15, . 

a Department of Neurological Surgery, Mayo Clinic, Rochester, MN, United States
b Department of Neurosurgery, Washington University, St. Louis, MO, United States


Abstract
Object. In this paper the authors' goal was to review the clinical features and outcome of patients with intracranial dural arteriovenous fistulas (DAVFs) who presented withhemorrhage. Methods. A retrospective study of 28 patients with DAVFs who presented with intracranial hemorrhage to 2 separate institutions was performed. The information reviewedincluded clinical presentation, location and size of hemorrhage, angiographic features, treatment, and clinical and radiologically documented outcomes. Clinical and radiological follow-up were available in 27 of 28 patients (mean follow-up 17 months). Results. The vast majority of patients were male (86%), and the most common presenting symptom was suddenonset headache. All DAVFs had cortical venous drainage, and about one-third were associated with a venous varix. The most common location was tentorial (75%). Treatment ranged from endovascular (71%), surgical (43%), Gamma Knife surgery (4%), or a combination of modalities. The majority of fistulas (75%) were completely obliterated, and most patients experienced excellent clinical outcome (71%, modified Rankin Scale score of 0 or 1). There were no complications in this series. Conclusions. Case series, including the current one, suggest that the vast majority of patients who present with intracranial hemorrhage from a DAVF are male. The most common location for DAVFs presenting with hemorrhage is tentorial. Excellent outcomes are achieved with individualized treatment, which includes various therapeutic strategies alone or in combination. Despite the hemorrhagic presentation, almost two-thirds of patients experience a full recovery with no or minimal residual symptoms. © AANS, 2013.


Author Keywords
Cortical venous drainage;  Embolization;  Hemorrhage;  Intracranial dural arteriovenous fistula;  Surgery

Document Type: Article
Source: Scopus

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Zaidman, C.M.a , Seelig, M.J.b , Baker, J.C.c , Mackinnon, S.E.d , Pestronk, A.a
Detection of peripheral nerve pathology: Comparison of ultrasound and MRI
(2013) Neurology, 80 (18), pp. 1634-1640. Cited 1 time.

a Department of Neurology, Washington University, School of Medicine, St. Louis, MO, United States
b Department of Surgery, Washington University, School of Medicine, St. Louis, MO, United States
c Mallinckrodt Institute of Radiology, Washington University, School of Medicine, St. Louis, MO, United States
d Vanderbilt University, Nashville, TN, United States


Abstract
Objective: To compare accuracy of ultrasound and MRI for detecting focal peripheral nerve pathology, excluding idiopathic carpal or cubital tunnel syndromes. Methods: We performed a retrospective review of patients referred for neuromuscular ultrasound to identify patients who had ultrasound and MRI of the same limb for suspected brachial plexopathy or mononeuropathies, excluding carpal/cubital tunnel syndromes. Ultrasound and MRI results were compared to diagnoses determined by surgical or, if not performed, clinical/ electrodiagnostic evaluation. Results: We identified 53 patients who had both ultrasound and MRI of whom 46 (87%) had nerve pathology diagnosed by surgical (n = 39) or clinical/electrodiagnostic (n = 14) evaluation. Ultrasound detected the diagnosed nerve pathology (true positive)more often than MRI (43/46 vs 31/46, p<0.001). Nerve pathology was correctly excluded (true negative) with equal frequency by MRI and ultrasound (both 6/7). In 25%(13/53), ultrasound was accurate (true positive or true negative) when MRI was not. These pathologies were typically (10/13) long (>2 cm) and only occasionally (2/13) outside the MRI field of view. MRI missed multifocal pathology identified with ultrasound in 6 of 7 patients, often (5/7) because pathology was outside the MRI field of view. Conclusions: Imaging frequently detects peripheral nerve pathology and contributes to the differential diagnosis in patients with mononeuropathies and brachial plexopathies. Ultrasound is more sensitive than MRI (93% vs 67%), has equivalent specificity (86%), and better identifies multifocal lesions than MRI. In sonographically accessible regions ultrasound is the preferred initial imaging modality for anatomic evaluation of suspected peripheral nervous system lesions. © 2013 American Academy of Neurology.

Document Type: Article
Source: Scopus

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Parrella, E.a , Maxim, T.a , Maialetti, F.b , Zhang, L.a , Wan, J.a , Wei, M.a , Cohen, P.a , Fontana, L.c d e , Longo, V.D.a
Protein restriction cycles reduce IGF-1 and phosphorylated tau, and improve behavioral performance in an Alzheimer's disease mouse model
(2013) Aging Cell, 12 (2), pp. 257-268. 

a Longevity Institute, Davis School of Gerontology, and Department of Biological Sciences, University of Southern California, Los Angeles, CA, United States
b Division of Nutrition and Aging, Istituto Superiore di Sanità, Rome, Italy
c Division of Geriatrics and Nutritional Science, Washington University in St. Louis, St. Louis, MO, United States
d Department of Medicine, Salerno University School of Medicine, Salerno, Italy
e Healthy Aging Platform, CEINGE Biotecnologie Avanzate, Napoli, Italy


Abstract
In laboratory animals, calorie restriction (CR) protects against aging, oxidative stress, and neurodegenerative pathologies. Reduced levels of growth hormone and IGF-1, which mediate some of the protective effects of CR, can also extend longevity and/or protect against age-related diseases in rodents and humans. However, severely restricted diets are difficult to maintain and are associated with chronically low weight and other major side effects. Here we show that 4 months of periodic protein restriction cycles (PRCs) with supplementation of nonessential amino acids in mice already displaying significant cognitive impairment and Alzheimer's disease (AD)-like pathology reduced circulating IGF-1 levels by 30-70% and caused an 8-fold increase in IGFBP-1. Whereas PRCs did not affect the levels of b amyloid (Ab), they decreased tau phosphorylation in the hippocampus and alleviated the age-dependent impairment in cognitive performance. These results indicate that periodic protein restriction cycles without CR can promote changes in circulating growth factors and tau phosphorylation associated with protection against age-related neuropathologies. © 2013 The Authors. © 2013 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.


Author Keywords
Aging;  Alzheimer;  IGF-1;  IGFBP-1;  Protein restriction;  Tau

Document Type: Article
Source: Scopus

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Gronski, M.P.a , Niemann, A.b , Berg, C.c
Participation patterns of urban preschoolers attending head start
(2013) OTJR Occupation, Participation and Health, 33 (2), pp. 68-75. 

a Program in Occupational Therapy, Washington University School of Medicine, St. Louis, MO, United States
b Department of Occupational Therapy and Neurology, Washington University School of Medicine, St. Louis, MO, United States
c Affton School District, St. Louis, MO, United States


Abstract
Awareness of the impact of poverty on early childhood participation is crucial in providing adequate and effective services for young children and their families. Through a university-community partnership to support Head Start teachers to broaden their developmental evaluations, the Preschool Activity Card Sort (PACS) was administered to the parents of 81 preschoolers in a semi-structured interview format. Fifty-two (64%) of the children were served by a Head Start program and 29 (36%) were a convenience sample control group. Results from the PACS demonstrate that all of the preschoolers participate in a range of age-appropriate activities. Comparison between the Head Start and control groups revealed differences, with Bonferroni correction, in participation in community mobility (p =.000). It is imperative to provide opportunities for early childhood participation because many community activities are implicitly tied to school readiness. To fully meet the needs of families in impoverished communities, occupational therapists need to seek out the voice of parents and focus on learning opportunities arising naturally in the context of daily living and community experiences. Copyright © American Occupational Therapy Foundation.


Author Keywords
Community;  Poverty;  Preschool

Document Type: Article
Source: Scopus

 

 

June 12, 2013

Documents

Roest, A.M.a , Carney, R.M.b , Freedland, K.E.b , Martens, E.J.c , Denollet, J.c , De Jonge, P.a c c 
Changes in cognitive versus somatic symptoms of depression and event-free survival following acute myocardial infarction in the Enhancing Recovery in Coronary Heart Disease (ENRICHD) study
(2013) Journal of Affective Disorders, 149 (1-3), pp. 335-341. Cited 2 times.
a Department of Psychiatry, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, Netherlands
b Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
c CoRPS - Center of Research on Psychology in Somatic Diseases, Department of Medical Psychology, Tilburg University, Tilburg, Netherlands

Abstract
Background: Randomized controlled trials focusing on the effects of antidepressant treatment in cardiac patients have found modest effects on depressive symptoms but not on cardiac outcomes. A secondary analysis was conducted on data from the Enhancing Recovery in Coronary Heart Disease trial to assess whether changes in somatic or cognitive depressive symptoms following acute MI predicted event-free survival and whether the results differed per treatment arm (cognitive behavior therapy or care as usual). Methods: Patients who met depression criteria and completed the 6th month depression assessment (n=1254) were included in this study. Measurements included demographic and clinical data and the Beck Depression Inventory at baseline and 6 months. The primary endpoint was a composite of recurrent MI and mortality over 2.4 years (standard deviation=0.9 years). Results: Positive changes (per 1 point increase) in somatic depressive symptoms (HR: 0.95; 95% CI: 0.92-0.98; p=0.001) but not in cognitive depressive symptoms (HR: 0.98; 95% CI: 0.96-1.01; p=0.19) were related to a reduced risk of recurrent MI and mortality after adjustment for baseline depression scores. There was a trend for an interaction effect between changes in somatic depressive symptoms and the intervention (p=0.08). After controlling for demographic and clinical variables, the association between changes in somatic depressive symptoms and event-free survival remained significant in the intervention arm (HR: 0.93; 95% CI: 0.88-0.98; p=0.01) only. Limitations: Secondary analyses. Conclusions: Changes in somatic depressive symptoms, and not cognitive symptoms, were related to improved outcomes in the intervention arm, independent of demographic and clinical variables. © 2013 Elsevier B.V.

Author Keywords
Cognitive behavior therapy;  Depression;  Dimensions;  Mortality;  Myocardial infarction

Document Type: Article
Source: Scopus

Sacco, P.a , Kuerbis, A.b c , Goge, N.a , Bucholz, K.K.d 
Help seeking for drug and alcohol problems among adults age 50 and older: A comparison of the NLAES and NESARC surveys
(2013) Drug and Alcohol Dependence, 131 (1-3), pp. 157-161. 
a School of Social Work, University of Maryland-Baltimore, United States
b Department of Mental Health Services Policy and Research, Research Foundation for Mental Hygiene, Inc., 1052 Riverside Drive, New York, NY 10032, United States
c Department of Psychiatry, Columbia University College of Physicians and Surgeons, 3 Columbus Circle, Ste. 1404, New York, NY 10019, United States
d Midwest Alcoholism Research Center, Department of Psychiatry, Washington University School of Medicine, Campus Box 8134, St. Louis, MO 63108, United States

Abstract
Background: Due to population aging and generational changes in alcohol and drug use, substance use disorders and treatment need are projected to increase among adults over 50. We analyzed data from two national surveys conducted 10 years apart [(NLAES (1991-1992) and NESARC (2001-2002)] to explore changes in help-seeking for alcohol and drug problems among adults over age 50. Methods: Data were pooled on help seeking for substance related problems, sociodemographic and clinical variables, and services type (i.e., formal and informal). Differences between the surveys were assessed, and help seeking among those under age 50 was compared to younger individuals; changes in the sociodemographic and clinical correlates of help seeking among those over age 50 were examined. Results: Among those 50 and older, rates of lifetime help seeking for any substance problem were higher in NESARC than NLAES, and percentages of those considering but not getting help were also higher in NESARC. Among those 50+, rates of past-year help seeking for drug use were higher in NESARC, but among those with lifetime substance use disorders, help seeking rates for alcohol and any substance were lower in the NESARC. Older help seekers in the NESARC were less likely to be White, more likely to be low income, and more likely to be current or former drug users than NLAES help seekers. Conclusions: This study documents increased rates of help seeking for substance related problems among those 50 and older and identifies cohort differences in profile of past-year help seekers. © 2012 Elsevier Ireland Ltd.

Author Keywords
Age;  Epidemiology;  Services;  Treatment;  Trends

Document Type: Article
Source: Scopus

Holtzman, N.S., Strube, M.J.
People With Dark Personalities Tend to Create a Physically Attractive Veneer
(2013) Social Psychological and Personality Science, 4 (4), pp. 461-467. 

Department of Psychology, Washington University, St. Louis, MO, United States

Abstract
Which personality traits are associated with physical attractiveness? Recent findings suggest that people high in some dark personality traits, such as narcissism and psychopathy, can be physically attractive. But what makes them attractive? Studies have confounded the more enduring qualities that impact attractiveness (i.e., unadorned attractiveness) and the effects of easily manipulated qualities such as clothing (i.e., effective adornment). In this multimethod study, we disentangle these components of attractiveness, collect self-reports and peer reports of eight major personality traits, and reveal the personality profile of people who adorn themselves effectively. Consistent with findings that dark personalities actively create positive first impressions, we found that the composite of the Dark Triad-Machiavellianism, narcissism, and psychopathy-correlates with effective adornment. This effect was also evident for psychopathy measured alone. This study provides the first experimental evidence that dark personalities construct appearances that act as social lures-possibly facilitating their cunning social strategies. © The Author(s) 2012.

Author Keywords
adornment;  attractiveness;  conscientiousness;  dark triad;  personality

Document Type: Review
Source: Scopus

 

Davie-Gray, A.a , Moor, S.b , Spencer, C.a c , Woodward, L.J.a d e f 
Psychosocial characteristics and poly-drug use of pregnant women enrolled in methadone maintenance treatment
(2013) Neurotoxicology and Teratology, 38, pp. 46-52. 

a Canterbury Child Development Research Group, Department of Psychology, University of Canterbury, Christchurch, New Zealand
b Dept of Psychological Medicine, University of Otago, Christchurch, New Zealand
c Neonatal Services, Canterbury District Health Board, New Zealand
d Van der Veer Institute for Parkinson's and Brain Research, Christchurch, New Zealand
e Department of Pediatrics, Washington University, St. Louis, MO, United States
f Department of Psychology, Washington University, St. Louis, MO, United States


Abstract
Pregnant women with substance dependency are a high-risk psychiatric and obstetric population, with their infants also at elevated neonatal risk. This paper draws on prospective, longitudinal data from a regional cohort of 81 methadone-maintained (MM) and 107 comparison women and their infants to describe the obstetric, socio-familial and mental health needs of women in methadone maintenance treatment during pregnancy. Of particular interest was the extent and pattern of maternal licit and illicit drug use over the course of pregnancy. Results showed that MM women had complex reproductive histories, chronic health problems, and were subject to high rates of socioeconomic adversity and comorbid mental health problems. During pregnancy, more than half continued to use licit and illicit drugs, although there was a general trend for drug use to reduce over time. No differences were observed between women maintained on low (12.5-61.0. mg/day) and high (61.1-195.0. mg/day) doses of methadone, with the exception of opiate abuse which was higher in the low dose group (p=.07). Findings highlight that pregnant women enrolled in MMT and their infants represent a vulnerable group with complex, social, obstetric and psychiatric needs. They also reinforce the need for services that can provide on-going wrap-around, multidisciplinary and multiagency care for these high risk dyads, both during pregnancy and in the transition to parenthood. © 2013 Elsevier Inc.


Author Keywords
Dose;  Drug use;  Maternal mental health;  Methadone;  Opiate;  Pregnancy
Document Type: Article
Source: Scopus

 

Carlson, E.N.a , Furr, R.M.b 
Resolution of Meta-Accuracy: Should People Trust Their Beliefs About How Others See Them?
(2013) Social Psychological and Personality Science, 4 (4), pp. 419-426. 

a Department of Psychology Washington University in St. Louis, St. Louis, MO, United States
b Department of Psychology, Wake Forest University, Winston-Salem, NC, United States

Abstract
Do people know when they can trust their metaperceptions (i.e., their beliefs about how they are seen)? The current study is the first to examine whether people can recognize which of their metaperceptions are more or less accurate, and it examines the source of this "resolution." In two samples, we assessed meta-accuracy, or the degree to which people's beliefs about the impressions they made corresponded to the actual impressions they made, for several close acquaintances (e.g., family, friends). We also assessed people's confidence in the accuracy of their metaperceptions for each acquaintance. Results showed that people recognized when they were more or less "meta-accurate," particularly in terms of the ways in which they were perceived as distinctive and unique individuals. This ability was partially driven by relationship quality. In sum, people seem to know when to trust their metaperceptions about individuals from their everyday lives. © The Author(s) 2012.

Author Keywords
interpersonal perception;  metacognition;  personality;  self-knowledge

Document Type: Article
Source: Scopus

 

Ji, J.a , Shimony, J.b , Gao, F.c , McKinstry, R.C.b , Gutmann, D.H.a 
Erratum to: Optic nerve tortuosity in children with neurofibromatosis type 1
(2013) Pediatric Radiology, p. 1. Article in Press. 

a Department of Neurology, Washington University School of Medicine, Box 8111, 660 S. Euclid Ave., St. Louis, 63110, United States
b Department of Radiology, Washington University School of Medicine, St. Louis, United States
c Division of Biostatistics, Washington University School of Medicine, St. Louis, United States

Document Type: Article in Press
Source: Scopus

 

Kapoor, M.a , Wang, J.-C.a , Wetherill, L.b , Le, N.a , Bertelsen, S.a , Hinrichs, A.L.a , Budde, J.a , Agrawal, A.a , Bucholz, K.a , Dick, D.c , Harari, O.a , Hesselbrock, V.d , Kramer, J.e , Nurnberger Jr., J.I.b , Rice, J.a , Saccone, N.i , Schuckit, M.f, Tischfield, J.g , Porjesz, B.h , Edenberg, H.J.b , Bierut, L.a , Foroud, T.b , Goate, A.a 
A meta-analysis of two genome-wide association studies to identify novel loci for maximum number of alcoholic drinks
(2013) Human Genetics, pp. 1-11. Article in Press. 

a Department of Psychiatry, B8134, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, 63110, United States
b Indiana University School of Medicine, Indianapolis, United States
c Virginia Commonwealth University, Richmond, United States
d University of Connecticut Health Center, Farmington, United States
e University of Iowa Carver College of Medicine, Iowa, United States
f University of California, San Diego, United States
g Rutgers University, Piscataway, United States
h SUNY Health Sciences Center, Brooklyn, United States
i Department of Genetics, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, United States

Abstract
Maximum number of alcoholic drinks consumed in a 24-h period (maxdrinks) is a heritable (&gt;50 %) trait and is strongly correlated with vulnerability to excessive alcohol consumption and subsequent alcohol dependence (AD). Several genome-wide association studies (GWAS) have studied alcohol dependence, but few have concentrated on excessive alcohol consumption. We performed two GWAS using maxdrinks as an excessive alcohol consumption phenotype: one in 118 extended families (N = 2,322) selected from the Collaborative Study on the Genetics of Alcoholism (COGA), and the other in a case-control sample (N = 2,593) derived from the Study of Addiction: Genes and Environment (SAGE). The strongest association in the COGA families was detected with rs9523562 (p = 2.1 × 10-6) located in an intergenic region on chromosome 13q31.1; the strongest association in the SAGE dataset was with rs67666182 (p = 7.1 × 10-7), located in an intergenic region on chromosome 8. We also performed a meta-analysis with these two GWAS and demonstrated evidence of association in both datasets for the LMO1 (p = 7.2 × 10-7) and PLCL1 genes (p = 4.1 × 10-6) with maxdrinks. A variant in AUTS2 and variants in INADL, C15orf32 and HIP1 that were associated with measures of alcohol consumption in a meta-analysis of GWAS studies and a GWAS of alcohol consumption factor score also showed nominal association in the current meta-analysis. The present study has identified several loci that warrant further examination in independent samples. Among the top SNPs in each of the dataset (p ≤ 10-4) far more showed the same direction of effect in the other dataset than would be expected by chance (p = 2 × 10-3, 3 × 10-6), suggesting that there are true signals among these top SNPs, even though no SNP reached genome-wide levels of significance. © 2013 Springer-Verlag Berlin Heidelberg.

Document Type: Article in Press
Source: Scopus

 

Barch, D.M.a b c , Burgess, G.C.d , Harms, M.P.b , Petersen, S.E.a c d e , Schlaggar, B.L.c d e f , Corbetta, M.c d e , Glasser, M.F.d , Curtiss, S.d , Dixit, S.b , Feldt, C.b , Nolan, D.b , Bryant, E.b , Hartley, T.b , Footer, O.b , Bjork, J.M.g , Poldrack, R.h i , Smith, S.j , Johansen-Berg, H.j , Snyder, A.Z.c , Van Essen, D.C.d 
Function in the human connectome: Task-fMRI and individual differences in behavior
(2013) NeuroImage, . Article in Press. 

a Department of Psychology, Washington University, St. Louis, MO, USA
b Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA
c Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA
d Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO, USA
e Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA
f Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA
g Division of Clinical Neuroscience and Behavioral Research, National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, USA
h Department of Psychology, University of Texas, Austin, TX, USA
i Department of Neuroscience and Imaging Research Center, University of Texas, Austin, TX, USA
j Centre for Functional MRI of the Brain (FMRIB), Oxford University, Oxford, UK

Abstract
The primary goal of the Human Connectome Project (HCP) is to delineate the typical patterns of structural and functional connectivity in the healthy adult human brain. However, we know that there are important individual differences in such patterns of connectivity, with evidence that this variability is associated with alterations in important cognitive and behavioral variables that affect real world function. The HCP data will be a critical stepping-off point for future studies that will examine how variation in human structural and functional connectivity play a role in adult and pediatric neurological and psychiatric disorders that account for a huge amount of public health resources. Thus, the HCP is collecting behavioral measures of a range of motor, sensory, cognitive and emotional processes that will delineate a core set of functions relevant to understanding the relationship between brain connectivity and human behavior. In addition, the HCP is using task-fMRI (tfMRI) to help delineate the relationships between individual differences in the neurobiological substrates of mental processing and both functional and structural connectivity, as well as to help characterize and validate the connectivity analyses to be conducted on the structural and functional connectivity data. This paper describes the logic and rationale behind the development of the behavioral, individual difference, and tfMRI batteries and provides preliminary data on the patterns of activation associated with each of the fMRI tasks, at both group and individual levels. © 2013.

Author Keywords
Cognitive;  Connectivity;  Emotion;  Individual differences;  Personality;  Sensory and motor function;  Task-fMRI

Document Type: Article in Press
Source: Scopus

 

Powers, A.D.a , Gleason, M.E.J.b , Oltmanns, T.F.a 
Symptoms of borderline personality disorder predict interpersonal (but not independent) stressful life events in a community sample of older adults
(2013) Journal of Abnormal Psychology, 122 (2), pp. 469-474. 

a Department of Psychology, Washington University, St. Louis, MO, United States
b Department of Human Development and Family Science, University of Texas at Austin, United States

Abstract
Individuals with borderline personality disorder (BPD) often experience stressful life events at a higher frequency than those without BPD. It is less clear what specific types of events are involved in this effect, and it has not been determined whether some features of BPD are more important than others in accounting for this effect. The latter issue is important in light of the heterogeneous nature of this diagnostic construct. These issues were examined in a large, representative community sample of men and women, ages 55-64. Ten Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev., DSM-IV-TR, Washington, DC, American Psychiatric Association, 2000) personality disorders were assessed at baseline using the Structured Interview for DSM-IV Personality: SIDP-IV (B. Pfohl, N. Blum, & M. Zimmerman, 1997, Washington, DC, American Psychiatric Press). Life events were measured at three sequential assessments following baseline at 6-month (N 1,294), 12-month (N 1,070), and 18-month (N 837) follow-ups. Stressful life events were identified using a self-report questionnaire (LTE-Q; List of Threatening Experiences Questionnaire: A subset of prescribed life events with considerable long-term contextual threat by T. Brugha, C. Bebbington, P. Tennant, and J. Hurry, 1985, Psychological Medicine, Vol. 15, pp. 189-194.) followed by a telephone interview. Only borderline personality pathology was related to an increase in the frequency of interpersonal stressful life events. Three specific symptoms of BPD were largely responsible for this connection: unstable interpersonal relationships, impulsivity, and chronic feelings of emptiness (negative association). Symptoms of avoidant and schizoid personality disorders were associated with a reduced number of stressful life events that are considered to be outside a person's control (e.g., serious illness, injury, or death of a loved one). None of the personality disorders predicted an increase in the number of stressful financial events (e.g., major financial crisis). These findings suggest that, as individuals approach later life, certain features of BPD continue to serve as important risk factors for stressful life events of an interpersonal nature. © 2013 American Psychological Association.

Author Keywords
Borderline personality disorder;  Interpersonal stressors;  Later adulthood;  Personality pathology;  Stressful life events

Document Type: Article
Source: Scopus

 

Barral, S.a , Cosentino, S.a , Costa, R.a , Andersen, S.L.b , Christensen, K.c , Eckfeldt, J.H.d e f , Newman, A.N.g , Perls, T.T.b , Province, M.A.h , Hadley, E.C.i , Rossi, W.K.i , Mayeux, R.a 
Exceptional memory performance in the Long Life Family Study
(2013) Neurobiology of Aging, . Article in Press. 

a Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, Department of Neurology, New York, NY, USA
b Section of Geriatrics, Department of Medicine, Boston University School of Medicine, and Boston Medical Center, Boston, MA, USA
c Department of Epidemiology, Graduate School of Public Health, Pittsburgh, PA, USA
d The Danish Aging Research Center, University of Southern Denmark, Odense C, Denmark
e Department of Clinical Genetics, Odense University Hospital, Odense C, Denmark
f Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense C, Denmark
g Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA
h Division of Statistical Genomics, Data Management Coordinating Center, Washington University School of Medicine, St. Louis, MI, USA
i National Institute on Aging, Bethesda, MD, USA

Abstract
Research to understand variability at the highest end of the cognitive performance distribution has been scarce. Our aim was to define a cognitive endophenotype based on exceptional episodic memory (EM) performance and to investigate familial aggregation of EM in families from the Long Life Family Study (LLFS). Using a sample of 1911 nondemented offspring of long-lived probands, we created a quantitative phenotype, EM (memory z ≥ 1.5), and classified LLFS families as EM and non-EM families based on the number of EM offspring. We then assessed differences in memory performance between LLFS relatives in the parental generation of EM families and those in non-EM families using multivariate analysis adjusted for APOE Apolipoprotein E genotype. LLFS relatives in the proband generation from EM families showed better EM performance than those from non-EM families (β = 0.74, standard error = 0.19, p = 1.4 × 10-4). We demonstrated that there is a familial correlation of the EM endophenotype, suggesting that genetic variants might influence memory performance in long-lived families. © 2013 Elsevier Inc. All rights reserved.

Author Keywords
Exceptional memory;  Genetic variants;  Long Life Family Study;  Quantitative trait

Document Type: Article in Press
Source: Scopus

 

Karch, C.M., Jeng, A.T., Skorupa, T., Cruchaga, C., Goate, A.M.
Novel progranulin variants do not disrupt progranulin secretion and cleavage
(2013) Neurobiology of Aging, . Article in Press. 

Department of Psychiatry and Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, USA

Abstract
A subset of frontotemporal dementia cases are neuropathologically defined by tau-negative, TAR DNA-binding protein-43, and ubiquitin-positive inclusions in the brain and are associated with mutations in the progranulin gene (GRN). Deep sequencing of families exhibiting late-onset dementia revealed several novel variants in GRN. Because of the small size of these families and limited availability of samples, it was not possible to determine whether the variants segregated with the disease. Furthermore, none of these families had autopsy confirmation of diagnosis. We sought to determine if these novel GRN variants alter progranulin (PGRN) protein stability, PGRN secretion, and PGRN cleavage in cultured cells. All the novel GRN variants behave like PGRN wild-type protein, suggesting that these variants represent rare polymorphisms. However, it remains possible that these variants affect other aspects of PGRN function or represent risk factors for dementia when combined with other modifying genes. © 2013 Elsevier Inc. All rights reserved.

Author Keywords
Frontotemporal dementia;  Granulin;  Late-onset Alzheimer's disease;  Progranulin

Document Type: Article in Press
Source: Scopus

 

Tsytsarev, V.a b d , Rao, B.a , Maslov, K.I.a , Li, L.a c e , Wang, L.V.a 
Photoacoustic and optical coherence tomography of epilepsy with high temporal and spatial resolution and dual optical contrasts
(2013) Journal of Neuroscience Methods, 216 (2), pp. 142-145. 

a Optical Imaging Laboratory, Department of Biomedical Engineering, Washington University in St. Louis, One Brookings Drive, St. Louis, MO 63130, United States
b University of Maryland School of Medicine, Department of Anatomy and Neurobiology, 20 Penn Street, HSF-II, Baltimore, MD 22201, United States
c Massachusetts General Hospital, Harvard Medical School, Wellman Center for Photomedicine, 40 Parkman Street, Ruth Sleeper Hall, Boston, MA 02114, United States
d University of Maryland School of Medicine, Department of Anatomy and Neu-robiology, HSF II Room S251, 20 Penn Street, Baltimore, MD 21201-1075, United States
e Massachusetts General Hospital, Harvard Medical School, Wellman Center for Photomedicine, 40 Parkman Street, Ruth Sleeper Hall, Boston, MA 02114, United States

Abstract
Epilepsy mapping with high spatial and temporal resolution has great significance for both fundamental research on epileptic neurons and the clinical management of epilepsy. In this communication, we demonstrate for the first time in vivo epilepsy mapping with high spatial and temporal resolution and dual optical contrasts in an animal model. Through the variations of a depthresolved optical coherence tomography signal with optical scattering contrast, we observed that epileptic neuron activities modulated the optical refractive index of epileptic neurons and their surrounding tissue. Simultaneously, through neurovasculature coupling mechanisms and optical absorption contrast, we used photoacoustic signals to document the hemodynamic changes of the microvasculature surrounding the epileptic neurons. The epilepsy mapping results were confirmed by a simultaneously recorded electroencephalogram signal during epileptic seizure. Our new epilepsy mapping tool, with high temporal and spatial resolution and dual optical contrasts, may find many applications, such as drug development and epilepsy surgery. © 2013 Elsevier B.V.

Author Keywords
4-Aminopyridine;  Epileptic seizures;  Optical coherence tomography;  Photoacoustic microscopy

Document Type: Article
Source: Scopus

 

Johnson, P.J., Wood, M.D., Moore, A.M.., Mackinnon, S.E.
Tissue engineered constructs for peripheral nerve surgery
(2013) European Surgery - Acta Chirurgica Austriaca, pp. 1-14. Article in Press. 

Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine, 660 South Euclid, Saint Louis, 63110, United States

Abstract
Background: Tissue engineering has been defined as "an interdisciplinary field that applies the principles of engineering and life sciences toward the development of biological substitutes that restore, maintain, or improve tissue function or a whole organ". Traumatic peripheral nerve injury resulting in significant tissue loss at the zone of injury necessitates the need for a bridge or scaffold for regenerating axons from the proximal stump to reach the distal stump. Methods: A review of the literature was used to provide information on the components necessary for the development of a tissue engineered peripheral nerve substitute. Then, a comprehensive review of the literature is presented composed of the studies devoted to this goal. Results: Extensive research has been directed toward the development of a tissue engineered peripheral nerve substitute to act as a bridge for regenerating axons from the proximal nerve stump seeking the distal nerve. Ideally this nerve substitute would consist of a scaffold component that mimics the extracellular matrix of the peripheral nerve and a cellular component that serves to stimulate and support regenerating peripheral nerve axons. Conclusions: The field of tissue engineering should consider its challenge to not only meet the autograft "gold standard" but also to understand what drives and inhibits nerve regeneration in order to surpass the results of an autograft. © 2013 Springer-Verlag Wien.

Author Keywords
Acellular nerve allograft;  Nerve conduits;  Neural crest cells;  Peripheral nerve surgery;  Stem cells;  Tissue engineering

Document Type: Article in Press
Source: Scopus

 

Cohen, K.J.a , Gibbs, I.C.b , Fisher, P.G.c , Hayashi, R.J.d , MacY, M.E.e , Gore, L.e 
A phase i trial of arsenic trioxide chemoradiotherapy for infiltrating astrocytomas of childhood
(2013) Neuro-Oncology, 15 (6), pp. 783-787. 

a Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 1800 Orleans St, Baltimore, MD 21287, United States
b Department of Radiation Oncology, Stanford University Medical Center, Palo Alto, CA, United States
c Department of Neurology, Stanford University Medical Center, Palo Alto, CA, United States
d Department of Pediatrics, Division of Hematology/Oncology, Washington University School of Medicine, St. Louis, MO, United States
e University of Colorado Anschutz Medical Campus, Children's Hospital Colorado, Aurora, CO, United States

Abstract
BackgroundArsenic trioxide (ATO) has demonstrated preclinical evidence of activity in the treatment of infiltrating astrocytomas.MethodsWe conducted a phase I trial of ATO given concomitantly with radiation therapy in children with newly diagnosed anaplastic astrocytoma, glioblastoma, or diffuse intrinsic pontine glioma. Eligible patients received a fixed daily dose of 0.15 mg/kg of ATO once a week, with each subsequent cohort of patients receiving an additional dose per week up to a planned frequency of ATO administration 5 days per week as tolerated. Twenty-four children were enrolled and 21 children were evaluable.ResultsATO was well tolerated throughout the entire dose escalation, resulting in confirmation of safety when administered 5 days per week during irradiation.ConclusionsThe recommended dose of ATO during conventional irradiation is 0.15 mg/kg given on a daily basis with each fraction of radiation therapy administered. © 2013 The Author(s).

Author Keywords
arsenic trioxide;  astrocytoma;  chemoradiotherapy;  pediatrics

Document Type: Article
Source: Scopus

 

Lanier, P.a , Bollinger, S.a , Krueger, R.F.b 
Advances in the Conceptualization of Personality Disorders: Issues Affecting Social Work Practice and Research
(2013) Clinical Social Work Journal, 41 (2), pp. 155-162. Cited 1 time.

a George Warren Brown School of Social Work, Washington University in St. Louis, One Brookings Drive, CB# 1196, St. Louis, MO, 63130, United States
b Department of Psychology, University of Minnesota, Minneapolis, MN, United States

Abstract
This article provides a review of the research that has informed the proposed changes to the DSM-5 conceptualization of personality psychopathology with a focus on implications for social work practice and research. A paradigm shift to a dimensional model is likely to replace the current categorical model of personality disorders and will have profound implications for the profession. While establishing a diagnostic system that is grounded in empirical knowledge is the primary benefit, this tool will also be more consistent with social work's orienting theories and values. Social workers should gain knowledge about the proposed changes and actively participate in the review process. © 2011 Springer Science+Business Media, LLC.

Author Keywords
Clinical social work;  DSM-5;  Five-factor model;  Personality disorders

Document Type: Review
Source: Scopus

 

O'Brien, D.E.a b , Brenner, D.S.a b c , Gutmann, D.H.a d , Gereau IV, R.W.a b 
Assessment of Pain and Itch Behavior in a Mouse Model of Neurofibromatosis Type 1
(2013) Journal of Pain, 14 (6), pp. 628-637. 

a Neuroscience Program, School of Medicine, Washington University, St. Louis, MO 63110, United States
b Department of Anesthesiology, Washington University Pain Center, St. Louis, MO, United States
c Medical Scientist Training Program, Washington University, School of Medicine, St. Louis, MO, United States
d Department of Neurology, Washington University Neurofibromatosis Center, St. Louis, MO, United States

Abstract
Neurofibromatosis type 1 (NF1) is characterized primarily by tumor formation in the nervous system, but patients report other neurological complications including pain and itch. Individuals with NF1 harbor 1 mutated NF1 allele causing heterozygous expression in all of their cells. In mice, Nf1 heterozygosity leads to hyperexcitability of sensory neurons and hyperproliferation of mast cells, both of which could lead to increased hypersensitivity and scratching in response to noxious and pruritic stimuli. To determine whether Nf1 heterozygosity may increase pain and itch behaviors independent of secondary effects of tumor formation, we used mice with a targeted, heterozygous Nf1 gene deletion (Nf1±) that lack tumors. Nf1± mice exhibited normal baseline responses to thermal and mechanical stimuli. Moreover, similar to wild-type littermates, Nf1± mice developed inflammation-induced heat and mechanical hypersensitivity, capsaicin-induced nocifensive behavior, histamine-dependent or -independent scratching, and chronic constriction injury-induced cold allodynia. However, Nf1± mice exhibited an attenuated first phase of formalin-induced spontaneous behavior and expedited resolution of formalin-induced heat hypersensitivity. These results are not consistent with the hypothesis that Nf1 heterozygosity alone is sufficient to increase pain and itch sensation in mice, and they suggest that additional mechanisms may underlie reports of increased pain and itch in NF1 patients. Perspective: This study assessed whether Nf1 heterozygosity in mice increased hypersensitivity and scratching following noxious and pruritic stimuli. Using Nf1± mice lacking tumors, this study finds no increases in pain or itch behavior, suggesting that there is no predisposition for either clinical symptom solely due to Nf1 heterozygosity. © 2013 by the American Pain Society.

Author Keywords
itch;  Neurofibromatosis;  pain;  Ras-GAP
Document Type: Article
Source: Scopus

 

Dahiya, S.a , Haydon, D.H.b , Alvarado, D.c , Gurnett, C.A.c , Gutmann, D.H.c , Leonard, J.R.b 
BRAFV600E mutation is a negative prognosticator in pediatric ganglioglioma
(2013) Acta Neuropathologica, 125 (6), pp. 901-910. 

a Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States
b Department of Neurological Surgery, Washington University School of Medicine, 1 Children's Place, St. Louis, MO 63110, United States
c Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States

Abstract
Gangliogliomas are typically low-grade neuroepithelial tumors seen in the pediatric and young adult populations. Despite their often bland histologic appearance, these tumors recur with varying frequencies; however, little data exist that adequately predict ganglioglioma recurrence in children. To identify potential histopathologic features predictive of recurrence-free survival, a series of 53 patients with World Health Organization (WHO) grade I gangliogliomas were evaluated, representing the largest cohort of pediatric gangliogliomas with accompanying histopathologic and survival data. Fifteen patients (28 %) exhibited disease recurrence during the study period. BRAF V600E immunohistochemistry was performed on 47 of these tumors. Histopathologic features associated with shorter recurrence-free survival included an absence of oligodendroglial morphology, higher glial cell density, microvascular proliferation, and the presence of a high lymphoplasmacytic inflammatory infiltrate. Eighteen tumors (38.3 %) had positive BRAF V600E staining, which was associated with shorter recurrence-free survival. Collectively, the combined use of histopathologic and molecular features to stratify grade I gangliogliomas into low and high-risk groups provides important information relevant to the management of children and young adults with these rare tumors. © 2013 Springer-Verlag Berlin Heidelberg.

Author Keywords
BRAFV600E;  Children;  Ganglioglioma;  Recurrence-free survival

Document Type: Article
Source: Scopus

 

Jarskog, L.F.a , Dong, Z.b , Kangarlu, A.b , Colibazzi, T.b , Girgis, R.R.b , Kegeles, L.S.b , Barch, D.M.c , Buchanan, R.W.d , Csernansky, J.G.e , Goff, D.C.f , Harms, M.P.c , Javitt, D.C.b , Keefe, R.S.g , McEvoy, J.P.g , McMahon, R.P.d , Marder, S.R.h , Peterson, B.S.b , Lieberman, J.A.b 
Effects of davunetide on N-acetylaspartate and choline in dorsolateral prefrontal cortex in patients with schizophrenia
(2013) Neuropsychopharmacology, 38 (7), pp. 1245-1252. Cited 1 time.

a Department of Psychiatry, University of North Carolina, Chapel Hill School of Medicine, 101 Manning Drive, Chapel Hill, NC 27599-7160, United States
b New York State Psychiatric Institute and Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, United States
c Department of Psychiatry, Washington University School of Medicine, St Louis, MO, United States
d Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, United States
e Department of Psychiatry, Northwestern Feinberg School of Medicine, Chicago, IL, United States
f Nathan Kline Institute for Psychiatric Research and Department of Psychiatry, New York University Langone Medical Center, New York, NY, United States
g Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, United States
h UCLA Semel Institute for Neuroscience and Human Behavior, Veterans Administration VISN 22 Mental Illness Research, Education and Clinical Center, Los Angeles, CA, United States

Abstract
Schizophrenia is associated with extensive neurocognitive and behavioral impairments. Studies indicate that N-acetylaspartate (NAA), a marker of neuronal integrity, and choline, a marker of cell membrane turnover and white matter integrity, may be altered in schizophrenia. Davunetide is a neurotrophic peptide that can enhance cognitive function in animal models of neurodegeneration. Davunetide has recently demonstrated modest functional improvement in a study of people with schizophrenia. In a subset of these subjects, proton magnetic resonance spectroscopy (1 H-MRS) was conducted to explore the effects of davunetide on change in NAA/creatine (NAA/Cr) and choline/creatine (choline/Cr) over 12 weeks of treatment. Of 63 outpatients with schizophrenia who received randomized davunetide (5 and 30 mg/day) or placebo in the parent clinical trial, 18 successfully completed 1 H-MRS in dorsolateral prefrontal cortex (DLPFC) at baseline and at 12 weeks. Cognition was assessed using the MATRICS Consensus Cognitive Battery (MCCB). NAA/Cr was unchanged for combined high-and low-dose davunetide groups (N=11). NAA/Cr in the high-dose davunetide group (N=8) suggested a trend increase of 8.0% (P=0.072) over placebo (N=7). Choline/Cr for combined high-and low-dose davunetide groups suggested a 6.4% increase (P=0.069), while the high-dose group showed a 7.9% increase (P=0.040) over placebo. Baseline NAA/Cr correlated with the composite MCCB score (R=0.52, P=0.033), as did individual cognitive domains of attention/vigilance, verbal learning, and social cognition; however, neither metabolite correlated with functional capacity. In this exploratory study, 12 weeks of adjunctive davunetide appeared to produce modest increases in NAA/Cr and choline/Cr in DLPFC in people with schizophrenia. This is consistent with a potential neuroprotective mechanism for davunetide. The data also support use of MRS as a useful biomarker of baseline cognitive function in schizophrenia. Future clinical and preclinical studies are needed to fully define the mechanism of action and cognitive effects of davunetide in schizophrenia. © 2013 American College of Neuropsychopharmacology.

Author Keywords
cognition;  MRS;  neuroprotective;  neurotrophic;  proton magnetic resonance spectroscopy

Document Type: Article
Source: Scopus

 

Richmond-Rakerd, L.S.a b , Slutske, W.S.a b , Heath, A.C.b c , Martin, N.G.d 
Effects of Sibship Size and Composition on Younger Brothers' and Sisters' Alcohol Use Initiation: Findings from an Australian Twin Sample
(2013) Alcoholism: Clinical and Experimental Research, 37 (6), pp. 1016-1024. 

a Department of Psychological Sciences, University of Missouri, Columbia, MO, United States
b Midwest Alcoholism Research Center, University of Missouri, Columbia, Missouri and Washington University, St. Louis, MO, United States
c Department of Psychiatry, Washington University, St. Louis, MO, United States
d Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Australia

Abstract
Background: The effects of sibship size and structure on delinquency are well established. Specifically, having a large family and many brothers has been shown to predict offending. However, despite strong links between delinquency and alcohol use, the contribution of sibship factors to drinking behaviors remains largely unexplored. The current study investigated the impact of sibship size and composition on younger brothers' and sisters' ages of drinking and intoxication onset. Methods: We employed a sample of 4,281 same-sex twins from the Australian Twin Register to examine whether (i) large sibship size facilitates earlier age at first drink (AFD) and age at first intoxication (AFI) in males and females, (ii) having many older brothers predicts earlier ages of AFD and AFI in males, and (iii) having many older brothers results in later AFD and AFI in females. We tested whether effects were moderated by parental divorce and alcohol misuse and mediated by familial religion. Results: Sibling effects were minimal before accounting for family context. However, when parental divorce and excessive parental drinking were included as moderators, sibling effects were significantly amplified among individuals from homes of divorce, and effects were strongest when siblings were close in age. Conclusions: Strong close in age older sibling effects indicate that proximal sibling attitudes and behaviors about alcohol likely interact with structural factors to influence younger siblings' drinking. Sibship factors were much more influential in one population (individuals from homes of divorce) than another (respondents with a parental history of excessive drinking), suggesting that sibling effects vary depending on the type of co-occurring familial risk. Prevention efforts performed at the family level, and introduced before first use of alcohol, are likely to delay drinking initiation and help prevent future alcohol problems. © 2012 by the Research Society on Alcoholism.

Author Keywords
Age at First Drink;  Close in Age;  Siblings;  Sibship Composition;  Twins

Document Type: Article
Source: Scopus

 

Arnold, K.M., McDermott, K.B.
Free recall enhances subsequent learning
(2013) Psychonomic Bulletin and Review, 20 (3), pp. 507-513. 

Department of Psychology, CB1125, Washington University in St. Louis, St. Louis, MO, 63130-4899, United States

Abstract
Testing, or retrieval practice, has become a central topic in memory research. One potentially important effect of retrieval practice has received little attention, however: It may enhance, or potentiate, subsequent learning. We introduce a paradigm that can measure the indirect, potentiating effect of free recall tests on subsequent learning, and then test a hypothesis for why tests may have this potentiating effect. In two experiments, the benefit of a restudy trial was enhanced when prior free recall tests had been taken. The results from a third, correlational study suggested that this effect might be mediated by the effect of testing on organization. Not only do encoding conditions affect later retrievability, but also retrieval attempts affect subsequent encoding effectiveness. © 2012 Psychonomic Society, Inc.

Author Keywords
Learning;  Memory;  Recall

Document Type: Article
Source: Scopus

 

Stone, J.a , Landau, W.b 
Neuroprosthetic control and tetraplegia
(2013) The Lancet, 381 (9881), p. 1900. 

a Department of Clinical Neurosciences, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, United Kingdom
b Washington University, School of Medicine, St Louis, MO, United States

Document Type: Letter
Source: Scopus

 

Becske, T.a , Kallmes, D.F.b , Saatci, I.c , McDougall, C.G.d , Szikora, I.e , Lanzino, G.b , Moran, C.J.f , Woo, H.H.g , Lopes, D.K.h , Berez, A.L.i , Cher, D.J.i , Siddiqui, A.H.j , Levy, E.I.j , Albuquerque, F.C.d , Fiorella, D.J.g , Berentei, Z.e , Marosfoi, M.e , Cekirge, S.H.c , Nelson, P.K.a 
Pipeline for uncoilable or failed aneurysms: Results from a multicenter clinical trial
(2013) Radiology, 267 (3), pp. 858-868. 

a Neurointerventional Service, Departments of Radiology and Neurology, New York University Medical Center, 560 First Ave, New York, NY 10016, United States
b Department of Neurosurgery, Mayo Clinic, Rochester, MN, United States
c Department of Radiology, Hacettepe University Hospitals, Ankara, Turkey
d Division of Neurologic Surgery, Barrow Neurologic Institute, Phoenix, AZ, United States
e National Institute of Neurosciences, Budapest, Hungary
f Division of Interventional Neuroradiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, MO, United States
g Department of Neurologic Surgery, Stony Brook University, Stony Brook, NY, United States
h Department of Neurologic Surgery, Rush University, Chicago, IL, United States
i Covidien, Menlo Park, CA, United States
j Department of Neurosurgery, University at Buffalo, Buffalo, NY, United States

Abstract
Purpose: To evaluate the safety and effectiveness of the Pipeline Embolization Device (PED; ev3/Covidien, Irvine, Calif) in the treatment of complex intracranial aneurysms. Materials and Methods: The Pipeline for Uncoilable or Failed Aneurysms is a multicenter, prospective, interventional, single-arm trial of PED for the treatment of uncoilable or failed aneurysms of the internal carotid artery. Institutional review board approval of the HIPAA-compliant study protocol was obtained from each center. After providing informed consent, 108 patients with recently unruptured large and giant wide-necked aneurysms were enrolled in the study. The primary effectiveness endpoint was angiographic evaluation that demonstrated complete aneurysm occlusion and absence of major stenosis at 180 days. The primary safety endpoint was occurrence of major ipsilateral stroke or neurologic death at 180 days. Results: PED placement was technically successful in 107 of 108 patients (99.1%). Mean aneurysm size was 18.2 mm; 22 aneurysms (20.4%) were giant (>25 mm). Of the 106 aneurysms, 78 met the study's primary effectiveness endpoint (73.6%; 95% posterior probability interval: 64.4%-81.0%). Six of the 107 patients in the safety cohort experienced a major ipsilateral stroke or neurologic death (5.6%; 95% posterior probability interval: 2.6%-11.7%). Conclusion: PED offers a reasonably safe and effective treatment of large or giant intracranial internal carotid artery aneurysms, demonstrated by high rates of complete aneurysm occlusion and low rates of adverse neurologic events; even in aneurysms failing previous alternative treatments. © RSNA, 2013.

Document Type: Article
Source: Scopus

 

Creeley, C.a , Dikranian, K.b , Dissen, G.c , Martin, L.c , Olney, J.a , Brambrink, A.c d 
Propofol-induced apoptosis of neurones and oligodendrocytes in fetal and neonatal rhesus macaque brain
(2013) British Journal of Anaesthesia, 110 (SUPPL.1), pp. i29-i38. Cited 1 time.

a Departments of Psychiatry, United States
b Anatomy and Neurobiology, Washington University School of Medicine, St Louis, MO, United States
c Division of Neuroscience, Oregon National Primate Research Center, OR, United States
d Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, Portland, OR, United States

Abstract
BackgroundExposure of the fetal or neonatal non-human primate (NHP) brain to isoflurane or ketamine for 5 h causes widespread apoptotic degeneration of neurones, and exposure to isoflurane also causes apoptotic degeneration of oligodendrocytes (OLs). The present study explored the apoptogenic potential of propofol in the fetal and neonatal NHP brain.MethodFetal rhesus macaques at gestational age 120 days were exposed in utero, or postnatal day 6 rhesus neonates were exposed directly for 5 h to propofol anaesthesia (n=4 fetuses; and n=4 neonates) or to no anaesthesia (n=4 fetuses; n=5 neonates), and the brains were systematically evaluated 3 h later for evidence of apoptotic degeneration of neurones or glia.ResultsExposure of fetal or neonatal NHP brain to propofol caused a significant increase in apoptosis of neurones, and of OLs at a stage when OLs were just beginning to myelinate axons. Apoptotic degeneration affected similar brain regions but to a lesser extent than we previously described after isoflurane. The number of OLs affected by propofol was approximately equal to the number of neurones affected at both developmental ages. In the fetus, neuroapoptosis affected particularly subcortical and caudal regions, while in the neonate injury involved neocortical regions in a distinct laminar pattern and caudal brain regions were less affected.ConclusionsPropofol anaesthesia for 5 h caused death of neurones and OLs in both the fetal and neonatal NHP brain. OLs become vulnerable to the apoptogenic action of propofol when they are beginning to achieve myelination competence. © 2013 © The Author [2013].

Author Keywords
anaesthetics i.v., propofol;  developing brain;  neurones;  non-human primates;  oligodendroglia;  toxicity

Document Type: Article
Source: Scopus

 

Scott, B.a , Sun, C.-L.a , Mao, X.a , Yu, C.a , Vohra, B.P.S.b , Milbrandt, J.c d e , Crowder, C.M.a c d 
Role of oxygen consumption in hypoxia protection by translation factor depletion
(2013) Journal of Experimental Biology, 216 (12), pp. 2283-2292. 

a Department of Anesthesiology, Washington University, School of Medicine, St Louis, MO 63110, United States
b Department of Genetics, Washington University, School of Medicine, St Louis, MO 63110, United States
c Department of Developmental Biology, Washington University, School of Medicine, St Louis, MO 63110, United States
d HOPE Center for Neurological Disorders, Washington University, School of Medicine, St Louis, MO 63110, United States
e Department of Biology, University of Central Arkansas, Conway, AR 72034, United States

Abstract
The reduction of protein synthesis has been associated with resistance to hypoxic cell death. Which components of the translation machinery control hypoxic sensitivity and the precise mechanism has not been systematically investigated, although a reduction in oxygen consumption has been widely assumed to be the mechanism. Using genetic reagents in Caenorhabditis elegans, we examined the effect on organismal survival after hypoxia of knockdown of 10 factors functioning at the three principal steps in translation. Reduction-of-function of all 10 translation factors significantly increased hypoxic survival to varying degrees, not fully accounted for by the level of translational suppression. Measurement of oxygen consumption showed that strong hypoxia resistance was possible without a significant decrease in oxygen consumption. Hypoxic sensitivity had no correlation with lifespan or reactive oxygen species sensitivity, two phenotypes associated with reduced translation. Resistance to tunicamycin, which produces misfolded protein toxicity, was the only phenotype that significantly correlated with hypoxic sensitivity. Translation factor knockdown was also hypoxia protective for mouse primary neurons. These data show that translation factor knockdown is hypoxia protective in both C. elegans and mouse neurons and that oxygen consumption does not necessarily determine survival; rather, mitigation of misfolded protein toxicity is more strongly associated with hypoxic protection. © 2013. Published by The Company of Biologists Ltd.

Author Keywords
C. elegans;  Hypoxia;  Ischemia;  Translation factors

Document Type: Article
Source: Scopus

 

Bugg, J.M.a , Scullin, M.K.a b , McDaniel, M.A.a 
Strengthening encoding via implementation intention formation increases prospective memory commission errors
(2013) Psychonomic Bulletin and Review, 20 (3), pp. 522-527. 

a Department of Psychology, Washington University in St. Louis, St. Louis, MO, 63130-4899, United States
b Emory University School of Medicine, Atlanta, GA, United States

Abstract
Prospective memory refers to the ability to remember to execute future intentions (e.g., taking medication with dinner). Although most prior research on prospective memory errors has focused on omission errors (i.e., failures to perform an intention in response to a target cue), there has been a recent surge in research on commission errors, the erroneous performance of a finished intention. Existing studies have examined factors at retrieval that lead to commission errors; the present study extends this research by investigating the impact of encoding strength. We found that relative to standard encoding, implementation intention encoding doubled the risk of commission errors in our laboratory paradigm for both young and older adults. This novel finding demonstrates the impact of encoding strength on commission errors and documents the potential challenges of deactivating the effects of implementation intentions upon completion of a prospective memory task. © 2013 Psychonomic Society, Inc.

Author Keywords
Aging;  Commission errors;  Finished intentions;  Implementation intentions;  Prospective memory

Document Type: Article
Source: Scopus

 

Antenor-Dorsey, J.A.V.a , Hershey, T.a b c , Rutlin, J.a , Shimony, J.S.b , McKinstry, R.C.b d , Grange, D.K.d , Christ, S.E.e, White, D.A.f 
White matter integrity and executive abilities in individuals with phenylketonuria
(2013) Molecular Genetics and Metabolism, 109 (2), pp. 125-131. 

a Department of Psychiatry, Washington University School of Medicine, Campus Box 8134, St. Louis, MO 63110, United States
b Mallinckrodt Institute of Radiology, Washington University School of Medicine, Campus Box 8131, St. Louis, MO 63110, United States
c Department of Neurology, Washington University School of Medicine, Campus Box 8111, St. Louis, MO 63110, United States
d Department of Pediatrics, Washington University School of Medicine, Campus Box 8116, St. Louis, MO 63110, United States
e Department of Psychological Sciences, University of Missouri, 210 McAlester Hall, Columbia, MO 65211, United States
f Department of Psychology, Washington University, Campus Box 1125, St. Louis, MO 63130, United States


Abstract
Previous studies have revealed white matter abnormalities in the brains of individuals with phenylketonuria (PKU), but the microstructural nature of these abnormalities and their relationship to phenylalanine (Phe) levels and cognitive outcomes are poorly understood. In the current study, the microstructural integrity of white matter in 29 individuals with early-treated PKU and 12 healthy controls was examined using two complementary diffusion tensor imaging (DTI) approaches: region-of-interest (ROI) based analysis and voxel-wise tract based spatial statistics (TBSS) analysis. Relationships among DTI, executive abilities, and Phe level findings were explored. DTI revealed widespread lowering of mean diffusivity (MD) in the white matter of the PKU group in comparison with the control group. Executive abilities were also poorer for individuals with PKU than controls. Within the PKU group, lower MD was associated with higher Phe level and poorer executive abilities. These findings are the first to demonstrate the interplay among microstructural white matter integrity, executive abilities, and Phe control in individuals with PKU. © 2013 Elsevier Inc.

Author Keywords
Brain;  Cognition;  Executive;  Phenylketonuria;  White matter

Document Type: Article
Source: Scopus

 

Liu, Z.a b , Liu, Z.c d , Walters, B.J.a , Owen, T.a e , Kopan, R.c d , Zuo, J.a 
In Vivo Visualization of Notch1 Proteolysis Reveals the Heterogeneity of Notch1 Signaling Activity in the Mouse Cochlea
(2013) PLoS ONE, 8 (5), art. no. e64903, . 

a Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, United States
b Integrated Program in Biomedical Sciences, University of Tennessee Health Science Center, Memphis, TN, United States
c Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, United States
d Division of Dermatology, Washington University School of Medicine, St. Louis, MO, United States
e University of Bath, Bath, United Kingdom


Abstract
Mechanosensory hair cells (HCs) and surrounding supporting cells (SCs) in the mouse cochlea are important for hearing and are derived from the same prosensory progenitors. Notch1 signaling plays dual but contrasting and age-dependent roles in mouse cochlear development: early lateral induction and subsequent lateral inhibition. However, it has been difficult to directly visualize mouse cochlear cells experiencing various levels of Notch1 activity at single cell resolution. Here, we characterized two knock-in mouse lines, Notch1Cre (Low)/+ and Notch1Cre (High)/+, with different Cre recombinase activities, that can detect Notch1 receptor proteolysis or Notch1 activity at high and low thresholds, respectively. Using both lines together with a highly sensitive Cre reporter line, we showed that Notch1 activity is nearly undetectable during lateral induction but increases to medium and high levels during lateral inhibition. Furthermore, we found that within the neonatal organ of Corti, the vast majority of cells that experience Notch1 activity were SCs not HCs, suggesting that HCs kept undetectable Notch1 activity during the entire lineage development. Furthermore, among SC subtypes, ~85-99% of Deiters' and outer pillar cells but only ~19-38% of inner pillar cells experience medium and high levels of Notch1 activity. Our results demonstrate that Notch1 activity is highly heterogeneous: 1) between lateral induction and inhibition; 2) between HC and SC lineages; 3) among different SC subtypes; 4) among different cells within each SC subtype. Such heterogeneity should elucidate how the development of the cochclear sensory epithelium is precisely controlled and how HC regeneration can be best achieved in postnatal cochleae. © 2013 Liu et al.

Document Type: Article
Source: Scopus

 

Babetto, E.a , Beirowski, B.b , Russler, E.a , Milbrandt, J.b c , DiAntonio, A.a c 
The Phr1 Ubiquitin Ligase Promotes Injury-Induced Axon Self-Destruction
(2013) Cell Reports, 3 (5), pp. 1422-1429. 

a Department of Developmental Biology, Washington University, School of Medicine, St. Louis, MO 63110, United States
b Department of Genetics, Washington University, School of Medicine, St. Louis, MO 63110, United States
c Hope Center for Neurological Disorders, Washington University, School of Medicine, St. Louis, MO 63110, United States

Abstract
Axon degeneration is an evolutionarily conserved process that drives the loss of damaged axons and is an early event in many neurological disorders, so it is important to identify the molecular constituents of this poorly understood mechanism. Here, we demonstrate that the Phr1 E3 ubiquitin ligase is a central component of this axon degeneration program. Loss of Phr1 results in prolonged survival of severed axons in both the peripheral and central nervous systems, as well as preservation of motorand sensory nerve terminals. Phr1 depletion increases the axonal level of the axon survival molecule nicotinamide mononucleotide adenyltransferase 2 (NMNAT2), and NMNAT2 is necessary for Phr1-dependent axon stability. The profound long-term protection of peripheral and central mammalian axons following Phr1 deletion suggests that pharmacological inhibition of Phr1 function may be an attractive therapeutic candidate for amelioration of axon loss in neurological disease. © 2013 The Authors.

Document Type: Article
Source: Scopus

 

Blackburn, S.L.a , Kadkhodayan, Y.a , Shekhtman, E.b , Derdeyn, C.P.a , Cross III, D.T.a , Moran, C.J.a 
Treatment of basilar tip aneurysms with horizontal PCA to PCA stent-assisted coiling: Case series
(2013) Journal of NeuroInterventional Surgery, 5 (3), pp. 212-216. 

a Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, MO, United States
b Department of Neurosurgery, New York University, New York, NY, United States

Abstract
Backgroun and objective: Coiling of wide-necked basilar tip aneurysms is technically challenging and is often assisted by the placement of a stent. Stent placement in an anterograde fashion either with a single or Y-stent is typical. However, in some cases the posterior cerebral artery (PCA) angle of origin at the base of the aneurysm precludes anterograde catheterization. A series of patients with wide-necked basilar tip aneurysms treated with a single stent placed via the posterior communicating artery from PCA to PCA is presented. Methods: A retrospective database review was performed to identify all stent-coiled basilar tip aneurysms. Patients with attempted horizontal P1-P1 stenting via the posterior communicating artery were identified. Procedural imaging, follow-up angiography and clinical notes were reviewed. Results: P1-P1 stenting was attempted in 10 patients and was successful in eight. Angiographic follow-up was available in six patients, all of whom had >90% obliteration at last follow-up. There was one procedure-related subarachnoid hemorrhage that resulted in patient death. There were no cases of significant PCA stenosis on angiographic follow-up. Conclusions: This stenting technique is an effective way to treat wide-necked basilar tip aneurysms but is limited by the anatomy of the posterior communicating arteries and P1 segments.

Document Type: Article
Source: Scopus

 

Armstrong, R.A.a , Cairns, N.J.b 
Different molecular pathologies result in similar spatial patterns of cellular inclusions in neurodegenerative disease: A comparative study of eight disorders
(2012) Journal of Neural Transmission, 119 (12), pp. 1551-1560. 

a Vision Sciences, Aston University, Birmingham B4 7ET, United Kingdom
b Departments of Neurology and Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63108, United States

Abstract
Recent research suggests cell-to-cell transfer of pathogenic proteins such as tau and α-synuclein may play a role in neurodegeneration. Pathogenic spread along neural pathways may give rise to specific spatial patterns of the neuronal cytoplasmic inclusions (NCI) characteristic of these disorders. Hence, the spatial patterns of NCI were compared in four tauopathies, viz., Alzheimer's disease, Pick's disease, corticobasal degeneration, and progressive supranuclear palsy, two synucleinopathies, viz., dementia with Lewy bodies and multiple system atrophy, the 'fused in sarcoma' (FUS)-immunoreactive inclusions in neuronal intermediate filament inclusion disease, and the transactive response DNA-binding protein (TDP-43)-immunoreactive inclusions in frontotemporal lobar degeneration, a TDP-43 proteinopathy (FTLD-TDP). Regardless of molecular group or morphology, NCI were most frequently aggregated into clusters, the clusters being regularly distributed parallel to the pia mater. In a significant proportion of regions, the regularly distributed clusters were in the size range 400-800 μm, approximating to the dimension of cell columns associated with the cortico-cortical pathways. The data suggest that cortical NCI in different disorders exhibit a similar spatial pattern in the cortex consistent with pathogenic spread along anatomical pathways. Hence, treatments designed to protect the cortex from neurodegeneration may be applicable across several different disorders. © 2012 Springer-Verlag.

Author Keywords
Cell to cell transfer;  FUS proteinopathy;  Neuronal cytoplasmic inclusions (NCI);  Spatial patterns;  Synucleinopathy;  Tauopathy;  TDP-43 proteinopathy

Document Type: Article
Source: Scopus

 

Liu, Y., Zhang, C., Wang, L.V.
Effects of light scattering on optical-resolution photoacoustic microscopy.
(2012) Journal of biomedical optics, 17 (12), p. 126014. 

Washington University in St. Louis, Department of Biomedical Engineering, Optical Imaging Laboratory, One Brookings Drive, Saint Louis, Missouri 63130, USA.


Abstract
The imaging depth of ballistic optical imaging technologies is limited by light scattering. To study the effects of scattering on optical-resolution photoacoustic microscopy (OR-PAM), the signals were divided into target and background signals. A method to simulate the point spread function (PSF) of the PAM system considering both optical illumination and acoustic detection was proposed, then the PSF was used to calculate the contribution of each class of signal at different depths of the focal plane (zf). How image contrast is degraded when there is a uniformly absorbing background as well as when there are small targets densely packed in the acoustic resolution cell were studied. By using the hyperboloid-focusing-based Monte Carlo method, optical focusing into a scattering medium was simulated. It was found that the lateral resolution provided by optical focusing is degraded by only 14% when zf=1.1 transport mean free path (l t'), compared with the case of no scattering. When zf=1.7 lt', the fluence at 50 μm radial distance away from the focal point is 93% of that at the focal point, which shows optical focusing is very weak at this depth. The method to simulate the PSF of PAM can be used in the future to optimize parameters so as to improve the system performance.

Document Type: Article
Source: Scopus

 

Collins, A.M., Wen, J., Blankenship, R.E.
Photosynthetic light-harvesting complexes
(2012) RSC Energy and Environment Series, 2012 (1), pp. 85-106. 

Departments of Biology and Chemistry, Washington University in St. Louis, St. Louis, MO 63130, United States

Document Type: Article

Source: Scopus

June 6, 2013

Documents

Marzetti, L.a b , Della Penna, S.a b , Snyder, A.Z.c d , Pizzella, V.a b , Nolte, G.e , de Pasquale, F.a b , Romani, G.L.a b , Corbetta, M.a b c d
Frequency specific interactions of MEG resting state activity within and across brain networks as revealed by the multivariate interaction measure
(2013) NeuroImage, 79, pp. 172-183. 

a Department of Neuroscience and Imaging, G.d'Annunzio University Chieti-Pescara, Chieti, Italy
b Institute for Advanced Biomedical Technologies, G.d'Annunzio University Foundation, Chieti, Italy
c Department of Neurology, Washington University, St. Louis, MO, United States
d Departments of Radiology, Washington University, St. Louis, MO, United States
e Department of Neurophysiology and Pathophysiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Abstract
Resting state networks (RSNs) are sets of brain regions exhibiting temporally coherent activity fluctuations in the absence of imposed task structure. RSNs have been extensively studied with fMRI in the infra-slow frequency range (nominally &lt;10-1Hz). The topography of fMRI RSNs reflects stationary temporal correlation over minutes. However, neuronal communication occurs on a much faster time scale, at frequencies nominally in the range of 100-102Hz. We examined phase-shifted interactions in the delta (2-3.5Hz), theta (4-7Hz), alpha (8-12Hz) and beta (13-30Hz) frequency bands of resting-state source space MEG signals. These analyses were conducted between nodes of the dorsal attention network (DAN), one of the most robust RSNs, and between the DAN and other networks. Phase shifted interactions were mapped by the multivariate interaction measure (MIM), a measure of true interaction constructed from the maximization of imaginary coherency in the virtual channels comprised of voxel signals in source space. Non-zero-phase interactions occurred between homologous left and right hemisphere regions of the DAN in the delta and alpha frequency bands. Even stronger non-zero-phase interactions were detected between networks. Visual regions bilaterally showed phase-shifted interactions in the alpha band with regions of the DAN. Bilateral somatomotor regions interacted with DAN nodes in the beta band. These results demonstrate the existence of consistent, frequency specific phase-shifted interactions on a millisecond time scale between cortical regions within RSN as well as across RSNs. © 2013 Elsevier Inc.

Author Keywords
Imaginary coherence;  Magnetoencephalography;  Resting state networks

Document Type: Article
Source: Scopus

Root, C.G., London, D.A., Schroeder, N.S., Calfee, R.P.
Anatomical relationships and branching patterns of the dorsal cutaneous branch of the ulnar nerve
(2013) Journal of Hand Surgery, 38 (6), pp. 1131-1136. 

Department of Orthopaedic Surgery, Washington University, School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, United States

Abstract
Purpose: To describe the variable branching patterns of the dorsal cutaneous branch of the ulnar nerve (DCBUN) relative to identifiable anatomical landmarks on the ulnar side of the wrist. Methods: We dissected the ulnar nerve in 28 unmatched fresh-frozen cadavers to identify the DCBUN and its branches from its origin to the level of the metacarpophalangeal joints. The number and location of branches of the DCBUN were recorded relative to the distal ulnar articular surface. Relationships to the subcutaneous border of the ulna, the pisotriquetral joint, and the extensor carpi ulnaris tendon were defined in the pronated wrist. Results: On average, 2 branches of the DCBUN were present at the level of the distal ulnar articular surface (range, 1-4). On average, 2.2 branches were present 2 cm distal to the ulnar articular surface (range, 1-4). At least 1 longitudinal branch crossed dorsal to the extensor carpi ulnaris tendon prior to its insertion at the base of the fifth metacarpal in 23 of 28 specimens (82%). In 27 of 28 specimens (96%), all longitudinal branches of the DCBUN coursed between the dorsal-volar midpoint of the subcutaneous border of the ulna and the pisotriquetral joint. In 20 of 28 specimens (71%), a transverse branch of the DCBUN to the distal radioulnar joint was present. Conclusions: During exposure of the dorsal and ulnar areas of the wrist, identification and protection of just a single branch of the DCBUN are unlikely to ensure safe dissection because multiple branches normally are present. The 6U, 6R, and ulnar midcarpal arthroscopy portals may place these branches at risk. In the pronated forearm, the area between the DCBUN and the pisotriquetral joint contained all longitudinal branches of the DCBUN in 96% of specimens. Clinical relevance: During surgery involving the dorsal and ulnar areas of the wrist, multiple longitudinal branches and a transverse branch of the DCBUN are normally present and must be respected. © 2013 American Society for Surgery of the Hand.

Author Keywords
Cutaneous;  dorsal nerve;  sensory;  ulnar nerve

Document Type: Article
Source: Scopus

Surratt, H.L.a b , Kurtz, S.P.a b , Cicero, T.J.c , O'Grady, C.a b , Levi-Minzi, M.A.a b
Antiretroviral medication diversion among HIV-positive substance abusers in South Florida
(2013) American Journal of Public Health, 103 (6), pp. 1026-1028. 

a Center for Applied Research on Substance Use and Health Disparities, Nova Southeastern University, 2 NE 40th St, Miami, FL 33137, United States
b Center for Drug and Alcohol Studies, University of Delaware, Newark, United States
c Department of Psychiatry, Washington University, School of Medicine, St Louis, MO, United States

Abstract
The high cost of life-saving antiretroviral (ARV) therapy for HIV represents an expense that impedes accessibility and affordability by patients. This price structure also appears to motivate the diversion of ARVs and the targeting of HIVpositive patients by pill brokers in the illicit market. Our field research with indigent, HIV-positive substance abusers links ARV diversion to high levels of competing needs, including psychiatric disorders, HIV stigma, and homelessness. Interventions to reduce diversion must address the needs of highly vulnerable patients.

Document Type: Article
Source: Scopus

Bland, M.D.a b , Sturmoski, A.c , Whitson, M.d , Harris, H.d , Connor, L.T.b e f , Fucetola, R.b , Edmiaston, J.d , Huskey, T.b , Carter, A.b , Kramper, M.c , Corbetta, M.b f , Lang, C.E.a f b f
Clinician adherence to a standardized assessment battery across settings and disciplines in a poststroke rehabilitation population
(2013) Archives of Physical Medicine and Rehabilitation, 94 (6), pp. 1048-1053. 

a Program in Physical Therapy, Washington University, Campus Box 8502, 4444 Forest Park, Saint Louis, MO 63108, United States
b Department of Neurology, Washington University, Saint Louis, MO, United States
c Rehabilitation Institute of Saint Louis, Saint Louis, MO, United States
d Barnes Jewish Hospital Rehabilitation Services, Saint Louis, MO, United States
e Program in Occupational Therapy, Washington University, Saint Louis, MO, United States
f Department of Radiology, Washington University, Saint Louis, MO, United States

Abstract
Objectives: (1) To examine clinician adherence to a standardized assessment battery across settings (acute hospital, inpatient rehabilitation facilities [IRFs], outpatient facility), professional disciplines (physical therapy [PT], occupational therapy, speech-language pathology), and time of assessment (admission, discharge/monthly), and (2) to evaluate how specific implementation events affected adherence. Design: Retrospective cohort study. Setting: Acute hospital, IRF, and outpatient facility with approximately 118 clinicians (physical therapists, occupational therapists, speech-language pathologists). Participants: Participants (N=2194) with stroke who were admitted to at least 1 of the above settings. All persons with stroke underwent standardized clinical assessments. Interventions: Not applicable. Main Outcome Measures: Adherence to Brain Recovery Core assessment battery across settings, professional disciplines, and time. Visual inspections of 17 months of time-series data were conducted to see if the events (eg, staff meetings) increased adherence ≥5% and if so, how long the increase lasted. Results: Median adherence ranged from.52 to.88 across all settings and professional disciplines. Both the acute hospital and the IRF had higher adherence than the outpatient setting (P≤.001), with PT having the highest adherence across all 3 disciplines (P<.004). Of the 25 events conducted across the 17-month period to improve adherence, 10 (40%) resulted in a ≥5% increase in adherence the following month, with 6 services (60%) maintaining their increased level of adherence for at least 1 additional month. Conclusions: Actual adherence to a standardized assessment battery in clinical practice varied across settings, disciplines, and time. Specific events increased adherence 40% of the time with those gains maintained for >1 month 60% of the time. © 2013 by the American Congress of Rehabilitation Medicine.

Author Keywords
Outcome assessment (health care);  Rehabilitation;  Stroke

Document Type: Article
Source: Scopus

Constantino, J.N.a , Frazier, T.W.b
Commentary: The observed association between autistic severity measured by the Social Responsiveness Scale (SRS) and general psychopathology - A response to Hus et al.(2013)
(2013) Journal of Child Psychology and Psychiatry and Allied Disciplines, 54 (6), pp. 695-697. Cited 1 time.

a Washington University, School of Medicine - Psychiatry, 660 South Euclid Ave. Campus Box 8134, St. Louis, MO 63110, United States
b Cleveland Clinic Children's Hospital Center, Center for Pediatric Behavioral Health, Cleveland, OH, United States

Author Keywords
Autistic disorder;  child behavior check list;  diagnosis;  pervasive developmental disorder;  social behavior

Document Type: Letter
Source: Scopus

Rogers, J.a b , Raveendran, M.a , Fawcett, G.L.a , Fox, A.S.c d , Shelton, S.E.e f , Oler, J.A.e f , Cheverud, J.g , Muzny, D.M.a , Gibbs, R.A.a , Davidson, R.J.c d e f , Kalin, N.H.c d e f
CRHR1 genotypes, neural circuits and the diathesis for anxiety and depression
(2013) Molecular Psychiatry, 18 (6), pp. 700-707. 

a Human Genome Sequencing Center, Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, United States
b Southwest National Primate Research Center, San Antonio, TX, United States
c Department of Psychology, University of Wisconsin, Madison, WI, United States
d Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin, Madison, WI, United States
e Department of Psychiatry, University of Wisconsin, Madison, WI, United States
f HealthEmotions Research Institute, University of Wisconsin, Madison, WI, United States
g Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO, United States

Abstract
The corticotrophin-releasing hormone (CRH) system integrates the stress response and is associated with stress-related psychopathology. Previous reports have identified interactions between childhood trauma and sequence variation in the CRH receptor 1 gene (CRHR1) that increase risk for affective disorders. However, the underlying mechanisms that connect variation in CRHR1 to psychopathology are unknown. To explore potential mechanisms, we used a validated rhesus macaque model to investigate association between genetic variation in CRHR1, anxious temperament (AT) and brain metabolic activity. In young rhesus monkeys, AT is analogous to the childhood risk phenotype that predicts the development of human anxiety and depressive disorders. Regional brain metabolism was assessed with 18 F-labeled fluoro-2-deoxyglucose (FDG) positron emission tomography in 236 young, normally reared macaques that were also characterized for AT. We show that single nucleotide polymorphisms (SNPs) affecting exon 6 of CRHR1 influence both AT and metabolic activity in the anterior hippocampus and amygdala, components of the neural circuit underlying AT. We also find evidence for association between SNPs in CRHR1 and metabolism in the intraparietal sulcus and precuneus. These translational data suggest that genetic variation in CRHR1 affects the risk for affective disorders by influencing the function of the neural circuit underlying AT and that differences in gene expression or the protein sequence involving exon 6 may be important. These results suggest that variation in CRHR1 may influence brain function before any childhood adversity and may be a diathesis for the interaction between CRHR1 genotypes and childhood trauma reported to affect human psychopathology. © 2013 Macmillan Publishers Limited. All rights reserved 1359-4184/13.

Author Keywords
amygdala;  corticotrophin-releasing hormone;  genetic association;  hippocampus;  non-human primate;  rhesus macaque

Document Type: Article
Source: Scopus

Dick, D.M.a , Aliev, F.a , Latendresse, S.a , Porjesz, B.b , Schuckit, M.c , Rangaswamy, M.b , Hesselbrock, V.d , Edenberg, H.e , Nurnberger, J.e , Agrawal, A.f , Bierut, L.f , Wang, J.f , Bucholz, K.f , Kuperman, S.g , Kramer, J.g
How phenotype and developmental stage affect the genes we find: GABRA2 and impulsivity
(2013) Twin Research and Human Genetics, 16 (3), pp. 661-669. 

a Departments of Psychiatry Human and Molecular Genetics, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, PO Box 980126, Richmond, VA 23298-0126, United States
b Department of Psychiatry and Behavioral Sciences, State University of New York (SUNY), Downstate Medical Center, Brooklyn, NY, United States
c Department of Psychiatry, University of California, San Diego VA Medical Center, San Diego, CA, United States
d Department of Psychiatry, University of Connecticut Health Center, Farmington, CT, United States
e Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, United States
f Department of Psychiatry, Washington University, St. Louis, MS, United States
g Department of Psychiatry, University of Iowa College of Medicine, Iowa City, IA, United States

Abstract
Context: The detection and replication of genes involved in psychiatric outcome has been notoriously difficult. Phenotypic measurement has been offered as one explanation, although most of this discussion has focused on problems with binary diagnoses. Objective: This article focuses on two additional components of phenotypic measurement that deserve further consideration in evaluating genetic associations: (1) the measure used to reflect the outcome of interest, and (2) the developmental stage of the study population. We focus our discussion of these issues around the construct of impulsivity and externalizing disorders, and the association of these measures with a specific gene, GABRA2. Design, Setting, and Participants: Data were analyzed from the Collaborative Study on the Genetics of Alcoholism Phase IV assessment of adolescents and young adults (ages 12-26; N = 2,128). Main Outcome Measures: Alcohol dependence, illicit drug dependence, childhood conduct disorder, and adult antisocial personality disorder symptoms were measured by psychiatric interview; Achenbach youth/adult self-report externalizing scale; Zuckerman Sensation-Seeking scale; Barratt Impulsivity scale; NEO extraversion and consciousness. Results: GABRA2 was associated with subclinical levels of externalizing behavior as measured by the Achenbach in both the adolescent and young adult samples. Contrary to previous associations in adult samples, it was not associated with clinical-level DSM symptom counts of any externalizing disorders in these younger samples. There was also association with sensation-seeking and extraversion, but only in the adolescent sample. There was no association with the Barratt impulsivity scale or conscientiousness. Conclusions: Our results suggest that the pathway by which GABRA2 initially confers risk for eventual alcohol problems begins with a predisposition to sensation-seeking early in adolescence. The findings support the heterogeneous nature of impulsivity and demonstrate that both the measure used to assess a construct of interest and the age of the participants can have profound implications for the detection of genetic associations. © 2013 The Authors.

Author Keywords
adolescence;  association;  externalizing;  GABRA2;  impulsivity;  sensation-seeking

Document Type: Article
Source: Scopus

Ambati, J.a b , Atkinson, J.P.c , Gelfand, B.D.a d e
Immunology of age-related macular degeneration
(2013) Nature Reviews Immunology, 13 (6), pp. 438-451. 

a Department of Ophthalmology and Visual Sciences, University of Kentucky, Lexington, KY 40506, United States
b Department of Physiology, University of Kentucky, Lexington, KY 40506, United States
c Division of Rheumatology, Department of Medicine, Washington University, St. Louis, MO 63110, United States
d Department of Biomedical Engineering, University of Kentucky, Lexington, KY 40506, United States
e Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, Lexington, KY 40506, United States

Abstract
Age-related macular degeneration (AMD) is a leading cause of blindness in aged individuals. Recent advances have highlighted the essential role of immune processes in the development, progression and treatment of AMD. In this Review we discuss recent discoveries related to the immunological aspects of AMD pathogenesis. We outline the diverse immune cell types, inflammatory activators and pathways that are involved. Finally, we discuss the future of inflammation-directed therapeutics to treat AMD in the growing aged population. © 2013 Macmillan Publishers Limited. All rights reserved.

Document Type: Review
Source: Scopus

Tonduti, D.a , Vanderver, A.b , Berardinelli, A.a , Schmidt, J.L.b , Collins, C.D.c , Novara, F.d , Genni, A.D.a , Mita, A.a , Triulzi, F.e , Brunstrom-Hernandez, J.E.f , Zuffardi, O.d , Balottin, U.g , Orcesi, S.a
MCT8 deficiency: Extrapyramidal symptoms and delayed myelination as prominent features
(2013) Journal of Child Neurology, 28 (6), pp. 792-797. 

a Child Neurology and Psychiatry Unit, IRCCS C. Mondino National Institute of Neurology Foundation, Via Mondino 2, 27100 Pavia, Italy
b Department of Neurology, Children's National Medical Center, Washington, DC, United States
c Emory Genetics Laboratory, Department of Human Genetics, Emory University, Atlanta, GA, United States
d Department of Molecular Medicine, University of Paviac, Pavia, Italy
e Departments of Radiology and Neuroradiology, Children's Hospital V. Buzzi-Istituti Clinici di Perfezionamento, Milan, Italy
f Departments of Neurology and Pediatrics, Washington University School of Medicine, St. Louis Children's Hospital, St. Louis, MO, United States
g Department of Public Health, Neuroscience, Experimental and Forensic Medicine, Unit of Child Neurology and Psychiatry, University of Pavia, Italy

Abstract
Monocarboxylate transporter 8 (MCT8) deficiency is an X-linked disorder resulting from an impairment of the transcellular transportation of thyroid hormones. Within the central nervous system thyroid hormone transport is normally mediated by MCT8. Patients are described as affected by a static or slowly progressive clinical picture which consists of variable degrees of mental retardation, hypotonia, spasticity, ataxia and involuntary movements, occasionally paroxysmal. The authors describe the clinical and neuroradiological picture of 3 males patients with marked delayed brain myelination and in which the clinical picture was dominated by early onset nonparoxismal extrapyramidal symptoms. In one subject a novel mutation is described. © The Author(s) 2012.

Author Keywords
extrapyramidal;  hypomyelination;  leukodystrophy;  MCT8;  movement disorder;  thyroid;  X-linked

Document Type: Article
Source: Scopus

Balan, S.a , Widner, G.a , Shroff, M.a , van den Berk-Clark, C.a b , Scherrer, J.a b c , Price, R.K.a b
Drug use disorders and post-traumatic stress disorder over 25 adult years: Role of psychopathology in relational networks
(2013) Drug and Alcohol Dependence, . Article in Press. 

a Department of Psychiatry, Washington University School of Medicine, Medical Box 8134, St. Louis, MO 63110, United States
b Research Service, VA St. Louis Health Care System, 915 North Grand Blvd, St. Louis, MO 63106, United States
c Department of Family and Community Medicine, Saint Louis University School of Medicine, 1402 South Grand Blvd, St. Louis, MO 63104, United States

Abstract
Background: In traumatized populations, drug use disorders and post-traumatic stress disorder (PTSD) persist for many years. Relational factors that mediate this persistence have rarely been systematically examined. Our aim is to examine the relative effects of psychopathology in familial and non-familial networks on the persistence of both disorders over adulthood. Methods: We utilized longitudinal data from an epidemiologically ascertained sample of male Vietnam veterans (n = 642). Measures included DSM-IV drug use disorders, other psychiatric disorders, network problem history and time-varying marital and employment characteristics. Longitudinal measures of veterans' psychopathology and social functioning were retrospectively obtained for each year over a 25 year period. We used generalized estimating equations (GEE) to estimate the relative effects of network problems on veteran's drug use disorders and PTSD after adjusting for covariates. Results: Veterans' mean age was 47 years in 1996. Prevalence of illicit drug disorders declined from 29.8% in 1972 to 8.3% in 1996, but PTSD remained at 11.7% from 13.2% in 1972. While 17.0% of veterans reported a familial drug use problem, 24.9% reported a non-familial drug use problem. In full GEE models, a non-familial drug problem was a significant predictor of illicit drug use disorders over 25 years (OR = 2.21, CI = 1.59-3.09), while both familial depression (OR = 1.69, CI = 1.07-2.68) and non-familial drinking problem (OR = 1.66, CI = 1.08-2.54) were significant predictors of PTSD over 25 years. Conclusions: Familial and non-familial problems in networks differentially affect the persistence of drug use disorders and PTSD in traumatized male adults. © 2013 Elsevier Ireland Ltd.

Author Keywords
Drug disorder;  Familial and non-familial networks;  Post-traumatic stress disorder;  Veterans

Document Type: Article in Press
Source: Scopus

Chen, Y.a , Williams, S.H.b , McNulty, A.L.c , Hong, J.H.a d , Lee, S.H.a , Rothfusz, N.E.c , Parekh, P.K.a , Moore, C.a , Gereau IV, R.W.h , Taylor, A.B.e f , Wang, F.g , Guilak, F.c , Liedtke, W.a d i
Temporomandibular joint pain: A critical role for Trpv4 in the trigeminal ganglion
(2013) Pain, . Article in Press. 

a Department of Medicine, Duke University, Durham, NC, USA
b Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, USA
c Department of Orthopaedic Surgery, Duke University, Durham, NC, USA
d Duke Clinics for Pain and Palliative Care, Durham, NC, USA
e Department of Community and Family Medicine, Duke University, Durham, NC, USA
f Department of Evolutionary Anthropology, Duke University, Durham, NC, USA
g Department of Cell Biology, Duke University, Durham, NC, USA
h Department of Anesthesiology, Washington University, St. Louis, MO, USA
i Duke Center for Neuroengineering, Durham, NC, USA

Abstract
Temporomandibular joint disorder (TMJD) is known for its mastication-associated pain. TMJD is medically relevant because of its prevalence, severity, chronicity, the therapy-refractoriness of its pain, and its largely elusive pathogenesis. Against this background, we sought to investigate the pathogenetic contributions of the calcium-permeable TRPV4 ion channel, robustly expressed in the trigeminal ganglion sensory neurons, to TMJ inflammation and pain behavior. We demonstrate here that TRPV4 is critical for TMJ-inflammation-evoked pain behavior in mice and that trigeminal ganglion pronociceptive changes are TRPV4-dependent. As a quantitative metric, bite force was recorded as evidence of masticatory sensitization, in keeping with human translational studies. In Trpv4-/- mice with TMJ inflammation, attenuation of bite force was significantly less than in wildtype (WT) mice. Similar effects were seen with systemic application of a specific TRPV4 inhibitor. TMJ inflammation and mandibular bony changes were apparent after injections of complete Freund adjuvant but were remarkably independent of the Trpv4 genotype. It was intriguing that, as a result of TMJ inflammation, WT mice exhibited significant upregulation of TRPV4 and phosphorylated extracellular-signal-regulated kinase (ERK) in TMJ-innervating trigeminal sensory neurons, which were absent in Trpv4-/- mice. Mice with genetically-impaired MEK/ERK phosphorylation in neurons showed resistance to reduction of bite force similar to that of Trpv4-/- mice. Thus, TRPV4 is necessary for masticatory sensitization in TMJ inflammation and probably functions upstream of MEK/ERK phosphorylation in trigeminal ganglion sensory neurons in vivo. TRPV4 therefore represents a novel pronociceptive target in TMJ inflammation and should be considered a target of interest in human TMJD. © 2013 International Association for the Study of Pain.

Author Keywords
Bite force;  ERK activation;  Temporomandibular joint disorder;  Trigeminal ganglion;  Trpv4

Document Type: Article in Press
Source: Scopus

Peterson, D.a , Munger, C.a , Crowley, J.a , Corcoran, C.b c , Cruchaga, C.d , Goate, A.M.d e , Norton, M.C.c f g , Green, R.C.h , Munger, R.G.i , Breitner, J.C.S.j , Welsh-Bohmer, K.A.k , Lyketsos, C.l , Tschanz, J.c g , Kauwe, J.S.K.a
Variants in PPP3R1 and MAPT are associated with more rapid functional decline in Alzheimer's disease: The Cache County Dementia Progression Study
(2013) Alzheimer's and Dementia, . Article in Press. 

a Department of Biology, Brigham Young University, Provo, UT, USA
b Department of Mathematics and Statistics, Utah State University, Logan, UT, USA
c Center for Epidemiologic Studies, Utah State University, Logan, UT, USA
d Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA
e Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, USA
f Department of Family Consumer and Human Development, Utah State University, Logan, UT, USA
g Department of Psychology, Utah State University, Logan, UT, USA
h Division of Genetics, Department of Medicine and Partners Center for Personalized Genetic Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
i Department of Nutrition Dietetics and Food Sciences, Utah State University, Logan, UT, USA
j Department of Psychiatry, McGill University, Montreal, Quebec, Canada
k Departments of Psychiatry and Medicine, Duke University, Durham, NC, USA
l Department of Psychiatry, Johns Hopkins Bayview Medical Center, Baltimore, MD, USA

Abstract
Background: Single-nucleotide polymorphisms (SNPs) located in the gene encoding the regulatory subunit of the protein phosphatase 2B (PPP3R1, rs1868402) and the microtubule-associated protein tau (MAPT, rs3785883) gene were recently associated with higher cerebrospinal fluid (CSF) tau levels in samples from the Knight Alzheimer's Disease Research Center at Washington University (WU) and Alzheimer's Disease Neuroimaging Initiative (ADNI). In these same samples, these SNPs were also associated with faster functional decline, or progression of Alzheimer's disease (AD) as measured by the Clinical Dementia Rating sum of boxes scores (CDR-sb). We attempted to validate the latter association in an independent, population-based sample of incident AD cases from the Cache County Dementia Progression Study (DPS). Methods: All 92 AD cases from the DPS with a global CDR-sb ≤1 (mild) at initial clinical assessment who were later assessed on CDR-sb data on at least two other time points were genotyped at the two SNPs of interest (rs1868402 and rs3785883). We used linear mixed models to estimate associations between these SNPs and CDR-sb trajectory. All analyses were performed using Proc Mixed in SAS. Results: Although we observed no association between rs3785883 or rs1868402 alone and change in CDR-sb (P > .10), there was a significant association between a combined genotype model and change in CDR-sb: carriers of the high-risk genotypes at both loci progressed >2.9 times faster than noncarriers (P = .015). When data from DPS were combined with previously published data from WU and ADNI, change in CDR-sb was 30% faster for each copy of the high-risk allele at rs3785883 (P = .0082) and carriers of both high-risk genotypes at both loci progressed 6 times faster (P < .0001) than all others combined. Conclusions: We replicate a previous report by Cruchaga et al that specific variations in rs3785883 and rs1868402 are associated with accelerated progression of AD. Further characterization of this association will provide a better understanding of how genetic factors influence the rate of progression of AD and could provide novel insights into preventative and therapeutic strategies. © 2013 The Alzheimer's Association.

Author Keywords
Alzheimer's disease;  Association;  Genetics;  MAPT;  PPP3R1;  Rate of progression

Document Type: Article in Press
Source: Scopus

Taylor, R.J.a , Forsythe-Brown, I.b , Taylor, H.O.c , Chatters, L.M.d
Patterns of Emotional Social Support and Negative Interactions among African American and Black Caribbean Extended Families
(2013) Journal of African American Studies, pp. 1-17. Article in Press. 

a School of Social Work, Institute for Social Research, University of Michigan, Michigan, United States
b Department of Sociology, University of Michigan-Dearborn, Dearborn, United States
c George Warren Brown School of Social Work, Washington University in St. Louis, St. Louis, United States
d School of Social Work, School of Public Health, Institute for Social Research, University of Michigan, Ann Arbor, United States

Abstract
This study examines patterns of emotional support and negative interaction (i.e., criticism, conflict) from extended family members using data on African Americans and Caribbean Blacks from the National Survey of American Life. A pattern variable was constructed that describes four types of extended family networks: (1) high emotional support and high negative interaction (ambivalent), (2) high emotional support and low negative interaction (optimal), (3) low emotional support and low negative interaction (estranged) and (4) low emotional support and high negative interaction (strained). Multi-nominal logistic regression was used to investigate the sociodemographic and familial (e.g., frequency of family contact) correlates of the patterns of extended family networks. Family closeness and contact, as well as gender, age and marital status were associated with extended family network types. Optimal family networks were associated with higher levels of family contact and closeness; women, younger adults and unmarried persons were more likely than their counterparts to have more advantageous extended family networks. Overall, findings for African Americans and Caribbean Blacks revealed both important similarities (e.g., gender, marital status, family closeness and contact) and differences (e.g., age) in the sociodemographic and familial correlates of diverse extended family networks. © 2013 Springer Science+Business Media New York.

Author Keywords
Afro-Caribbean;  Black family;  Informal social support;  Kinship network;  Mental health;  Support network;  West Indians

Document Type: Article in Press
Source: Scopus

Connolly, A.M.a b , Florence, J.M.a , Cradock, M.M.b , Malkus, E.C.a , Schierbecker, J.R.a , Siener, C.A.a , Wulf, C.O.a , Anand, P.a , Golumbek, P.T.a b , Zaidman, C.M.a b , Philip Miller, J.c , Lowes, L.P.d , Alfano, L.N.d , Viollet-Callendret, L.d , Flanigan, K.M.d , Mendell, J.R.d , McDonald, C.M.e , Goude, E.e , Johnson, L.e , Nicorici, A.e , Karachunski, P.I.f , Day, J.W.f , Dalton, J.C.f , Farber, J.M.f , Buser, K.K.f , Darras, B.T.g , Kang, P.B.g , Riley, S.O.g , Shriber, E.g , Parad, R.g , Bushby, K.h , Eagle, M.h
Motor and cognitive assessment of infants and young boys with Duchenne Muscular Dystrophy: results from the Muscular Dystrophy Association DMD Clinical Research Network
(2013) Neuromuscular Disorders, . Article in Press. 

a Department of Neurology, Washington University School of Medicine, Saint Louis, MO, USA
b Department of Pediatrics, Washington University School of Medicine, Saint Louis, MO, USA
c Division of Biostatistics, Washington University School of Medicine, Saint Louis, MO, USA
d Department of Pediatrics, Nationwide Children's Hospital, Ohio State University, Columbus, OH, USA
e Department Physical Medicine and Rehabilitation, University of California, Davis Medical Center, Sacramento, CA, USA
f Department of Neurology, University of Minnesota, Minneapolis, MN, USA
g Department of Neurology, Harvard University, Boston Children's Hospital, Boston, MA, USA
h Department of Neurology and Institute of Genetic Medicine, Newcastle upon Tyne, Newcastle, UK

Abstract
Therapeutic trials in Duchenne Muscular Dystrophy (DMD) exclude young boys because traditional outcome measures rely on cooperation. The Bayley III Scales of Infant and Toddler Development (Bayley III) have been validated in developing children and those with developmental disorders but have not been studied in DMD. Expanded Hammersmith Functional Motor Scale (HFMSE) and North Star Ambulatory Assessment (NSAA) may also be useful in this young DMD population. Clinical evaluators from the MDA-DMD Clinical Research Network were trained in these assessment tools. Infants and boys with DMD (n = 24; 1.9 ± 0.7 years) were assessed. The mean Bayley III motor composite score was low (82.8 ± 8; p ≤ .0001) (normal = 100 ± 15). Mean gross motor and fine motor function scaled scores were low (both p ≤ .0001). The mean cognitive comprehensive (p = .0002), receptive language (p ≤ .0001), and expressive language (p = .0001) were also low compared to normal children. Age was negatively associated with Bayley III gross motor (r = -0.44; p = .02) but not with fine motor, cognitive, or language scores. HFMSE (n = 23) showed a mean score of 31 ± 13. NSAA (n = 18 boys; 2.2 ± 0.4 years) showed a mean score of 12 ± 5. Outcome assessments of young boys with DMD are feasible and in this multicenter study were best demonstrated using the Bayley III. © 2013 Elsevier B.V. All rights reserved.

Author Keywords
Bayley III Scales of Infant and Toddler Development;  Duchenne Muscular Dystrophy;  Hammersmith Functional Motor Scale Extended;  Infant;  North Star Ambulatory Assessment

Document Type: Article in Press
Source: Scopus

Ferradal, S.L.a b , Eggebrecht, A.T.b , Hassanpour, M.b c , Snyder, A.Z.b d , Culver, J.P.a b c
Atlas-based head modeling and spatial normalization for high-density diffuse optical tomography: In vivo validation against fMRI
(2013) NeuroImage, . Article in Press. 

a Department of Biomedical Engineering, Washington University, Whitaker Hall, One Brookings Dr., St. Louis, MO, 63130, USA
b Department of Radiology, Washington University School of Medicine, East Bldg., 4525 Scott Ave, St. Louis, MO, 63110, USA
c Department of Physics, Washington University, One Brookings Dr., St. Louis, MO, 63130, USA
d Department of Neurology, Washington University School of Medicine, 660 S. Euclid Ave, St. Louis, MO, 63110, USA

Abstract
Diffuse optical imaging (DOI) is increasingly becoming a valuable neuroimaging tool when fMRI is precluded. Recent developments in high-density diffuse optical tomography (HD-DOT) overcome previous limitations of sparse DOI systems, providing improved image quality and brain specificity. These improvements in instrumentation prompt the need for advancements in both i) realistic forward light modeling for accurate HD-DOT image reconstruction, and ii) spatial normalization for voxel-wise comparisons across subjects. Individualized forward light models derived from subject-specific anatomical images provide the optimal inverse solutions, but such modeling may not be feasible in all situations. In the absence of subject-specific anatomical images, atlas-based head models registered to the subject's head using cranial fiducials provide an alternative solution. In addition, a standard atlas is attractive because it defines a common coordinate space in which to compare results across subjects. The question therefore arises as to whether atlas-based forward light modeling ensures adequate HD-DOT image quality at the individual and group level. Herein, we demonstrate the feasibility of using atlas-based forward light modeling and spatial normalization methods. Both techniques are validated using subject-matched HD-DOT and fMRI data sets for visual evoked responses measured in five healthy adult subjects. HD-DOT reconstructions obtained with the registered atlas anatomy (i.e. atlas DOT) had an average localization error of 2.7 mm relative to reconstructions obtained with the subject-specific anatomical images (i.e. subject-MRI DOT), and 6.6 mm relative to fMRI data. At the group level, the localization error of atlas DOT reconstruction was 4.2 mm relative to subject-MRI DOT reconstruction, and 6.1 mm relative to fMRI. These results show that atlas-based image reconstruction provides a viable approach to individual head modeling for HD-DOT when anatomical imaging is not available. © 2013 Elsevier Inc. All rights reserved.

Author Keywords
Anatomical atlas;  Brain mapping;  Diffuse optical tomography;  Functional magnetic resonance imaging;  Group analysis;  Non-linear registration;  Spatial normalization

Document Type: Article in Press
Source: Scopus

Avanaki, M.R.N., Xia, J., Wang, L.V.
High resolution functional photoacoustic computed tomography of the mouse brain during electrical stimulation
(2013) Progress in Biomedical Optics and Imaging - Proceedings of SPIE, 8581, art. no. 85813K, . 

Optical Imaging Laboratory, Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO 63130, United States

Abstract
Photoacoustic computed tomography (PACT) is an emerging imaging technique which is based on the acoustic detection of optical absorption from tissue chromophores, such as oxy-hemoglobin and deoxy-hemoglobin. An important application of PACT is functional brain imaging of small animals. The conversion of light to acoustic waves allows PACT to provide high resolution images of cortical vasculatures through the intact scalp. Here, PACT was utilized to study the activated areas of the mouse brain during forepaw and hindpaw stimulations. Temporal PACT images were acquired enabling computation of hemodynamic changes during stimulation. The stimulations were performed by trains of pulses at different stimulation currents (between 0.1 to 2 mA) and pulse repetition rates (between 0.05 Hz to 0.01Hz). The response at somatosensory cortex-forelimb, and somatosensory cortex-hindlimb, were investigated. The Paxinos mouse brain atlas was used to confirm the activated regions. The study shows that PACT is a promising new technology that can be used to study brain functionality with high spatial resolution. © 2013 Copyright SPIE.

Author Keywords
Electrical Stimulation;  Functional Imaging;  Photoacoustic Tomography

Document Type: Conference Paper
Source: Scopus

Yao, J.a , Xia, J.a , Maslov, K.a , Avanaki, M.R.N.a , Tsytsarev, V.b , Demchenko, A.V.c , Wang, L.V.a
Noninvasive photoacoustic computed tomography of mouse brain metabolism in vivo
(2013) Progress in Biomedical Optics and Imaging - Proceedings of SPIE, 8581, art. no. 85814A, . 

a Optical Imaging Laboratory, Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO 63130, United States
b Department of Anatomy and Neurobiology, University of Maryland, School of Medicine, Baltimore, MD 21201, United States
c Department of Chemistry and Biochemistry, University of Missouri-St. Louis, St. Louis, MO 63121, United States

Abstract
To control the overall action of the body, brain consumes a large amount of energy in proportion to its volume. In humans and many other species, the brain gets most of its energy from oxygen-dependent metabolism of glucose. An abnormal metabolic rate of glucose and/or oxygen usually reflects a diseased status of brain, such as cancer or Alzheimer's disease. We have demonstrated the feasibility of imaging mouse brain metabolism using photoacoustic computed tomography (PACT), a fast, noninvasive and functional imaging modality with optical contrast and acoustic resolution. Brain responses to forepaw stimulations were imaged transdermally and transcranially. 2-NBDG, which diffuses well across the blood-brain-barrier, provided exogenous contrast for photoacoustic imaging of glucose response. Concurrently, hemoglobin provided endogenous contrast for photoacoustic imaging of hemodynamic response. Glucose and hemodynamic responses were quantitatively unmixed by using two-wavelength measurements. We found that glucose uptake and blood perfusion around the somatosensory region of the contralateral hemisphere were both increased by stimulations, indicating elevated neuron activity. The glucose response amplitude was about half that of the hemodynamic response. While the glucose response area was more homogenous and confined within the somatosensory region, the hemodynamic response area showed a clear vascular pattern and spread about twice as wide as that of the glucose response. The PACT of mouse brain metabolism was validated by high-resolution open-scalp OR-PAM and fluorescence imaging. Our results demonstrate that 2-NBDG-enhanced PACT is a promising tool for noninvasive studies of brain metabolism. © 2013 Copyright SPIE.

Author Keywords
blood flow dynamics;  functional brain imaging;  glucose dynamics;  glucose metabolism;  Photoacoustic computed tomography

Document Type: Conference Paper
Source: Scopus

Veeraraghavalu, K.a , Zhang, C.b , Miller, S.b , Hefendehl, J.K.c , Rajapaksha, T.W.d , Ulrich, J.e , Jucker, M.c , Holtzman, D.M.e f g , Tanzi, R.E.b , Vassar, R.d , Sisodia, S.S.a
Comment on "ApoE-directed therapeutics rapidly clear β-amyloid and reverse deficits in AD mouse models"
(2013) Science, 340 (6135), p. 924. Cited 1 time.

a Department of Neurobiology, University of Chicago, Chicago, IL 60637, United States
b Department of Neurology, Massachusetts General Institute for Neurodegenerative Disease, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129-2060, United States
c Department of Cellular Neurology, Hertie-Institute for Clinical Brain Research, University of Tübingen, Otfried-Müller Strasse 27, D-72076 Tübingen, Germany
d Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States
e Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, United States
f Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, United States
g Charles F and Joanne Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110, United States

Abstract
Cramer et al. (Reports, 23 March 2012, p. 1503; published online 9 February 2012) reported that bexarotene rapidly reduces β-amyloid (Aβ) levels and plaque burden in two mouse models of Aβ deposition in Alzheimer's disease (AD). We now report that, although bexarotene reduces soluble Aβ40 levels in one of the mouse models, the drug has no impact on plaque burden in three strains that exhibit Aβ amyloidosis.

Document Type: Note
Source: Scopus

Van Essen, D.C., Glasser, M.F.
In vivo architectonics: A cortico-centric perspective
(2013) NeuroImage, . Article in Press. 

Department of Anatomy and Neurobiology, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA

Abstract
Recent advances in noninvasive structural imaging have opened up new approaches to cortical parcellation, many of which are described in this special issue on In Vivo Brodmann Mapping. In this introductory article, we focus on the emergence of cortical myelin maps as a valuable way to assess cortical organization in humans and nonhuman primates. We demonstrate how myelin maps are useful in three general domains: (i) as a way to identify cortical areas and functionally specialized regions in individuals and group averages; (ii) as a substrate for improved intersubject registration; and (iii) as a basis for interspecies comparisons. We also discuss how myelin-based cortical parcellation is complementary in important ways to connectivity-based parcellation using functional MRI or diffusion imaging and tractography. These observations and perspectives provide a useful background and context for other articles in this special issue. © 2013 Elsevier Inc. All rights reserved.

Author Keywords
Cortical areas;  Myelin;  Networks;  Parcellation;  Registration

Document Type: Article in Press
Source: Scopus

Landreth, G.E.a , Cramer, P.E.a , Lakner, M.M.a , Cirrito, J.R.b , Wesson, D.W.c , Brunden, K.R.d , Wilson, D.A.e
Response to comments on "ApoE-directed therapeutics rapidly clear β-amyloid and reverse deficits in AD mouse models"
(2013) Science, 340 (6135), p. 924. 

a Alzheimer Research Laboratory, Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, United States
b Department of Neurology, Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, United States
c Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, United States
d Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States
e Emotional Brain Institute, Nathan Kline Institute for Psychiatric Research, New York University School of Medicine, Orangeburg, NY 10962, United States

Abstract
The data reported in the Technical Comments by Fitz et al., Price et al., Tesseur et al., and Veeraraghavalu et al. replicate and validate our central conclusion that bexarotene stimulates the clearance of soluble β-amyloid peptides and results in the reversal of behavioral deficits in mouse models of Alzheimer's disease (AD). The basis of the inability to reproduce the drug-stimulated microglial-mediated reduction in plaque burden is unexplained. However, we concluded that plaque burden is functionally unrelated to improved cognition and memory elicited by bexarotene.

Document Type: Note
Source: Scopus

Fowler, P.J.a , Henry, D.B.b , Schoeny, M.c , Landsverk, J.d , Chavira, D.e , Taylor, J.J.e
Inadequate Housing Among Families Under Investigation for Child Abuse and Neglect: Prevalence from a National Probability Sample
(2013) American Journal of Community Psychology, pp. 1-9. Article in Press. 

a George Warren Brown School of Social Work, Washington University in St. Louis, Campus Box 1196, One Brookings Drive, St. Louis, 63130, United States
b Institute for Health Research and Policy, University of Illinois at Chicago, Chicago, United States
c School of Social Service Administration, University of Chicago, Chicago, United States
d Child and Adolescent Services Research Center, Rady Children's Hospital - San Diego, San Diego, United States
e DePaul University, Chicago, United States

Abstract
This study aimed to estimate the prevalence of inadequate housing that threaten out-of-home placement among families under investigation by child welfare. Data came from the National Survey of Child and Adolescent Well-Being, a nationally representative longitudinal survey of child welfare-involved families. Child protective services caseworkers as well as caregivers provided information on families whose child remained in the home after initial investigation (N = 3,867). Multilevel latent class analyses tested the presence of inadequately housed subgroups using 4 housing problem indicators at baseline. Logistic regressions assessed convergent and predictive validity. A two class latent solution best fit the data. Findings indicated that inadequate housing contributed to risk for out-of-home placement in approximately 16 % of intact families under investigation by child protective services. These families were 4 times more likely to need housing services 12 months later. Federal legislation emphasizes integration of social services as necessary to end homelessness. This study demonstrates overlap across public agencies. Enhanced coordination of child welfare and housing services facilitates interventions to prevent and mitigate homelessness. © 2013 Society for Community Research and Action.

Author Keywords
Child welfare;  Homelessness;  Housing;  Latent class analysis;  Policy;  Systems of care

Document Type: Article in Press
Source: Scopus

Malaspina, D.a b , Owen, M.J.c , Heckers, S.d , Tandon, R.e , Bustillo, J.f , Schultz, S.g , Barch, D.M.h i , Gaebel, W.j , Gur, R.E.k l , Tsuang, M.m , Van Os, J.n , Carpenter, W.o p
Schizoaffective Disorder in the DSM-5
(2013) Schizophrenia Research, . Article in Press. 

a Department of Psychiatry, New York University, New York, NY, USA
b Creedmoor Psychiatric Center, New York State Office of Mental Health, USA
c MRC Centre for Neuropsychiatric Genetics and Genomics and Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, Wales, United Kingdom
d Department of Psychiatry, Vanderbilt University, Nashville, TN, USA
e Department of Psychiatry, University of Florida Medical School, Gainesville, FL, USA
f Department of Psychiatry, University of New Mexico, Albuquerque, NM, USA
g Department of Psychiatry, University of Iowa School of Medicine, Iowa City, IA, USA
h Department of Psychology, Washington University, St. Louis, MO, USA
i Department of Psychiatry and Radiology, Washington University, St. Louis, MO, USA
j Department of Psychiatry, Duesseldorf, Germany
k Department of Psychiatry, Perlman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
l Department of Neurology and Radiology, Perlman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
m Department of Psychiatry, UCSD, CA, USA
n Maastricht University Medical Centre, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht, The Netherlands
o King's College London, King's Health Partners, Department of Psychosis Studies, Institute of Psychiatry, London, United Kingdom
p Department of Psychiatry, Maryland Psychiatric Research Center, Baltimore, MD, USA

Abstract
Characterization of patients with both psychotic and mood symptoms either concurrently or at different points during their illness has always posed a nosological challenge and this is reflected in the poor reliability, low diagnostic stability, and questionable validity of DSM-IV Schizoaffective Disorder. The clinical reality of the frequent co-occurrence of psychosis and Mood Episodes has also resulted in over-utilization of a diagnostic category that was originally intended to rarely needed. In the Diagnostic and Statistical Manual of Mental Disorders, fifth edition, an effort is made to improve reliability of this condition by providing more specific criteria and the concept of Schizoaffective Disorder shifts from an episode diagnosis in DSM-IV to a life course of the illness in DSM-5. When psychotic symptoms occur exclusively during a Mood Episode, DSM-5 indicates that the diagnosis is the appropriate Mood Disorder with Psychotic Features, but when such a psychotic condition includes at least a two-week period of psychosis without prominent mood symptoms, the diagnosis may be either Schizoaffective Disorder or Schizophrenia. In the DSM-5, the diagnosis of Schizoaffective Disorder can be made only if full Mood Disorder episodes have been present for the majority of the total active and residual course of illness, from the onset of psychotic symptoms up until the current diagnosis. In earlier DSM versions the boundary between Schizophrenia and Schizoaffective Disorder was only qualitatively defined, leading to poor reliability. This change will provide a clearer separation between Schizophrenia with mood symptoms from Schizoaffective Disorder and will also likely reduce rates of diagnosis of Schizoaffective Disorder while increasing the stability of this diagnosis once made. © 2013 Elsevier B.V. All rights reserved.

Author Keywords
Affective disorder;  Depression;  Diagnosis;  DSM-5;  Mania;  Psychosis;  Schizoaffective Disorder;  Schizophrenia

Document Type: Article in Press
Source: Scopus

Heckers, S.a , Barch, D.M.b , Bustillo, J.c , Gaebel, W.d , Gur, R.e , Malaspina, D.f , Owen, M.J.g , Schultz, S.h , Tandon, R.i , Tsuang, M.j , Van Os, J.k , Carpenter, W.l
Structure of the psychotic disorders classification in DSM 5
(2013) Schizophrenia Research, . Article in Press. 

a Department of Psychiatry, Vanderbilt University, Nashville, TN, USA
b Departments of Psychology, Psychiatry and Radiology, Washington University, St. Louis, MO, USA
c Department of Psychiatry, University of New Mexico, Albuquerque, NM, USA
d Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany
e Departments of Psychiatry, Neurology and Radiology, Perlman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
f Department of Psychiatry, New York University, New York, NY, and New York State Office of Mental Health, Creedmoor Psychiatric Center, Queens, NY, USA
g MRC Centre for Neuropsychiatric Genetics and Genomics and Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, Wales
h Department of Psychiatry, University of Iowa School of Medicine, Iowa City, IA, USA
i Department of Psychiatry, University of Florida Medical School, Gainesville, FL, USA
j Department of Psychiatry, UCSD, CA, USA
k Maastricht University Medical Centre, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht, The Netherlands
l Department of Psychiatry, Maryland Psychiatric Research Center, Baltimore, MD, USA

Abstract
Schizophrenia spectrum disorders attract great interest among clinicians, researchers, and the lay public. While the diagnostic features of schizophrenia have remained unchanged for more than 100 years, the mechanism of illness has remained elusive. There is increasing evidence that the categorical diagnosis of schizophrenia and other psychotic disorders contributes to this lack of progress. The 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) continues the categorical classification of psychiatric disorders since the research needed to establish a new nosology of equal or greater validity is lacking. However, even within a categorical system, the DSM-5 aims to capture the underlying dimensional structure of psychosis. The domains of psychopathology that define psychotic disorders are presented not simply as features of schizophrenia. The level, the number, and the duration of psychotic signs and symptoms are used to demarcate psychotic disorders from each other. Finally, the categorical assessment is complemented with a dimensional assessment of psychosis that allows for more specific and individualized assessment of patients. The structure of psychosis as outlined in the DSM-5 may serve as a stepping-stone towards a more valid classification system, as we await new data to redefine psychotic disorders. © 2013 Elsevier B.V. All rights reserved.

Author Keywords
Diagnosis;  DSM;  Nosology;  Psychotic disorders;  Schizophrenia

Document Type: Article in Press
Source: Scopus

Freedland, K.E., Carney, R.M.
Depression as a risk factor for adverse outcomes in coronary heart disease
(2013) BMC Medicine, 11 (1), art. no. 131, . 

Department of Psychiatry, Washington University, School of Medicine, 4320 Forest Park Avenue, Suite 301, St Louis, MO 63108, United States

Abstract
Background: Depression is firmly established as an independent predictor of mortality and cardiac morbidity in patients with coronary heart disease (CHD). However, it has been difficult to determine whether it is a causal risk factor, and whether treatment of depression can improve cardiac outcomes. In addition, research on biobehavioral mechanisms has not yet produced a definitive causal model of the relationship between depression and cardiac outcomes.Discussion: Key challenges in this line of research concern the measurement of depression, the definition and relevance of certain subtypes of depression, the temporal relationship between depression and CHD, underlying biobehavioral mechanisms, and depression treatment efficacy.Summary: This article examines some of the methodological challenges that will have to be overcome in order to determine whether depression should be regarded as a key target of secondary prevention in CHD. © 2013 Freedland and Carney; licensee BioMed Central Ltd.

Author Keywords
Acute coronary syndrome;  Antidepressive agents;  Coronary disease;  Depression;  Depressive disorder;  Mortality;  Myocardial infarction;  Psychotherapy

Document Type: Article
Source: Scopus

Maksaev, G., Haswell, E.S.
Recent characterizations of MscS and its homologs provide insight into the basis of ion selectivity in mechanosensitive channels
(2013) Channels, 7 (3), pp. 215-220. 

Department of Biology, Washington University in St. Louis, St. Louis, MO, United States

Abstract
The bacterial mechanosensitive channel MscS provides an excellent model system for the study of mechanosensitivity and for investigations into the cellular response to hypoosmotic shock. Numerous studies have elucidated the structure, function and gating mechanism of Escherichia coli MscS, providing a wealth of information for the comparative analysis of MscS family members in bacteria, archaea, fungi and plants. We recently reported the electrophysiological characterization of MscS-Like (MSL)10, a MscS homolog from the model flowering plant Arabidopsis thaliana. Here, we summarize our results and briefly compare MSL10 to previously described members of the MscS family. Finally, we comment on how this and other recently published studies illuminate the possible mechanisms by which ion selectivity is accomplished in this fascinating family of channels. ©2013 Landes Bioscience.

Author Keywords
Arabidopsis;  Ion channel;  Mechanosensitive;  MscS;  MscS-Like;  Xenopus oocyte

Document Type: Article
Source: Scopus

 

Kadkhodayan, Y., Rhodes, N., Blackburn, S., Derdeyn, C.P., Cross 3rd., D.T., Moran, C.J.
Comparison of Enterprise with Neuroform stent-assisted coiling of intracranial aneurysms.
(2013) AJR. American journal of roentgenology, 200 (4), pp. 872-878. 

Mallinckrodt Institute of Radiology, Interventional Neuroradiology Section, Washington University School of Medicine, St. Louis, MO, USA.

Abstract
The Enterprise stent is the first closed-cell stent designed to treat wide-necked intracranial aneurysms. Advantages of the design can include improvement in keeping coils within an aneurysm and the ability of the stent to be recaptured. We compared the technical and clinical complications of the Enterprise stent with the open-cell Neuroform stent, its primary alternative. Patients undergoing Enterprise and Neuroform stent-assisted aneurysm coiling were enrolled in prospective registries starting in March 2007 and February 2003, respectively. All consecutive patients through December 2011 were included. Deployment success and difficulty, stent movement and misplacement, and procedural complications were compared. Enterprise deployment success was high (108 of 115 attempts, 93.9%) with 102 aneurysms receiving a stent compared with Neuroform (173 of 214 attempts, 80.8%, p = 0.001) with 163 aneurysms. Enterprise was easier to deploy (1.7% vs 15.9% difficult deployment, p < 0.0001). There were no significant differences in the rates of stent movement, misplacement, or symptomatic hemorrhage. Symptomatic thromboembolic events, however, were more frequent with the Enterprise stent (8.7% vs 1.4%, p = 0.0021). The Enterprise stent enabled treatment of 10 additional aneurysms that could not be treated with Neuroform and had a higher rate of immediate aneurysm occlusion (87.3% vs 73.0%, p = 0.0058). Enterprise was easier to deploy and enabled treatment of additional aneurysms; however, there were more thromboembolic complications. On the basis of these findings, we prefer to use the Neuroform stent first and rely on the Enterprise stent as an easy-to-deliver backup for stent-assisted coiling.

Document Type: Article
Source: Scopus

Jerger, S.a , Damian, M.F.b , Mills, C.a , Bartlett, J.a , Tye-Murray, N.c , Abdi, H.a
Effect of perceptual load on semantic access by speech in children
(2013) Journal of Speech, Language, and Hearing Research, 56 (2), pp. 388-403. 

a University of Texas, Dallas, United States
b University of Bristol, United Kingdom
c Central Institute for the Deaf, Washington University School of Medicine, St. Louis, MO, United States

Abstract
Purpose: To examine whether semantic access by speech requires attention in children. Method: Children (N = 200) named pictures and ignored distractors on a cross-modal (distractors: auditory-no face) or multimodal (distractors: auditory-static face and audiovisual- dynamic face) picture word task. The cross-modal task had a low load, and the multimodal task had a high load (i.e., respectively naming pictures displayed on a blank screen vs. below the talker's face on his T-shirt). Semantic content of distractors was manipulated to be related vs. unrelated to the picture (e.g., picture "dog" with distractors "bear" vs. "cheese"). If irrelevant semantic content manipulation influences naming times on both tasks despite variations in loads, Lavie's (2005) perceptual load model proposes that semantic access is independent of capacity-limited attentional resources; if, however, irrelevant content influences naming only on the cross-modal task (low load), the perceptual load model proposes that semantic access is dependent on attentional resources exhausted by the higher load task. Results: Irrelevant semantic content affected performance for both tasks in 6- to 9-year-olds but only on the cross-modal task in 4- to 5-year-olds. The addition of visual speech did not influence results on the multimodal task. Conclusion: Younger and older children differ in dependence on attentional resources for semantic access by speech. © American Speech-Language-Hearing Association.

Author Keywords
Audiovisual speech;  Children;  Development;  Perceptual load;  Picture word task;  Semantic access

Document Type: Article
Source: Scopus

Geers, A.E.a , Nicholas, J.G.b
Enduring advantages of early cochlear implantation for spoken language development
(2013) Journal of Speech, Language, and Hearing Research, 56 (2), pp. 643-653. 

a University of Texas, Dallas, United States
b Washington University, Saint Louis, MO, United States

Abstract
Purpose: In this article, the authors sought to determine whether the precise age of implantation (AOI) remains an important predictor of spoken language outcomes in later childhood for those who received a cochlear implant (CI) between 12 and 38 months of age. Relative advantages of receiving a bilateral CI after age 4.5 years, better pre-CI-aided hearing, and longer CI experience were also examined. Method: Sixty children participated in a prospective longitudinal study of outcomes at 4.5 and 10.5 years of age. Twenty-nine children received a sequential second CI. Test scores were compared with normative samples of hearing age mates, and predictors of outcomes were identified. Results: Standard scores on language tests at 10.5 years of age remained significantly correlated with age of first cochlear implantation. Scores were not associated with receipt of a second, sequentially acquired CI. Significantly higher scores were achieved for vocabulary as compared with overall language, a finding not evident when the children were tested at younger ages. Conclusion: Age-appropriate spoken language skills continued to be more likely with younger AOI, even after an average of 8.6 years of additional CI use. Receipt of a second implant between ages 4 and 10 years and longer duration of device use did not provide significant added benefit. © American Speech-Language-Hearing Association.

Author Keywords
Bilateral;  Children;  Cochlear implant;  Deaf;  Deafness;  Language

Document Type: Article
Source: Scopus

Yan, Y.a b , MacEwan, M.R.a b , Hunter, D.A.a b , Farber, S.a b , Newton, P.a b , Tung, T.H.a b , Mackinnon, S.E.a b , Johnson, P.J.a b
Nerve regeneration in rat limb allografts: Evaluation of acute rejection rescue
(2013) Plastic and Reconstructive Surgery, 131 (4), pp. 499e-511e. 

a Division of Plastic and Reconstructive Surgery, Washington University, School of Medicine, Campus Box 8238, St. Louis, MO 63110, United States
b Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, United States

Abstract
Background: Successful nerve regeneration is critical to the functional success of composite tissue allografts. The present study was designed to characterize the effect of acute rejection on nerve regeneration and functional recovery in the setting of orthotopic limb transplantation. Methods: A rat orthotopic limb transplantation model was used to evaluate the effects of acute rejection on nerve regeneration and motor recovery. Continuous administration of FK506 (full suppression), administration of FK506 for the first 8 of 12 weeks (late rejection), or delayed administration of FK506/dexamethasone following noticeable rejection (early rejection) was used to preclude or induce rejection following limb transplantation. Twelve weeks postoperatively, nerve regeneration was assessed by means of histomorphometric analysis of explanted sciatic nerve, and motor recovery was assessed by means of evoked muscle force measurement in extensor digitorum longus muscle. Results: A single episode of acute rejection that occurs immediately or late after reconstruction does not significantly alter the number of regenerating axonal fibers. Acute rejection occurring late after reconstruction adversely affects extensor digitorum longus muscle function in composite tissue allografts. Conclusions: Collected data reinforce that adequate immunosuppressant administration in cases of allogeneic limb transplantation ensures levels of nerve regeneration and motor functional recovery equivalent to that of syngeneic transplants. Prompt rescue following acute rejection was further demonstrated not to significantly affect nerve regeneration and functional recovery postoperatively. However, instances of acute rejection that occur late after reconstruction affect graft function. In total, the present study begins to characterize the effect of immunosuppression regimens on nerve regeneration and motor recovery in the setting of composite tissue allografts. Copyright © 2013 by the American Society of Plastic Surgeons.

Document Type: Article
Source: Scopus

 

Cottler, L.B.a , Ajinkya, S.b , Merlo, L.J.c , Nixon, S.J.c , Abdallah, A.B.d , Gold, M.S.e f
Lifetime psychiatric and substance use disorders among impaired physicians in a physicians health program: Comparison to a general treatment population psychopathology of impaired physicians
(2013) Journal of Addiction Medicine, 7 (2), pp. 108-112. 

a Department of Epidemiology, Colleges of Medicine and Public Health and Health Professions, University of Florida, 1225 Center Drive, PO Box 100231, Gainesville, FL 32611, United States
b Department of Epidemiology, Colleges of Medicine and Public Health and Health Professions, University of Florida, United States
c Department of Psychiatry, College of Medicine, University of Florida, United States
d INQUIRI, Department of Anesthesiology, Washington University in St. Louis, United States
e Donald R. Dizney Eminent Scholar, Department of Psychiatry, United States
f Departments of Psychiatry, Neuroscience, Anesthesiology, Community Health and Family Medicine, College of Medicine and McKnight Brain Institute, University of Florida, United States

Abstract
Objectives: The prevalence of substance abuse and other psychiatric disorders among physicians is not well-established. We determined differences in lifetime substance use, and abuse/dependence as well as other psychiatric disorders, comparing physicians undergoing monitoring with a general population that had sought treatment for substance use. Methods: Participants were 99 physicians referred to a Physician's Health Program (PHP) because of suspected impairment, who were administered the Computerized Diagnostic Interview Schedule Version IV (CDIS-IV) to assess the presence of psychiatric disorders. Referred physicians were compared with an age, gender, and education status-matched comparison group from National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) Wave 1, in a 1:1 ratio. Results: Although referred physicians did not differ from their counterparts on lifetime use of alcohol, opiates, or sedatives, they did have significantly higher conditional odds of meeting criteria for alcohol, opiate, and sedative The Diagnostic and Statistical Manual of Mental Disorders IV abuse/dependence disorders. Physicians referred to the PHP had significantly lower odds of obsessive-compulsive disorder, major depression, and specific phobia compared with their counterparts. Conclusions: Physicians referred to a PHP have significantly higher odds of abuse/dependence disorders for cannabinoids and cocaine/ crack compared with a matched general population sample that had ever sought treatment for substance use, even though physicians were less likely to report use of those substances. Although the rate of alcohol use was similar between the 2 populations, physicians had higher odds of abuse/dependence for opiates, sedatives, and alcohol. More research is needed to understand patterns of use, abuse/dependence, and psychiatric morbidity among physicians. Copyright © 2013 American Society of Addiction Medicine.

Author Keywords
Drug abuse;  Epidemiology;  MDs;  Physician impairment;  Psychopathology;  Substance abuse

Document Type: Article
Source: Scopus

Cole, F.S., Alleyne, C., Barks, J.D., Boyle, R.J., Carroll, J.L., Dokken, D., Edwards, W.H., Georgieff, M., Gregory, K., Johnston, M.V., Kramer, M., Mitchell, C., Neu, J., Pursley, D.M., Robinson, W., Rowitch, D.H.
NIH consensus development conference: Inhaled nitric oxide therapy for premature infants.
(2010) NIH consensus and state-of-the-science statements, 27 (5), pp. 1-34. 

Department of Pediatrics, Division of Newborn Medicine, Washington University School of Medicine, and St. Louis Children's Hospital, St. Louis, Missouri, USA.

Abstract
To provide healthcare providers, patients, and the general public with a responsible assessment of currently available data on the use of inhaled nitric oxide in early routine, early rescue, or later rescue regimens in the care of premature infants <34 weeks gestation who require respiratory support. A non-Department of Health and Human Services, nonadvocate 16-member panel representing the fields of biostatistics, child psychology, clinical trials, ethics, family-centered care, neonatology, neurodevelopmental follow-up, nursing, pediatric epidemiology, neurobehavior, neurological surgery, neurology, and pulmonology, perinatology, and research methodology. In addition, 18 experts from pertinent fields presented data to the panel and conference audience. Presentations by experts and a systematic review of the literature prepared by the Johns Hopkins University Evidence-based Practice Center, through the Agency for Healthcare Research and Quality. Scientific evidence was given precedence over anecdotal experience. The panel drafted its statement based on scientific evidence presented in open forum and on published scientific literature. The draft statement was presented on the final day of the conference and circulated to the audience for comment. The panel released a revised statement later that day at http://consensus.nih.gov. This statement is a report of the panel and is not a policy statement of the NIH or the Federal Government. (1) Taken as a whole, the available evidence does not support use of inhaled nitric oxide in early routine, early rescue, or later rescue regimens in the care of premature infants <34 weeks gestation who require respiratory support. (2) There are rare clinical situations, including pulmonary hypertension or hypoplasia, that have been inadequately studied in which inhaled nitric oxide may have benefit in infants <34 weeks gestation. In such situations, clinicians should communicate with families regarding the current evidence on its risks and benefits as well as remaining uncertainties. (3) Basic research and animal studies have contributed to important understandings of inhaled nitric oxide benefits on lung development and function in infants at high risk of bronchopulmonary dysplasia. These promising results have only partly been realized in clinical trials of inhaled nitric oxide treatment in premature infants. Future research should seek to understand this gap. (4) Predefined subgroup and post hoc analyses of previous trials showing potential benefit of inhaled nitric oxide have generated hypotheses for future research for clinical trials. Prior strategies shown to be ineffective are discouraged unless new evidence emerges. The positive results of one multicenter trial, which was characterized by later timing, higher dose, and longer duration of treatment, require confirmation. Future trials should attempt to quantify the individual effects of each of these treatment-related variables (timing, dose, and duration), ideally by randomizing them separately. (5) Based on assessment of currently available data, hospitals, clinicians, and the pharmaceutical industry should avoid marketing inhaled nitric oxide for premature infants <34 weeks gestation.

Document Type: Review
Source: Scopus

Zhang, W.
Data mining methods for modeling gene expression regulation and their applications
(2006) Proceedings - IEEE International Conference on Data Mining, ICDM, art. no. 4053029, p. 7. 

Department of Computer Science and Engineering, Washington University in St. Louis, St. Louis, MO 63130, United States

 

Document Type: Conference Paper
Source: Scopus