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WUSTL Neuroscience Publications Archive - July 2014

July 2014

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July 22, 2014

Cook, P.A.a , McMillan, C.T.b , Avants, B.B.a , Peelle, J.E.c , Gee, J.C.a , Grossman, M.b
Relating brain anatomy and cognitive ability using a multivariate multimodal framework
(2014) NeuroImage, 99, pp. 477-486. 


a Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States
b Penn Frontotemporal Degeneration Center, Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States
c Department of Otolaryngology, Washington University in St Louis, St Louis, MO 63110, United States


Abstract
Linking structural neuroimaging data from multiple modalities to cognitive performance is an important challenge for cognitive neuroscience. In this study we examined the relationship between verbal fluency performance and neuroanatomy in 54 patients with frontotemporal degeneration (FTD) and 15 age-matched controls, all of whom had T1- and diffusion-weighted imaging. Our goal was to incorporate measures of both gray matter (voxel-based cortical thickness) and white matter (fractional anisotropy) into a single statistical model that relates to behavioral performance. We first used eigenanatomy to define data-driven regions of interest (DD-ROIs) for both gray matter and white matter. Eigenanatomy is a multivariate dimensionality reduction approach that identifies spatially smooth, unsigned principal components that explain the maximal amount of variance across subjects. We then used a statistical model selection procedure to see which of these DD-ROIs best modeled performance on verbal fluency tasks hypothesized to rely on distinct components of a large-scale neural network that support language: category fluency requires a semantic-guided search and is hypothesized to rely primarily on temporal cortices that support lexical-semantic representations; letter-guided fluency requires a strategic mental search and is hypothesized to require executive resources to support a more demanding search process, which depends on prefrontal cortex in addition to temporal network components that support lexical representations. We observed that both types of verbal fluency performance are best described by a network that includes a combination of gray matter and white matter. For category fluency, the identified regions included bilateral temporal cortex and a white matter region including left inferior longitudinal fasciculus and frontal-occipital fasciculus. For letter fluency, a left temporal lobe region was also selected, and also regions of frontal cortex. These results are consistent with our hypothesized neuroanatomical models of language processing and its breakdown in FTD. We conclude that clustering the data with eigenanatomy before performing linear regression is a promising tool for multimodal data analysis. © 2014 Elsevier Inc.


Author Keywords
FTD;  Language;  Multimodal;  Verbal fluency


Document Type: Article
Source: Scopus

Neta, M.a , Schlaggar, B.L.a b c d , Petersen, S.E.a b d e f g
Separable responses to error, ambiguity, and reaction time in cingulo-opercular task control regions
(2014) NeuroImage, 99, pp. 59-68. 


a Department of Neurology, Washington University School of Medicine, United States
b Department of Radiology, Washington University School of Medicine, United States
c Department of Pediatrics, Washington University School of Medicine, United States
d Department of Anatomy and Neurobiology, Washington University School of Medicine, United States
e Department of Neurosurgery, Washington University School of Medicine, United States
f Department of Psychology, Washington University, St. Louis, MO, United States
g Department of Biomedical Engineering, Washington University, St. Louis, MO, United States


Abstract
The dorsal anterior cingulate (dACC), along with the closely affiliated anterior insula/frontal operculum, have been demonstrated to show three types of task control signals across a wide variety of tasks. One of these signals, a transient signal that is thought to represent performance feedback, shows greater activity to error than correct trials. Other work has found similar effects for uncertainty/ambiguity or conflict, though some argue that dACC activity is, instead, modulated primarily by other processes more reflected in reaction time. Here, we demonstrate that, rather than a single explanation, multiple information processing operations are crucial to characterizing the function of these brain regions, by comparing operations within a single paradigm. Participants performed two tasks in an fMRI experimental session: (1) deciding whether or not visually presented word pairs rhyme, and (2) rating auditorily presented single words as abstract or concrete. A pilot was used to identify ambiguous stimuli for both tasks (e.g., word pair: BASS/GRACE; single word: CHANGE). We found greater cingulo-opercular activity for errors and ambiguous trials than clear/correct trials, with a robust effect of reaction time. The effects of error and ambiguity remained when reaction time was regressed out, although the differences decreased. Further stepwise regression of response consensus (agreement across participants for each stimulus; a proxy for ambiguity) decreased differences between ambiguous and clear trials, but left error-related differences almost completely intact. These observations suggest that trial-wise responses in cingulo-opercular regions monitor multiple performance indices, including accuracy, ambiguity, and reaction time. © 2014 Elsevier Inc.


Document Type: Article
Source: Scopus

Womer, F.Y.a , Wang, L.b , Alpert, K.I.b , Smith, M.J.b , Csernansky, J.G.b , Barch, D.M.a c d , Mamah, D.a
Basal ganglia and thalamic morphology in schizophrenia and bipolar disorder
(2014) Psychiatry Research - Neuroimaging, 223 (2), pp. 75-83. 


a Department of Psychiatry, Washington University School of Medicine, St. Louis, United States
b Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
c Department of Psychology, Washington University, St. Louis, MO, United States
d Department or Radiology, Washington University, St. Louis, MO, United States


Abstract
In this study, we examined the morphology of the basal ganglia and thalamus in bipolar disorder (BP), schizophrenia-spectrum disorders (SCZ-S), and healthy controls (HC) with particular interest in differences related to the absence or presence of psychosis. Volumetric and shape analyses of the basal ganglia and thalamus were performed in 33 BP individuals [12 without history of psychotic features (NPBP) and 21 with history of psychotic features (PBP)], 32 SCZ-S individuals [28 with SCZ and 4 with schizoaffective disorder], and 27 HC using FreeSurfer-initiated large deformation diffeomorphic metric mapping. Significant volume differences were found in the caudate and globus pallidus, with volumes smallest in the NPBP group. Shape abnormalities showing inward deformation of superior regions of the caudate were observed in BP (and especially in NPBP) compared with HC. Shape differences were also found in the globus pallidus and putamen when comparing BP and SCZ-S groups. No significant differences were seen in the nucleus accumbens and thalamus. In summary, structural abnormalities in the caudate and globus pallidus are present in BP and SCZ-S. Differences were more apparent in the NPBP subgroup. The findings herein highlight the potential importance of separately examining BP subgroups in neuroimaging studies. © 2014 Elsevier Ireland Ltd.


Author Keywords
Basal ganglia;  Morphometry;  Structural magnetic resonance imaging;  Thalamus


Document Type: Article
Source: Scopus

Albers, M.W.a , Gilmore, G.C.b , Kaye, J.c , Murphy, C.d , Wingfield, A.e , Bennett, D.A.f , Boxer, A.L.g , Buchman, A.S.f , Cruickshanks, K.J.h i , Devanand, D.P.j , Duffy, C.J.k , Gall, C.M.l , Gates, G.A.m , Granholm, A.-C.n o , Hensch, T.p , Holtzer, R.q , Hyman, B.T.a , Lin, F.R.r , McKee, A.C.s , Morris, J.C.t , Petersen, R.C.u , Silbert, L.C.c , Struble, R.G.v , Trojanowski, J.Q.w , Verghese, J.q , Wilson, D.A.x , Xu, S.f , Zhang, L.I.y
At the interface of sensory and motor dysfunctions and Alzheimer's disease
(2014) Alzheimer's and Dementia, . Article in Press. 


a Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA
b Jack, Joseph and Morton Mandel School of Applied Social Sciences, Case Western Reserve University, Cleveland, OH, USA
c Department of Neurology, Oregon Heath and Science University, Portland, OR, USA
d SDSU/UCSD Joint Doctoral Program in Clinical Psychology, San Diego State University, San Diego, CA, USA
e Volen National Center for Complex Systems and Department of Psychology, Brandeis University, Waltham, MA, USA
f Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA
g Department of Neurology, University of California, San Francisco, San Francisco, CA, USA
h Department of Ophthalmology and Visual Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA
i Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA
j Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY, USA
k Dept. of Neurology, School of Medicine and Dentistry, University of Rochester, Rochester, NY, USA
l Department of Anatomy and Neurobiology, University of California, Irvine, Irvine, CA, USA
m Bloedel Hearing Research Center, University of Washington, Seattle, WA, USA
n Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA
o Center on Aging, Medical University of South Carolina, Charleston, SC, USA
p Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA, USA
q Department of Neurology, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY, USA
r Division of Otology, Neurotology, and Skull Base Surgery, Johns Hopkins School of Medicine, Baltimore, MD, USA
s Departments of Neurology and Pathology, Boston University School of Medicine, Bedford, MA, USA
t Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA
u Mayo Alzheimer's Disease Research Center, Mayo Clinic College of Medicine, Rochester, MN, USA
v Center for Alzheimer Disease and Related Disorders, Southern Illinois University School of Medicine, Springfield, IL, USA
w Center for Neurodegenerative Disease Research and Institute on Aging, the Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA, USA
x Emotional Brain Institute, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA
y Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA


Abstract
Recent evidence indicates that sensory and motor changes may precede the cognitive symptoms of Alzheimer's disease (AD) by several years and may signify increased risk of developing AD. Traditionally, sensory and motor dysfunctions in aging and AD have been studied separately. To ascertain the evidence supporting the relationship between age-related changes in sensory and motor systems and the development of AD and to facilitate communication between several disciplines, the National Institute on Aging held an exploratory workshop titled "Sensory and Motor Dysfunctions in Aging and AD." The scientific sessions of the workshop focused on age-related and neuropathologic changes in the olfactory, visual, auditory, and motor systems, followed by extensive discussion and hypothesis generation related to the possible links among sensory, cognitive, and motor domains in aging and AD. Based on the data presented and discussed at this workshop, it is clear that sensory and motor regions of the central nervous system are affected by AD pathology and that interventions targeting amelioration of sensory-motor deficits in AD may enhance patient function as AD progresses. © 2014 The Alzheimers Association.


Author Keywords
Aging;  Alzheimer's disease;  Auditory function;  Motor;  Olfaction;  Sensory;  Vision


Document Type: Article in Press
Source: Scopus

Amunts, K.a b , Hawrylycz, M.J.c , Van Essen, D.C.d , Van Horn, J.D.e , Harel, N.f , Poline, J.-B.g , De Martino, F.h , Bjaalie, J.G.i , Dehaene-Lambertz, G.j , Dehaene, S.j , Valdes-Sosa, P.k l , Thirion, B.m , Zilles, K.n o , Hill, S.L.p , Abrams, M.B.p , Tass, P.A.a q r , Vanduffel, W.s , Evans, A.C.t , Eickhoff, S.B.a u
Interoperable atlases of the human brain
(2014) NeuroImage, . Article in Press. 


a Institute of Neuroscience and Medicine, INM-1, Research Centre Jülich, Germany
b C. and O. Vogt Institute for Brain Research, Heinrich Heine University, Düsseldorf, Germany
c Allen Institute for Brain Science, Seattle, WA, USA
d Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO, USA
e The Institute for Neuroimaging and Informatics (INI) and Laboratory for Neuro Imaging (LONI), Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
f Center for Magnetic Resonance Research, Departments of Radiology and Neurosurgery, University of Minnesota School of Medicine, Minneapolis, MN, USA
g Hellen Wills Neuroscience Institute, Brain Imaging Center, University of California at Berkeley, CA, USA
h Department of Cognitive Neuroscience, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, The Netherlands
i Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
j INSERM, U992, Cognitive Neuroimaging Unit, F-91191 Gif/Yvette, France
k Cuban Neuroscience Center, Havana, Cuba
l Key Laboratory for Neuroinformation, Chengudu, China
m Parietal Research Team, French Institute for Research in Computer Science and Automation (INRIA), Gif sur Yvette, France
n Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH University Aachen, Aachen, Germany
o Jülich-Aachen Research Alliance (JARA), Translational Brain Medicine, Jülich, Germany
p International Neuroinformatics Coordinating Facility Secretariat (INCF), Stockholm, Sweden
q Department of Neuromodulation, University of Cologne, Cologne, Germany
r Department of Neurosurgery, Stanford University, Stanford, USA
s Department of Neurosciences, KU Leuven, Leuven, Belgium
t Montreal Neurological Institute, McGill University, Montreal, Canada
u Institute for Clinical Neuroscience and Medical Psychology, Heinrich-Heine University, Düsseldorf, Germany


Abstract
The last two decades have seen an unprecedented development of human brain mapping approaches at various spatial and temporal scales. Together, these have provided a large fundus of information on many different aspects of the human brain including micro- and macrostructural segregation, regional specialization of function, connectivity, and temporal dynamics. Atlases are central in order to integrate such diverse information in a topographically meaningful way. It is noteworthy, that the brain mapping field has been developed along several major lines such as structure vs. function, postmortem vs. in vivo, individual features of the brain vs. population-based aspects, or slow vs. fast dynamics. In order to understand human brain organization, however, it seems inevitable that these different lines are integrated and combined into a multimodal human brain model. To this aim, we held a workshop to determine the constraints of a multi-modal human brain model that are needed to enable (i) an integration of different spatial and temporal scales and data modalities into a common reference system, and (ii) efficient data exchange and analysis. As detailed in this report, to arrive at fully interoperable atlases of the human brain will still require much work at the frontiers of data acquisition, analysis, and representation. Among them, the latter may provide the most challenging task, in particular when it comes to representing features of vastly different scales of space, time and abstraction. The potential benefits of such endeavor, however, clearly outweigh the problems, as only such kind of multi-modal human brain atlas may provide a starting point from which the complex relationships between structure, function, and connectivity may be explored. © 2014 Elsevier Inc. All rights reserved.


Document Type: Article in Press
Source: Scopus

Gooblar, J.a , Carpenter, B.D.a , Coats, M.A.b , Morris, J.C.b c d e f , Snider, B.J.b c
The influence of cerebrospinal fluid (CSF) biomarkers on clinical dementia evaluations
(2014) Alzheimer's and Dementia, . Article in Press. 


a Department of Psychology, St. Louis, MO, USA
b Knight Alzheimer's Disease Research Center, St. Louis, MO, USA
c Department of Neurology, St. Louis, MO, USA
d Department of Pathology and Immunology, St. Louis, MO, USA
e Department of Physical Therapy, St. Louis, MO, USA
f Department of Occupational Therapy of the School of Medicine, Washington University, St. Louis, MO, USA


Abstract
Background: Cerebrospinal fluid (CSF) proteins have become accepted biomarkers of Alzheimer's disease (AD) in research settings. The extent of their use, perceived utility, and influence on decision making in clinical settings, however, are less well studied. Methods: Clinicians who evaluate older adults (N = 193) were randomized to view normal, borderline, AD-consistent, or no CSF information in two vignettes portraying patients with borderline and mild AD symptoms. Clinicians also reported on the use and perceived utility of CSF biomarkers. Results: Although clinicians reported infrequent use and low perceived utility of CSF biomarkers, viewing AD-consistent CSF values made clinicians more likely to make an AD-related diagnosis, increased diagnostic confidence, and led clinicians to initiate treatment more often than clinicians who had no CSF information. Conclusions: CSF biomarkers influence decision making depending on the extent to which biomarkers reflect AD pathology, consistency between clinical-pathologic information, and the ambiguity of protein values. © 2014 The Alzheimer's Association.


Author Keywords
Alzheimer's disease;  Biomarkers;  Cerebrospinal fluid;  Dementia;  Diagnosis


Document Type: Article in Press
Source: Scopus

Wakao, N.a b , Takeuchi, M.a , Nishimura, M.c , Riew, K.D.d , Kamiya, M.a b , Hirasawa, A.a , Kawanami, K.a , Imagama, S.e , Sato, K.b , Takayasu, M.a
Vertebral artery variations and osseous anomaly at the C1-2 level diagnosed by 3D CT angiography in normal subjects
(2014) Neuroradiology, . Article in Press. 


a Department of Spine Center, Aichi Medical University, Nagakute 21, Aichi, 480-1195, Japan
b Department of Orthopedic Surgery, Aichi Medical University, Nagakute, Aichi, Japan
c Department of Radiology, Aichi Medical University, Nagakute, Aichi, Japan
d Department of Orthopedic Surgery, Washington University, St. Louis, MO, United States
e Department of Orthopedic Surgery, Nagoya University, Nagoya, Aichi, Japan


Abstract
Introduction The craniovertebral junction is anatomically complicated. Representative vertebral artery (VA) variations include the persistent first intersegmental artery (FIA), fenestration of the VA above and below C1 (FEN), posterior inferior cerebellar artery (PICA) from C1/2, and high-riding VA (HRVA). The ponticulus posticus (PP) is a well-known osseous anomaly at C1. Although those anomalies are frequent in patients with cervical deformity, the prevalence of these in subjects with normal cervical spines is still unknown. The aim of this study is to investigate the variations and prevalence of vascular and osseous anomalies based on three-dimensional computed tomographic (3D CT) angiography in patients without any cervical diseases, such as rheumatoid arthritis, Klippel-Feil syndrome, or Down syndrome. Methods Eligible subjects were patients who underwent 3D CT angiography by the Department of Otorhinolaryngology and Internal Medicine from January 2009 to October 2013 in our institution. The authors defined a HRVA as a C2 pedicle with a maximum diameter of 4 mm or less. Results Among 480 subjects with a mean age of 63.1 years, 387 patients were eligible. One hundred and eighteen subjects were female, and 269 were male. HRVA was observed in 10.1 % of patients (39 out of 387 cases), FIA in 1.8 % (7 cases), FEN in 1.3 % (5 cases), and PICA in 1.3 % (5 cases). PP was observed in 6.2 % of patients (24 cases). Conclusion According to past reports, many VA anomalies could be attributed to congenital or acquired conditions (e.g., rheumatoid arthritis). However, VA anomalies appear to exist even in patients without any such cervical diseases. © 2014 Springer-Verlag Berlin Heidelberg.


Author Keywords
3D CT angiography;  Osseous anomaly;  V3 segment;  Vascular anomaly;  Vertebral artery


Document Type: Article in Press
Source: Scopus

Herrick, R., McKay, M., Olsen, T., Horton, W., Florida, M., Moore, C.J., Marcus, D.S.
Data dictionary services in XNAT and the Human Connectome Project
(2014) Frontiers in Neuroinformatics, 8 (JULY), art. no. 65, . 


Neuroinformatics Research Group, Department of Radiology, Washington University School of Medicine, St. Louis, MO, United States


Abstract
The XNAT informatics platform is an open source data management tool used by biomedical imaging researchers around the world. An important feature of XNAT is its highly extensible architecture: users of XNAT can add new data types to the system to capture the imaging and phenotypic data generated in their studies. Until recently, XNAT has had limited capacity to broadcast the meaning of these data extensions to users, other XNAT installations, and other software. We have implemented a data dictionary service for XNAT, which is currently being used on ConnectomeDB, the Human Connectome Project (HCP) public data sharing website. The data dictionary service provides a framework to define key relationships between data elements and structures across the XNAT installation. This includes not just core data representing medical imaging data or subject or patient evaluations, but also taxonomical structures, security relationships, subject groups, and research protocols. The data dictionary allows users to define metadata for data structures and their properties, such as value types (e.g., textual, integers, floats) and valid value templates, ranges, or field lists. The service provides compatibility and integration with other research data management services by enabling easy migration of XNAT data to standards-based formats such as the Resource Description Framework (RDF), JavaScript Object Notation (JSON), and Extensible Markup Language (XML). It also facilitates the conversion of XNAT's native data schema into standard neuroimaging vocabularies and structures. © 2014 Herrick, McKay, Olsen, Horton, Florida, Moore and Marcus.


Author Keywords
Human computer interaction;  Human connectome;  Ontologies;  Publishing;  Translations;  XNAT


Document Type: Article
Source: Scopus

Karch, C.M., Cruchaga, C., Goate, A.M.
Alzheimer's disease genetics: From the bench to the clinic
(2014) Neuron, 83 (1), pp. 11-26. 


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


Abstract
Alzheimer's disease (AD) is a clinically heterogeneous neurodegenerative disease with a strong genetic component. Several genes have been associated with AD risk for nearly 20 years. However, it was not until the recent technological advances that allow for the analysis of millions of polymorphisms in thousands of subjects that we have been able to advance our understanding of the genetic complexity of AD susceptibility. Genome-wide association studies and whole-exome and whole-genome sequencing have revealed more than 20 loci associated with AD risk. These studies have provided insights into the molecular pathways that are altered in AD pathogenesis, which have, in turn, provided insight into novel therapeutic targets. Karch etal. discuss how the recent technological advances in human genetics have led to an increased understanding of the genetic architecture and molecular pathways involved in Alzheimer's disease. © 2014 Elsevier Inc.


Document Type: Review
Source: Scopus

Cole, M.W.a b , Bassett, D.S.c , Power, J.D.d , Braver, T.S.b , Petersen, S.E.b d
Intrinsic and task-evoked network architectures of the human brain
(2014) Neuron, 83 (1), pp. 238-251. 


a Center for Molecular and Behavioral Neuroscience, Rutgers University, Newark, NJ 07102, United States
b Department of Psychology, Washington University, St. Louis, MO 63130, United States
c Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, United States
d Department of Neurology, Washington University, St. Louis, MO 63110, United States


Abstract
Many functional network properties of the human brain have been identified during rest and task states, yet it remains unclear how the two relate. We identified a whole-brain network architecture present across dozens of task states that was highly similar to the resting-state network architecture. The most frequent functional connectivity strengths across tasks closely matched the strengths observed at rest, suggesting this is an "intrinsic," standard architecture of functional brain organization. Furthermore, a set of small but consistent changes common across tasks suggests the existence of a task-general network architecture distinguishing task states from rest. These results indicate the brain's functional network architecture during task performance is shaped primarily by an intrinsic network architecture that is also present during rest, and secondarily by evoked task-general and task-specific network changes. This establishes astrong relationship between resting-state functional connectivity and task-evoked functional connectivity-areas of neuroscientific inquiry typically considered separately. © 2014 Elsevier Inc.


Document Type: Article
Source: Scopus

Yamada, T.a b , Yang, Y.a b , Hemberg, M.c , Yoshida, T.d , Cho, H.Y.a b , Murphy, J.P.e , Fioravante, D.b f , Regehr, W.G.b , Gygi, S.P.e , Georgopoulos, K.d , Bonni, A.a b
Promoter decommissioning by the NuRD chromatin remodeling complex triggers synaptic connectivity in the mammalian brain
(2014) Neuron, 83 (1), pp. 122-134. 


a Department of Anatomy and Neurobiology, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, United States
b Department of Neurobiology, Harvard Medical School, Boston, MA 02115, United States
c Department of Ophthalmology, Children's Hospital Boston, Boston, MA 02115, United States
d Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, United States
e Department of Cell Biology, Harvard Medical School, Boston, MA 02115, United States
f Center for Neuroscience, University of California Davis, Davis, CA 95618, United States


Abstract
Precise control of gene expression plays fundamental roles in brain development, but the roles of chromatin regulators in neuronal connectivity have remained poorly understood. We report that depletion of the NuRD complex by invivo RNAi and conditional knockout of the core NuRD subunit Chd4 profoundly impairs the establishment of granule neuron parallel fiber/Purkinje cell synapses in the rodent cerebellar cortex invivo. By interfacing genome-wide sequencing of transcripts and ChIP-seq analyses, we uncover a network of repressed genes and distinct histone modifications at target gene promoters that are developmentally regulated by the NuRD complex in the cerebellum invivo. Finally, in a targeted invivo RNAi screen of NuRD target genes, we identify a program of NuRD-repressed genes that operate as critical regulators of presynaptic differentiation in the cerebellar cortex. Our findings define NuRD-dependent promoter decommissioning as a developmentally regulated programming mechanism that drives synaptic connectivity in the mammalian brain. © 2014 Elsevier Inc.


Document Type: Article
Source: Scopus

Luby, J.L., Gaffrey, M.S., Tillman, R., April, L.M., Belden, A.C.
Trajectories of preschool disorders to full DSM depression at school age and early adolescence: Continuity of preschool depression
(2014) American Journal of Psychiatry, 171 (7), pp. 768-776. 


Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States


Abstract
Objective: Preschool-onset depression, a developmentally adapted form of depression arising between ages 3 and 6, has demonstrated numerous validated features, including characteristic alterations in stress reactivity and brain function. This syndrome is characterized by subthreshold DSM criteria for major depressive disorder, raising questions about its clinical significance. To clarify the utility and public health significance of the preschool-onset depression construct, the authors investigated diagnostic outcomes of preschool children at school age and in adolescence. Method: In a longitudinal prospective study of preschool children, the authors assessed the likelihood of meeting full criteria for major depressive disorder at age 6 or later as a function of preschool depression, other preschool axis I disorders, maternal history of depression, non-supportive parenting, and traumatic life events. Results: Preschool-onset depression emerged as a robust predictor of major depressive disorder in later childhood even after accounting for the effect of maternal history of depression and other risk factors. Preschool-onset conduct disorder also predicted major depression in later childhood, but this association was partially mediated by nonsupportive parenting, reducing by 21% the effect of preschool conduct disorder in predicting major depression. Conclusions: Study findings provide evidence that this preschool depressive syndrome is a robust risk factor for developing full criteria for major depression in later childhood, over and above other established risk factors. The results suggest that attention to preschool depression and conduct disorder in addition to maternal history of depression and exposure to trauma may be important in identifying young children at highest risk for later major depression and applying early interventions.


Document Type: Article
Source: Scopus

Satoh, A., Imai, S.-I.
Systemic regulation of mammalian ageing and longevity by brain sirtuins
(2014) Nature Communications, 5, art. no. 4211, . 


Department of Developmental Biology, Washington University School of Medicine, Campus Box 8103, 660 South Euclid Avenue, St Louis, MO 63110, United States


Abstract
Sirtuins regulate numerous important biological processes in mammals, including various age-associated pathophysiologies. However, whether sirtuins are critical to control ageing and longevity in mammals has been controversial. Recent studies have demonstrated critical roles of sirtuins in the brain, especially the hypothalamus, in governing multiple physiological functions. These data provide strong evidence that brain sirtuins regulate mammalian ageing and longevity at the organismal level. © 2014 Macmillan Publishers Limited. All rights reserved.


Document Type: Review
Source: Scopus

Lucey, B.P.a , Bateman, R.J.a b c
Amyloid-β diurnal pattern: Possible role of sleep in Alzheimer's disease pathogenesis
(2014) Neurobiology of Aging, 35 (SUPPL.2), pp. S29-S34. 


a Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
b Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, United States
c Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, United States


Abstract
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline that is a growing public health crisis with a prevalence projected to more than double in the next 20years. Sleep is frequently impaired in individuals with AD. Further, recent studies have linked numerous age-related sleep disturbances such as poor sleep efficiency and sleep apnea, to future risk of cognitive impairment. Aggregation of amyloid-β (Aβ) into extracellular plaques in the brain is a key step in AD pathogenesis and likely begins 20years before the onset of dementia. Aβ concentrations in both humans and mouse models show Aβ concentrations rise during wakefulness and fall during sleep, that is, an Aβ diurnal pattern. There is evidence in animal models that changes in sleep time alter Aβ deposition, suggesting that sleep may play a role in AD pathogenesis. A hypothetical model for the role of sleep and the Aβ diurnal pattern in AD pathogenesis is proposed. © 2014 Elsevier Inc.


Author Keywords
Alzheimer's disease;  Amyloid-β;  Diurnal pattern;  Sleep


Document Type: Review
Source: Scopus

Barnard, N.D.a b , Bush, A.I.c , Ceccarelli, A.d , Cooper, J.a , de Jager, C.A.e , Erickson, K.I.f , Fraser, G.g , Kesler, S.h , Levin, S.M.b , Lucey, B.i , Morris, M.C.j , Squitti, R.k l
Dietary and lifestyle guidelines for the prevention of Alzheimer's disease
(2014) Neurobiology of Aging, 35 (SUPPL.2), pp. S74-S78. 


a Department of Medicine, George Washington University School of Medicine, Washington, DC, United States
b Physicians Committee for Responsible Medicine, Washington, DC, United States
c Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Australia
d Department of Neurology, Brigham and Women's Hospital, Laboratory for Neuroimaging Research, Partners MS Center, Harvard Medical School, Boston, MA, United States
e Oxford Project to Investigate Memory and Ageing (OPTIMA), Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom
f Department of Psychology, University of Pittsburgh, Pittsburgh, PA, United States
g Department of Epidemiology and Biostatistics, School of Public Health, Loma Linda University, Loma Linda, CA, United States
h Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, United States
i Department of Neurology, Washington University School of Medicine, St Louis, MO, United States
j Section on Nutrition and Nutritional Epidemiology, Department of Internal Medicine, Rush University, Chicago, IL, United States
k Department of Neuroscience, AFaR-Fatebenefratelli Hospital San Giovanni Calibita, Rome, Italy
l Laboratory of Neurodegeneration, Istituto Di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Pisana, Rome, Italy


Abstract
Risk of developing Alzheimer's disease is increased by older age, genetic factors, and several medical risk factors. Studies have also suggested that dietary and lifestyle factors may influence risk, raising the possibility that preventive strategies may be effective. This body of research is incomplete. However, because the most scientifically supported lifestyle factors for Alzheimer's disease are known factors for cardiovascular diseases and diabetes, it is reasonable to provide preliminary guidance to help individuals who wish to reduce their risk. At the International Conference on Nutrition and the Brain, Washington, DC, July 19-20, 2013, speakers were asked to comment on possible guidelines for Alzheimer's disease prevention, with an aim of developing a set of practical, albeit preliminary, steps to be recommended to members of the public. From this discussion, 7 guidelines emerged related to healthful diet and exercise habits. © 2014 Elsevier Inc.


Author Keywords
Alzheimer's disease;  Copper;  Dementia;  Exercise;  Iron;  Nutrition;  Prevention;  Saturated fat;  Trans fatty acids;  Vitamin E


Document Type: Review
Source: Scopus

Vinberg, F., Kolesnikov, A.V., Kefalov, V.J.
Ex vivo ERG analysis of photoreceptors using an in vivo ERG system
(2014) Vision Research, 101, pp. 108-117. 


Washington University School of Medicine, Department of Ophthalmology and Visual Sciences, 660 S. Euclid Avenue, St. Louis, MO 63110, United States


Abstract
The Function of the retina and effects of drugs on it can be assessed by recording transretinal voltage across isolated retina that is perfused with physiological medium. However, building ex vivo ERG apparatus requires substantial amount of time, resources and expertise. Here we adapted a commercial in vivo ERG system for transretinal ERG recordings from rod and cone photoreceptors and compared rod and cone signaling between ex vivo and in vivo environments. We found that the rod and cone a- and b-waves recorded with the transretinal ERG adapter and a standard in vivo ERG system are comparable to those obtained from live anesthetized animals. However, ex vivo responses are somewhat slower and their oscillatory potentials are suppressed as compared to those recorded in vivo. We found that rod amplification constant (A) was comparable between ex vivo and in vivo conditions, ~10-30s-2 depending on the choice of response normalization. We estimate that the A in cones is between 3 and 6s-2 in ex vivo conditions and by assuming equal A in vivo we arrive to light funnelling factor of 3 for cones in the mouse retina. The ex vivo ERG adapter provides a simple and affordable alternative to designing a custom-built transretinal recordings setup for the study of photoreceptors. Our results provide a roadmap to the rigorous quantitative analysis of rod and cone responses made possible with such a system. © 2014 Elsevier Ltd.


Author Keywords
A-Wave;  B-Wave;  Electroretinogram;  Photoreceptor;  Transretinal ERG


Document Type: Article
Source: Scopus

Mullins, N.a , Perroud, N.b , Uher, R.a c , Butler, A.W.a d , Cohen-Woods, S.e , Rivera, M.a f , Malki, K.a , Euesden, J.a , Power, R.A.a , Tansey, K.E.g , Jones, L.h , Jones, I.g , Craddock, N.g , Owen, M.J.g , Korszun, A.i , Gill, M.j , Mors, O.k , Preisig, M.l , Maier, W.m , Rietschel, M.m n , Rice, J.P.o , Müller-Myhsok, B.p , Binder, E.B.p , Lucae, S.p , Ising, M.p , Craig, I.W.a , Farmer, A.E.a , Mcguffin, P.a , Breen, G.a q , Lewis, C.M.a r
Genetic relationships between suicide attempts, suicidal ideation and major psychiatric disorders: A genome-wide association and polygenic scoring study
(2014) American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, 165 (5), pp. 428-437. 


a MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, United Kingdom
b Psychiatry, University Hospital of Geneva, Geneva, Switzerland
c Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada
d Department of Psychiatry, University of Hong Kong, Hong Kong, Special Administrative Region, China
e Department of Psychiatry, University of Adelaide, Adelaide, Australia
f Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, University of Granada, Granada, Spain
g MRC Centre for Neuropsychiatric Genetics and Genomics, Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, United Kingdom
h Department of Psychiatry, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, United Kingdom
i Barts and The London Medical School, Queen Mary University of London, London, United Kingdom
j Department of Psychiatry, Trinity Centre for Health Science, Dublin, Ireland
k Research Department P, Aarhus University Hospital, Risskov, Denmark
l University Hospital Center and University of Lausanne, Lausanne, Switzerland
m Department of Psychiatry, University of Bonn, Bonn, Germany
n Division of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany
o Department of Psychiatry, Washington University, St. Louis, MO, United States
p Max Planck Institute of Psychiatry, Munich, Germany
q NIHR Biomedical Research Centre for Mental Health, South London and Maudsley NHS Foundation Trust and Institute of Psychiatry, King's College London, London, United Kingdom
r Division of Genetics and Molecular Medicine, King's College London School of Medicine, Guy's Hospital, London, United Kingdom


Abstract
Epidemiological studies have recognized a genetic diathesis for suicidal behavior, which is independent of other psychiatric disorders. Genome-wide association studies (GWAS) on suicide attempt (SA) and ideation have failed to identify specific genetic variants. Here, we conduct further GWAS and for the first time, use polygenic score analysis in cohorts of patients with mood disorders, to test for common genetic variants for mood disorders and suicide phenotypes. Genome-wide studies for SA were conducted in the RADIANT and GSK-Munich recurrent depression samples and London Bipolar Affective Disorder Case-Control Study (BACCs) then meta-analysis was performed. A GWAS on suicidal ideation during antidepressant treatment had previously been conducted in the Genome Based Therapeutic Drugs for Depression (GENDEP) study. We derived polygenic scores from each sample and tested their ability to predict SA in the mood disorder cohorts or ideation status in the GENDEP study. Polygenic scores for major depressive disorder, bipolar disorder and schizophrenia from the Psychiatric Genomics Consortium were used to investigate pleiotropy between psychiatric disorders and suicide phenotypes. No significant evidence for association was detected at any SNP in GWAS or meta-analysis. Polygenic scores for major depressive disorder significantly predicted suicidal ideation in the GENDEP pharmacogenetics study and also predicted SA in a combined validation dataset. Polygenic scores for SA showed no predictive ability for suicidal ideation. Polygenic score analysis suggests pleiotropy between psychiatric disorders and suicidal ideation whereas the tendency to act on such thoughts may have a partially independent genetic diathesis. © 2014 Wiley Periodicals, Inc.


Author Keywords
Association;  Meta-analysis;  Pleiotropy;  Prediction


Document Type: Article
Source: Scopus

Van Den Berg, S.M.a ay , De Moor, M.H.M.b , McGue, M.c d , Pettersson, E.e , Terracciano, A.f g , Verweij, K.J.H.h i , Amin, N.j , Derringer, J.k , Esko, T.l , Van Grootheest, G.m , Hansell, N.K.h , Huffman, J.n , Konte, B.o , Lahti, J.p q , Luciano, M.r s , Matteson, L.K.c , Viktorin, A.e , Wouda, J.b , Agrawal, A.t , Allik, J.u v , Bierut, L.t , Broms, U.w x , Campbell, H.y , Smith, G.D.z , Eriksson, J.G.q x aa ab ac , Ferrucci, L.f , Franke, B.ad ae af , Fox, J.-P.a , De Geus, E.J.C.b , Giegling, I.o , Gow, A.J.ag , Grucza, R.t , Hartmann, A.M.o , Heath, A.C.t , Heikkilä, K.w , Iacono, W.G.c , Janzing, J.ae , Jokela, M.p ah , Kiemeney, L.ai aj , Lehtimäki, T.ah , Madden, P.A.F.t , Magnusson, P.K.E.e , Northstone, K.z , Nutile, T.ak , Ouwens, K.G.b , Palotie, A.al am , Pattie, A.r s , Pesonen, A.-K.p , Polasek, O.an , Pulkkinen, L.ao , Pulkki-Råback, L.p , Raitakari, O.T.ap aq , Realo, A.u , Rose, R.J.ar , Ruggiero, D.ak , Seppälä, I.ah , Slutske, W.S.as , Smyth, D.C.h , Sorice, R.ak , Starr, J.M.s , Sutin, A.R.f g , Tanaka, T.f , Verhagen, J.at , Vermeulen, S.af ai , Vuoksimaa, E.w au , Widen, E.am , Willemsen, G.b , Wright, M.J.h , Zgaga, L.y av , Rujescu, D.o , Metspalu, A.l v , Wilson, J.F.y , Ciullo, M.ak , Hayward, C.n , Rudan, I.y , Deary, I.J.r s , Räikkönen, K.p q x , Arias Vasquez, A.ad ae af aw , Costa, P.T.ax , Keltikangas-Järvinen, L.p , Van Duijn, C.M.j , Penninx, B.W.J.H.m , Krueger, R.F.c , Evans, D.M.z , Kaprio, J.w x am , Pedersen, N.L.e , Martin, N.G.h , Boomsma, D.I.b
Harmonization of neuroticism and extraversion phenotypes across inventories and cohorts in the Genetics of Personality Consortium: An application of item response theory
(2014) Behavior Genetics, 44 (4), pp. 295-313. 


a Department of Research Methodology, Measurement and Data-Analysis, University of Twente, Enschede, Netherlands
b Department of Biological Psychology, VU University, Amsterdam, Netherlands
c Department of Psychology, University of Minnesota, Elliott Hall, Minneapolis, MN, United States
d Institute of Public Health, University of Southern Denmark, Odense, Denmark
e Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
f National Institute on Aging, NIH, Baltimore, MD, United States
g College of Medicine, Florida State University, Tallahassee, FL, United States
h QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
i Department of Developmental Psychology, EMGO Institute for Health and Care Research, VU University Amsterdam, Amsterdam, Netherlands
j Department of Epidemiology, Erasmus University Medical Center, Rotterdam, Netherlands
k Department of Psychology, University of Illinois at Urbana-Champaign, Champaign, IL, United States
l Estonian Genome Center, University of Tartu, Tartu, Estonia
m Department of Psychiatry, Neuroscience Campus Amsterdam, VU University Medical Center Amsterdam, Amsterdam, Netherlands
n MRC Human Genetics, Western General Hospital, University of Edinburgh, Edinburgh, United Kingdom
o Department of Psychiatry, University of Halle, Halle, Germany
p Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland
q Folkhälsan Research Center, Helsinki, Finland
r Department of Psychology, University of Edinburgh, Edinburgh, United Kingdom
s Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom
t Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
u Department of Psychology, University of Tartu, Tartu, Estonia
v Estonian Academy of Sciences, Tallinn, Estonia
w Department of Public Health, Hjelt Institute, University of Helsinki, Helsinki, Finland
x National Institute for Health and Welfare (THL), Helsinki, Finland
y Centre for Population Health Sciences, Medical School, University of Edinburgh, Edinburgh, United Kingdom
z MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom
aa Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland
ab Unit of General Practice, Helsinki University Central Hospital, Helsinki, Finland
ac Vasa Central Hospital, Vaasa, Finland
ad Donders Institute for Cognitive Neuroscience, Radboud University Nijmegen, Nijmegen, Netherlands
ae Department of Psychiatry, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands
af Department of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands
ag Department of Psychology, School of Life Sciences, Heriot-Watt University, Edinburgh, United Kingdom
ah Department of Clinical Chemistry, School of Medicine, University of Tampere, Tampere, Finland
ai Department of Health Evidence, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands
aj Department of Urology, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands
ak Institute of Genetics and Biophysics A. Buzzati-Traverso - CNR, Naples, Italy
al Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom
am Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland
an Department of Public Health, Faculty of Medicine, University of Split, Split, Croatia
ao Department of Psychology, University of Jyväskylä, Jyväskylä, Finland
ap Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland
aq Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland
ar Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, United States
as Department of Psychological Sciences, Missouri Alcoholism Research Center, University of Missouri, Columbia, MO, United States
at Department of Psychological Methods, University of Amsterdam, Amsterdam, Netherlands
au Department of Psychiatry, University of California, San Diego, CA, United States
av Department of Public Health and Primary Care, Trinity College Dublin, Dublin, Ireland
aw Department of Cognitive Neuroscience, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands
ax Behavioral Medicine Research Center, Duke University School of Medicine, Durham, NC, United States
ay Department of Behavioural Sciences, OMD, University of Twente, PO Box 217, 7500 AE Enschede, Netherlands


Abstract
Mega- or meta-analytic studies (e.g. genome-wide association studies) are increasingly used in behavior genetics. An issue in such studies is that phenotypes are often measured by different instruments across study cohorts, requiring harmonization of measures so that more powerful fixed effect meta-analyses can be employed. Within the Genetics of Personality Consortium, we demonstrate for two clinically relevant personality traits, Neuroticism and Extraversion, how Item-Response Theory (IRT) can be applied to map item data from different inventories to the same underlying constructs. Personality item data were analyzed in >160,000 individuals from 23 cohorts across Europe, USA and Australia in which Neuroticism and Extraversion were assessed by nine different personality inventories. Results showed that harmonization was very successful for most personality inventories and moderately successful for some. Neuroticism and Extraversion inventories were largely measurement invariant across cohorts, in particular when comparing cohorts from countries where the same language is spoken. The IRT-based scores for Neuroticism and Extraversion were heritable (48 and 49 %, respectively, based on a meta-analysis of six twin cohorts, total N = 29,496 and 29,501 twin pairs, respectively) with a significant part of the heritability due to non-additive genetic factors. For Extraversion, these genetic factors qualitatively differ across sexes. We showed that our IRT method can lead to a large increase in sample size and therefore statistical power. The IRT approach may be applied to any mega- or meta-analytic study in which item-based behavioral measures need to be harmonized. © 2014 The Author(s).


Author Keywords
Consortium;  Genome-wide association studies;  Item-Response Theory;  Measurement;  Meta-analysis;  Personality


Document Type: Article
Source: Scopus

Lohse, K.R.a b , Lang, C.E.d , Boyd, L.A.c
Is more better? Using metadata to explore dose-response relationships in stroke rehabilitation
(2014) Stroke, 45 (7), pp. 2053-2058. 


a School of Kinesiology, Auburn University, AL, United States
b School of Kinesiology, University of British Columbia, 210-6081 University Blvd, Vancouver, BC V6T 1Z1, Canada
c Department of Physical Therapy, University of British Columbia, Vancouver, BC, Canada
d Program in Physical Therapy, Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States


Abstract
BACKGROUND AND PURPOSE - : Neurophysiological models of rehabilitation and recovery suggest that a large volume of specific practice is required to induce the neuroplastic changes that underlie behavioral recovery. The primary objective of this meta-analysis was to explore the relationship between time scheduled for therapy and improvement in motor therapy for adults after stroke by (1) comparing high doses to low doses and (2) using metaregression to quantify the dose-response relationship further. METHODS - : Databases were searched to find randomized controlled trials that were not dosage matched for total time scheduled for therapy. Regression models were used to predict improvement during therapy as a function of total time scheduled for therapy and years after stroke. RESULTS - : Overall, treatment groups receiving more therapy improved beyond control groups that received less (g=0.35; 95% confidence interval, 0.26-0.45). Furthermore, increased time scheduled for therapy was a significant predictor of increased improvement by itself and when controlling for linear and quadratic effects of time after stroke. CONCLUSIONS - : There is a positive relationship between the time scheduled for therapy and therapy outcomes. These data suggest that large doses of therapy lead to clinically meaningful improvements, controlling for time after stroke. Currently, trials report time scheduled for therapy as a measure of therapy dose. Preferable measures of dose would be active time in therapy or repetitions of an exercise. © 2014 American Heart Association, Inc.


Author Keywords
rehabilitation;  stroke;  therapy


Document Type: Article
Source: Scopus

Tung, T.H.
Nerve transfers
(2014) Clinics in Plastic Surgery, 41 (3), pp. 551-559. 


Division of Plastic and Reconstructive Surgery, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8238, St Louis, MO 63110, United States


Abstract
This article provides an update of the current state of motor and sensory nerve transfers for the functional reconstruction of proximal and distal nerve lesions of the upper extremity. General principles, indications, surgical options, and functional outcomes are summarized for conventional transfers used in brachial plexus reconstruction, more recently described distal nerve transfers for isolated nerve injuries in the extremity, and sensory nerve transfers performed both proximally and distally. © 2014 Elsevier Inc.


Author Keywords
Brachial plexus;  Nerve injury;  Nerve reconstruction;  Nerve repair;  Nerve transfer


Document Type: Review
Source: Scopus

Eszter, K.a b , Mária, S.-S.c , Anna, S.a
Neurocognitive endophenotypes in psychiatric genetics [Neurokognitív endofenotípusok a pszichiátriai genetikában]
(2014) Neuropsychopharmacologia Hungarica, 16 (2), pp. 85-90. 


a Eötvös Loránd Tudományegyetem, Pszichológiai Intézet, Budapest, Hungary
b Department of Psychology, Washington University in St. Louis, United States
c Semmelweis Egyetem, Orvosi Vegytani, Molekuláris Biológiai és Pathobiokémiai Intézet, Budapest, Hungary


Abstract
Psychiatric genetics aims to map genetic factors of psychiatric disorders with complex inheritance. The most commonly used phenotype is the categorical variable of the presence or absence of a disease (case-control model). However, the biological background of various psychiatric disease categories often overlaps. Thus, the use of endophenotypes based on specific biological mechanisms seems to be a more efficient approach in genetic association studies. Results confirm that categorical variables as phenotypes are statistically not so sensitive in identification of a genetic association as well-chosen endophenotypes. Current literature advocates a growing significance of analyzing dimensional neurocognitive endophenotypes in genetic association studies, as well as in developing diagnostic category systems with biological backgrounds.


Author Keywords
Genetic association studies;  Neurocognitive endophenotype;  Psychiatric genetics


Document Type: Review
Source: Scopus

Liu, B.a , Murphy, R.K.J.b , Mercer, D.b , Tychsen, L.c , Smyth, M.D.b
Pseudopapilledema and association with idiopathic intracranial hypertension
(2014) Child's Nervous System, 30 (7), pp. 1197-1200. 


a Washington University, St. Louis, MO, United States
b Department of Pediatric Neurosurgery, St. Louis Children's Hospital, One Children's Place, St. Louis, MO 63110-1077, United States
c Department of Pediatric Ophthalmology, St. Louis Children's Hospital, St. Louis, MO, United States


Abstract
Purpose: Diagnosing idiopathic intracranial hypertension (IIH), or pseudotumor cerebri, can be challenging in children. Diagnosis is based on lumbar puncture, opening pressures, and appearance of the optic disk. Misdiagnosis of papilledema, a typical finding, may lead to unnecessary treatments and procedures. We report 52 children over a 6-year period to better identify the true incidence of pseudopapilledema and other factors that may confound the diagnosis of IIH. Methods: A retrospective chart review approved by the Institutional Review Board was performed. Fifty-two children under the age of 21 referred to us based on suspected IIH or papilledema from 2007 to 2013 are included in this study. Patients were assessed by a pediatric ophthalmologist and a neurosurgeon. Results: Fifty-two children were initially diagnosed with IIH and/or papilledema; 26 diagnoses were revised to pseudopapilledema after pediatric ophthalmological review. Out of those 26 patients with pseudopapilledema, 14 had undergone lumbar punctures, 19 had MRIs, 9 had CTs, and 12 were taking medications-these medications were discontinued upon revision of the diagnoses. The difference in the CSF opening pressure between children diagnosed with true IIH (32.7 cm H2O) and children diagnosed with pseudopapilledema (24.7 cm H2O) was statistically significant. Conclusions: IIH diagnosis is heavily reliant on the appearance of the optic disk. Pediatric ophthalmological assessment is essential to carefully examine the optic disk and prevent further unnecessary investigation and treatments. Close communication between pediatricians, ophthalmologists, and neurosurgeons can avoid invasive procedures for children who do have pseudopapilledema, and not IIH or associated papilledema. © 2014 Springer-Verlag.


Author Keywords
Idiopathic intracranial hypertension;  Optic nerve drusen;  Papilledema;  Pseudopapilledema;  Pseudotumor cerebri


Document Type: Article
Source: Scopus

Vretzakis, G.a , Bareka, M.a , Aretha, D.b , Karanikolas, M.c
Regional anesthesia for laparoscopic surgery: A narrative review
(2014) Journal of Anesthesia, 28 (3), pp. 429-446. 


a Department of Anesthesiology, University Hospital of Larissa, Larissa, Greece
b Department of Anaesthesiology, Pyrgos General Hospital, 76 Stratigou Konstantinopoulou St, Aroi, 26331 Patras, Greece
c Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, United States


Abstract
Laparoscopic surgery has advanced remarkably in recent years, resulting in reduced morbidity and shorter hospital stay compared with open surgery. Despite challenges from the expanding array of laparoscopic procedures performed with the use of pneumoperitoneum on increasingly sick patients, anesthesia has remained largely unchanged. At present, most laparoscopic operations are usually performed under general anesthesia, except for patients deemed "too sick" for general anesthesia. Recently, however, several large, retrospective studies questioned the widely held belief that general anesthesia is the best anesthetic method for laparoscopic surgery and suggested that regional anesthesia could also be a reasonable choice in certain settings. This narrative review is an attempt to critically summarize current evidence on regional anesthesia for laparoscopic surgery. Because most available data come from large, retrospective studies, large, rigorous, prospective clinical trials comparing regional vs. general anesthesia are needed to evaluate the true value of regional anesthesia in laparoscopic surgery. © 2013 Japanese Society of Anesthesiologists.


Author Keywords
Anesthesia;  Epidural;  Laparoscopic surgery;  Local;  Neuraxial;  Regional;  Spinal


Document Type: Review
Source: Scopus

Sahrmann, S.A.
The human movement system: Our professional identity
(2014) Physical Therapy, 94 (7), pp. 1034-1042. 


FAPTA, Washington University School of Medicine, 4444 Forest Park Ave, Box 8502, St Louis, MO 63108, United States


Abstract
The 2013 House of Delegates of the American Physical Therapy Association adopted a vision statement that addresses the role of physical therapy in transforming society through optimizing movement. The accompanying guidelines address the movement system as key to achieving this vision. The profession has incorporated movement in position statements and documents since the early 1980s, but movement as a physiological system has not been addressed. Clearly, those health care professions identified with a system of the body are more easily recognized for their expertise and role in preventing, diagnosing, and treating dysfunctions of the system than health professions identified with intervention but not a system. This perspective article provides a brief history of how leaders in the profession have advocated for clear identification of a body of knowledge. The reasons are discussed for why movement can be considered a physiological system, as are the advantages of promoting the system rather than just movement. In many ways, a focus on movement is more restrictive than incorporating the concept of the movement system. Promotion of the movement system also provides a logical context for the diagnoses made by physical therapists. In addition, there is growing evidence, particularly in relation to musculo-skeletal conditions, that the focus is enlarging from pathoanatomy to pathokinesiol-ogy, further emphasizing the timeliness of promoting the role of movement as a system. Discussion also addresses musculoskeletal conditions as lifestyle issues in the same way that general health has been demonstrated to be clearly related to lifestyle. The suggestion is made that the profession should be addressing kinesiopathologic conditions and not just pathokinesiologic conditions, as would be in keeping with the physical therapist's role in prevention and as a life-span practitioner. © 2014 American Physical Therapy Association.


Document Type: Article
Source: Scopus

Panagopoulos, V.N.a b , Ralevski, E.c
The role of ghrelin in addiction: A review
(2014) Psychopharmacology, 231 (14), pp. 2725-2740. 


a Department of Psychiatry, VA St. Louis Health Care System, 915 North Grand Blvd, St. Louis MO 63106, United States
b Department of Psychiatry, Washington University, 1 Brookings Dr., St. Louis MO 63130, United States
c Department of Psychiatry, VA Connecticut Healthcare System, Yale University School of Medicine, West Haven CT, United States


Abstract
Rationale: Ghrelin is a fast-acting hormone that is produced primarily by the stomach and by the brain although in smaller quantities. The regulation and the secretion of ghrelin are complex and not limited to aspects of feeding. Ghrelin exerts powerful effects on multiple processes, and it has been demonstrated that it mediates the rewarding properties of food as well as of drugs of abuse. Objectives: The purpose of this review is to summarize the findings of preclinical and clinical studies related to ghrelin's possible role in addiction for each specific class of substances. Questions related to ghrelin's involvement in addiction are highlighted. Recurrent methodological issues that render the interpretation of the findings challenging are discussed. Also, the potential of targeting ghrelin as a pharmacologic treatment strategy for addiction is explored. Results: Ghrelin signaling is implicated in the mediation of behavioral and biochemical effects of drugs of abuse that are cardinal for the development of addiction, especially for alcohol, nicotine, and stimulants. The available literature implicating ghrelin in opioid or cannabis use disorders is currently limited and inconclusive. Conclusions: There is intriguing, although not always consistent, evidence for the involvement of ghrelin signaling in aspects of addiction, especially in the cases of alcohol, nicotine, and stimulants. Further research, particularly in humans, is recommended to replicate and expand on the findings of the current literature. Improved and novel methodologies that take into account the volatile and complex nature of ghrelin are required to clarify the inconsistencies of the findings. © 2014 Springer-Verlag Berlin Heidelberg.


Author Keywords
Alcohol;  Cannabis;  Ghrelin;  Nicotine;  Opioids;  Review;  Reward;  Stimulants

 


Document Type: Review
Source: Scopus

 

July 15, 2014

Jonasson, L.S.a b c , Axelsson, J.a , Riklund, K.a b , Braver, T.S.d , Ögren, M.a , Bäckman, L.e , Nyberg, L.a b f
Dopamine release in nucleus accumbens during rewarded task switching measured by [11C]raclopride
(2014) NeuroImage, 99, pp. 357-364. 


a Department of Radiation Sciences, Umeå University, SE-901 87 Umeå, Sweden
b Umeå Center for Functional Brain Imaging (UFBI), Umeå University, SE-901 87 Umeå, Sweden
c Centre for Population Studies, Ageing and Living Conditions, Umeå University, SE-901 87 Umeå, Sweden
d Department of Psychology, Washington University, St Louis, MO 63130, United States
e Aging Research Center, Karolinska Institute, SE-113 30 Stockholm, Sweden
f Department of Integrative Medical Biology, Physiology, Umeå University, SE-901 87 Umeå, Sweden


Abstract
Reward and motivation have positive influences on cognitive-control processes in numerous settings. Models of reward implicate corticostriatal loops and the dopamine (DA) system, with special emphasis on D2 receptors in nucleus accumbens (NAcc). In this study, 11 right-handed males (35-40 years) were scanned with positron emission tomography (PET) in a single [11C]raclopride dynamic scan during rewarded and non-rewarded task switching. Rewarded task switching (relative to baseline task switching) decreased [11C]raclopride binding in NAcc. Decreasing NAcc [11C]raclopride binding was strongly associated with task reaction time measures that reflect individual differences in effort and control strategies. Voxelwise analyses additionally revealed reward-related DA release in anterodorsal caudate, a region previously associated with task-switching. These PET findings provide evidence for striatal DA release during motivated cognitive control, and further suggest that NAcc DA release predicts the task reaction time benefits of reward incentives. © 2014 The Authors.


Author Keywords
Dopamine;  Motivation;  Nucleus accumbens;  PET;  Reward;  Working memory


Document Type: Article
Source: Scopus

Bauer, A.Q.a , Kraft, A.W.b , Wright, P.W.a b c , Snyder, A.Z.a b , Lee, J.-M.a b c , Culver, J.P.a c d
Optical imaging of disrupted functional connectivity following ischemic stroke in mice
(2014) NeuroImage, 99, pp. 388-401. 


a Department of Radiology, Washington University, Saint Louis, MO 63110, United States
b Department of Neurology, Washington University, Saint Louis, MO 63110, United States
c Washington University, Biomedical Engineering, Saint Louis, MO 63110, United States
d Department of Physics, Washington University, Saint Louis, MO 63110, United States


Abstract
Recent human neuroimaging studies indicate that spontaneous fluctuations in neural activity, as measured by functional connectivity magnetic resonance imaging (fcMRI), are significantly affected following stroke. Disrupted functional connectivity is associated with behavioral deficits and has been linked to long-term recovery potential. FcMRI studies of stroke in rats have generally produced similar findings, although subacute cortical reorganization following focal ischemia appears to be more rapid than in humans. Similar studies in mice have not been published, most likely because fMRI in the small mouse brain is technically challenging. Extending functional connectivity methods to mouse models of stroke could provide a valuable tool for understanding the link between molecular mechanisms of stroke repair and human fcMRI findings at the system level. We applied functional connectivity optical intrinsic signal imaging (fcOIS) to mice before and 72. h after transient middle cerebral artery occlusion (tMCAO) to examine how graded ischemic injury affects the relationship between functional connectivity and infarct volume, stimulus-induced response, and behavior. Regional changes in functional connectivity within the MCA territory were largely proportional to infarct volume. However, subcortical damage affected functional connectivity in the somatosensory cortex as much as larger infarcts of cortex and subcortex. The extent of injury correlated with cortical activations following electrical stimulation of the affected forelimb and with functional connectivity in the somatosensory cortex. Regional homotopic functional connectivity in motor cortex correlated with behavioral deficits measured using an adhesive patch removal test. Spontaneous hemodynamic activity within the infarct exhibited altered temporal and spectral features in comparison to intact tissue; failing to account for these regional differences significantly affected apparent post-stroke functional connectivity measures. Thus, several results were strongly dependent on how the resting-state data were processed. Specifically, global signal regression alone resulted in apparently distorted functional connectivity measures in the intact hemisphere. These distortions were corrected by regressing out multiple sources of variance, as performed in human fcMRI. We conclude that fcOIS provides a sensitive imaging modality in the murine stroke model; however, it is necessary to properly account for altered hemodynamics in injured brain to obtain accurate measures of functional connectivity. © 2014 Elsevier Inc.


Author Keywords
Functional connectivity;  Functional recovery;  Global signal regression;  Mice;  Stroke


Document Type: Article
Source: Scopus

Conway, K.P.a , Vullo, G.C.a b , Kennedy, A.P.c , Finger, M.S.a , Agrawal, A.d , Bjork, J.M.e , Farrer, L.A.f , Hancock, D.B.g , Hussong, A.h , Wakim, P.i , Huggins, W.g , Hendershot, T.g , Nettles, D.S.g , Pratt, J.g , Maiese, D.g , Junkins, H.A.j , Ramos, E.M.j , Strader, L.C.g , Hamilton, C.M.g , Sher, K.J.k
Data compatibility in the addiction sciences: An examination of measure commonality
(2014) Drug and Alcohol Dependence, 141, pp. 153-158. 


a Division of Epidemiology Services and Prevention Research, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, United States
b Kelly Government Solutions, Bethesda, MD, United States
c Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, United States
d Washington University in St. Louis, St. Louis, MO, United States
e Division of Clinical Neuroscience and Behavioral Research, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, United States
f Boston University, Boston, MA, United States
g RTI International, Research Triangle Park, NC, United States
h University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
i Center for the Clinical Trials Network, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, United States
j National Human Genome Research Institute, Bethesda, MD, United States
k University of Missouri, Columbia, MO, United States


Abstract
The need for comprehensive analysis to compare and combine data across multiple studies in order to validate and extend results is widely recognized. This paper aims to assess the extent of data compatibility in the substance abuse and addiction (SAA) sciences through an examination of measure commonality, defined as the use of similar measures, across grants funded by the National Institute on Drug Abuse (NIDA) and the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Data were extracted from applications of funded, active grants involving human-subjects research in four scientific areas (epidemiology, prevention, services, and treatment) and six frequently assessed scientific domains. A total of 548 distinct measures were cited across 141 randomly sampled applications. Commonality, as assessed by density (range of 0-1) of shared measurement, was examined. Results showed that commonality was low and varied by domain/area. Commonality was most prominent for (1) diagnostic interviews (structured and semi-structured) for substance use disorders and psychopathology (density of 0.88), followed by (2) scales to assess dimensions of substance use problems and disorders (0.70), (3) scales to assess dimensions of affect and psychopathology (0.69), (4) measures of substance use quantity and frequency (0.62), (5) measures of personality traits (0.40), and (6) assessments of cognitive/neurologic ability (0.22). The areas of prevention (density of 0.41) and treatment (0.42) had greater commonality than epidemiology (0.36) and services (0.32). To address the lack of measure commonality, NIDA and its scientific partners recommend and provide common measures for SAA researchers within the PhenX Toolkit. © 2014.


Author Keywords
Data harmonization;  Gene-environment interactions;  Measure commonality;  Standard measures;  Substance use, abuse, and addiction


Document Type: Article
Source: Scopus

Jiang, X.a , Perez-Torres, C.J.b , Thotala, D.c , Engelbach, J.A.b , Yuan, L.d , Cates, J.c , Gao, F.g h , Drzymala, R.E.c d , Rich, K.M.c d , Schmidt, R.E.e , Ackerman, J.J.H.a b f h , Hallahan, D.E.c h , Garbow, J.R.b h
A GSK-3β inhibitor protects against radiation necrosis in mouse brain
(2014) International Journal of Radiation Oncology Biology Physics, 89 (4), pp. 714-721. 


a Department of Chemistry, Washington University, St. Louis, MO, United States
b Department of Radiology, Washington University, St. Louis, MO, United States
c Department of Radiation Oncology, Washington University, St. Louis, MO, United States
d Department of Neurosurgery, Washington University, St. Louis, MO, United States
e Department of Neuropathology, Washington University, St. Louis, MO, United States
f Department of Internal Medicine, Washington University, St. Louis, MO, United States
g Division of Biostatistics, Washington University, St. Louis, MO, United States
h Alvin J. Siteman Cancer Center, Washington University, St. Louis, MO, United States


Abstract
Purpose To quantify the effectiveness of SB415286, a specific inhibitor of GSK-3β, as a neuroprotectant against radiation-induced central nervous system (brain) necrosis in a mouse model. Methods and Materials Cohorts of mice were treated with SB415286 or dimethyl sulfoxide (DMSO) prior to irradiation with a single 45-Gy fraction targeted to the left hemisphere (brain) using a gamma knife machine. The onset and progression of radiation necrosis (RN) were monitored longitudinally by noninvasive in vivo small-animal magnetic resonance imaging (MRI) beginning 13 weeks postirradiation. MRI-derived necrotic volumes for SB415286- and DMSO-treated mice were compared. MRI results were supported by correlative histology. Results Mice treated with SB415286 showed significant protection from radiation-induced necrosis, as determined by in vivo MRI with histologic validation. MRI-derived necrotic volumes were significantly smaller at all postirradiation time points in SB415286-treated animals. Although the irradiated hemispheres of the DMSO-treated mice demonstrated many of the classic histologic features of RN, including fibrinoid vascular necrosis, vascular telangiectasia, hemorrhage, and tissue loss, the irradiated hemispheres of the SB415286-treated mice consistently showed only minimal tissue damage. These studies confirmed that treatment with a GSK-3β inhibitor dramatically reduced delayed time-to-onset necrosis in irradiated brain. Conclusions The unilateral cerebral hemispheric stereotactic radiation surgery mouse model in concert with longitudinal MRI monitoring provided a powerful platform for studying the onset and progression of RN and for developing and testing new neuroprotectants. Effectiveness of SB415286 as a neuroprotectant against necrosis motivates potential clinical trials of it or other GSK-3β inhibitors. © 2014 Elsevier Inc.


Document Type: Article
Source: Scopus

Tian, L.a , Karimi, M.a , Brown, C.A.a , Loftin, S.K.a , Perlmutter, J.S.a b c d e
In vivo measures of nigrostriatal neuronal response to unilateral MPTP treatment
(2014) Brain Research, 1571, pp. 49-60. 


a Neurology, Washington University, St. Louis, MO 63110, United States
b Radiology, Washington University, St. Louis, MO 63110, United States
c Neurobiology, Washington University, St. Louis, MO 63110, United States
d Occupational Therapy, Washington University, St. Louis, MO 63110, United States
e Physical Therapy, Washington University, St. Louis, MO 63110, United States


Abstract
A single unilateral intracarotid infusion of 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) into non-human primates causes injury to the nigrostriatal pathway including nigral cell bodies, axons and striatal terminal fields. In this model, motor parkinsonism correlates well with the loss of nigral dopaminergic cell bodies but only correlates with in vitro measures of nigrostriatal terminal fields when nigral cell loss does not exceed 50%. The goals of this study are to determine the relationship of motor parkinsonism with the degree of injury to nigrostriatal axons, as reflected by in vitro fiber length density measures, and compare in vivo with in vitro measures of striatal terminal fields. We determined axon integrity by measuring fiber length density with tyrosine hydroxylase (TH) immunohistology and dopamine transporter (DAT) density with DAT immunohistology. We then calculated the terminal arbor size and compared these measures with previously published data of quantified in vivo positron emission tomography (PET) measures of presynaptic dopaminergic neurons, autoradiographic measures of DAT and vesicular monoamine transporter type 2 (VMAT2), striatal dopamine, nigral cell counts, and parkinsonian motor ratings in the same animals. Our data demonstrate that in vivo and in vitro measures of striatal terminal fields correlate with each other regardless of the method of measurement. PET-based in vivo striatal measures accurately reflect in vitro measures of DAT and VMAT2. Terminal arbor size and other terminal field measures correlate with nigral TH immunoreactive (TH-ir) cell counts only when nigral TH-ir cell loss does not exceed 50%. Fiber length density was the only striatal measure that linearly correlated with motor ratings (Spearman: r=-0.81, p<0.001, n=16). © 2014 Elsevier B.V.


Author Keywords
MPTP;  Nigrostriatal;  PET;  Striatal terminal field


Document Type: Article
Source: Scopus

Pepose, J.S.a , Qazi, M.A.a , Chu, R.b , Stahl, J.c
A Prospective Randomized Clinical Evaluation of 3 Presbyopia-Correcting Intraocular Lenses after Cataract Extraction
(2014) American Journal of Ophthalmology, . Article in Press. 


a Pepose Vision Institute and the Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri
b Chu Eye Associates, Fort Worth, Texas
c Durrie Vision, Overland Park, Kansas


Abstract
Purpose: To compare contrast sensitivity, visual acuity (VA), and halos in subjects bilaterally implanted with 1 of 3 FDA-approved presbyopia-correcting intraocular lenses. Design: Prospective, randomized, partially masked, multicenter clinical trial. Methods: Seventy-eight subjects were randomized sequentially for bilateral implantation with the Crystalens AO (Bausch & Lomb Surgical), AcrySof IQ ReSTOR +3.0 (Alcon Laboratories), or Tecnis Multifocal (Abbott Medical Optics) lenses. Subjects were evaluated through visit 4 (4 to 6 months after surgery) with the following monocular and binocular assessments: high- and low-contrast VA, contrast sensitivity without glare, halos or starbursts, defocus curves, optical scatter, retinal point spread function, and safety. Results: The Crystalens AO and ReSTOR +3.0 demonstrated better monocular and binocular contrast sensitivity without glare at low to mid spatial frequencies compared with the Tecnis Multifocal lens. Binocular uncorrected distance VA was not significantly different between the 3 lenses. The Crystalens AO had significantly better binocular low-contrast distance-corrected VA than the ReSTOR +3.0 and better mean monocular low-contrast DCVA than the Tecnis Multifocal lens. The Crystalens AO demonstrated significantly better monocular and binocular uncorrected and distance-corrected intermediate VA than the ReSTOR +3.0 or Tecnis Multifocal lenses. The ReSTOR+3.0 lens had significantly better monocular and binocular uncorrected and distance-corrected near VA tested at 40 cm compared with the Crystalens AO and Tecnis Multifocal lens. The Crystalens AO elicited significantly less halos than the Tecnis Multifocal lens and less optical scatter than the ReSTOR +3.0 or Tecnis Multifocal lens. Conclusions: The Crystalens AO had statistically better uncorrected intermediate VA and distance-corrected intermediate VA than the ReSTOR +3.0 or Tecnis Multifocal lenses and fewer photic phenomenon than the Tecnis Multifocal lens. Both multifocals had better distance-corrected near VA and uncorrected near VA than the Crystalens AO. These findings may guide intraocular lens selection for individual patients seeking to optimize vision at specific vergences or lighting conditions. © 2014 Elsevier Inc. All rights reserved.


Document Type: Article in Press
Source: Scopus

Friess, S.H.a , Sutton, R.M.b , French, B.c , Bhalala, U.d , Maltese, M.R.b , Naim, M.Y.b , Bratinov, G.b , Arciniegas Rodriguez, S.b , Weiland, T.R.b , Garuccio, M.b , Nadkarni, V.M.b , Becker, L.B.e , Berg, R.A.b
Hemodynamic directed CPR improves cerebral perfusion pressure and brain tissue oxygenation
(2014) Resuscitation, . Article in Press. 


a St. Louis Children's Hospital, Washington University in St. Louis School of Medicine, Department of Pediatrics, 660 S. Euclid Avenue, St. Louis, MO 63110, United States
b The Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Department of Anesthesiology and Critical Care Medicine, 34th Street and Civic Center Boulevard, Philadelphia, PA 19104, United States
c University of Pennsylvania Perelman School of Medicine, Department of Biostatistics and Epidemiology, 423 Guardian Drive, Philadelphia, PA 19104, United States
d Bloomberg Children's Center, Johns Hopkins Hospital, Johns Hopkins University School of Medicine, Department of Anesthesiology and Critical Care Medicine, 1800 Orleans Street, Baltimore, MD 21287, United States
e The Hospital of the University of Pennsylvania, University of Pennsylvania Perelman School of Medicine, Department of Emergency Medicine, 3400 Spruce Street, Philadelphia, PA 19104, United States


Abstract
Aim: Advances in cardiopulmonary resuscitation (CPR) have focused on the generation and maintenance of adequate myocardial blood flow to optimize the return of spontaneous circulation and survival. Much of the morbidity associated with cardiac arrest survivors can be attributed to global brain hypoxic ischemic injury. The objective of this study was to compare cerebral physiological variables using a hemodynamic directed resuscitation strategy versus an absolute depth-guided approach in a porcine model of ventricular fibrillation (VF) cardiac arrest. Methods: Intracranial pressure and brain tissue oxygen tension probes were placed in the frontal cortex prior to induction of VF in 21 female 3-month-old swine. After 7 min of VF, animals were randomized to receive one of three resuscitation strategies: (1) hemodynamic directed care (CPP-20): chest compressions (CCs) with depth titrated to a target systolic blood pressure of 100 mmHg and titration of vasopressors to maintain coronary perfusion pressure (CPP) >20 mmHg; (2) depth 33 mm (D33): target CC depth of 33 mm with standard American Heart Association (AHA) epinephrine dosing; or (3) depth 51 mm (D51): target CC depth of 51 mm with standard AHA epinephrine dosing. Results: Cerebral perfusion pressures (CerePP) were significantly higher in the CPP-20 group compared to both D33 (p < 0.01) and D51 (p = 0.046), and higher in survivors compared to non-survivors irrespective of treatment group (p < 0.01). Brain tissue oxygen tension was also higher in the CPP-20 group compared to both D33 (p < 0.01) and D51 (p = 0.013), and higher in survivors compared to non-survivors irrespective of treatment group (p < 0.01). Subjects with a CPP >20 mmHg were 2.7 times more likely to have a CerePP >30 mmHg (p < 0.001). Conclusions: Hemodynamic directed resuscitation strategy targeting coronary perfusion pressure >20 mmHg following VF arrest was associated with higher cerebral perfusion pressures and brain tissue oxygen tensions during CPR. © 2014 Elsevier Ireland Ltd. All rights reserved.


Author Keywords
Brain tissue oxygen tension;  Cardiopulmonary resuscitation;  Cerebral perfusion pressure;  Coronary perfusion pressure;  Intracranial pressure;  Ventricular fibrillation


Document Type: Article in Press
Source: Scopus

Napoli, N.a , Shah, K.b , Waters, D.L.c , Sinacore, D.R.d e , Qualls, C.a f , Villareal, D.T.d g h
Effect of weight loss, exercise, or both on cognition and quality of life in obese older adults
(2014) American Journal of Clinical Nutrition, 100 (1), pp. 189-198. 


a Division of Endocrinology, University Campus Bio-Medico Di Roma, Rome, Italy
b Division of Geriatrics and Aging, University of Rochester, School of Medicine, Rochester, NY, United States
c Department of Preventive and Social Medicine, University of Otago, Dunedin School of Medicine, Dunedin, New Zealand
d Division of Geriatrics and Nutritional Science, Washington University, School of Medicine, St Louis, MO, United States
e Program in Physical Therapy, Washington University, School of Medicine, St Louis, MO, United States
f Department of Mathematics and Statistics, University of New Mexico, School of Medicine, Albuquerque, NM, United States
g Division of Geriatrics, University of New Mexico, School of Medicine, Albuquerque, NM, United States
h Section of Geriatrics, New Mexico VA Health Care System, Geriatrics (111K), 1501 San Pedro Drive, Albuquerque, NM 87108, United States


Abstract
Background: Obesity impairs cognition and health-related quality of life (HRQOL) in older adults; however, the appropriate treatment of obese older adults remains controversial. Objective: The objective was to determine the independent and combined effects of weight loss and exercise on cognition, mood, and HRQOL in obese older adults. Design: One hundred seven frail, obese older adults were randomly assigned to a control, weight-management (diet), exercise, or weight-management-plus-exercise (diet-exercise) group for 1 y. In this secondary analysis, main outcomes were Modified Mini-Mental State Examination (3MS) and total Impact of Weight on Quality of Life-Lite (IWQOL) scores. Other outcomes included Word Fluency Test, Trail Making Test Parts A and B, and Geriatric Depression Scale (GDS) scores. Results: Scores on the 3MS improved more in the diet (mean ± SE: 1.7 ± 0.4), exercise (2.8 ± 0.4), and diet-exercise (2.9 ± 0.4) groups than in the control group (0.1 ± 0.4) (between-group P = 0.0001-0.04); scores in the diet-exercise group improved more than in the diet group but not more than in the exercise group. Scores on the Word Fluency Test improved more in the exercise (4.1 ± 0.8) and diet-exercise (4.2 ± 0.7) groups than in the control group (20.8 ± 0.8; both P = 0.001). For the Trail Making Test Part A, scores in the diet-exercise group (211.8 ± 1.9) improved more than in the control group (20.8 ± 1.9) (P = 0.001); a similar finding was observed for the Trail Making Test Part B. Scores on the IWQOL improved more in the diet (7.6 ± 1.6), exercise (10.1 ± 1.6), and diet-exercise (14.0 ± 1.4) groups than in the control group (0.3 ± 1.6) (P = 0.0001-0.03); scores in the diet-exercise group improved more than in the diet group but not more than in the exercise group. In the diet-exercise group, peak oxygen consumption and strength changes were independent predictors of 3MS changes; weight and strength changes were independent predictors of IWQOL changes. GDS scores did not change. Conclusions: Weight loss and exercise each improve cognition and HRQOL, but their combination may provide benefits similar to exercise alone. These findings could inform practice guidelines with regard to optimal treatment strategies for obese older adults. This trial was registered at clinicaltrials.gov as NCT00146107. © 2014 American Society for Nutrition.


Document Type: Article
Source: Scopus

Salminen, L.E.a , Schofield, P.R.b c , Pierce, K.D.b , Conturo, T.E.d , Tate, D.F.e , Lane, E.M.f , Heaps, J.M.a , Bolzenius, J.D.a , Baker, L.M.a , Akbudak, E.d , Paul, R.H.a
Impact of the AGTR1 A1166C polymorphism on subcortical hyperintensities and cognition in healthy older adults
(2014) AGE, 36 (4), . Article in Press. 


a Department of Psychology, University of Missouri-Saint Louis, 1 University Boulevard, Stadler Hall 442 A, St. Louis, MO 63121, United States
b Neuroscience Research Australia, Barker Street Randwick, Sydney, NSW 2031, Australia
c School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia
d Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 S. Kingshighway, St. Louis, MO 63110, United States
e San Antonio Military Medical Center, 3551 Roger Brooke Drive, Fort Sam, Houston, TX 78234-6200, United States
f Vanderbilt University Medical Center, 1211 Medical Center Drive, Nashville, TN 37232, United States


Abstract
Vascular aging consists of complex and multifaceted processes that may be influenced by genetic polymorphisms of the renin-angiotensin system. A polymorphism in the angiotensin II type 1 receptor gene (AGTR1/rs5186) has been associated with an increased risk for arterial stiffness, hypertension, and ischemic stroke. Despite these identified relationships, the impact of AGTR1 A1166C on white matter integrity and cognition is less clear in a healthy aging population. The present study utilized indices of neuroimaging and neuropsychological assessment to examine the impact of the A1166C polymorphism on subcortical hyperintensities (SH) and cognition in 49 healthy adults between ages 51-85. Using a dominant statistical model (CC + CA (risk) vs. AA), results revealed significantly larger SH volume for individuals with the C1166 variant (p &lt; 0.05, partial eta2 = 0.117) compared with those with the AA genotype. Post hoc analyses indicated that increased SH volume in C allele carriers could not be explained by vascular factors such as pulse pressure or body mass index. In addition, cognitive performance did not differ significantly between groups and was not significantly associated with SH in this cohort. Results suggest that presence of the C1166 variant may serve as a biomarker of risk for suboptimal brain integrity in otherwise healthy older adults prior to changes in cognition. © 2014 American Aging Association.


Author Keywords
A1166C;  AGTR1;  Cerebrovascular aging;  Cognition;  Subcortical hyperintensities


Document Type: Article in Press
Source: Scopus

Xie, J.a e , Macewan, M.R.a e , Liu, W.b , Jesuraj, N.a , Li, X.a , Hunter, D.c , Xia, Y.b d
Nerve guidance conduits based on double-layered scaffolds of electrospun nanofibers for repairing the peripheral nervous system
(2014) ACS Applied Materials and Interfaces, 6 (12), pp. 9472-9480. 


a Department of Biomedical Engineering, Washington University, St. Louis, MO 63130, United States
b School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA 30332, United States
c Department of Surgery, School of Medicine, Washington University, St. Louis, MO 63110, United States
d Wallace H. Coulter Department of Biomedical Engineering, School of Chemistry and Biochemistry, Emory University, Atlanta, GA 30332, United States
e Mary and Dick Holland Regenerative Medicine Program, Medical Center, University of Nebraska, Omaha, NE 68198, United States


Abstract
Compared to the nerve guidance conduits (NGCs) constructed from a single layer of aligned nanofibers, bilayer NGCs with random and aligned nanofibers in the outer and inner layers are more robust and tear-resistant during surgical procedures thanks to an isotropic mechanical property provided by the random nanofibers. However, it remains unclear whether the random nanofibers will interfere with the aligned nanofibers to alter the extension pattern of the neurites and impede regeneration. To answer this question, we seeded dorsal root ganglia (DRG) on a double-layered scaffold, with aligned and random nanofibers on the top and bottom layers, respectively, and evaluated the outgrowth of neurites. The random nanofibers in the bottom layer exerted a negative impact on the extension of neurites projecting from the DRG, giving neurites a less ordered structure compared to those cultured on a single layer of aligned nanofibers. The negative impact of the random nanofibers could be effectively mitigated by preseeding the double-layered scaffold with Schwann cells. DRG cultured on top of such a scaffold exhibited a neurite outgrowth pattern similar to that for DRG cultured on a single layer of aligned nanofibers. We further fabricated bilayer NGCs from the double-layered scaffolds and tested their ability to facilitate nerve regeneration in a rat sciatic nerve injury model. Both histomorphometric analysis and functional characterization demonstrated that bilayer NGCs with an inner surface that was preseeded with Schwann cells could reach 54%, 64.2%, and 74.9% of the performance of isografts in terms of nerve fiber number, maximum isometric tetanic force, and mass of the extensor digitorum longus muscle, respectively. It can be concluded that the bilayer NGCs hold great potential in facilitating motor axon regeneration and functional motor recovery. © 2014 American Chemical Society.


Author Keywords
electrospun nanofiber;  nerve guidance conduit;  neural tissue engineering;  neurite extension;  peripheral nerve repair;  regenerative medicine


Document Type: Article
Source: Scopus

Stein, L.R., Imai, S.-I.
Specific ablation of Nampt in adult neural stem cells recapitulates their functional defects during aging
(2014) EMBO Journal, 33 (12), pp. 1321-1340. Cited 1 time.


Department of Developmental Biology, Washington University School of Medicine, St. Louis MO, United States


Abstract
Neural stem/progenitor cell (NSPC) proliferation and self-renewal, as well as insult-induced differentiation, decrease markedly with age. The molecular mechanisms responsible for these declines remain unclear. Here, we show that levels of NAD+ and nicotinamide phosphoribosyltransferase (Nampt), the rate-limiting enzyme in mammalian NAD+ biosynthesis, decrease with age in the hippocampus. Ablation of Nampt in adult NSPCs reduced their pool and proliferation in vivo. The decrease in the NSPC pool during aging can be rescued by enhancing hippocampal NAD+ levels. Nampt is the main source of NSPC NAD+ levels and required for G1/S progression of the NSPC cell cycle. Nampt is also critical in oligodendrocytic lineage fate decisions through a mechanism mediated redundantly by Sirt1 and Sirt2. Ablation of Nampt in the adult NSPCs in vivo reduced NSPC-mediated oligodendrogenesis upon insult. These phenotypes recapitulate defects in NSPCs during aging, giving rise to the possibility that Nampt-mediated NAD+ biosynthesis is a mediator of age-associated functional declines in NSPCs. Synopsis Levels of NAD+ and the NAD+ biosynthetic enzyme Nampt decline in the hippocampus during aging. Nampt ablation in adult neural stem/progenitor cells reduces self-renewal, proliferation, and oligodendrogenesis. Age-associated decreases in the stem cell pool are reversed by the administration of nicotinamide mononucleotide, a key NAD+ intermediate. Nampt is expressed in adult neural/progenitor stem cells and is the main source of their NAD+ levels. Loss of Nampt reduces proliferation by stalling progression of the neural stem/progenitor cell cycle at G0/G1. The NAD +-dependent sirtuins Sirt1 and Sirt2 redundantly mediate neural stem/progenitor cell fate decisions into oligodendrocytes. Loss of Nampt reduces neural stem/progenitor cell-derived oligodendrocyte regeneration after cuprizone-induced demyelination. NAD+ and the NAD+ biosynthetic enzyme Nampt decline in the aging hippocampus. Nampt ablation in adult neural stem cells in vivo reduces cell numbers, proliferation, and oligodendrogenesis. Decreases in the stem cell pool are reversed by enhancing hippocampal NAD+. © 2014 The Authors.


Author Keywords
adult neural stem cells;  aging;  differentiation;  Nampt;  proliferation


Document Type: Article
Source: Scopus

Korhonen, T.a b c , Loukola, A.a b , Wedenoja, J.a , Nyman, E.b d , Latvala, A.a b , Broms, U.a b , Häppölä, A.a , Paunio, T.b d e , Schrage, A.J.f , Vink, J.M.g , Mbarek, H.g , Boomsma, D.I.g , Penninx, B.W.J.H.h , Pergadia, M.L.f , Madden, P.A.F.f , Kaprio, J.a b d
Role of nicotine dependence in the association between the Dopamine Receptor gene DRD3 and major depressive disorder
(2014) PLoS ONE, 9 (6), art. no. e98199, . 


a Department of Public Health, Hjelt Institute, University of Helsinki, Helsinki, Finland
b Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, Finland
c Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
d Institute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland
e Department of Psychiatry, Helsinki University Central Hospital, Helsinki, Finland
f Washington University School of Medicine, Department of Psychiatry, Saint Louis, MI, United States
g Department of Biological Psychology/Netherlands Twin Register, VU University, Amsterdam, Netherlands
h Department of Psychiatry, VU University Medical Center/GGZ InGeest, Amsterdam, United States


Abstract
Background: The aims of this study were to analyze associations of dopamine receptor genes (DRD1-5 ) with Major Depressive Disorder (MDD) and nicotine dependence (ND), and to investigate whether ND moderates genetic influences on MDD. Methods: The sample was ascertained from the Finnish Twin Cohort. Twin pairs concordant for smoking history were recruited along with their family members, as part of the multisite Nicotine Addiction Genetics consortium. Genetic association analyses were based on 1428 adults. Total of 70 tagging single nucleotide polymorphisms within the dopamine receptor genes were genotyped and analyzed for association with MDD, ND, and MD-ND co-morbidity. Individual level logistic regression analyses were based on 1296 adults with data on ND and MDD diagnoses, as well as on dopamine receptor genotypes adjusted for sex, age, and alcohol use. Four independent samples, such as population-based and casecontrol samples, were used for replication. Results: Rs2399496, located 1.5 kb downstream of DRD3, showed suggestive association for MDD (p = 0.00076) and significant association for MDD-ND co-morbidity (p = 0.000079). Suggestive gene-(rs2399496) by-ND-interaction justified analyses by genetic risk variant and ND status. Individuals with ND and two minor alleles (AA) of rs2399496 had almost sixfold risk for MDD (OR 5.74, 95%CI 3.12-10.5, p = 9.010e-09) compared to individuals without ND and with two major alleles (TT). Conclusions: Significant association between a variant downstream of DRD3 and a co-morbid MDD-ND phenotype was detected. Our results further suggest that nicotine dependence may potentiate the influence of the DRD3 genetic variant on MDD. © 2014 Korhonen et al.


Document Type: Article
Source: Scopus

Escott-Price, V.a , Bellenguez, C.b c d , Wang, L.-S.e , Choi, S.-H.f , Harold, D.a , Jones, L.a , Holmans, P.a , Gerrish, A.a , Vedernikov, A.a , Richards, A.a , DeStefano, A.L.f , Lambert, J.-C.b c d , Ibrahim-Verbaas, C.A.g , Naj, A.C.h , Sims, R.a , Jun, G.f i j , Bis, J.C.k , Beecham, G.W.l m , Grenier-Boley, B.b c d , Russo, G.n , Thornton-Wells, T.A.o , Denning, N.a , Smith, A.V.p q , Chouraki, V.b c d r , Thomas, C.a , Arfan Ikram, M.s t , Zelenika, D.u , Vardarajan, B.N.i aa ab , Kamatani, Y.v , Lin, C.-F.e , Schmidt, H.w , Kunkle, B.l , Dunstan, M.L.a , Vronskaya, M.a , Johnson, A.D.y , Ruiz, A.z , Bihoreau, M.-T.u , Reitz, C.aa ab , Pasquier, F.c ac , Hollingworth, P.a , Hanon, O.ad , Fitzpatrick, A.L.k ae , Buxbaum, J.D.af ag ah , Campion, D.ai , Crane, P.K.aj , Becker, C.B.T.i ak eg , Gudnason, V.p q , Cruchaga, C.al , Craig, D.am , Amin, N.an , Berr, C.ao , Lopez, O.L.ap , De Jager, P.L.aq ar , Deramecourt, V.c ac , Johnston, J.A.am , Evans, D.as , Lovestone, S.at , Letenneur, L.au , Hernández, I.z , Rubinsztein, D.C.av , Eiriksdottir, G.q , Sleegers, K.aw ax , Goate, A.M.al , Fiévet, N.b d , Huentelman, M.J.ay , Gill, M.az , Brown, K.ba , Kamboh, M.I.bb bc , Keller, L.bd , Barberger-Gateau, P.at , McGuinness, B.am , Larson, E.B.aj be , Myers, A.J.bf , Dufouil, C.au , Todd, S.am , Wallon, D.ai , Love, S.bg , Rogaeva, E.bh , Gallacher, J.bi , St George-Hyslop, P.bh bj , Clarimon, J.bk bl , Lleo, A.bk bl , Bayer, A.bi , Tsuang, D.W.bm , Yu, L.bn , Tsolaki, M.bo , Bossù, P.bp , Spalletta, G.bp , Proitsi, P.at , Collinge, J.bq , Sorbi, S.br bs , Sanchez Garcia, F.bt , Fox, N.C.bu , Hardy, J.bv , Naranjo, M.C.D.bt , Bosco, P.bw , Clarke, R.bx , Brayne, C.by , Galimberti, D.bz , Scarpini, E.bz , Bonuccelli, U.ca , Mancuso, M.ca , Siciliano, G.ca , Moebus, S.cb , Mecocci, P.cc , Del Zompo, M.cd , Maier, W.ce cu , Hampel, H.cf cg , Pilotto, A.ch , Frank-García, A.ci cj ck , Panza, F.cl , Solfrizzi, V.cl , Caffarra, P.cm cn , Nacmias, B.br bs , Perry, W.l m , Mayhaus, M.co , Lannfelt, L.cp , Hakonarson, H.cq , Pichler, S.co , Carrasquillo, M.M.cr , Ingelsson, M.cp , Beekly, D.cs , Alvarez, V.ct , Zou, F.cr , Valladares, O.e , Younkin, S.G.cr , Coto, E.ct , Hamilton-Nelson, K.L.l , Gu, W.co , Razquin, C.cv , Pastor, P.cv cw , Mateo, I.cx , Owen, M.J.a , Faber, K.M.cy , Jonsson, P.V.p cz , Combarros, O.cx , O'Donovan, M.C.a , Cantwell, L.B.e , Soininen, H.da db , Blacker, D.dc dd , Mead, S.bq , Mosley Jr., T.H.de , Bennett, D.A.bn df , Harris, T.B.dg , Fratiglioni, L.dh di , Holmes, C.dj , De Bruijn, R.F.A.G.dk , Passmore, P.am , Montine, T.J.dl , Bettens, K.aw ax , Rotter, J.I.dm , Brice, A.dn do , Morgan, K.ba , Foroud, T.M.cy , Kukull, W.A.dp , Hannequin, D.ai , Powell, J.F.at , Nalls, M.A.dq , Ritchie, K.ao dr , Lunetta, K.L.f , Kauwe, J.S.K.ds , Boerwinkle, E.ds dt du , Riemenschneider, M.cu , Boada, M.z dv , Hiltunen, M.da db , Martin, E.R.l m , Schmidt, R.dw , Rujescu, D.cg , Dartigues, J.-F.au dx , Mayeux, R.aa ab , Tzourio, C.dy , Hofman, A.s t , Nöthen, M.M.dz , Graff, C.di ea , Psaty, B.M.k eb , Haines, J.L.ec ed , Lathrop, M.j v ee , Pericak-Vance, M.A.l m , Launer, L.J.dg , Van Broeckhoven, C.aw ax , Farrer, L.A.f i j r ef , Van Duijn, C.M.t an eh , Ramirez, A.ei , Seshadri, S.r ej , Schellenberg, G.D.e , Amouyel, P.b c d x ac , Williams, J.a
Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease
(2014) PLoS ONE, 9 (6), art. no. e94661, . 


a Institute of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, United Kingdom
b Inserm U744, Lille, France
c Université Lille 2, Lille, France
d Institut Pasteur de Lille, Lille, France
e Department of Pathology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, United States
f Department of Biostatistics, Boston University School of Public Health, Boston, MA, United States
g Department of Epidemiology and Neurology, Erasmus MC University Medical Center, Rotterdam, Netherlands
h Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
i Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, United States
j Department of Ophthalmology, Boston University School of Medicine, Boston, MA, United States
k Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, United States
l John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, United States
m Dr. John T. Macdonald Foundation, Department of Human Genetics, University of Miami, Miami, FL, United States
n Functional Genomics Center Zurich, ETH, University of Zurich, Zurich, Switzerland
o Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, United States
p University of Iceland, Faculty of Medicine, Reykjavik, Iceland
q Icelandic Heart Association, Kopavogur, Iceland
r Department of Neurology, Boston University School of Medicine, Boston, MA, United States
s Departments of Epidemiology, Neurology and Radiology, Erasmus MC University Medical Center, Rotterdam, Netherlands
t Netherlands Consortium for Healthy Aging, Leiden, Netherlands
u Centre National de Genotypage, Institut Genomique, Commissariat À l'Énergie Atomique, Evry, France
v Fondation Jean Dausset, CEPH, Paris, France
w Institute for Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria
x Centre Hospitalier Régional Universitaire de Lille, Lille, France
y NHLBI Cardiovascular Epidemiology, Human Genomics Branch, Framingham Heart Study, Framingham, MA, United States
z Memory Clinic of Fundació ACE, Institut Català de Neurociències Aplicades, Barcelona, Spain
aa Taub Institute on Alzheimer's Disease and the Aging Brain, Department of Neurology, Columbia University New York, New York, NY, United States
ab Gertrude H. Sergievsky Center, Department of Neurology, Columbia University, New York, NY, United States
ac CNR-MAJ, Centre Hospitalier Régional Universitaire de Lille, Lille, France
ad University Paris Descartes, Broca Hospital, Geriatrics Department, Paris, France
ae Departments of Epidemiology and Global Health, University of Washington, Seattle, WA, United States
af Department of Neuroscience, Mount Sinai School of Medicine, New York, NY, United States
ag Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, United States
ah Departments of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY, United States
ai CNR-MAJ, Inserm U1079, Rouen University Hospital, 76031 Rouen, France
aj Department of Medicine, University of Washington, Seattle, WA, United States
ak German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
al Department of Psychiatry, Hope Center Program on Protein Aggregation and Neurodegeneration, Washington University School of Medicine, St. Louis, MO, United States
am Ageing Group, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, United Kingdom
an Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, Netherlands
ao INSERM U1061, Faculty of Medicine, Hôpital la Colombière, Montpellier, France
ap Departments of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
aq Department of Neurology and Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
ar Program in Medical and Population Genetics, Broad Institute, Boston, MA, United States
as Rush Institute for Healthy Aging, Department of Internal Medicine, Rush University Medical Center, Chicago, IL, United States
at King's College London, Institute of Psychiatry, Department of Neuroscience, De Crespigny Park, Denmark Hill, London, United Kingom, United Kingdom
au Inserm U897, Victor Segalen University, F-33076, Bordeaux, France
av Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom
aw Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
ax Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium
ay Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, United States
az Discipline of Psychiatry, Trinity College, Dublin, Ireland
ba Institute of Genetics, Queen's Medical Centre, University of Nottingham, Nottingham, United Kingdom
bb Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, United States
bc Alzheimer's Disease Research Center, University of Pittsburgh, Pittsburgh, PA, United States
bd Department of Neurobiology, Karolinska Institutet, Stockholm University, Stockholm, Sweden
be Group Health Research Institute, Group Health, Seattle, WA, United States
bf Department of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, FL, United States
bg University of Bristol Institute of Clinical Neurosciences, School of Clinical Sciences, Frenchay Hospital, Bristol, United Kingdom
bh Tanz Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, ON, Canada
bi Institute of Primary Care and Public Health, Cardiff University, University Hospital of Wales, Heath Park, Cardiff, United Kingdom
bj Cambridge Institute for Medical Research, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom
bk Neurology Department, Sant Pau Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain
bl Center for Networker Biomedical Research in Neurodegenerative Diseases (CIBERNED), Barcelona, Spain
bm Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, United States
bn Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, United States
bo 3Rd Department of Neurology, Aristotle University of Thessaloniki, Thessaloniki, Greece
bp Clinical and Behavioral Neurology, Fondazione Santa Lucia, Roma, Italy
bq MRC Prion Unit, Department of Neurodegenerative Disease, UCL Institute of Neurology, London, United Kingdom
br NEUROFARBA Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy
bs Centro di Ricerca, Trasferimento e Alta Formazione DENOTHE, University of Florence, Florence, Italy
bt Department of Immunology, Hospital Universitario Dr. Negrin, Las Palmas de Gran Canaria, Spain
bu Dementia Research Center, Department of Neurodegenerative Disease, UCL Institute of Neurology, London, United Kingdom
bv Department of Molecular Neuroscience, Reta Lilla Weston Laboratories, Institute of Neurology, London, United Kingdom
bw IRCCS Associazione Oasi Maria SS, Troina, Italy
bx Oxford Healthy Aging Project (OHAP), Clinical Trial Service Unit, University of Oxford, Oxford, United Kingdom
by Cognitive Function and Ageing Study (CFAS), Institute of Public Health, University of Cambridge, Cambridge, United Kingdom
bz University of Milan, Fondazione Ca Granda, IRCCS Ospedale Policlinico, Milan, Italy
ca Neurological Clinic, University of Pisa, Pisa, Italy
cb Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, University Duisburg-Essen, Essen, Germany
cc Section of Gerontology and Geriatrics, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy
cd Section of Neuroscience and Clinical Pharmacology, Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy
ce Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany
cf Department of Psychiatry, University of Frankfurt am Main, Frankfurt am Main, Germany
cg Department of Psychiatry, Ludwig-Maximilians University, Munich, Germany
ch Gerontology and Geriatrics Research Laboratory, I.R.C.C.S. Casa Sollievo Della Sofferenza, San Giovanni Rotondo (FG), Italy
ci Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain
cj Centro de Investigacion Biomedica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
ck Instituto de Investigación Sanitaria Hospital la Paz (IdIPaz), Madrid, Spain
cl Department of Geriatrics, Center for Aging Brain, University of Bari, Bari, Italy
cm Department of Neuroscience, University of Parma, Parma, Italy
cn Center for Cognitive Disorders AUSL, Parma, Italy
co Department of Psychiatry, University Hospital, Saarland, Germany
cp Department of Public Health/Geriatrics, Uppsala University, Uppsala, Sweden
cq Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, United States
cr Department of Neuroscience, Mayo Clinic, Jacksonville, FL, United States
cs National Alzheimer's Coordinating Center, University of Washington, Seattle, WA, United States
ct Genetica Molecular-Huca-Oviedo, Oviedo, Spain
cu German Center for Neurodegenerative Diseases (DZNE, Bonn), Bonn, Germany
cv Division of Neurosciences, Center for Applied Medical Research, University of Navarra School of Medicine, Pamplona, Spain
cw CIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Madrid, Spain
cx Neurology Service, CIBERNED, Marqués de Valdecilla University Hospital (University of Cantabria and IFIMAV), Santander, Spain
cy Department of Medical and Molecular Genetics, Indiana University, Indianapolis, IN, United States
cz Landspitali University Hospital, Reykjavik, Iceland
da Institute of Clinical Medicine - Neurology, University of Eastern Finland, Kuopio, Finland
db Department of Neurology, Kuopio University Hospital, Kuopio, Finland
dc Department of Epidemiology, Harvard School of Public Health, Boston, MA, United States
dd Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
de Department of Medicine (Geriatrics), University of Mississippi Medical Center, Jackson, MS, United States
df Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, United States
dg Laboratory of Epidemiology, Demography, and Biometry, National Institute of Health, Bethesda, MD, United States
dh Department Neurobiology, Karolinska Institutet, Stockholm University, Stockholm, Sweden
di Department Geriatric Medicine, Genetics Unit, Karolinska University Hospital Huddinge, Stockholm, Sweden
dj Division of Clinical Neurosciences, School of Medicine, University of Southampton, Southampton, United Kingdom
dk Departments of Neurology and Epidemiology, Erasmus MC University Medical Center, Rotterdam, Netherlands
dl Department of Pathology, University of Washington, Seattle, WA, United States
dm Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, United States
dn Université Pierre et Marie Curie, Centre de Recherche de l'Institut du Cerveau et de la Moëlle Épinière-CRICM, Hôpital de la Salpêtrière, Paris, France
do AP-HP, Hôpital de la Pitié-Salpêtrière, Paris, France
dp Department of Epidemiology, University of Washington, Seattle, WA, United States
dq Laboratory of Neurogenetics, Intramural Research Program, National Institute on Aging, Bethesda, MD, United States
dr Imperial College, London, United Kingdom
ds Department of Biology, Brigham Young University, Provo, UT, United States
dt Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, United States
du Human Genetics Center, Div. of Epidemiology, University of Texas Health Sciences Center at Houston, Houston, TX, United States
dv Hospital Universitari Vall d'Hebron - Institut de Recerca, Universitat Autònoma de Barcelona. (VHIR-UAB), Barcelona, Spain
dw Department of Neurology, Medical University Graz, Graz, Austria
dx Centre de Mémoire de Ressources et de Recherche de Bordeaux, CHU de Bordeaux, Bordeaux, France
dy Inserm U708, Victor Segalen University, Bordeaux, France
dz Institute of Human Genetics, Department of Genomics, University of Bonn, Bonn, Germany
ea Karolinska Institutet, Department of Neurobiology, KIADRC, Stockholm, Sweden
eb Group Health Research Institute, Group Health Cooperative, Seattle, WA, United States
ec Vanderbilt Center for Human Genetics Research, Vanderbilt University, Nashville, TN, United States
ed Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, United States
ee McGill University, Génome Québec Innovation Centre, Montreal, QC, Canada
ef Department of Epidemiology, Boston University School of Public Health, Boston, MA, United States
eg Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn, Germany
eh Center for Medical Systems Biology, Leiden, Netherlands
ei Department of Psychiatry and Psychotherapy, Institute of Human Genetics, University of Bonn, Bonn, Germany
ej Framingham Heart Study, Framingham, MA, United States


Abstract
Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4×10-6) and 14 (IGHV1-67 p = 7.9×10-8) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.


Document Type: Article
Source: Scopus

Benitez, B.A.a , Jin, S.C.a , Guerreiro, R.l m , Graham, R.i , Lord, J.aa , Harold, D.h , Sims, R.h , Lambert, J.-C.ac ad ae , Gibbs, J.R.l m , Bras, J.l , Sassi, C.l m , Harari, O.a , Bertelsen, S.a , Lupton, M.K.ab , Powell, J.ab , Bellenguez, C.ac ad ae , Brown, K.aa , Medway, C.aa , Haddick, P.C.G.i , Van der Brug, M.P.i , Bhangale, T.j , Ortmann, W.k , Behrens, T.k , Mayeux, R.o p , Pericak-Vance, M.A.q r , Farrer, L.A.s t u v w x , Schellenberg, G.D.y , Haines, J.L.z , Turton, J.aa , Braae, A.aa , Barber, I.aa , Fagan, A.M.b f g , Holtzman, D.M.b e f g , Morris, J.C.b c f g , Williams, J.h , Kauwe, J.S.K.n , Amouyel, P.ac ad ae , Morgan, K.aa , Singleton, A.k , Hardy, J.k , Goate, A.M.a b d f g , Cruchaga, C.a g ad
Missense variant in TREML2 protects against Alzheimer's disease
(2014) Neurobiology of Aging, 35 (6), pp. 1510e19-1510e26. 


a Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
b Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
c Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States
d Department of Genetics, Washington University School of Medicine, St. Louis, MO, United States
e Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, United States
f Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, United States
g Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, United States
h Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, United Kingdom
i Diagnostic Discovery Department, Genentech Inc, South San Francisco, CA, United States
j Department of Bioinformatics and Computational Biology, Genentech Inc, South San Francisco, CA, United States
k Human Genetics Department, Genentech Inc, South San Francisco, CA, United States
l Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom
m Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, United States
n Department of Biology, Brigham Young University, Provo, UT, United States
o Department of Neurology, Taub Institute on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, United States
p Gertrude H. Sergievsky Center, Columbia University, New York, NY, United States
q John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, United States
r Dr John T. Macdonald Foundation Department of Human Genetics, University of Miami, Miami, FL, United States
s Department of Medicine, Boston University Schools of Medicine and Public Health, Boston, MA, United States
t Department of Biomedical Genetics, Boston University Schools of Medicine and Public Health, Boston, MA, United States
u Department of Neurology, Boston University Schools of Medicine and Public Health, Boston, MA, United States
v Department of Ophthalmology, Boston University Schools of Medicine and Public Health, Boston, MA, United States
w Department of Epidemiology, Boston University Schools of Medicine and Public Health, Boston, MA, United States
x Department of Biostatistics, Boston University Schools of Medicine and Public Health, Boston, MA, United States
y Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
z Department of Molecular Physiology and Biophysics, Vanderbilt Center for Human Genetics Research, Vanderbilt University, Nashville, TN, United States
aa Human Genetics, School of Molecular Medical Sciences, University of Nottingham, Nottingham, United Kingdom
ab Institute of Psychiatry, King's College London, London, United Kingdom
ac Inserm, Lille, France
ad Universite Lille 2, Lille, France
ae Institut Pasteur de Lille, Lille, France


Abstract
TREM and TREM-like receptors are a structurally similar protein family encoded by genes clustered on chromosome 6p21.11. Recent studies have identified a rare coding variant (p.R47H) in TREM2 that confers a high risk for Alzheimer's disease (AD). In addition, common single nucleotide polymorphisms in this genomic region are associated with cerebrospinal fluid biomarkers for AD and a common intergenic variant found near the TREML2 gene has been identified to be protective for AD. However, little is known about the functional variant underlying the latter association or its relationship with the p.R47H. Here, we report comprehensive analyses using whole-exome sequencing data, cerebrospinal fluid biomarker analyses, meta-analyses (16,254 cases and 20,052 controls) and cell-based functional studies to support the role of the TREML2 coding missense variant p.S144G (rs3747742) as a potential driver of the meta-analysis AD-associated genome-wide association studies signal. Additionally, we demonstrate that the protective role of TREML2 in AD is independent of the role of TREM2 gene as a risk factor for AD. © 2014 Elsevier Inc.


Author Keywords
Alzheimer's disease;  Association;  Conditional analysis;  Endophenotype;  Gene;  Genome-wide association studies;  TREM2


Document Type: Article
Source: Scopus

Sun, C.-L.a , Kim, E.a , Crowder, C.M.a b
Delayed innocent bystander cell death following hypoxia in Caenorhabditis elegans
(2014) Cell Death and Differentiation, 21 (4), pp. 557-567. 


a Department of Anesthesiology, Washington University School of Medicine, 660 S. Euclid, St. Louis, MO 63110, United States
b Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, United States


Abstract
After hypoxia, cells may die immediately or have a protracted course, living or dying depending on an incompletely understood set of cell autonomous and nonautonomous factors. In stroke, for example, some neurons are thought to die from direct hypoxic injury by cell autonomous primary mechanisms, whereas other so called innocent bystander neurons die from factors released from the primarily injured cells. A major limitation in identifying these factors is the inability of current in vivo models to selectively target a set of cells for hypoxic injury so that the primarily injured cells and the innocent bystanders are clearly delineated. In order to develop such a model, we generated transgenic Caenorhabditis elegans strains where 2-3% of somatic cells were made selectively sensitive to hypoxia. This was accomplished by cell type-specific wild-type rescue in either pharyngeal myocytes or GABAergic neurons of a hypoxia resistance-producing translation factor mutation. Surprisingly, hypoxic targeting of these relatively small subsets of non-essential cells produced widespread innocent bystander cell injury, behavioral dysfunction and eventual organismal death. The hypoxic injury phenotypes of the myocyte or neuron sensitized strains were virtually identical. Using this model, we show that the C. elegans insulin receptor/FOXO transcription factor pathway improves survival when activated only after hypoxic injury and blocks innocent bystander death. © 2014 Macmillan Publishers Limited All rights reserved.


Author Keywords
cell nonautonomous injury;  ischemic penumbra;  secondary hypoxic injury


Document Type: Article
Source: Scopus

Smith, M.J.a , Cobia, D.J.a , Wang, L.a b , Alpert, K.I.a , Cronenwett, W.J.a , Goldman, M.B.a , Mamah, D.c , Barch, D.M.c d e , Breiter, H.C.a f , Csernansky, J.G.a
Cannabis-related working memory deficits and associated subcortical morphological differences in healthy individuals and schizophrenia subjects
(2014) Schizophrenia Bulletin, 40 (2), pp. 287-299. Cited 1 time.


a Department of Psychiatry and Behavioral Sciences, Northwestern University, Feinberg School of Medicine, 710 N. Lake Shore Drive, Chicago, IL 60611, United States
b Department of Radiology, Northwestern University, Feinberg School of Medicine, Chicago, IL, United States
c Department of Psychiatry, Washington University, St Louis, MO, United States
d Department of Psychology, Washington University, St Louis, MO, United States
e Department of Radiology, Washington University, St Louis, MO, United States
f Warren Wright Adolescent Center, Northwestern University, Feinberg School of Medicine, Chicago, IL, United States


Abstract
Cannabis use is associated with working memory (WM) impairments; however, the relationship between cannabis use and WM neural circuitry is unclear. We examined whether a cannabis use disorder (CUD) was associated with differences in brain morphology between control subjects with and without a CUD and between schizophrenia subjects with and without a CUD, and whether these differences related to WM and CUD history. Subjects group-matched on demographics included 44 healthy controls, 10 subjects with a CUD history, 28 schizophrenia subjects with no history of substance use disorders, and 15 schizophrenia subjects with a CUD history. Large-deformation high-dimensional brain mapping with magnetic resonance imaging was used to obtain surface-based representations of the striatum, globus pallidus, and thalamus, compared across groups, and correlated with WM and CUD history. Surface maps were generated to visualize morphological differences. There were significant cannabis-related parametric decreases in WM across groups. Similar cannabis-related shape differences were observed in the striatum, globus pallidus, and thalamus in controls and schizophrenia subjects. Cannabis-related striatal and thalamic shape differences correlated with poorer WM and younger age of CUD onset in both groups. Schizophrenia subjects demonstrated cannabis-related neuroanatomical differences that were consistent and exaggerated compared with cannabis-related differences found in controls. The cross-sectional results suggest that both CUD groups were characterized by WM deficits and subcortical neuroanatomical differences. Future longitudinal studies could help determine whether cannabis use contributes to these observed shape differences or whether they are biomarkers of a vulnerability to the effects of cannabis that predate its misuse. © 2013 The Author. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved.


Author Keywords
cannabis;  marijuana;  schizophrenia;  structural neuroimaging;  working memory


Document Type: Article
Source: Scopus

Kasasbeh, A.S.a , Gurnett, C.A.b , Smyth, M.D.c
Palliative epilepsy surgery in Aicardi syndrome: A case series and review of literature
(2014) Child's Nervous System, 30 (3), pp. 497-503. 


a Neural Engineering Laboratory, Mayo Clinic, 200 First Street SW, Rochester, MN 55902, United States
b Department of Neurology, Saint Louis Children's Hospital, Washington University in St. Louis, St. Louis, MO, United States
c Department of Neurological Surgery, Saint Louis Children's Hospital, Washington University in St. Louis, St. Louis, MO, United States


Abstract
Purpose: Aicardi syndrome (AS) is a severe neurodevelopmental disorder characterized by the triad of seizures, agenesis of corpus callosum, and chorioretinal lacunae. Seizures in AS are typically frequent, of various types, and refractory to medical therapy. Optimal treatment of seizures in AS remains undetermined. Methods: We report a series of four patients with Aicardi syndrome who underwent surgical management of their epilepsy including two with corpus callosotomy (CC) of a partial corpus callosum and three with vagus nerve stimulator implantation. Results: Seizure outcome was variable and ranged from near complete resolution of seizures to worsening of seizure profile. The most favorable seizure outcome was seen in a patient with partial agenesis of the corpus callosum treated with CC. Conclusions: Seizure outcome following CC or vagus nerve stimulation in patients with Aicardi syndrome is variable. Although palliative epilepsy surgery may result in improvement in the seizure profile in some patients, studies on larger patient cohorts are needed to identify the precise role that surgery may play in the multidisciplinary approach to controlling seizures in Aicardi syndrome. © 2013 Springer-Verlag.


Author Keywords
Aicardi syndrome;  Corpus callosotomy;  Epilepsy surgery;  Vagus nerve stimulation


Document Type: Article
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 , Almasy, L.c , Bucholz, K.a , Dick, D.M.d , Harari, O.a , Xiaoling, X.b , Hesselbrock, V.e , Kramer, J.f , Nurnberger, J.I.b , Rice, J.a , Schuckit, M.g , Tischfield, J.h , Porjesz, B.i , Edenberg, H.J.b , Bierut, L.a , Foroud, T.b , Goate, A.a
Genome-wide survival analysis of age at onset of alcohol dependence in extended high-risk COGA families
(2014) Drug and Alcohol Dependence, . Article in Press. 


a Washington University School of Medicine, United States
b Indiana University School of Medicine, United States
c Southwest Foundation for Biomedical Research, United States
d Virginia Commonwealth University, United States
e University of Connecticut Health Center, United States
f University of Iowa Carver College of Medicine, United States
g University of California, San Diego, United States
h Rutgers University, United States
i SUNY Health Sciences Center, United States


Abstract
Background: The age at onset of alcohol dependence (AD) is a critical moderator of genetic associations for alcohol dependence. The present study evaluated whether single nucleotide polymorphisms (SNPs) can influence the age at onset of AD in large high-risk families from the Collaborative Study on the Genetics of Alcoholism (COGA). Methods: Genomewide SNP genotyping was performed in 1788 regular drinkers from 118 large European American families densely affected with alcoholism. We used a genome-wide Cox proportional hazards regression model to test for association between age at onset of AD and SNPs. Results: This family-based analysis identified an intergenic SNP, rs2168784 on chromosome 3 that showed strong evidence of association (P =5×10-9) with age at onset of AD among regular drinkers. Carriers of the minor allele of rs2168784 had 1.5 times the hazard of AD onset as compared with those homozygous for the major allele. By the age of 20 years, nearly 30% of subjects homozygous for the minor allele were alcohol dependent while only 19% of those homozygous for the major allele were. We also identified intronic SNPs in the ADP-ribosylation factor like 15 (ARL15) gene on chromosome 5 (P =1.11×10-8) and the UTP20 small subunit (UTP20) gene on chromosome 12 (P =4.32×10-8) that were associated with age at onset of AD. Conclusions: This extended family based genome-wide cox-proportional hazards analysis identified several loci that might be associated with age at onset of AD. © 2014 Elsevier Ireland Ltd.


Author Keywords
Age at onset;  Alcohol dependence;  GWAS;  SNP;  Survival analysis


Document Type: Article in Press
Source: Scopus

Jerger, S.a , Damian, M.F.b , Tye-Murray, N.c , Abdi, H.a
Children use visual speech to compensate for non-intact auditory speech
(2014) Journal of Experimental Child Psychology, 126, pp. 295-312. 


a School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX 75080, United States
b School of Experimental Psychology, University of Bristol, Bristol BS8 1TU, United Kingdom
c Department of Otolaryngology, Washington University School of Medicine, St. Louis, MO 63110, United States


Abstract
We investigated whether visual speech fills in non-intact auditory speech (excised consonant onsets) in typically developing children from 4 to 14. years of age. Stimuli with the excised auditory onsets were presented in the audiovisual (AV) and auditory-only (AO) modes. A visual speech fill-in effect occurs when listeners experience hearing the same non-intact auditory stimulus (e.g., /-b/ag) as different depending on the presence/absence of visual speech such as hearing /bag/ in the AV mode but hearing /ag/ in the AO mode. We quantified the visual speech fill-in effect by the difference in the number of correct consonant onset responses between the modes. We found that easy visual speech cues /b/ provided greater filling in than difficult cues /g/. Only older children benefited from difficult visual speech cues, whereas all children benefited from easy visual speech cues, although 4- and 5-year-olds did not benefit as much as older children. To explore task demands, we compared results on our new task with those on the McGurk task. The influence of visual speech was uniquely associated with age and vocabulary abilities for the visual speech fill-in effect but was uniquely associated with speechreading skills for the McGurk effect. This dissociation implies that visual speech-as processed by children-is a complicated and multifaceted phenomenon underpinned by heterogeneous abilities. These results emphasize that children perceive a speaker's utterance rather than the auditory stimulus per se. In children, as in adults, there is more to speech perception than meets the ear. © 2014 Elsevier Inc.


Author Keywords
Audiovisual speech perception;  Children;  Development;  Lipreading;  McGurk effect;  Speechreading


Document Type: Article
Source: Scopus

Anderson, J.L.a , Levy, P.T.b , Leonard, K.B.a , Smyser, C.D.c , Tychsen, L.d , Cole, F.S.b
Congenital lymphocytic choriomeningitis virus: When to consider the diagnosis
(2014) Journal of Child Neurology, 29 (6), pp. 837-842. 


a Edward Mallinckrodt Department of Pediatrics, Washington University, Medical School, Louis, MO, United States
b Division of Newborn Medicine, Edward Mallinckrodt Department of Pediatrics, Washington University, Campus Box 8116, Louis, MO 63110, United States
c Division of Pediatric Neurology, Department of Neurology, Washington University, Louis, MO, United States
d Department of Ophthalmology and Visual Sciences, Washington University, Louis, MO, United States


Abstract
Lymphocytic choriomeningitis virus is a rodent-borne arenavirus that can cause congenital infection affecting the developing central nervous system. When the infection occurs during pregnancy, the virus targets the fetal brain and retina, potentially causing ventriculomegaly, hydrocephalus, chorioretinitis, and neurodevelopmental abnormalities. It has been previously suggested that lymphocytic choriomeningitis virus be added to the list of congenital infections currently included in the TORCH acronym (toxoplasmosis, rubella, cytomegalovirus, herpes, and syphilis). We present 2 neonates with antenatally known ventriculomegaly that were diagnosed with congenital lymphocytic choriomeningitis virus infection after birth. In addition to ventriculomegaly, one had nonimmune hydrops fetalis and the other had intracranial hemorrhage. In view of the seroprevalence of lymphocytic choriomeningitis virus (4.7%-10%), our findings suggest that screening for congenital lymphocytic choriomeningitis virus infection should be considered in fetuses and newborns with ventriculomegaly as well as other abnormal neuroimaging findings such as intracranial hemorrhage. © The Author(s) 2013.


Author Keywords
Arenavirus;  Congenital lymphocytic choriomeningitis virus;  Hydrocephalus;  TORCH;  Ventriculomegaly


Document Type: Article
Source: Scopus

Phillips, B.Z., Franco, M.J., Yee, A., Tung, T.H., Mackinnon, S.E., Fox, I.K.
Direct radial to ulnar nerve transfer to restore intrinsic muscle function in combined proximal median and ulnar nerve injury: Case report and surgical technique
(2014) Journal of Hand Surgery, 39 (7), pp. 1358-1362. 


Division of Plastic and Reconstructive Surgery, Washington University School of Medicine, Box 8238, Saint Louis, MO 63110, United States


Abstract
A distal median to ulnar nerve transfer for timely restoration of critical intrinsic muscle function is possible in isolated ulnar nerve injuries but not for combined ulnar and median nerve injuries. We used a distal nerve transfer to restore ulnar intrinsic function in the case of a proximal combined median and ulnar nerve injury. Transfer of the nonessential radial nerve branches to the abductor pollicis longus, extensor pollicis brevis, and extensor indicis proprius to the motor branch of the ulnar nerve was performed in a direct end-to-end fashion via an interosseous tunnel. This method safely and effectively restored intrinsic function before terminal muscle degeneration. © 2014 ASSH r Published by Elsevier, Inc. All rights reserved.


Author Keywords
Intrinsic function;  median nerve;  nerve transfer;  ulnar nerve


Document Type: Article
Source: Scopus

Bailey, H.R.a d , Dunlosky, J.b , Hertzog, C.c
Does strategy training reduce age-related deficits in working memory?
(2014) Gerontology, 60 (4), pp. 346-356. 


a Department of Psychology, Washington University in St. Louis, St. Louis, MO, United States
b Department of Psychology, Kent State University, Kent, OH, United States
c School of Psychology, Georgia Institute of Technology, Atlanta, GA, United States
d Department of Psychology, Washington University, Campus Box 1125, One Brookings Drive, Saint Louis, MO 63130, United States


Abstract
Background: Older adults typically perform worse on measures of working memory (WM) than do young adults; however, age-related differences in WM performance might be reduced if older adults use effective encoding strategies. Objective: The purpose of the current experiment was to evaluate WM performance after training individuals to use effective encoding strategies. Methods: Participants in the training group (older adults: n = 39; young adults: n = 41) were taught about various verbal encoding strategies and their differential effectiveness and were trained to use interactive imagery and sentence generation on a list-learning task. Participants in the control group (older: n = 37; young: n = 38) completed an equally engaging filler task. All participants completed a pre- and post-training reading span task, which included self-reported strategy use, as well as two transfer tasks that differed in the affordance to use the trained strategies - a paired-associate recall task and the self-ordered pointing task. Results: Both young and older adults were able to use the target strategies on the WM task and showed gains in WM performance after training. The age-related WM deficit was not greatly affected, however, and the training gains did not transfer to the other cognitive tasks. In fact, participants attempted to adapt the trained strategies for a paired-associate recall task, but the increased strategy use did not benefit their performance. Conclusions: Strategy training can boost WM performance, and its benefits appear to arise from strategy-specific effects and not from domain-general gains in cognitive ability. © 2014 S. Karger AG, Basel.


Author Keywords
Aging;  Strategy use;  Training;  Transfer effects;  Working memory


Document Type: Article
Source: Scopus

Suzuki, H., Luby, J.L., Botteron, K.N., Dietrich, R., McAvoy, M.P., Barch, D.M.
Early life stress and trauma and enhanced limbic activation to emotionally valenced faces in depressed and healthy children
(2014) Journal of the American Academy of Child and Adolescent Psychiatry, 53 (7), pp. 800-813.e10. Cited 1 time.


Washington University School of Medicine, Department of Psychiatry, Campus-Box 8134, 660 Euclid Avenue, Saint Louis, MO 63110, United States


Abstract
Objective Previous studies have examined the relationships between structural brain characteristics and early life stress in adults. However, there is limited evidence for functional brain variation associated with early life stress in children. We hypothesized that early life stress and trauma would be associated with increased functional brain activation response to negative emotional faces in children with and without a history of depression. Method Psychiatric diagnosis and life events in children (starting at age 3-5 years) were assessed in a longitudinal study. A follow-up magnetic resonance imaging (MRI) study acquired data (N = 115 at ages 7-12, 51% girls) on functional brain response to fearful, sad, and happy faces relative to neutral faces. We used a region-of-interest mask within cortico-limbic areas and conducted regression analyses and repeated-measures analysis of covariance. Results Greater activation responses to fearful, sad, and happy faces in the amygdala and its neighboring regions were found in children with greater life stress. Moreover, an association between life stress and left hippocampal and globus pallidus activity depended on children's diagnostic status. Finally, all children with greater life trauma showed greater bilateral amygdala and cingulate activity specific to sad faces but not the other emotional faces, although right amygdala activity was moderated by psychiatric status. Conclusions These findings suggest that limbic hyperactivity may be a biomarker of early life stress and trauma in children and may have implications in the risk trajectory for depression and other stress-related disorders. However, this pattern varied based on emotion type and history of psychopathology.


Author Keywords
child;  early life stress;  early life trauma;  emotion;  fMRI


Document Type: Article
Source: Scopus

Marquardt, L.M.a , Day, D.b , Sakiyama-Elbert, S.E.a , Harkins, A.B.c d
Effects of borate-based bioactive glass on neuron viability and neurite extension
(2014) Journal of Biomedical Materials Research - Part A, 102 (8), pp. 2767-2775. 


a Department of Biomedical Engineering, Washington University in St. Louis, St. Louis MO 63130, United States
b Department of Materials Science and Engineering, Center for Bone and Tissue Repair and Regeneration, Missouri University of Science and Technology, Rolla MO 65409, United States
c Department of Pharmacological and Physiological Science, Saint Louis University, 1402 S. Grand Blvd., St. Louis, MO 63104, United States
d Department of Biomedical Engineering, Saint Louis University, St. Louis MO 63104, United States


Abstract
Bioactive glasses have recently been shown to promote regeneration of soft tissues by positively influencing tissue remodeling during wound healing. We were interested to determine whether bioactive glasses have the potential for use in the treatment of peripheral nerve injury. In these experiments, degradable bioactive borate glass was fabricated into rods and microfibers. To study the compatibility with neurons, embryonic chick dorsal root ganglia (DRG) were cultured with different forms of bioactive borate glass. Cell viability was measured with no media exchange (static condition) or routine media exchange (transient condition). Neurite extension was measured within fibrin scaffolds with embedded glass microfibers or aligned rod sheets. Mixed cultures of neurons, glia, and fibroblasts growing in static conditions with glass rods and microfibers resulted in decreased cell viability. However, the percentage of neurons compared with all cell types increased by the end of the culture protocol compared with culture without glass. Furthermore, bioactive glass and fibrin composite scaffolds promoted neurite extension similar to that of control fibrin scaffolds, suggesting that glass does not have a significant detrimental effect on neuronal health. Aligned glass scaffolds guided neurite extension in an oriented manner. Together these findings suggest that bioactive glass can provide alignment to support directed axon growth. © 2013 Wiley Periodicals, Inc.


Author Keywords
alignment;  dorsal root ganglia;  fibrin scaffolds;  microfibers;  peripheral nerve injury


Document Type: Article
Source: Scopus

Hammen, G.F.a b , Turaga, D.a b , Holy, T.E.a , Meeks, J.P.c
Functional organization of glomerular maps in the mouse accessory olfactory bulb
(2014) Nature Neuroscience, 17 (7), pp. 953-961. 


a Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MI, United States
b MD-PhD Program, Washington University School of Medicine, St. Louis, MI, United States
c Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, United States


Abstract
The mammalian accessory olfactory system extracts information about species, sex and individual identity from social odors, but its functional organization remains unclear. We imaged presynaptic Ca 2+ signals in vomeronasal inputs to the accessory olfactory bulb (AOB) during peripheral stimulation using light sheet microscopy. Urine- and steroid-responsive glomeruli densely innervated the anterior AOB. Glomerular activity maps for sexually mature female mouse urine overlapped maps for juvenile and/or gonadectomized urine of both sexes, whereas maps for sexually mature male urine were highly distinct. Further spatial analysis revealed a complicated organization involving selective juxtaposition and dispersal of functionally grouped glomerular classes. Glomeruli that were similarly tuned to urines were often closely associated, whereas more disparately tuned glomeruli were selectively dispersed. Maps to a panel of sulfated steroid odorants identified tightly juxtaposed groups that were disparately tuned and dispersed groups that were similarly tuned. These results reveal a modular, nonchemotopic spatial organization in the AOB. © 2014 Nature America, Inc. All rights reserved.


Document Type: Article
Source: Scopus

Anokhin, A.P.
Genetic psychophysiology: Advances, problems, and future directions
(2014) International Journal of Psychophysiology, 93 (2), pp. 173-197. 


Washington University School of Medicine, Department of Psychiatry, 660 S. Euclid, Box 8134, St. Louis, MO 63110, United States


Abstract
This paper presents an overview of historical advances and the current state of genetic psychophysiology, a rapidly developing interdisciplinary research linking genetics, brain, and human behavior, discusses methodological problems, and outlines future directions of research. The main goals of genetic psychophysiology are to elucidate the neural pathways and mechanisms mediating genetic influences on cognition and emotion, identify intermediate brain-based phenotypes for psychopathology, and provide a functional characterization of genes being discovered by large association studies of behavioral phenotypes. Since the initiation of this neurogenetic approach to human individual differences in the 1970s, numerous twin and family studies have provided strong evidence for heritability of diverse aspects of brain function including resting-state brain oscillations, functional connectivity, and event-related neural activity in a variety of cognitive and emotion processing tasks, as well as peripheral psychophysiological responses. These data indicate large differences in the presence and strength of genetic influences across measures and domains, permitting the selection of heritable characteristics for gene finding studies. More recently, candidate gene association studies began to implicate specific genetic variants in different aspects of neurocognition. However, great caution is needed in pursuing this line of research due to its demonstrated proneness to generate false-positive findings. Recent developments in methods for physiological signal analysis, hemodynamic imaging, and genomic technologies offer new exciting opportunities for the investigation of the interplay between genetic and environmental factors in the development of individual differences in behavior, both normal and abnormal. © 2014 Elsevier B.V.


Author Keywords
Brain;  EEG;  Endophenotype;  ERP;  Genetics;  Heritability


Document Type: Review
Source: Scopus

Kumar, M.G.a , Emnett, R.J.b , Bayliss, S.J.a , Gutmann, D.H.b
Glomus tumors in individuals with neurofibromatosis type 1
(2014) Journal of the American Academy of Dermatology, 71 (1), pp. 44-48. 


a Division of Dermatology, Department of Internal Medicine, Washington University School of Medicine, Saint Louis, MO, United States
b Department of Neurology, Washington University School of Medicine, Box 8111, 660 S Euclid Ave, St. Louis, MO 63110, United States


Abstract
Background Glomus tumors have recently been reported in individuals with the neurofibromatosis type 1 (NF1) cancer disposition syndrome. We compare the clinical and molecular features of these painful hamartomas in a series of sporadic and NF1-associated cases. Objective We sought to evaluate the association of NF1 with glomus tumors and to compare NF1-associated glomus tumors with sporadic glomus tumors. Methods We conducted a retrospective cohort study of all individuals with a histopathologic diagnosis of glomus tumor at a large tertiary care center from January 1998 to January 2013. Charts were reviewed for a coexisting diagnosis of NF1. Results A total of 42 glomus tumors were identified in 34 individuals. Twelve (28.6%) were found in 6 patients with NF1. In 28 individuals with 30 sporadic tumors, there was no coexisting medical condition. Although multifocal tumors (16.7%) and tumor recurrence (33.3%) were more common in association with NF1, these trends did not reach statistical significance. NF1-associated glomus tumors exhibited no neurofibromin immunoreactivity, whereas their sporadic counterparts retained neurofibromin expression. Limitations The retrospective design resulted in incomplete data capture. Conclusions Detection of glomus tumors should raise suspicion for a concurrent diagnosis of NF1. © 2014 by the American Academy of Dermatology, Inc.


Author Keywords
glomus tumor;  neurofibromatosis;  neurofibromatosis type 1;  neurofibromin;  tumor disposition syndrome


Document Type: Article
Source: Scopus

Wagner, J.M.a , Kremer, T.R.b , Van Dillen, L.R.c , Naismith, R.T.d
Plantarflexor weakness negatively impacts walking in persons with multiple sclerosis more than plantarflexor spasticity
(2014) Archives of Physical Medicine and Rehabilitation, 95 (7), pp. 1358-1365. 


a Program in Physical Therapy, Doisy College of Health Sciences, Saint Louis University, St Louis, MO 63104, United States
b School of Medicine, Saint Louis University, St Louis, MO, United States
c Program in Physical Therapy, Washington University School of Medicine, St Louis, MO, United States
d Department of Neurology, Washington University School of Medicine, St Louis, MO, United States


Abstract
Objectives To determine whether plantarflexor (PF) spasticity or ankle strength best predicts variance in walking capacity or self-perceived limitations in walking in persons with multiple sclerosis (MS) and whether persons with MS with PF spasticity are weaker and have greater walking dysfunction than do persons with MS without PF spasticity. Design Cross-sectional study. Setting University research laboratory. Participants Forty-two adults with MS (mean age, 42.9±10.1y; Expanded Disability Status Scale score, median=3.0, range=0-6) and 14 adults without disability (mean age, 41.9±10.1y). Intervention Not applicable. Main Outcome Measures PF spasticity and dorsiflexion and PF maximum voluntary isometric torque were assessed using the modified Ashworth Scale and a computerized dynamometer, respectively. The Timed 25-Foot Walk Test was the primary outcome measure of walking capacity. Secondary measures included the 6-Minute Walk Test and the 12-item Multiple Sclerosis Walking Scale. Results PF strength was the most consistent predictor of variance in walking capacity (Timed 25-Foot Walk Test: R2 change=.23-.29, P≤ 6-Minute Walk Test: R;bsupesup&amp; change=.12-.29, P≤.012), and self-perceived limitations of walking (12-item Multiple Sclerosis Walking Scale: R2 change=.04-.14, P&lt;.18). There were no significant differences (P&gt;.05) between persons with MS with PF spasticity and persons with MS without PF spasticity for any of the outcome measures. Conclusions Our study suggests a unique contribution of PF weakness to walking dysfunction in persons with MS, and highlights the importance of evaluating PF strength in this clinical population. © 2014 by the American Congress of Rehabilitation Medicine.


Author Keywords
Ankle;  Multiple sclerosis;  Muscle spasticity;  Muscle strength dynamometer;  Rehabilitation;  Walking


Document Type: Article
Source: Scopus

Ichinose, T.a b c , Fyk-Kolodziej, B.b , Cohn, J.a d
Roles of ON cone bipolar cell subtypes in temporal coding in the mouse retina
(2014) Journal of Neuroscience, 34 (26), pp. 8761-8771. 


a Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, United States
b Departments of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI 48201, United States
c Departments of Ophthalmology, Wayne State University School of Medicine, Detroit, MI 48201, United States
d Department of Neuroscience, University of Texas at Austin, 2506 Speedway, NMS 5.234, Austin, TX 78751, United States


Abstract
In the visual system, diverse image processing starts with bipolar cells, which are the second-order neurons of the retina. Thirteen subtypes of bipolar cells have been identified, which are thought to encode different features of image signaling and to initiate distinct signal-processing streams. Although morphologically identified, the functional roles of each bipolar cell subtype in visual signal encoding are not fully understood. Here, we investigated how ON cone bipolar cells of the mouse retina encode diverse temporal image signaling. We recorded bipolar cell voltage changes in response to two different input functions: sinusoidal light and step light stimuli. Temporal tuning in ON cone bipolar cells was diverse and occurred in a subtype-dependent manner. Subtypes 5s and 8 exhibited low-pass filtering property in response to a sinusoidal light stimulus, and responded with sustained fashion to step-light stimulation. Conversely, subtypes 5f, 6, 7, and XBC exhibited bandpass filtering property in response to sinusoidal light stimuli, and responded transiently to step-light stimuli. In particular, subtypes 7 and XBC were high-temporal tuning cells. We recorded responses in different ways to further examine the underlying mechanisms of temporal tuning. Current injection evoked low-pass filtering, whereas light responses in voltage-clamp mode produced bandpass filtering in all ON bipolar cells. These findings suggest that cone photoreceptor inputs shape bandpass filtering in bipolar cells, whereas intrinsic properties of bipolar cells shape low-pass filtering. Together, our results demonstrate that ON bipolar cells encode diverse temporal image signaling in a subtype-dependent manner to initiate temporal visual information-processing pathways. © 2014 the authors.


Author Keywords
Light response;  Parallel processing;  Patch-clamp;  Sine wave;  Subtypes;  Voltage-gated channels


Document Type: Article
Source: Scopus

Brausch, A.M.a , Decker, K.M.b
Self-esteem and social support as moderators of depression, body image, and disordered eating for suicidal ideation in adolescents
(2014) Journal of Abnormal Child Psychology, 42 (5), pp. 779-789. 


a Department of Psychological Sciences, Western Kentucky University, 1906 College Heights Blvd., Bowling Green KY 42101, United States
b Department of Psychology, Washington University, 1 Brookings Drive Campus Box 1125, St. Louis MO 63130, United States


Abstract
The current study investigated risk factors for suicidal ideation in a community sample of 392 adolescents (males 51.9 %; females 48.1 %), while also evaluating self-esteem, perceived parent support, and perceived peer support as protective factors and potential moderators between suicidal ideation and the 3 risk factors. Disordered eating, depression, parent support, and peer support were found to be significant predictors of current suicidal ideation, but body satisfaction was not. The relationship between depression and suicidal ideation was significantly moderated by both self-esteem and parent support, while the relationship between disordered eating and suicidal ideation was significantly moderated by peer support. Results underscore the importance of examining protective factors for suicide risk, as they have the potential to reduce suicidal ideation in adolescents. © 2013 Springer Science+Business Media New York.


Author Keywords
Adolescents;  Depression;  Disordered eating;  Self-esteem;  Social support;  Suicidal ideation


Document Type: Article
Source: Scopus

Patel, G.H.a b e , Kaplan, D.M.c , Snyder, L.H.d
Topographic organization in the brain: Searching for general principles
(2014) Trends in Cognitive Sciences, 18 (7), pp. 351-363. 


a Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY 10032, United States
b New York State Psychiatric Institute, New York, NY 10032, United States
c Department of Cognitive Science, Macquarie University, Sydney, NSW 2109, Australia
d Department of Anatomy and Neurobiology, Washington University School of Medicine, Saint Louis, MO 63110, United States
e Department of Psychiatry, Columbia University College of Physicians and Surgeons, 1051 Riverside Dr. Unit 21, New York, NY 10032, United States


Abstract
The neurons comprising many cortical areas have long been known to be arranged topographically such that nearby neurons have receptive fields at nearby locations in the world. Although this type of organization may be universal in primary sensory and motor cortex, in this review we demonstrate that associative cortical areas may not represent the external world in a complete and continuous fashion. After reviewing evidence for novel principles of topographic organization in macaque lateral intraparietal area (LIP) - one of the most-studied associative areas in the parietal cortex - we explore the implications of these new principles for brain function. © 2014 Elsevier Ltd.


Document Type: Review
Source: Scopus

 

July 2, 2014

Strauss, M.E.a , McLouth, C.J.a , Barch, D.M.b , Carter, C.S.c , Gold, J.M.d , Luck, S.J.e , MacDonald, A.W.f , Ragland, J.D.c , Ranganath, C.e , Keane, B.P.g h , Silverstein, S.M.g
Temporal stability and moderating effects of age and sex on CNTRaCS task performance
(2014) Schizophrenia Bulletin, 40 (4), pp. 835-844. Cited 1 time.


a Department of Psychology, University of New Mexico, PO Box 3837, Corrales, Albuquerque, NM 87048, United States
b Department of Psychology, Washington University, St Louis, MO, United States
c Department of Psychiatry, University of California, Davis, CA, United States
d Department of Psychiatry, Maryland Psychiatric Research Center, Baltimore, MD, United States
e Department of Psychology, University of California, Davis, CA, United States
f Department of Psychology, University of Minnesota, Minneapolis, MN, United States
g Department of Psychiatry, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ, United States
h Center for Cognitive Science, Rutgers University, New Brunswick, NJ, United States


Abstract
Research in schizophrenia has increasingly focused on incorporating measures from cognitive neuroscience, but little is known about their psychometric characteristics. Here, we extend prior research by reporting on temporal stability, as well as age and sex effects, for cognitive neuroscience paradigms optimized as part of the Cognitive Neuroscience Test Reliability and Clinical applications for Schizophrenia consortium. Ninety-nine outpatients with schizophrenia and 131 healthy controls performed 5 tasks assessing 4 constructs at 3 sessions. The constructs were (1) Goal maintenance (Dot Probe Expectancy [DPX] and AX continuous performance tasks [AX-CPT]); (2) Episodic memory (Relational and Item-Specific Encoding and Retrieval task [RiSE]); (3) Visual integration (Jittered Orientation Visual Integration task [JOVI]); and (4) Perceptual gain control (Contrast-Contrast Effect Task [CCE]). Patients performed worse than controls on all but the CCE, and the magnitude of these group differences was stable across sessions, with no sex differences observed. Improvements over sessions were seen for the AX-CPT, the DPX, and the JOVI though practice effects for the AX-CPT and the DPX were primarily present in older participants. For the AX-CPT and the JOVI, practice effects were larger for T1 to T2 than for T2 to T3. Age was associated with poor associative recognition on the RiSE and accuracy on the JOVI. Test-rest reliability ranged from poor for the JOVI threshold score to adequate to good for the DPX, AX-CPT, and JOVI accuracy measures, with RiSE and CCE measures in the moderate range. These results suggest that group differences in DPX, AX-CPT, RiSE, and JOVI are robust and consistent across repeated testing. © 2014 The Author.


Author Keywords
cognitive neuroscience;  episodic memory;  goal maintenance;  psychometrics;  schizophrenia;  visual integration


Document Type: Article
Source: Scopus

Xu, X.a , Clark, U.S.b c d , David, S.P.e f g , Mulligan, R.C.c h , Knopik, V.S.b i , McGeary, J.b c i j , MacKillop, J.c k , McCaffery, J.b l , Niaura, R.S.m , Sweet, L.H.b k
The effects of nicotine deprivation and replacement on BOLD-fMRI response to smoking cues as a function of DRD4 VNTR genotype
(2014) Nicotine and Tobacco Research, 16 (7), art. no. ntu010, pp. 939-947. 


a Department of Psychology, Idaho State University, Pocatello, ID, United States
b Department of Psychiatry and Human Behavior, Warren Alpert Medical School of Brown University, Providence, RI, United States
c Center for Alcohol and Addiction Studies, Department of Behavioral and Social Sciences, Brown University, Providence, RI, United States
d Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, United States
e Division of General Medical Disciplines, Department of Medicine, Stanford University School of Medicine, Population Health Sciences Building, Palo Alto, CA, United States
f Center for Health Sciences, Biosciences Division, SRI International, Menlo Park, CA, United States
g Department of Family Medicine, Warren Alpert Medical School of Brown University, Pawtucket, RI, United States
h Department of Psychiatry, Washington University, St. Louis School of Medicine, St. Louis, MO, United States
i Division of Behavioral Genetics, Rhode Island Hospital, Bradley Hasbro Children's Research Center, Providence, RI, United States
j Providence Veterans Affairs Medical Center, Providence, RI, United States
k Department of Psychology, University of Georgia, Athens, GA, United States
l Weight Control and Diabetes Research Center, The Miriam Hospital, Providence, RI, United States
m LEGACY, The Schroeder Institute for Tobacco Research and Policy Studies, Washington, DC, United States


Abstract
Introduction: Reactivity to smoking cues is an important factor in the motivation to smoke and has been associated with the dopamine receptor 4 variable number tandem repeat (DRD4 exon III VNTR) polymorphism, but little is known about the associated neural mechanisms. Methods: Non-treatment-seeking Caucasian smokers completed overnight abstinence and viewed smoking and neutral cues, during 2 separate functional magnetic resonance imaging scans, while wearing either a nicotine or placebo patch (order randomized) and were genotyped for the DRD4 VNTR. We conducted mixed-effects repeated-measures analyses of variance (withinsubject factor: nicotine or placebo patch; between-subject factor: DRD4 long [L: ≥1 copy of ≥7 repeats] or short [S: 2 copies ≤6 repeats] genotype) of 6 a priori regions of interest. Results: Relative to neutral cues, smoking cues elicited greater activity in bilateral ventral striatum and left amygdala during nicotine replacement and deactivation in these regions during nicotine deprivation. A patch × DRD4 interaction was observed in the left amygdala, an area associated with appetitive reinforcement and relapse risk, such that S allele carriers demonstrated greater activation on active patch than on placebo patch. Conclusions: Brain systems associated with reward salience may become primed and overreactive at nicotine replacement doses intended for the first step of smoking cessation and may become inhibited during nicotine withdrawal in DRD4 S but not in DRD4 L carriers. These findings are consistent with the role of these regions in drug reinforcement and suggest a differential influence of nicotine replacement on amygdala activation in the association of incentive salience with smoking stimuli across DRD4 genotypes. © The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved.


Document Type: Article
Source: Scopus

 

Ebbinghaus, M., Gajda, M., Holtzman, M.J., Schulz, S., Schaible, H.-G.
Does chloride channel accessory 3 have a role in arthritis pain? A study on murine antigen-induced arthritis
(2014) Neuroscience Letters, 576, pp. 40-44. 


Document Type: Article
Source: Scopus

Rohrlich, J.T., Sadhu, A., Sebastian, A., Ahn, N.U.
Risk factors for nonorganic low back pain in patients with worker's compensation
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Park, M.S., Kelly, M.P., Lee, D.-H., Min, W.-K., Rahman, R.K., Riew, K.D.
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Document Type: Article
Source: Scopus

Sanders, D.W., Kaufman, S.K., DeVos, S.L., Sharma, A.M., Mirbaha, H., Li, A., Barker, S.J., Foley, A.C., Thorpe, J.R., Serpell, L.C., Miller, T.M., Grinberg, L.T., Seeley, W.W., Diamond, M.I.
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Source: Scopus

Silberman, D.M., Ross, K., Sande, P.H., Kubota, S., Ramaswamy, S., Apte, R.S., Mostoslavsky, R.
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(2014) PLoS ONE, 9 (6), art. no. e98831, . 


Document Type: Article
Source: Scopus

Germany, R., Joseph, S., James, K., Kao, A.
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Document Type: Review
Source: Scopus

Ben-Shahar, Y.
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Source: Scopus

Küpper-Tetzel, C.E., Kapler, I.V., Wiseheart, M.
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Frazier, T.W., Youngstrom, E.A., Embacher, R., Hardan, A.Y., Constantino, J.N., Law, P., Findling, R.L., Eng, C.
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Linsenbardt, A.J., Taylor, A., Emnett, C.M., Doherty, J.J., Krishnan, K., Covey, D.F., Paul, S.M., Zorumski, C.F., Mennerick, S.
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(2014) Neuropharmacology, 85, pp. 232-242. 


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Weiner, M.W., Veitch, D.P., Hayes, J., Neylan, T., Grafman, J., Aisen, P.S., Petersen, R.C., Jack, C., Jagust, W., Trojanowski, J.Q., Shaw, L.M., Saykin, A.J., Green, R.C., Harvey, D., Toga, A.W., Friedl, K.E., Pacifico, A., Sheline, Y., Yaffe, K., Mohlenoff, B.
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(2014) Alzheimer's and Dementia, 10 (3 SUPPL.), pp. S226-S235. 


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Source: Scopus

Johnson, K.J., Mueller, N.L., Williams, K., Gutmann, D.H.
Evaluation of participant recruitment methods to a rare disease online registry
(2014) American Journal of Medical Genetics, Part A, 164 (7), pp. 1686-1694. 


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Source: Scopus

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Frontotemporal dementia and its subtypes: A genome-wide association study
(2014) The Lancet Neurology, 13 (7), pp. 686-699. 


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Source: Scopus

Sapir, A., Jackson, K., Butler, J., Paul, M.A., Abrams, R.A.
Inhibition of return affects contrast sensitivity
(2014) Quarterly Journal of Experimental Psychology, 67 (7), pp. 1305-1316. 


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Source: Scopus

Prakash, V., Batanian, J.R., Guzman, M.A., Duncavage, E.J., Geller, T.J.
Malignant transformation of a desmoplastic infantile ganglioglioma in an infant carrier of a nonsynonymous tp53 mutation
(2014) Pediatric Neurology, 51 (1), pp. 138-143. 


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Source: Scopus

Zaidman, C.M., Wu, J.S., Wilder, S., Darras, B.T., Rutkove, S.B.
Minimal training is required to reliably perform quantitative ultrasound of muscle
(2014) Muscle and Nerve, 50 (1), pp. 124-128. 


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Source: Scopus

Anderson, K.A., Shattuck, P.T., Cooper, B.P., Roux, A.M., Wagner, M.
Prevalence and correlates of postsecondary residential status among young adults with an autism spectrum disorder
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Source: Scopus

Raghavan, R., Brown, D.S., Allaire, B.T., Garfield, L.D., Ross, R.E., Snowden, L.R.
Racial/ethnic differences in Medicaid expenditures on psychotropic medications among maltreated children
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Document Type: Article
Source: Scopus

Brace, E.J., Wu, C., Valakh, V., DiAntonio, A.
SkpA restrains synaptic terminal growth during development and promotes axonal degeneration following injury
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Document Type: Article
Source: Scopus