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Neuroscience Publications Archive - September 2017

Weekly Scopus Report

September 18, 2017

September 11, 2017

September 4, 2017


September 18, 2017 


Tanabe, Y., Naito, Y., Vasuta, C., Lee, A.K., Soumounou, Y., Linhoff, M.W., Takahashi, H.
IgSF21 promotes differentiation of inhibitory synapses via binding to neurexin2α
(2017) Nature Communications, 8 (1), art. no. 408, . 

DOI: 10.1038/s41467-017-00333-w

a Synapse Development and Plasticity Research Unit, Institut de Recherches, Cliniques de Montréal, Montreal, QC, Canada
b Integrated Program in Neuroscience, McGill University, Montreal, QC, Canada
c Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO, United States
d Brain Research Centre and Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada
e Vollum Institute, Oregon Health and Science University, Portland, OR, United States
f Department of Medicine, Université de Montréal, Montreal, QC, Canada
g Division of Experimental Medicine, McGill University, Montreal, QC, Canada

Coordinated development of excitatory and inhibitory synapses is essential for higher brain function, and impairment in this development is associated with neuropsychiatric disorders. In contrast to the large body of accumulated evidence regarding excitatory synapse development, little is known about synaptic adhesion and organization mechanisms underlying inhibitory synapse development. Through unbiased expression screens and proteomics, we identified immunoglobulin superfamily member 21 (IgSF21) as a neurexin2α-interacting membrane protein that selectively induces inhibitory presynaptic differentiation. IgSF21 localizes postsynaptically and recruits axonal neurexin2α in a trans-interaction manner. Deleting IgSF21 in mice impairs inhibitory presynaptic organization, especially in the hippocampal CA1 stratum radiatum, and also diminishes GABA-mediated synaptic transmission in hippocampal CA1 neurons without affecting their excitatory synapses. Finally, mice lacking IgSF21 show a sensorimotor gating deficit. These findings suggest that IgSF21 selectively regulates inhibitory presynaptic differentiation through interacting with presynaptic neurexin2α and plays a crucial role in synaptic inhibition in the brain. © 2017 The Author(s).

Document Type: Article
Source: Scopus



Morizane, A., Kikuchi, T., Hayashi, T., Mizuma, H., Takara, S., Doi, H., Mawatari, A., Glasser, M.F., Shiina, T., Ishigaki, H., Itoh, Y., Okita, K., Yamasaki, E., Doi, D., Onoe, H., Ogasawara, K., Yamanaka, S., Takahashi, J.
MHC matching improves engraftment of iPSC-derived neurons in non-human primates
(2017) Nature Communications, 8 (1), art. no. 385, . 

DOI: 10.1038/s41467-017-00926-5

a Department of Clinical Application, Center for IPS Cell Research and Application, Kyoto University, Kyoto, Japan
b RIKEN Center for Life Science Technologies (CLST), Hyogo, Japan
c Department of Neuroscience, Washington University School of Medicine, St. Louis, MO, United States
d Department of Molecular Life Science, Tokai University, School of Medicine, Kanagawa, Japan
e Department of Pathology, Shiga University of Medical Science, Shiga, Japan
f Department of Life Science Frontiers, Center for IPS Cell Research and Application, Kyoto University, Kyoto 606-8507, Japan
g Department of Neuroscience, Kyoto University Graduate School of Medicine, Kyoto, Japan
h Gladstone Institute of Cardiovascular Disease, San Francisco, CA, United States
i Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan

The banking of human leukocyte antigen (HLA)-homozygous-induced pluripotent stem cells (iPSCs) is considered a future clinical strategy for HLA-matched cell transplantation to reduce immunological graft rejection. Here we show the efficacy of major histocompatibility complex (MHC)-matched allogeneic neural cell grafting in the brain, which is considered a less immune-responsive tissue, using iPSCs derived from an MHC homozygous cynomolgus macaque. Positron emission tomography imaging reveals neuroinflammation associated with an immune response against MHC-mismatched grafted cells. Immunohistological analyses reveal that MHC-matching reduces the immune response by suppressing the accumulation of microglia (Iba-1+) and lymphocytes (CD45+) into the grafts. Consequently, MHC-matching increases the survival of grafted dopamine neurons (tyrosine hydroxylase: TH+). The effect of an immunosuppressant, Tacrolimus, is also confirmed in the same experimental setting. Our results demonstrate the rationale for MHC-matching in neural cell grafting to the brain and its feasibility in a clinical setting. © 2017 The Author(s).

Document Type: Article
Source: Scopus



Burke, N.L., Shomaker, L.B., Brady, S., Reynolds, J.C., Young, J.F., Wilfley, D.E., Sbrocco, T., Stephens, M., Olsen, C.H., Yanovski, J.A., Tanofsky-Kraff, M.
Impact of age and race on outcomes of a program to prevent excess weight gain and disordered eating in adolescent girls
(2017) Nutrients, 9 (9), art. no. 947, . 

DOI: 10.3390/nu9090947

a Department of Medical and Clinical Psychology, Uniformed Services University of the Health Sciences (USUHS), 4301 Jones Bridge Road, Bethesda, MD, United States
b Section on Growth and Obesity, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), US Department of Health and Human Services (DHHS), 10 Center Drive, Bethesda, MD, United States
c Department of Human Development and Family Studies, Colorado State University, 303 Behavioral Sciences Building, 1570 Campus Delivery, Fort Collins, CO, United States
d Radiology and Imaging Sciences Department, Warren Grant Magnuson Clinical Center, National Institutes of Health (NIH), US Department of Health and Human Services (DHHS), 10 Center Drive, Bethesda, MD, United States
e Department of Child and Adolescent Psychiatry and Behavioral Sciences, Children’s Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA, United States
f Department of Psychiatry, Washington University School of Medicine, 660 South Euclid, Campus Box 8134, St. Louis, MO, United States
g Department of Family and Community Medicine, Pennsylvania State University, 1850 E. Park Avenue, Suite 207, State College, PA, United States
h Department of Preventative Medicine & Biometrics, Uniformed Services University of the Health Sciences (USUHS), 4301 Jones Bridge Road, Bethesda, MD, United States

Interpersonal psychotherapy (IPT) prevents weight gain and reduces loss-of-control (LOC)-eating in adults. However, IPT was not superior to health-education (HE) for preventing excess weight gain and reducing LOC-eating over 1-year in adolescent girls at risk for excess weight gain and eating disorders. Limited data suggest that older and non-White youth may be especially responsive to IPT. In secondary analyses, we examined if age or race moderated weight and LOC-eating outcomes. The 113 participants (12–17 years; 56.6% White) from the original trial were re-contacted 3 years later for assessment. At baseline and follow-up visits through 3 years, we assessed BMI, adiposity by dual energy X-ray absorptiometry, and LOC-eating presence. In linear mixed models, baseline age moderated 3-year BMI outcome; older girls in IPT had the lowest 3-year BMI gain compared to younger girls in IPT and all girls in HE, p = 0.04. A similar pattern was observed for adiposity. Race moderated 3-year LOC-eating; non-White girls in IPT were most likely to abstain from LOC-eating at 3 years compared to all other girls, p = 0.04. This hypothesis-generating analysis suggests future studies should determine if IPT is especially efficacious at reducing LOC-eating in older, non-White adolescents. © 2017 by the authors. Licensee MDPI, Basel, Switzerland.

Author Keywords
Adiposity;  Adolescent;  Age;  BMI;  Interpersonal psychotherapy;  Loss-of-control eating;  Obesity;  Race

Document Type: Article
Source: Scopus



Skeath, J.B., Wilson, B.A., Romero, S.E., Snee, M.J., Zhu, Y., Lacin, H.
The extracellular Metalloprotease AdamTS-A anchors neural lineages in place within and preserves the architecture of the central nervous system
(2017) Development (Cambridge), 144 (17), pp. 3102-3113. 

DOI: 10.1242/dev.145854

a Department of Genetics, Washington University School of Medicine, 4523 Clayton Avenue, St Louis, MO, United States
b Janelia Farm Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, VA, United States

The extracellular matrix (ECM) regulates cell migration and sculpts organ shape. AdamTS proteins are extracellular metalloproteases known to modify ECM proteins and promote cell migration, but demonstrated roles for AdamTS proteins in regulating CNS structure and ensuring cell lineages remain fixed in place have not been uncovered. Using forward genetic approaches in Drosophila, we find that reduction of AdamTS-A function induces both the mass exodus of neural lineages out of the CNS and drastic perturbations to CNS structure. Expressed and active in surface glia, AdamTS-A acts in parallel to perlecan and in opposition to viking/collagen IV and βPSintegrin to keep CNS lineages rooted in place and to preserve the structural integrity of the CNS. viking/collagen IV and βPS-integrin are known to promote tissue stiffness and oppose the function of perlecan, which reduces tissue stiffness. Our work supports a model in which AdamTS-A anchors cells in place and preserves CNS architecture by reducing tissue stiffness. © 2017. Published by The Company of Biologists Ltd.

Author Keywords
AdamTS proteins;  Cell migration;  Collagen IV;  Extra-cellular matrix;  Glia

Document Type: Article
Source: Scopus



Argov, Z., Bronstein, F., Esposito, A., Feinsod-Meiri, Y., Florence, J.M., Fowler, E., Greenberg, M.B., Malkus, E.C., Rebibo, O., Siener, C.S., Caraco, Y., Kolodny, E.H., Lau, H.A., Pestronk, A., Shieh, P., Skrinar, A.M., Mayhew, J.E.
Characterization of Strength and Function in Ambulatory Adults with GNE Myopathy
(2017) Journal of Clinical Neuromuscular Disease, 19 (1), pp. 19-26. 

DOI: 10.1097/CND.0000000000000181

a Clinical Outcomes Research and Evaluation, Ultragenyx Pharmaceutical, Inc, 60 Leveroni Court, Novato, CA, United States
b Physical Medicine and Rehabilitation Department, NYU Langone Medical Center-Rusk Institute, New York, NY, United States
c Clinical Research Unit, Hadassah University Medical Center, Jerusalem, Israel
d Washington University School of Medicine, Neuromuscular Division, St. Louis, MO, United States
e UCLA Department of Orthopaedic Surgery, Kameron Gait and Motion Analysis Laboratory, Los Angeles, CA, United States
f NYU Division of Neurogenetics, New York, NY, United States
g UCLA Department of Neurology, Los Angeles, CA, United States
h Clinical Outcomes Research and Evaluation, Ultragenyx Pharmaceutical, Inc, Novato, CA, United States

Objective: To characterize the pattern and extent of muscle weakness and impact on physical functioning in adults with GNEM. Methods: Strength and function were assessed in GNEM subjects (n = 47) using hand-held dynamometry, manual muscle testing, upper and lower extremity functional capacity tests, and the GNEM-Functional Activity Scale (GNEM-FAS). Results: Profound upper and lower muscle weakness was measured using hand-held dynamometry in a characteristic pattern, previously described. Functional tests and clinician-reported outcomes demonstrated the consequence of muscle weakness on physical functioning. Conclusions: The characteristic pattern of upper and lower muscle weakness associated with GNEM and the resulting functional limitations can be reliably measured using these clinical outcome assessments of muscle strength and function. © 2017 The Author(s). Published by Wolters Kluwer Health, Inc.

Author Keywords
distal myopathy with rimmed vacuoles (DMRV);  GNE myopathy;  hereditary inclusion body myopathy (HIBM);  muscle function;  muscle strength;  Nonaka disease

Document Type: Article
Source: Scopus



Kafaie, J., Al Balushi, A., Kim, M., Pestronk, A.
Clinical and Laboratory Profiles of Idiopathic Small Fiber Neuropathy in Children: Case Series
(2017) Journal of Clinical Neuromuscular Disease, 19 (1), pp. 31-37. 

DOI: 10.1097/CND.0000000000000178

a Department of Neurology, Neuromuscular Division, Saint Louis University School of Medicine, 1438 S Grand Boulevard, St. Louis, MO, United States
b Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States

The role of autoimmune mechanisms in idiopathic small fiber neuropathy (SFN) is not completely understood. Serum IgM binding to trisulfated disaccharide IdoA2S-GlcNS-6S (TS-HDS) and IgG to fibroblast growth factor receptor 3 were associated with sensory motor polyneuropathies and sensory neuronopathy among others. In this retrospective case review, we describe the clinical and laboratory findings of idiopathic SFN in a small cohort of pediatric patients. Eight children were diagnosed with SFN clinically and confirmed by reduced epidermal nerve fiber density. No involvement of large fibers was confirmed by clinical examination and electrophysiological tests. Possible triggering factors were infectious mononucleosis in 4 patients and human papilloma virus vaccination in 1 patient. Tilt table test was positive in 1 patient, and clinical autonomic dysfunctions were noted in 6 patients. Five patients had positive IgM against TS-HDS, 3 of whom had lower extremity predominant paresthesia. In conclusion, a high proportion of patients with idiopathic SFN in our cohort had a positive IgM TS-HDS antibody. © 2017 Wolters Kluwer Health, Inc. All rights reserved.

Author Keywords
autoimmune;  idiopathic;  small fiber neuropathy;  TS-HDS antibody

Document Type: Article
Source: Scopus



Das, S., Kim, A.H., Chang, S., Berger, M.S.
Management of elderly patients with glioblastoma after CE.6
(2017) Frontiers in Oncology, 7 (AUG), art. no. 196, . 

DOI: 10.3389/fonc.2017.00196

a Division of Neurosurgery, Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada
b Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Kids, Toronto, ON, Canada
c Department of Neurosurgery, Washington University School of Medicine, Siteman Cancer Center, St. Louis, MO, United States
d Department of Neurosurgery, University of California San Francisco, San Francisco, CA, United States

Author Keywords
Adjuvant;  Chemotherapy;  Elderly patients;  Glioblastoma;  Radiation therapy;  Survival;  Temozolomide

Document Type: Article
Source: Scopus



Finder, J., Mayer, O.H., Sheehan, D., Sawnani, H., Abresch, R.T., Benditt, J., Birnkrant, D.J., Duong, T., Henricson, E., Kinnett, K., McDonald, C.M., Connolly, A.M.
Pulmonary Endpoints in Duchenne Muscular Dystrophy. A Workshop Summary
(2017) American journal of respiratory and critical care medicine, 196 (4), pp. 512-519. 

DOI: 10.1164/rccm.201703-0507WS

a 1 Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
b 2 Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
c 3 Department of Pediatrics, University at Buffalo, The State University of New York, Buffalo, New York
d 4 Division of Pulmonology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
e 5 Department of Physical Medicine and Rehabilitation and
f 6 Division of Pulmonary and Critical Care Medicine, University of Washington School of Medicine, Seattle, Washington
g 7 MetroHealth Medical Center, Cleveland, Ohio
h 8 Case Western Reserve University, Cleveland, Ohio
i 9 Department of Neurology, Stanford University, Stanford, California
j 10 Parent Project Muscular Dystrophy, Hackensack, New Jersey; and
k 11 Department of Pediatrics, University of California Davis, Sacramento, California
l 12 Department of Neurology, Washington University School of Medicine, Saint Louis, Missouri

Development of novel therapeutics for treatment of Duchenne muscular dystrophy (DMD) has led to clinical trials that include pulmonary endpoints that allow assessment of respiratory muscle status, especially in nonambulatory subjects. Parent Project Muscular Dystrophy (PPMD) convened a workshop in Bethesda, Maryland, on April 14 and 15, 2016, to summarize published respiratory data in DMD and give guidance to clinical researchers assessing the effect of interventions on pulmonary outcomes in DMD.

Author Keywords
Duchenne muscular dystrophy;  outcome;  respiratory failure

Document Type: Review
Source: Scopus



Galarza, M., Giménez, A., Amigó, J.M., Schuhmann, M., Gazzeri, R., Thomale, U., McAllister, J.P., 2Nd
Next generation of ventricular catheters for hydrocephalus based on parametric designs
(2017) Child's Nervous System, pp. 1-10. Article in Press. 

DOI: 10.1007/s00381-017-3565-0

a Regional Service of Neurosurgery, University of Murcia, Murcia, Spain
b Operations Research Center, University Miguel Hernández de Elche, Alacant, Spain
c Department of Neurosurgery, University Hospital Tuebingen, Eberhard-Karls-University, Tuebingen, Germany
d Department of Neurosurgery, San Giovanni Addolorata Hospital, Rome, Italy
e Charité Universitätsmedizin Berlin, Campus Virchow, Klinikum, Augustenburger Platz 1, Berlin, Germany
f Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MI, United States

Background: The flow pattern of the cerebrospinal fluid is probably the most important factor related to obstruction of ventricular catheters during the normal treatment of hydrocephalus. To better comprehend the flow pattern, we have carried out a parametric study via numerical models of ventricular catheters. In previous studies, the flow was studied under steady and, recently, in pulsatile boundary conditions by means of computational fluid dynamics (CFD) in three-dimensional catheter models. Objective: This study aimed to bring in prototype models of catheter CFD flow solutions as well to introduce the theory behind parametric development of ventricular catheters. Methods: A preceding study allowed deriving basic principles which lead to designs with improved flow patterns of ventricular catheters. The parameters chosen were the number of drainage segments, the distances between them, the number and diameter of the holes on each segment, as well as their relative angular position. Results: CFD results of previously unreleased models of ventricular catheter flow solutions are presented in this study. Parametric development guided new designs with better flow distribution while lowering the shear stress of the catheters holes. High-resolution 3D printed catheter solutions of three models and basic benchmark testing are introduced as well. Conclusions: The next generation of catheter with homogeneous flow patterns based on parametric designs may represent a step forward for the treatment of hydrocephalus, by possibly broadening their lifespan. © 2017 Springer-Verlag GmbH Germany

Author Keywords
Catheter obstruction;  Catheter prototypes;  Cerebral ventricle;  Cerebrospinal fluid;  Flow;  Shunt revision

Document Type: Article in Press
Source: Scopus



Bostwick, B.L., McLean, S., Posey, J.E., Streff, H.E., Gripp, K.W., Blesson, A., Powell-Hamilton, N., Tusi, J., Stevenson, D.A., Farrelly, E., Hudgins, L., Yang, Y., Xia, F., Wang, X., Liu, P., Walkiewicz, M., McGuire, M., Grange, D.K., Andrews, M.V., Hummel, M., Madan-Khetarpal, S., Infante, E., Coban-Akdemir, Z., Miszalski-Jamka, K., Jefferies, J.L., Members of the Undiagnosed Diseases Network, Rosenfeld, J.A., Emrick, L., Nugent, K.M., Lupski, J.R., Belmont, J.W., Lee, B., Lalani, S.R.
Phenotypic and molecular characterisation of CDK13-related congenital heart defects, dysmorphic facial features and intellectual developmental disorders
(2017) Genome medicine, 9 (1), p. 73. 

DOI: 10.1186/s13073-017-0463-8

a Department of Molecular and Human Genetics, Baylor College of Medicine, 6701 Fannin St, Suite 1560, Houston, TX, 77030, USA
b Department of Pediatrics, Baylor College of Medicine, San Antonio, TX, 78207, USA
c Division of Medical Genetics, A.I. duPont Hospital for Children/Nemours, Wilmington, DE, USA
d Division of Medical Genetics, Stanford University School of Medicine, Stanford, CA, USA
e Baylor Genetics, Baylor College of Medicine, Houston, TX, USA
f Division of Genetics and Genomic Medicine, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA
g Department of Pediatrics, Section of Medical Genetics, West Virginia University Health Sciences Center, Morgantown, WV, USA
h Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh, Pittsburgh, PA, USA
i Division of Magnetic Resonance Imaging, Silesian Center for Heart Disease, Zabrze, Poland
j The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
k Texas Children's Hospital, Houston, TX, 77030, USA
l Department of Pediatrics, Baylor College of Medicine, Houston, TX, 77030, USA
m Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, 77030, USA

BACKGROUND: De novo missense variants in CDK13 have been described as the cause of syndromic congenital heart defects in seven individuals ascertained from a large congenital cardiovascular malformations cohort. We aimed to further define the phenotypic and molecular spectrum of this newly described disorder.

METHODS: To minimise ascertainment bias, we recruited nine additional individuals with CDK13 pathogenic variants from clinical and research exome laboratory sequencing cohorts. Each individual underwent dysmorphology exam and comprehensive medical history review.

RESULTS: We demonstrate greater than expected phenotypic heterogeneity, including 33% (3/9) of individuals without structural heart disease on echocardiogram. There was a high penetrance for a unique constellation of facial dysmorphism and global developmental delay, as well as less frequently seen renal and sacral anomalies. Two individuals had novel CDK13 variants (p.Asn842Asp, p.Lys734Glu), while the remaining seven unrelated individuals had a recurrent, previously published p.Asn842Ser variant. Summary of all variants published to date demonstrates apparent restriction of pathogenic variants to the protein kinase domain with clustering in the ATP and magnesium binding sites.

CONCLUSIONS: Here we provide detailed phenotypic and molecular characterisation of individuals with pathogenic variants in CDK13 and propose management guidelines based upon the estimated prevalence of anomalies identified.

Author Keywords
Agenesis of the corpus callosum;  CDK13;  CHDFIDD;  Cyclin-dependent kinase;  De novo variant;  Developmental delay;  Hypertelorism;  Neurodevelopmental disorders;  Undiagnosed Diseases Network

Document Type: Article
Source: Scopus



Braude, S., Margulis, S., Broder, E.D.
The Study of Animal Behavior Provides Valuable Opportunities for Original Science Fair Projects: Recommendations from the Animal Behavior Society, Education Committee
(2017) American Biology Teacher, 79 (6), pp. 438-441. 

DOI: 10.1525/abt.2017.79.6.438

a Washington University in St. Louis, St Louis, MO, United States
b Department of Animal Behavior, Ecology and Conservation Assoc. of Biology, Buffalo, United States
c Interdisciplinary Research Incubator for the Study of (In)Equality, University of Denver, Denver, CO, United States

The study of Animal Behavior is critically important in understanding our living world and is a major program within the NSF. For students, animal behavior projects offer the opportunity to explore original questions in a scientifically rigorous manner. However, animal behavior projects are under-represented in science fairs and are often discouraged by teachers and judges. We give a sample of the types of questions that students could explore and we suggest appropriate judging criteria. © 2017 National Association of Biology Teachers. All rights reserved. Please direct all requests for permission to photocopy or reproduce article content through the University of California Press's Reprints and Permissions web page, .

Author Keywords
animal behavior;  Science fair

Document Type: Article
Source: Scopus



El Ters, N.M., Vesoulis, Z.A., Liao, S.M., Smyser, C.D., Mathur, A.M.
Impact of brain injury on functional measures of amplitude-integrated EEG at term equivalent age in premature infants
(2017) Journal of Perinatology, 37 (8), pp. 947-952. 

DOI: 10.1038/jp.2017.62

a Division of Newborn Medicine, Department of Pediatrics, Washington University School of Medicine, 1 Children's Place, Campus Box 8116, St Louis, MO, United States
b Division of Pediatric Neurology, Washington University School of Medicine, St Louis, MO, United States

Objective: To evaluate the association between qualitative and quantitative amplitude-integrated EEG (aEEG) measures at term equivalent age (TEA) and brain injury on magnetic resonance imaging (MRI) in preterm infants. Study Design: A cohort of premature infants born at <30 weeks of gestation and with moderate-to-severe MRI injury on a TEA MRI scan was identified. A contemporaneous group of gestational age-matched control infants also born at <30 weeks of gestation with none/mild injury on MRI was also recruited. Quantitative aEEG measures, including maximum and minimum amplitudes, bandwidth span and spectral edge frequency (SEF90), were calculated using an offline software package. The aEEG recordings were qualitatively scored using the Burdjalov system. MRI scans, performed on the same day as aEEG, occurred at a mean postmenstrual age of 38.0 (range 37 to 42) weeks and were scored for abnormality in a blinded manner using an established MRI scoring system. Results: Twenty-eight (46.7%) infants had a normal MRI or mild brain abnormality, while 32 (53.3%) infants had moderate-to-severe brain abnormality. Univariate regression analysis demonstrated an association between severity of brain abnormality and quantitative measures of left and right SEF90 and bandwidth span (β=-0.38, -0.40 and 0.30, respectively) and qualitative measures of cyclicity, continuity and total Burdjalov score (β=-0.10, -0.14 and -0.12, respectively). After correcting for confounding variables, the relationship between MRI abnormality score and aEEG measures of SEF90, bandwidth span and Burdjalov score remained significant. Conclusion: Brain abnormalities on MRI at TEA in premature infants are associated with abnormalities on term aEEG measures, suggesting that anatomical brain injury may contribute to delay in functional brain maturation as assessed using aEEG. © 2017 Nature America, Inc., part of Springer Nature. All rights reserved.

Document Type: Article
Source: Scopus



Almishaal, A.A., Mathur, P.D., Hillas, E., Chen, L., Zhang, A., Yang, J., Wang, Y., Yokoyama, W.M., Firpo, M.A., Park, A.H.
Natural killer cells attenuate cytomegalovirus-induced hearing loss in mice
(2017) PLoS Pathogens, 13 (8), art. no. e1006599, . 

DOI: 10.1371/journal.ppat.1006599

a Department of Communication Sciences and Disorders, University of Utah College of Health, Salt Lake City, UT, United States
b Department of Ophthalmology and Visual Sciences, University of Utah School of Medicine, Salt Lake City, UT, United States
c Department of Neurobiology and Anatomy, University of Utah School of Medicine, Salt Lake City, UT, United States
d Department of Surgery, University of Utah School of Medicine, Salt Lake City, UT, United States
e Division of Otolaryngology, University of Utah School of Medicine, Salt Lake City, UT, United States
f Division of Rheumatology, Washington University School of Medicine, St. Louis, MO, United States
g Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO, United States

Congenital cytomegalovirus (CMV) infection is the most common non-hereditary cause of sensorineural hearing loss (SNHL) yet the mechanisms of hearing loss remain obscure. Natural Killer (NK) cells play a critical role in regulating murine CMV infection via NK cell recognition of the Ly49H cell surface receptor of the viral-encoded m157 ligand expressed at the infected cell surface. This Ly49H NK receptor/m157 ligand interaction has been found to mediate host resistance to CMV in the spleen, and lung, but is much less effective in the liver, so it is not known if this interaction is important in the context of SNHL. Using a murine model for CMV-induced labyrinthitis, we have demonstrated that the Ly49H/m157 interaction mediates host resistance in the temporal bone. BALB/c mice, which lack functional Ly49H, inoculated with mCMV at post-natal day 3 developed profound hearing loss and significant outer hair cell loss by 28 days of life. In contrast, C57BL/6 mice, competent for the Ly49H/m157 interaction, had minimal hearing loss and attenuated outer hair cell loss with the same mCMV dose. Administration of Ly49H blocking antibody or inoculation with a mCMV viral strain deleted for the m157 gene rendered the previously resistant C57BL/6 mouse strain susceptible to hearing loss to a similar extent as the BALB/c mouse strain indicating a direct role of the Ly49H/m157 interaction in mCMV-dependent hearing loss. Additionally, NK cell recruitment to sites of infection was evident in the temporal bone of inoculated susceptible mouse strains. These results demonstrate participation of NK cells in protection from CMV-induced labyrinthitis and SNHL in mice. © 2017 Almishaal et al.

Document Type: Article
Source: Scopus



Blum, K., Gold, M., Demetrovics, Z., Archer, T., Thanos, P.K., Baron, D., Badgaiyan, R.D.
Substance use disorder a bio-directional subset of reward deficiency syndrome
(2017) Frontiers in bioscience (Landmark edition), 22, pp. 1534-1548. 

a Department of Psychiatry and McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL, USA,and Division of Nutrigenomics, LaVita RDS, Draper, UT, USA,
b Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA
c Eotvos Loránd University, Institute of Psychology, Budapest, Hungary
d Department of Psychology, University of Gothenburg, Gothenburg, Sweden
e Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Research Institute on Addictions, University at Buffalo, Buffalo, NY, USA
f Departments of Psychiatry & Behavioral Sciences, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA
g Department of Psychiatry, University at Minnesota, Minneapolis, MN, USA

This commentary is to inform clinicians challenged with an increase in people seeking treatment for Substance Use Disorder (SUD), that the ninety percent revolving door, is, in part, due to post-withdrawal, untreated neurotoxicity. This impairment attenuates neurotransmitter signaling and compromises resting state functional connectivity, leading to unwanted sequelae including depression, sleep disturbances, sensation seeking, lack of satisfaction and impulsivity. Neuroimaging studies indicate that neurobiological recovery can take years. Like a "double edge sword" SUD has a biological bi -directional (bio-directional) effect on the brain reward circuitry. The acute intake of psychoactive drugs results in heightened dopaminergic activity, while, the opposite, hypodopaminergia occurs following chronic abuse. Individuals with SUD can have a genetic predisposition, compounded by stress and neurotoxically induced, epigenetic insults that impact recovery from protracted abstinence. Follow-up post -short-term recovery usually includes supportive therapies and programs like 12 -steps and other fellowships. However, relapse will usually occur if post -short-term recovery hypodopaminergia is not treated with attempts at epigenetic manipulation of compromised brain neurochemistry using some manner of pro-dopamine regulation.

Document Type: Article
Source: Scopus



Carpenter, C.R.
In patients in the emergency department with acute pain, 10, 15, and 30 mg of ketorolac did not differ for pain relief
(2017) Annals of Internal Medicine, 166 (8), p. JC44. 

DOI: 10.7326/ACPJC-2017-166-8-044

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

Document Type: Note
Source: Scopus



Mundschenk, M.-B., Sachanandani, N.S., Borschel, G.H., Zuker, R.M., Snyder-Warwick, A.K.
Motor nerve to the masseter: A pediatric anatomic study and the "3:1 rule"
(2017) Journal of Plastic, Reconstructive and Aesthetic Surgery, . Article in Press. 

DOI: 10.1016/j.bjps.2017.08.017

a Division of Plastic and Reconstructive Surgery, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8238, St. Louis, MO 63110, USA
b Division of Plastic and Reconstructive Surgery, University of Toronto, 149 College Street, 5th Floor, Suite 508, Toronto, ON M5T 1P5, Canada

Document Type: Article in Press
Source: Scopus



Ulfers, S.S., Berg, C.
Occupational therapists with oncology exposure: Perceived needs on adults and older adults with cancer-related cognitive impairments
(2017) OTJR Occupation, Participation and Health, 37 (3), pp. 149-154. 

DOI: 10.1177/1539449217698105

Program of Occupational Therapy, Washington University in St. Louis, 4444 Forest Park Ave., St. Louis, MO, United States

Cancer-related cognitive impairments (CRCI) can limit participation in meaningful activities before, during, and after cancer treatment. This study explored occupational therapists' perceived knowledge gaps and needs regarding CRCI in adults and older adults. An online survey was sent to a convenience sample of 60 practitioners at facilities throughout the continuum of care and 176 directors and faculty in accredited occupational therapy programs. Using a snowball sampling approach, recipients were asked to forward the survey to other occupational therapists. One hundred seven occupational therapists participated. The majority (92%) responded that it would be beneficial to attend a face-to-face continuing education program; preferences for the content and design of a continuing competency seminar are described. These findings support the development and delivery of continuing competence programs tailored toward occupational therapists' CRCI knowledge needs. © The Author(s) 2017.

Author Keywords
Cancer;  Cognition;  Education;  Occupational therapy

Document Type: Article
Source: Scopus


September 11, 2017 


Radvansky, G.A., Zacks, J.M.
Event boundaries in memory and cognition
(2017) Current Opinion in Behavioral Sciences, 17, pp. 133-140. 

DOI: 10.1016/j.cobeha.2017.08.006

a University of Notre Dame, United States
b Washington University in Saint Louis, United States

Research on event cognition is rapidly developing and is revealing fundamental aspects of human cognition. In this paper, we review recent and current work that is driving this field forward. We first outline the Event Horizon Model, which broadly describes the impact of event boundaries on cognition and memory. Then, we address recent work on event segmentation, the role of event cognition in working memory and long-term memory, including event model updating, and long term retention. Throughout we also consider how event cognition varies across individuals and groups of people and consider the neural mechanisms involved. © 2017 Elsevier Ltd

Document Type: Review
Source: Scopus



Battaglia, P.J., Carbone-Hobbs, V., Guebert, G.M., Mackinnon, S.E., Kettner, N.W.
High-resolution ultrasonography and shear-wave sonoelastography of a cystic radial nerve Schwannoma
(2017) Journal of Ultrasound, 20 (3), pp. 261-266. 

DOI: 10.1007/s40477-017-0254-5

a Department of Radiology, Logan University, 1851 Schoettler Road, Chesterfield, MO, United States
b Private Practice, Arnold, MO, United States
c Shoenberg Professor and Chief Division of Plastic and Reconstructive Surgery, Washington University School of Medicine, 660 S Euclid Ave, St. Louis, MO, United States

Peripheral nerve tumors are often evaluated with magnetic resonance imaging (MRI), although there are many advantages offered with high-resolution ultrasonography (HRUS). This case report emphasizes the value of HRUS in the diagnosis and management of a patient with a cystic radial nerve Schwannoma. In addition, information on tumor stiffness, obtained with shear-wave sonoelastography (SWE), is presented. © 2017, Società Italiana di Ultrasonologia in Medicina e Biologia (SIUMB).

Author Keywords
Diagnostic ultrasound;  Neurilemmoma;  Schwannoma;  Sonoelastography

Document Type: Article
Source: Scopus



Chung, S.M., Custer, P.L.
Patient Safety: Its History and Relevance to Neuro-Ophthalmology
(2017) Journal of Neuro-Ophthalmology, 37 (3), pp. 225-229. 

DOI: 10.1097/WNO.0000000000000559

a Departments of Ophthalmology, Neurology, and Neurosurgery, Saint Louis University School of Medicine, 1755 South Grand Boulevard, St. Louis, MO, United States
b Department of Ophthalmology and Visual Sciences, Washington University in Saint Louis, St. Louis, MO, United States

Document Type: Review
Source: Scopus


Gutmann, D.H.
The Tropism of Pleiotrophin: Orchestrating Glioma Brain Invasion
(2017) Cell, 170 (5), pp. 821-822. 

DOI: 10.1016/j.cell.2017.08.011

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

The lateral ventricle (LV) is a preferential location for brain tumor spread; however, the instructive cues responsible for this unique tropism were previously unknown. In this issue, Qin et al. elucidate the underlying mechanism, demonstrating that LV-neural progenitors secrete a pleiotrophin (PTN)-containing complex, which attracts glioma cells through ROCK/Rho activation. © 2017 Elsevier Inc.

Document Type: Short Survey
Source: Scopus



Ju, Y.-E.S., Ooms, S.J., Sutphen, C., Macauley, S.L., Zangrilli, M.A., Jerome, G., Fagan, A.M., Mignot, E., Zempel, J.M., Claassen, J.A.H.R., Holtzman, D.M.
Slow wave sleep disruption increases cerebrospinal fluid amyloid-β levels
(2017) Brain, 140 (8), pp. 2104-2111. Cited 1 time.

DOI: 10.1093/brain/awx148

a Department of Neurology, Washington University, Saint Louis, MO, United States
b Hope Center for Neurological Disorders, Washington University, Saint Louis, MO, United States
c Department of Geriatric Medicine, Radboud University Medical Centre, Nijmegen, Netherlands
d Radboudumc Alzheimer Centre, Nijmegen, Netherlands
e Donders Institute for Brain, Cognition and Behaviour, Nijmegen, Netherlands
f Knight Alzheimer's Disease Research Center, Washington University, Saint Louis, MO, United States
g Stanford Center for Sleep Sciences and Medicine, Stanford University, Palo Alto, CA, United States

Sleep deprivation increases amyloid-β, suggesting that chronically disrupted sleep may promote amyloid plaques and other downstream Alzheimer's disease pathologies including tauopathy or inflammation. To date, studies have not examined which aspect of sleep modulates amyloid-β or other Alzheimer's disease biomarkers. Seventeen healthy adults (age 35-65 years) without sleep disorders underwent 5-14 days of actigraphy, followed by slow wave activity disruption during polysomnogram, and cerebrospinal fluid collection the following morning for measurement of amyloid-β, tau, total protein, YKL-40, and hypocretin. Data were compared to an identical protocol, with a sham condition during polysomnogram. Specific disruption of slow wave activity correlated with an increase in amyloid-β 40 (r = 0.610, P = 0.009). This effect was specific for slow wave activity, and not for sleep duration or efficiency. This effect was also specific to amyloid-β, and not total protein, tau, YKL-40, or hypocretin. Additionally, worse home sleep quality, as measured by sleep efficiency by actigraphy in the six nights preceding lumbar punctures, was associated with higher tau (r = 0.543, P = 0.045). Slow wave activity disruption increases amyloid-β levels acutely, and poorer sleep quality over several days increases tau. These effects are specific to neuronally-derived proteins, which suggests they are likely driven by changes in neuronal activity during disrupted sleep. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email:

Author Keywords
beta-amyloid;  EEG;  sleep;  slow wave activity;  tau

Document Type: Article
Source: Scopus



Wetherell, J.L., Hershey, T., Hickman, S., Tate, S.R., Dixon, D., Bower, E.S., Lenze, A.E.J.
Mindfulness-based stress reduction for older adults with stress disorders and neurocognitive difficulties: A randomized controlled trial
(2017) Journal of Clinical Psychiatry, 78 (7), pp. e736-e743. 

DOI: 10.4088/JCP.16m10947

a VA San Diego Healthcare System, San Diego, CA, United States
b Department of Psychiatry, University of California, 9500 Gilman Dr., Dept. 9111N-1, San Diego, CA, United States
c Healthy Mind Laboratory, Department of Psychiatry, Washington University, School of Medicine, St. Louis, MO, United States
d Joint Doctoral Program in Clinical Psychology, San Diego State University, University of California, San Diego, United States

Objective: To determine whether neurocognitive performance and clinical outcomes can be enhanced by a mindfulness intervention in older adults with stress disorders and cognitive complaints. To explore decreased hypothalamic-pituitary-adrenal (HPA) axis activity as a possible mechanism. Methods: 103 adults aged 65 years or older with an anxiety or depressive disorder (diagnosed according to DSM-IV criteria) and subjective neurocognitive difficulties were recruited in St. Louis, Missouri, or San Diego, California, from September 2012 through August 2013 and randomly assigned in groups of 5-8 to mindfulness-based stress reduction (MBSR) or a health education control condition matched for time, attention, and credibility. The primary outcomes were memory (assessed by immediate and delayed paragraph and list recall) and cognitive control (Delis-Kaplan Executive Function System Verbal Fluency Test and Color Word Interference Test). Other outcomes included clinical symptoms (worry, depression, anxiety, and global improvement). HPA axis activity was assessed using peak salivary cortisol. Outcomes were measured immediately postintervention and (for clinical outcomes only) at 3- and 6-month follow up. Results: On the basis of intent-to-treat principles using data from all 103 participants, the mindfulness group experienced greater improvement on a memory composite score (P =.046). Groups did not differ on change in cognitive control. Participants receiving MBSR also improved more on measures of worry (P =.042) and depression (P =.049) at posttreatment and on worry (P =.02), depression (P =.002), and anxiety (P =.002) at follow-up and were more likely to be rated as much or very much improved as rated by the Clinical Global Impressions-Improvement scale (47% vs 27%, χ2 = 4.5, P =.03). Cortisol level decreased to a greater extent in the mindfulness group, but only among those participants with high baseline cortisol. Conclusions: In this population of older adults with stress disorders and neurocognitive difficulties, a mindfulness intervention improves clinical outcomes such as excessive worry and depression and may include some forms of immediate memory performance. © 2017 Physicians Postgraduate Press, Inc.

Document Type: Article
Source: Scopus


Gruber, J., Van Meter, A., Gilbert, K.E., Youngstrom, E.A., Youngstrom, J.K., Feeny, N.C., Findling, R.L.
Positive Emotion Specificity and Mood Symptoms in an Adolescent Outpatient Sample
(2017) Cognitive Therapy and Research, 41 (3), pp. 393-405. 

DOI: 10.1007/s10608-016-9796-7

a Department of Psychology and Neuroscience, University of Colorado Boulder, 1905 Colorado Avenue, 345 UCB, Muenzinger D321C, Boulder, CO, United States
b Ferkauf Graduate School, Yeshiva University, New York, NY, United States
c Department of Psychiatry, Washington University in St. Louis, St. Louis, MO, United States
d Department of Psychology, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
e Case Western Reserve University, Cleveland, OH, United States
f Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, United States

Research on positive emotion disturbance has gained increasing attention, yet it is not clear which specific positive emotions are affected by mood symptoms, particularly during the critical period of adolescence. This is especially pertinent for identifying potential endophenotypic markers associated with mood disorder onset and course. The present study examined self-reported discrete positive and negative emotions in association with clinician-rated manic and depressive mood symptoms in a clinically and demographically diverse group of 401 outpatient adolescents between 11 and 18 years of age. Results indicated that higher self reported joy and contempt were associated with increased symptoms of mania, after controlling for symptoms of depression. Low levels of joy and high sadness uniquely predicted symptoms of depression, after controlling for symptoms of mania. Results were independent of age, ethnicity, gender and bipolar diagnosis. These findings extend work on specific emotions implicated in mood pathology in adulthood, and provide insights into associations between emotions associated with goal driven behavior with manic and depressive mood symptom severity in adolescence. In particular, joy was the only emotion associated with both depressive and manic symptoms across adolescent psychopathology, highlighting the importance of understanding positive emotion disturbance during adolescent development. © 2016, Springer Science+Business Media New York.

Author Keywords
Adolescence;  Depression;  Mania;  Positive emotion

Document Type: Article
Source: Scopus



McAllister, J.P., Guerra, M.M., Ruiz, L.C., Jimenez, A.J., Dominguez-Pinos, D., Sival, D., den Dunnen, W., Morales, D.M., Schmidt, R.E., Rodriguez, E.M., Limbrick, D.D.
Ventricular Zone Disruption in Human Neonates With Intraventricular Hemorrhage
(2017) Journal of neuropathology and experimental neurology, 76 (5), pp. 358-375. 

DOI: 10.1093/jnen/nlx017

From the Department of Neurosurgery, Washington University School of Medicine, St Louis, Missouri (JPM, LCR, DMM, DDL); Instituto de Antomía, Histologia y Patologia, Facultad de Medicina, Universidad Austral de Chile, Valdivia, Chile (MMG, EMR); Instituto de Biología Celular, Genética y Fisiología Facultad de Ciencias, Universidad de Malaga, Malaga, Spain and Instituto de Investigación Biomédica (IBIMA), Malaga, Spain (AJJ, DDP); Departments of Pediatrics, Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (DS, WD); Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri (RES); and Department of Pediatrics, Washington University School of Medicine, St Louis, Missouri (DDL)

To determine if ventricular zone (VZ) and subventricular zone (SVZ) alterations are associated with intraventricular hemorrhage (IVH) and posthemorrhagic hydrocephalus, we compared postmortem frontal and subcortical brain samples from 12 infants with IVH and 3 nonneurological disease controls without hemorrhages or ventriculomegaly. Birth and expiration estimated gestational ages were 23.0-39.1 and 23.7-44.1 weeks, respectively; survival ranges were 0-42 days (median, 2.0 days). Routine histology and immunohistochemistry for neural stem cells (NSCs), neural progenitors (NPs), multiciliated ependymal cells (ECs), astrocytes (AS), and cell adhesion molecules were performed. Controls exhibited monociliated NSCs and multiciliated ECs lining the ventricles, abundant NPs in the SVZ, and medial vs. lateral wall differences with a complex mosaic organization in the latter. In IVH cases, normal VZ/SVZ areas were mixed with foci of NSC and EC loss, eruption of cells into the ventricle, cytoplasmic transposition of N-cadherin, subependymal rosettes, and periventricular heterotopia. Mature AS populated areas believed to be sites of VZ disruption. The cytopathology and extension of the VZ disruption correlated with developmental age but not with brain hemorrhage grade or location. These results corroborate similar findings in congenital hydrocephalus in animals and humans and indicate that VZ disruption occurs consistently in premature neonates with IVH. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

Author Keywords
Astrocytes;  Ependyma;  Intraventricular hemorrhage;  Neural stem cells;  Posthemorrhagic hydrocephalus;  Subventricular zone;  Ventricular zone

Document Type: Article
Source: Scopus



Cohen, J.N., Taylor Dryman, M., Morrison, A.S., Gilbert, K.E., Heimberg, R.G., Gruber, J.
Positive and Negative Affect as Links Between Social Anxiety and Depression: Predicting Concurrent and Prospective Mood Symptoms in Unipolar and Bipolar Mood Disorders
(2017) Behavior Therapy, . Article in Press. 

DOI: 10.1016/j.beth.2017.07.003

a Temple University
b Stanford University
c Washington University in St. Louis
d University of Colorado Boulder

The co-occurrence of social anxiety and depression is associated with increased functional impairment and a more severe course of illness. Social anxiety disorder is unique among the anxiety disorders in sharing an affective profile with depression, characterized by low levels of positive affect (PA) and high levels of negative affect (NA). Yet it remains unclear how this shared affective profile contributes to the covariation of social anxiety and depressive symptoms. We examined whether self-reported PA and NA accounted for unique variance in the association between social anxiety and depressive symptoms across three groups (individuals with remitted bipolar disorder, type I [BD; n = 32], individuals with remitted major depressive disorder [MDD; n = 31], and nonpsychiatric controls [. n = 30]) at baseline and follow-ups of 6 and 12 months. Low levels of PA, but not NA, accounted for unique variance in both concurrent and prospective associations between social anxiety and depression in the BD group; in contrast, high levels of NA, but not PA, accounted for unique variance in concurrent and prospective associations between social anxiety and depression in the MDD group. Limitations include that social anxiety and PA/NA were assessed concurrently and all measurement was self-report. Few individuals with MDD/BD met current diagnostic criteria for social anxiety disorder. There was some attrition at follow-up assessments. Results suggest that affective mechanisms may contribute to the high rates of co-occurrence of social anxiety and depression in both MDD and BD. Implications of the differential role of PA and NA in the relationship between social anxiety and depression in MDD and BD and considerations for treatment are discussed. © 2017.

Author Keywords
Bipolar disorder;  Depression;  Negative affect;  Positive affect;  Social anxiety

Document Type: Article in Press
Source: Scopus



Kinnunen, K.M., Cash, D.M., Poole, T., Frost, C., Benzinger, T.L.S., Ahsan, R.L., Leung, K.K., Cardoso, M.J., Modat, M., Malone, I.B., Morris, J.C., Bateman, R.J., Marcus, D.S., Goate, A., Salloway, S.P., Correia, S., Sperling, R.A., Chhatwal, J.P., Mayeux, R.P., Brickman, A.M., Martins, R.N., Farlow, M.R., Ghetti, B., Saykin, A.J., Jack, C.R., Schofield, P.R., McDade, E., Weiner, M.W., Ringman, J.M., Thompson, P.M., Masters, C.L., Rowe, C.C., Rossor, M.N., Ourselin, S., Fox, N.C.
Presymptomatic atrophy in autosomal dominant Alzheimer's disease: A serial MRI study
(2017) Alzheimer's and Dementia, . Article in Press. 

DOI: 10.1016/j.jalz.2017.06.2268

a Department of Neurodegenerative Disease, Dementia Research Centre, UCL Institute of Neurology, London, UK
b Department of Medical Physics and Bioengineering, Translational Imaging Group, Centre for Medical Image Computing, University College London, London, UK
c Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK
d Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA
e Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA
f Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA
g Department of Neurology, Butler Hospital, Warren Alpert Medical School, Brown University, Providence, RI, USA
h Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
i Department of Neurology, Columbia University Medical Center, New York, NY, USA
j Centre of Excellence for Alzheimer's Disease Research and Care, School of Exercise, Biomedical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia
k Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, USA
l Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
m Department of Radiology and Imaging Sciences, Centre for Neuroimaging, Indiana University School of Medicine, Indianapolis, IN, USA
n Department of Radiology, Mayo Clinic, Rochester, MN, USA
o Neuroscience Research Australia, Randwick, NSW, Australia
p School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia
q Department of Radiology, School of Medicine, University of California, San Francisco, San Francisco, CA, USA
r Department of Neurology, Keck USC School of Medicine, Los Angeles, CA, USA
s Imaging Genetics Center, Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA
t The Florey Institute, University of Melbourne, Parkville, VIC, Australia
u Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, VIC, Australia
v Department of Medicine, University of Melbourne, Austin Health, Heidelberg, VIC, Australia

Introduction: Identifying at what point atrophy rates first change in Alzheimer's disease is important for informing design of presymptomatic trials. Methods: Serial T1-weighed magnetic resonance imaging scans of 94 participants (28 noncarriers, 66 carriers) from the Dominantly Inherited Alzheimer Network were used to measure brain, ventricular, and hippocampal atrophy rates. For each structure, nonlinear mixed-effects models estimated the change-points when atrophy rates deviate from normal and the rates of change before and after this point. Results: Atrophy increased after the change-point, which occurred 1-1.5 years (assuming a single step change in atrophy rate) or 3-8 years (assuming gradual acceleration of atrophy) before expected symptom onset. At expected symptom onset, estimated atrophy rates were at least 3.6 times than those before the change-point. Discussion: Atrophy rates are pathologically increased up to seven years before "expected onset". During this period, atrophy rates may be useful for inclusion and tracking of disease progression. © 2017 the Alzheimer's Association.

Author Keywords
Alzheimer's disease;  Atrophy;  Autosomal dominant;  Boundary Shift Integral;  Change-point;  Dementia;  Longitudinal;  MRI;  Neuroimaging;  Nonlinear modeling

Document Type: Article in Press
Source: Scopus



Hamilton, D.K., Buza, J.A., Passias, P., Jalai, C., Kim, H.J., Ailon, T., Gupta, M., Sciubba, D., Jain, A., Ames, C.P., Deviren, V., Daniels, A., Lafage, V., Bess, S., Klineberg, E., Shaffrey, C.I., Smith, J.S., Hart, R.
The Fate of Patients with Adult Spinal Deformity Incurring Rod Fracture After Thoracolumbar Fusion
(2017) World Neurosurgery, . Article in Press. 

DOI: 10.1016/j.wneu.2017.07.061

a Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
b Department of Orthopedic Surgery, NYU Langone Orthopedics, New York, New York, USA
c Department of Orthopaedic Surgery, Hospital for Special Surgery, New York, New York, USA
d Vancouver Spine Surgery Institute, Vancouver General Hospital, Vancouver, Canada
e Department of Orthopedic Surgery, Washington University Orthopedics, St. Louis, Missouri, USA
f Department of Orthopaedic Surgery, Johns Hopkins University, Baltimore, Maryland, USA
g Department of Neurological Surgery, University of California at San Francisco, San Francisco, California, USA
h Department of Orthopaedic Surgery, University of California at San Francisco, San Francisco, California, USA
i Department of Orthopaedic Surgery, Brown University, Providence, Rhode Island, USA
j Department of Orthopaedic Surgery, University of California, Davis, Sacramento, California, USA
k Department of Neurosurgery, University of Virginia, Charlottesville, Virginia, USA
l Department of Orthopaedic Surgery, Oregon Health and Science University, Portland, Oregon, USA

Objective: To report the outcome of adult spinal deformity (ASD) in patients with rod fracture (RF) after thoracolumbar fusion. Methods: Retrospective review of prospective, multicenter database. Operative patients with ASD ≥18 years old with RF after ASD surgery and with a minimum 6-month follow-up after RF were included. Health-related quality of life scores and radiographic alignment were compared with nonparametric paired and independent testing (P < 0.05). Results: A total of 51 of 343 patients with ASD (14.9%) sustained a RF, of whom 44 (86.3%) had at least 6-month follow up after RF (mean age = 61.2 years, mean body mass index = 29.6 kg/m2). Mean total follow-up was 37.8 months (range 24.5-66.7 months). Interbody fusion was used in 26 cases of RF (59.1%) (transforaminal lumbar interbody fusion, n = 17 [65.4%], anterior lumbar interbody fusion, n = 5 [19.2%]). RF was symptomatic in 26 of 44 (59.1%) of patients and discovered incidentally in 18 of 44 patients (40.9%). Overall, 28 RFs were revised (63.6%); 12 of 23 (52.2%) unilateral RF and 16 of 21 (76.2%) bilateral RF at last follow-up. Revision patients were significantly more likely to be symptomatic at the time of RF detection (78.6% vs. 25.0%, P = 0.0006), and had significantly worse Oswestry Disability Index and Scoliosis Research Society-22r pain scores. Conclusions: RFs were detected in 14.9% of patients with ASD and were most common at the L4-L5 and L5-S1 levels. Approximately 63.6% of patients underwent revision surgery. The decision to perform revision surgery may be based predominantly on symptoms referable to the RF, pain, and perceived disability, as radiographic parameters at the time of RF did not differ significantly between patients who did and did not undergo revision. © 2017 Elsevier Inc.

Author Keywords
Adult spinal deformity;  Health-related quality of life;  Oswestry Disability Index;  Pedicle subtraction osteotomy;  Revision;  Rod fracture

Document Type: Article in Press
Source: Scopus



Weller, M., Butowski, N., Tran, D.D., Recht, L.D., Lim, M., Hirte, H., Ashby, L., Mechtler, L., Goldlust, S.A., Iwamoto, F., Drappatz, J., O'Rourke, D.M., Wong, M., Hamilton, M.G., Finocchiaro, G., Perry, J., Wick, W., Green, J., He, Y., Turner, C.D., Yellin, M.J., Keler, T., Davis, T.A., Stupp, R., Sampson, J.H.
Rindopepimut with temozolomide for patients with newly diagnosed, EGFRvIII-expressing glioblastoma (ACT IV): A randomised, double-blind, international phase 3 trial
(2017) The Lancet Oncology, . Article in Press. 

DOI: 10.1016/S1470-2045(17)30517-X

a Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland
b Department of Oncology, University Hospital and University of Zurich, Zurich, Switzerland
c Department of Neurological Surgery, University of California, San Francisco, CA, USA
d Washington University, St Louis, MO, USA
e Stanford University Medical Center, Palo Alto, CA, USA
f The Johns Hopkins Hospital, Baltimore, MD, USA
g Juravinski Cancer Centre, Hamilton, ON, Canada
h Barrow Neurological Institute, Phoenix, AZ, USA
i DENT Neurologic Institute, Buffalo, NY, USA
j John Theurer Cancer Center, Hackensack, NJ, USA
k Columbia University Medical Center, New York, NY, USA
l University of Pittsburgh Medical Center, Pittsburgh, PA, USA
m Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
n Westmead Hospital, Westmead, NSW, Australia
o University of Calgary, Department of Clinical Neurosciences, Division of Neurosurgery, Foothills Hospital, Calgary, AB, Canada
p Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy
q Sunnybrook Health Sciences Centre, Toronto, ON, Canada
r The University of Heidelberg and German Cancer Research Center, Heidelberg, Germany
s Celldex Therapeutics, Inc, Hampton, NJ, USA
t The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA

Background: Rindopepimut (also known as CDX-110), a vaccine targeting the EGFR deletion mutation EGFRvIII, consists of an EGFRvIII-specific peptide conjugated to keyhole limpet haemocyanin. In the ACT IV study, we aimed to assess whether or not the addition of rindopepimut to standard chemotherapy is able to improve survival in patients with EGFRvIII-positive glioblastoma. Methods: In this randomised, double-blind, phase 3 trial, we recruited patients aged 18 years and older with glioblastoma from 165 hospitals in 22 countries. Eligible patients had newly diagnosed glioblastoma confirmed to express EGFRvIII by central analysis, and had undergone maximal surgical resection and completion of standard chemoradiation without progression. Patients were stratified by European Organisation for Research and Treatment of Cancer recursive partitioning analysis class, MGMT promoter methylation, and geographical region, and randomly assigned (1:1) with a prespecified randomisation sequence (block size of four) to receive rindopepimut (500 μg admixed with 150 μg GM-CSF) or control (100 μg keyhole limpet haemocyanin) via monthly intradermal injection until progression or intolerance, concurrent with standard oral temozolomide (150-200 mg/m2 for 5 of 28 days) for 6-12 cycles or longer. Patients, investigators, and the trial funder were masked to treatment allocation. The primary endpoint was overall survival in patients with minimal residual disease (MRD; enhancing tumour <2 cm2 post-chemoradiation by central review), analysed by modified intention to treat. This trial is registered with, number NCT01480479. Findings: Between April 12, 2012, and Dec 15, 2014, 745 patients were enrolled (405 with MRD, 338 with significant residual disease [SRD], and two unevaluable) and randomly assigned to rindopepimut and temozolomide (n=371) or control and temozolomide (n=374). The study was terminated for futility after a preplanned interim analysis. At final analysis, there was no significant difference in overall survival for patients with MRD: median overall survival was 20·1 months (95% CI 18·5-22·1) in the rindopepimut group versus 20·0 months (18·1-21·9) in the control group (HR 1·01, 95% CI 0·79-1·30; p=0·93). The most common grade 3-4 adverse events for all 369 treated patients in the rindopepimut group versus 372 treated patients in the control group were: thrombocytopenia (32 [9%] vs 23 [6%]), fatigue (six [2%] vs 19 [5%]), brain oedema (eight [2%] vs 11 [3%]), seizure (nine [2%] vs eight [2%]), and headache (six [2%] vs ten [3%]). Serious adverse events included seizure (18 [5%] vs 22 [6%]) and brain oedema (seven [2%] vs 12 [3%]). 16 deaths in the study were caused by adverse events (nine [4%] in the rindopepimut group and seven [3%] in the control group), of which one-a pulmonary embolism in a 64-year-old male patient after 11 months of treatment-was assessed as potentially related to rindopepimut. Interpretation: Rindopepimut did not increase survival in patients with newly diagnosed glioblastoma. Combination approaches potentially including rindopepimut might be required to show efficacy of immunotherapy in glioblastoma. Funding: Celldex Therapeutics, Inc. © 2017 Elsevier Ltd.

Document Type: Article in Press
Source: Scopus



Vogel, A.C., Gutmann, D.H., Morris, S.M.
Neurodevelopmental disorders in children with neurofibromatosis type 1
(2017) Developmental Medicine and Child Neurology, . Article in Press. 

DOI: 10.1111/dmcn.13526

a Departments of Psychiatry Washington University School of Medicine St. Louis, MO USA
b Department of Neurology Washington University School of Medicine St. Louis, MO USA

Over the past several decades, neurofibromatosis type 1 (NF1) has become increasingly recognized as a neurodevelopmental disorder conferring increased risk for several important neurodevelopmental problems. In this review, we summarize the specific neurodevelopmental problems encountered in the context of NF1. These include impairments in general cognitive function, deficits in specific cognitive domains such as executive function and visuospatial processing and risk for specific learning disorders, impairments in attention and social skills and the overlap with attention-deficit-hyperactivity disorder and autism spectrum disorder, and the risk of developing other psychiatric conditions including anxiety and depression. Early recognition of these developmental impairments is important for the effective treatment of children with NF1, and further characterization is essential to improve our understanding of how mutations in the NF1 gene create the diversity of clinical neuropsychiatric symptomatology observed in this at-risk population. © 2017 Mac Keith Press.

Document Type: Article in Press
Source: Scopus



Weston, S.J., Cox, K.S., Condon, D.M., Jackson, J.J.
A Comparison of Human Narrative Coding of Redemption and Automated Linguistic Analysis for Understanding Life Stories
(2016) Journal of Personality, 84 (5), pp. 594-606. 

DOI: 10.1111/jopy.12183

a Washington University in St. Louis, United States
b Medical University of South Carolina, United States
c Northwestern University, United States

The majority of life narrative research is performed using trained human coders. In contrast, automated linguistic analysis is oft employed in the study of verbal behaviors. These two methodological approaches are directly compared to determine the utility of automated linguistic analysis for the study of life narratives. In a study of in-person interviews (N = 158) and a second study of life stories collected online (N = 242), redemption scores are compared to the output of the Linguistic Inquiry and Word Count (Pennebaker, Francis & Booth, 2001). Additionally, patterns of language are found using exploratory principal components analysis. In both studies, redemption scores are modestly correlated with some LIWC categories and unassociated with the components. Patterns of language do not replicate across samples, indicating that the structure of language does not extend to a broader population. Redemption scores and linguistic components are independent predictors of life satisfaction up to 3 years later. These studies converge on the finding that human-coded redemption and automated linguistic analysis are complementary and nonredundant methods of analyzing life narratives, and considerations for the study of life narratives are discussed. © 2015 Wiley Periodicals, Inc.

Document Type: Article
Source: Scopus



Buchholz, K.R., Bruce, S.E., Koucky, E.M., Artime, T.M., Wojtalik, J.A., Brown, W.J., Sheline, Y.I.
Neural Correlates of Trait Rumination During an Emotion Interference Task in Women With PTSD
(2016) Journal of Traumatic Stress, 29 (4), pp. 317-324. 

DOI: 10.1002/jts.22112

a Department of Psychology, University of Missouri-St. Louis, St. Louis, MO, United States
b Department of Psychiatry, Washington University School of Medicine in St. Louis, St. Louis, MO, United States

Rumination, defined as repetitive, negative, self-focused thinking, is hypothesized to be a transdiagnostic factor that is associated with depression, anxiety, and posttraumatic stress disorder (PTSD). Theory has suggested that in individuals with PTSD, rumination serves as a cognitive avoidance factor that contributes to the maintenance of symptoms by inhibiting the cognitive and emotional processing of the traumatic event, subsequently interfering with treatment engagement and outcome. Little is known about the neural correlates of rumination in women with PTSD. The current study utilized functional magnetic resonance imaging (fMRI) to examine neural correlates during an emotion interference task of self-reported rumination in women with PTSD. Women with PTSD (39 participants) were recruited at a university-based trauma clinic and completed a clinical evaluation that included measures of PTSD symptoms, rumination, and depressive symptoms, as well as a neuroimaging session in which the participants were administered an emotion interference task. There was a significant relationship between self-reported rumination and activity in the right orbital frontal cortex, BA 11; t(37) = 5.62, p =.004, k = 46 during the task. This finding suggested that women with PTSD, who had higher levels of rumination, may experience greater difficulty inhibiting negative emotional stimuli compared to women with lower levels of rumination. Copyright © 2016 International Society for Traumatic Stress Studies

Document Type: Article
Source: Scopus



Iacovino, J.M., Bogdan, R., Oltmanns, T.F.
Personality Predicts Health Declines Through Stressful Life Events During Late Mid-Life
(2016) Journal of Personality, 84 (4), pp. 536-546. Cited 5 times.

DOI: 10.1111/jopy.12179

Washington University in St. Louis, United States

Personality predicts the occurrence of dependent stressful life events (SLE; i.e., events reliant, at least in part, on an individual's behavior). This process, termed stress generation, contributes to psychiatric outcomes, but its role in physical health is unknown. Data were included from 998 participants (aged 55–64) in the St. Louis Personality and Aging Network (SPAN) study. Assessments occurred every 6 months for 18 months. Neuroticism, impulsivity, and agreeableness were measured with the Revised NEO Personality Inventory. Dependent (e.g., divorce) and independent (e.g., family death) SLE occurring within 6 months following baseline were assessed with the List of Threatening Experiences and confirmed by interviews. Health problems occurring within a year after SLE were the outcome. Analyses examined whether neuroticism, impulsivity, and agreeableness indirectly predict the onset of new health problems through exposure to dependent SLE. Each personality trait was associated with dependent, but not independent, SLE. Only dependent SLE predicted new health problems. Each personality trait indirectly predicted the onset of new health problems through dependent SLE. Findings suggest that personality-driven stress generation influences physical health during late mid-life. Addressing personality in interventions may reduce the occurrence of SLE, in turn decreasing health risks. © 2015 Wiley Periodicals, Inc.

Document Type: Article
Source: Scopus



Greene, D.J., Church, J.A., Dosenbach, N.U.F., Nielsen, A.N., Adeyemo, B., Nardos, B., Petersen, S.E., Black, K.J., Schlaggar, B.L.
Multivariate pattern classification of pediatric Tourette syndrome using functional connectivity MRI
(2016) Developmental Science, 19 (4), pp. 581-598. Cited 10 times.

DOI: 10.1111/desc.12407

a Department of Psychiatry, Washington University School of Medicine, United States
b Department of Radiology, Washington University School of Medicine, United States
c Department of Neurology, Washington University School of Medicine, United States
d Department of Neuroscience, Washington University School of Medicine, United States
e Department of Pediatrics, Washington University School of Medicine, United States
f Department of Psychology, The University of Texas at Austin, United States

Tourette syndrome (TS) is a developmental neuropsychiatric disorder characterized by motor and vocal tics. Individuals with TS would benefit greatly from advances in prediction of symptom timecourse and treatment effectiveness. As a first step, we applied a multivariate method – support vector machine (SVM) classification – to test whether patterns in brain network activity, measured with resting state functional connectivity (RSFC) MRI, could predict diagnostic group membership for individuals. RSFC data from 42 children with TS (8–15 yrs) and 42 unaffected controls (age, IQ, in-scanner movement matched) were included. While univariate tests identified no significant group differences, SVM classified group membership with ~70% accuracy (p < .001). We also report a novel adaptation of SVM binary classification that, in addition to an overall accuracy rate for the SVM, provides a confidence measure for the accurate classification of each individual. Our results support the contention that multivariate methods can better capture the complexity of some brain disorders, and hold promise for predicting prognosis and treatment outcome for individuals with TS. © 2016 The Authors. Developmental Science Published by John Wiley & Sons Ltd.

Document Type: Article
Source: Scopus



Olin, L.
Burge on perception and sensation
(2016) Synthese, 193 (5), pp. 1479-1508. 

DOI: 10.1007/s11229-014-0531-1

Philosophy-Neuroscience-Psychology Program, Department of Philosophy, Washington University in Saint Louis, St Louis, MO, United States

In Origins of Objectivity Burge advances a theory of perception according to which perceptions are, themselves, objective representations. The possession of veridicality conditions by perceptual states—roughly, non-propositional analogues of truth-conditions—is central to Burge’s account of how perceptual states differ, empirically and metaphysically, from sensory states. Despite an impressive examination of the relevant empirical literatures, I argue here that Burge has not succeeded in securing a distinction between perception and “mere” sensation. © 2014, Springer Science+Business Media Dordrecht.

Author Keywords
Burge;  Perception;  Perceptual constancy;  Psychology;  Representation;  Sensation

Document Type: Article
Source: Scopus


September 4, 2017 


DeJesus, J.M., Hwang, H.G., Dautel, J.B., Kinzler, K.D.
Bilingual children's social preferences hinge on accent
(2017) Journal of Experimental Child Psychology, 164, pp. 178-191. 

DOI: 10.1016/j.jecp.2017.07.005

a Department of Psychology, Department of Pediatrics, University of Michigan, Ann Arbor, MI, United States
b Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, MO, United States
c School of Psychology, Queens University Belfast, Belfast, United Kingdom
d Department of Psychology, Cornell University, Ithaca, NY, United States

Past research finds that monolingual and bilingual children prefer native speakers to individuals who speak in unfamiliar foreign languages or accents. Do children in bilingual contexts socially distinguish among familiar languages and accents and, if so, how do their social preferences based on language and accent compare? The current experiments tested whether 5- to 7-year-olds in two bilingual contexts in the United States demonstrate social preferences among the languages and accents that are present in their social environments. We compared children's preferences based on language (i.e., English vs. their other native language) and their preferences based on accent (i.e., English with a native accent vs. English with a non-native [yet familiar] accent). In Experiment 1, children attending a French immersion school demonstrated no preference between English and French speakers but preferred American-accented English to French-accented English. In Experiment 2, bilingual Korean American children demonstrated no preference between English and Korean speakers but preferred American-accented English to Korean-accented English. Across studies, bilingual children's preferences based on accent (i.e., American-accented English over French- or Korean-accented English) were not related to their own language dominance. These results suggest that children from diverse linguistic backgrounds demonstrate social preferences for native-accented speakers. Implications for understanding the potential relation between social reasoning and language acquisition are discussed. © 2017 Elsevier Inc.

Author Keywords
Accent attitudes;  Bilingualism;  Cognitive development;  Language;  Social cognition;  Social preferences

Document Type: Article
Source: Scopus



Dougherty, J.D.
Generation and characterization of a mouse line for monitoring translation in dopaminergic neurons
(2017) Scientific Reports, 7 (1), art. no. 8117, . 

DOI: 10.1038/s41598-017-08618-2

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

We developed a mouse line targeting midbrain dopamine neurons for Translating Ribosome Affinity Purification(TRAP). Here, we briefly report on the basic characterization of this mouse line including confirmation of expression of the transgene in midbrain dopamine neurons and validation of its effectiveness in capturing mRNA from these cells. We also report a translational profile of these neurons which may be of use to investigators studying the gene expression of these cells. Finally, we have provided the line to Jackson Laboratories for distribution and use in future studies. © 2017 The Author(s).

Document Type: Article
Source: Scopus



Aum, D.J., Vellimana, A.K., Singh, I., Milner, E., Nelson, J.W., Han, B.H., Zipfel, G.J.
A novel fluorescent imaging technique for assessment of cerebral vasospasm after experimental subarachnoid hemorrhage
(2017) Scientific Reports, 7 (1), art. no. 9126, . 

DOI: 10.1038/s41598-017-09070-y

a Department of Neurological Surgery, 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 Pharmacology, A.T. Still University of Health Sciences, Kirksville, MO, United States

Various techniques have been developed to study changes in the cerebral vasculature in numerous neuropathological processes including subarachnoid hemorrhage (SAH). One of the most widely employed techniques uses India ink-gelatin casting, which presents numerous challenges due to its high viscosity, rapid solidification, and its impact on immunohistochemical analysis. To overcome these limitations, we developed a novel technique for assessing cerebral vasospasm using cerebrovascular perfusion with ROX, SE (5-Carboxy-X-Rhodamine, Succinimidyl Ester), a fluorescent labeling dye. We found that ROX SE perfusion achieves excellent delineation of the cerebral vasculature, was qualitatively and quantitatively superior to India ink-gelatin casting for the assessment of cerebral vasospasm, permits outstanding immunohistochemical examination of non-vasospasm components of secondary brain injury, and is a more efficient and cost-effective experimental technique. ROX SE perfusion is therefore a novel and highly useful technique for studying cerebrovascular pathology following experimental SAH. © 2017 The Author(s).

Document Type: Article
Source: Scopus



Singanamalli, A., Wang, H., Madabhushi, A., Weiner, M., Aisen, P., Petersen, R., Jack, C., Jagust, W., Trojanowki, J., Toga, A., Beckett, L., Green, R., Saykin, A., Morris, J., Shaw, L., Kaye, J., Quinn, J., Silbert, L., Lind, B., Carter, R., Dolen, S., Schneider, L., Pawluczyk, S., Beccera, M., Teodoro, L., Spann, B., Brewer, J., Vanderswag, H., Fleisher, A., Heidebrink, J., Lord, J., Mason, S., Albers, C., Knopman, D., Johnson, K., Doody, R., Villanueva-Meyer, J., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L., Bell, K., Ances, B., Carroll, M., Creech, M., Franklin, E., Mintun, M., Schneider, S., Oliver, A., Marson, D., Griffith, R., Clark, D., Geldmacher, D., Brockington, J., Roberson, E., Natelson Love, M., Grossman, H., Mitsis, E., Shah, R., Detoledo-Morrell, L., Duara, R., Varon, D., Greig, M., Roberts, P., Albert, M., Onyike, C., D'Agostino, D., Kielb, S., Galvin, J., Cerbone, B., Michel, C., Pogorelec, D., Rusinek, H., De Leon, M., Glodzik, L., De Santi, S., Doraiswamy, P., Petrella, J., Borges-Neto, S., Wong, T., Coleman, E., Smith, C., Jicha, G., Hardy, P., Sinha, P., Oates, E., Conrad, G., Porsteinsson, A., Goldstein, B., Martin, K., Makino, K., Ismail, M., Brand, C., Mulnard, R., Thai, G., Mc-Adams-Ortiz, C., Womack, K., Mathews, D., Quiceno, M., Levey, A., Lah, J., Cellar, J., Burns, J., Swerdlow, R., Brooks, W., Apostolova, L., Tingus, K., Woo, E., Silverman, D., Lu, P., Bartzokis, G., Graff-Radford, N., Parfitt, F., Kendall, T., Johnson, H., Farlow, M., Marie Hake, A., Matthews, B., Brosch, J., Herring, S., Hunt, C., Dyck, C., Carson, R., MacAvoy, M., Varma, P., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Caldwell, C., Robin Hsiung, G.-Y., Feldman, H., Mudge, B., Assaly, M., Finger, E., Pasternack, S., Rachisky, I., Trost, D., Kertesz, A., Bernick, C., Munic, D., Mesulam, M.-M., Lipowski, K., Weintraub, S., Bonakdarpour, B., Kerwin, D., Wu, C.-K., Johnson, N., Sadowsky, C., Villena, T., Scott Turner, R., Johnson, K., Reynolds, B., Sperling, R., Johnson, K., Marshall, G., Yesavage, J., Taylor, J., Lane, B., Rosen, A., Tinklenberg, J., Sabbagh, M., Belden, C., Jacobson, S., Sirrel, S., Kowall, N., Killiany, R., Budson, A., Norbash, A., Lynn Johnson, P., Obisesan, T., Wolday, S., Allard, J., Lerner, A., Ogrocki, P., Tatsuoka, C., Fatica, P., Fletcher, E., Maillard, P., Olichney, J., Decarli, C., Carmichael, O., Kittur, S., Borrie, M., Lee, T.-Y., Robbartha, Johnson, S., Asthana, S., Carlsson, C., Potkin, S., Preda, A., Nguyen, D., Tariot, P., Burke, A., Trncic, N., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D., Kataki, M., Adeli, A., Zimmerman, E., Celmins, D., Brown, A., Pearlson, G., Blank, K., Anderson, K., Flashman, L., Seltzer, M., Hynes, M., Santulli, R., Sink, K., Gordineer, L., Williamson, J., Garg, P., Watkins, F., Ott, B., Querfurth, H., Tremont, G., Salloway, S., Malloy, P., Correia, S., Rosen, H., Miller, B., Perry, D., Mintzer, J., Spicer, K., Bachman, D., Pomara, N., Hernando, R., Sarrael, A., Relkin, N., Chaing, G., Lin, M., Ravdin, L., Smith, A., Ashok Raj, B., Fargher, K.
Cascaded Multi-view Canonical Correlation (CaMCCo) for Early Diagnosis of Alzheimer's Disease via Fusion of Clinical, Imaging and Omic Features
(2017) Scientific Reports, 7 (1), art. no. 8137, . 

DOI: 10.1038/s41598-017-03925-0

a Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States
b Magnetic Resonance Unit at the VA Medical Center and Radiology Medicine, Psychiatry and Neurology, University of California, San Francisco, United States
c San Diego School of Medicine, University of CaliforniaCA, United States
d Mayo ClinicMN, United States
e Mayo Clinic, Rochester, United States
f University of California, Berkeley, United States
g University of PennsylvaniaPA, United States
h University of Southern CaliforniaCA, United States
i University of California, Davis, CA, United States
j MPH Brigham and Women's Hospital/Harvard Medical SchoolMA, United States
k Indiana UniversityIN, United States
l Washington University St. LouisMO, United States
m Oregon Health and Science University, Oregon, United States
n University of California-San Diego, California, United States
o University of Michigan, Michigan, United States
p Baylor College of Medicine, Houston, TX, United States
q Columbia University Medical CenterSC, United States
r University of Alabama - Birmingham, Alabama, United States
s Mount Sinai School of Medicine, New York, United States
t Rush University Medical Center, Rush UniversityIL, United States
u Wien Center, Florida, United States
v Johns Hopkins University, Maryland, United States
w New York UniversityNY, United States
x Duke University Medical Center, North Carolina, United States
y University of Kentucky, Kentucky, United States
z University of Rochester Medical CenterNY, United States
aa University of California, Irvine, CA, United States
ab University of Texas Southwestern Medical SchoolTX, United States
ac Emory UniversityGA, United States
ad University of Kansas, Medical Center, Kansas, United States
ae University of California, Los Angeles, California, United States
af Mayo Clinic, Jacksonville, United States
ag Yale University School of MedicineCT, United States
ah McGill University, Montreal-Jewish General Hospital, Montreal, Canada
ai Sunnybrook Health SciencesON, United States
aj U.B.C. Clinic for AD and Related Disorders, Vancouver, BC, Canada
ak Cognitive Neurology-St. Joseph'sON, United States
al Cleveland Clinic Lou Ruvo Center for Brain HealthOH, United States
am Northwestern University, San Francisco, United States
an Premiere Research Inst (Palm Beach Neurology), west Palm Beach, United States
ao Georgetown University Medical Center, Washington, DC, United States
ap Brigham and Women's HospitalMA, United States
aq Stanford University, California, United States
ar Banner Sun Health Research Institute, Sun City, AZ, United States
as Boston UniversityMA, United States
at Howard University, Washington, DC, United States
au Case Western Reserve University, Ohio, United States
av University of California, Davis - Sacramento, CA, United States
aw Neurological Care of CNY, Liverpool, NY, United States
ax Parkwood Hospital, Pennsylvania, United States
ay University of WisconsinWI, United States
az University of California, Irvine-BIC, United States
ba Banner Alzheimer's Institute, Phoenix, AZ, United States
bb Dent Neurologic InstituteNY, United States
bc Ohio State University, Ohio, United States
bd Albany Medical CollegeNY, United States
be Hartford Hospital, Olin Neuropsychiatry Research CenterCT, United States
bf Dartmouth-Hitchcock Medical Center, New Hampshire, United States
bg Wake Forest University Health Sciences, North Carolina, United States
bh Rhode Island Hospital, State of Rhode Island, Providence, RI, United States
bi Butler Hospital, Providence, RI, United States
bj University of California, San Francisco, United States
bk Medical University South Carolina, Charleston, SC, United States
bl Nathan Kline Institute, Orangeburg, NY, United States
bm Cornell University, Ithaca, NY, United States
bn USF Health Byrd Alzheimer's Institute, University of South Florida, Tampa, FL, United States

The introduction of mild cognitive impairment (MCI) as a diagnostic category adds to the challenges of diagnosing Alzheimer's Disease (AD). No single marker has been proven to accurately categorize patients into their respective diagnostic groups. Thus, previous studies have attempted to develop fused predictors of AD and MCI. These studies have two main limitations. Most do not simultaneously consider all diagnostic categories and provide suboptimal fused representations using the same set of modalities for prediction of all classes. In this work, we present a combined framework, cascaded multiview canonical correlation (CaMCCo), for fusion and cascaded classification that incorporates all diagnostic categories and optimizes classification by selectively combining a subset of modalities at each level of the cascade. CaMCCo is evaluated on a data cohort comprising 149 patients for whom neurophysiological, neuroimaging, proteomic and genomic data were available. Results suggest that fusion of select modalities for each classification task outperforms (mean AUC = 0.92) fusion of all modalities (mean AUC = 0.54) and individual modalities (mean AUC = 0.90, 0.53, 0.71, 0.73, 0.62, 0.68). In addition, CaMCCo outperforms all other multi-class classification methods for MCI prediction (PPV: 0.80 vs. 0.67, 0.63). © 2017 The Author(s).

Document Type: Article
Source: Scopus



Dosenbach, N.U.F., Koller, J.M., Earl, E.A., Miranda-Dominguez, O., Klein, R.L., Van, A.N., Snyder, A.Z., Nagel, B.J., Nigg, J.T., Nguyen, A.L., Wesevich, V., Greene, D.J., Fair, D.A.
Real-time motion analytics during brain MRI improve data quality and reduce costs
(2017) NeuroImage, 161, pp. 80-93. 

DOI: 10.1016/j.neuroimage.2017.08.025

a Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
b Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, United States
c Program in Occupational Therapy, Washington University, St. Louis, MO, United States
d Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
e Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, United States
f Department of Psychiatry, Oregon Health & Science University, Portland, OR, United States
g Department of Radiology, Washington University School of Medicine, St. Louis, MO, United States
h Advanced Imaging Research Center, Oregon Health & Science University, Portland, OR, United States

Head motion systematically distorts clinical and research MRI data. Motion artifacts have biased findings from many structural and functional brain MRI studies. An effective way to remove motion artifacts is to exclude MRI data frames affected by head motion. However, such post-hoc frame censoring can lead to data loss rates of 50% or more in our pediatric patient cohorts. Hence, many scanner operators collect additional ‘buffer data’, an expensive practice that, by itself, does not guarantee sufficient high-quality MRI data for a given participant. Therefore, we developed an easy-to-setup, easy-to-use Framewise Integrated Real-time MRI Monitoring (FIRMM) software suite that provides scanner operators with head motion analytics in real-time, allowing them to scan each subject until the desired amount of low-movement data has been collected. Our analyses show that using FIRMM to identify the ideal scan time for each person can reduce total brain MRI scan times and associated costs by 50% or more. © 2017 The Authors

Author Keywords
Functional MRI;  Head motion distortion;  MRI acquisition;  MRI methods;  Real-time quality control;  Resting state functional connectivity MRI;  Structural MRI

Document Type: Article
Source: Scopus



Mishra, S., Gordon, B.A., Su, Y., Christensen, J., Friedrichsen, K., Jackson, K., Hornbeck, R., Balota, D.A., Cairns, N.J., Morris, J.C., Ances, B.M., Benzinger, T.L.S.
AV-1451 PET imaging of tau pathology in preclinical Alzheimer disease: Defining a summary measure
(2017) NeuroImage, 161, pp. 171-178. 

DOI: 10.1016/j.neuroimage.2017.07.050

a Department of Radiology, Washington University in St. Louis, School of Medicine, 510 S. Kingshighway, MC 8131, Saint Louis, MO, United States
b Knight Alzheimer's Disease Research Center, Washington University in St. Louis, School of Medicine, 510 S. Kingshighway, MC 8131, Saint Louis, MO, United States
c Department of Psychological and Brain Sciences, Washington University in St. Louis, School of Medicine, 510 S. Kingshighway, MC 8131, Saint Louis, MO, United States
d Department of Neurology, Washington University in St. Louis, School of Medicine, 510 S. Kingshighway, MC 8131, Saint Louis, MO, United States
e Department of Pathology & Immunology, Washington University in St. Louis, School of Medicine, 510 S. Kingshighway, MC 8131, Saint Louis, MO, United States
f Department of Neurological Surgery, Washington University in St. Louis, School of Medicine, 510 S. Kingshighway, MC 8131, Saint Louis, MO, United States

Utilizing [18F]-AV-1451 tau positron emission tomography (PET) as an Alzheimer disease (AD) biomarker will require identification of brain regions that are most important in detecting elevated tau pathology in preclinical AD. Here, we utilized an unsupervised learning, data-driven approach to identify brain regions whose tau PET is most informative in discriminating low and high levels of [18F]-AV-1451 binding. 84 cognitively normal participants who had undergone AV-1451 PET imaging were used in a sparse k-means clustering with resampling analysis to identify the regions most informative in dividing a cognitively normal population into high tau and low tau groups. The highest-weighted FreeSurfer regions of interest (ROIs) separating these groups were the entorhinal cortex, amygdala, lateral occipital cortex, and inferior temporal cortex, and an average SUVR in these four ROIs was used as a summary metric for AV-1451 uptake. We propose an AV-1451 SUVR cut-off of 1.25 to define high tau as described by imaging. This spatial distribution of tau PET is a more widespread pattern than that predicted by pathological staging schemes. Our data-derived metric was validated first in this cognitively normal cohort by correlating with early measures of cognitive dysfunction, and with disease progression as measured by β-amyloid PET imaging. We additionally validated this summary metric in a cohort of 13 Alzheimer disease patients, and showed that this measure correlates with cognitive dysfunction and β-amyloid PET imaging in a diseased population. © 2017 Elsevier Inc.

Document Type: Article
Source: Scopus



Hulvershorn, L.A., King, J., Monahan, P.O., Wilcox, H.C., Mitchell, P.B., Fullerton, J.M., Edenberg, H.J., Roberts, G.M.P., Kamali, M., Glowinski, A.L., Ghaziuddin, N., McInnis, M., Iyer-Eimerbrink, P.A., Nurnberger, J.I., Jr.
Substance use disorders in adolescent and young adult relatives of probands with bipolar disorder: What drives the increased risk?
(2017) Comprehensive Psychiatry, 78, pp. 130-139. 

DOI: 10.1016/j.comppsych.2017.07.010

a Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, United States
b Department of Biostatistics, Indiana University School of Medicine IndianapolisIN, United States
c Johns Hopkins Schools of Medicine and Public Health, Baltimore, MD, United States
d School of Psychiatry, University of New South Wales, Black Dog Institute, Sydney, Australia
e Neuroscience Research Australia & School of Medical Sciences, University of New South Wales, Sydney, Australia
f Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, United States
g Department of Psychiatry and Depression Center, University of Michigan, Ann Arbor, MI, United States
h Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
i Sociology and Psychology Department, University of North Texas at Dallas, Dallas, TX, United States
j Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, United States
k Department of Psychiatry, Massachusetts General Hospital and Harvard University, Boston, MA, United States
l Child and Adolescent Psychiatry, Depression Center, University of Michigan, Ann Arbor, MI, United States

Background Adults with bipolar disorder (BD) have higher rates of substance use disorders (SUDs) compared to the general population. SUD rates in young offspring/relatives of BD probands, as well as factors which drive those rates, are not as well-characterized. Methods We aimed to examine SUD prevalence among adolescent/young adult offspring and relatives of probands with and without BD. Data were collected from five sites in the US and Australia during 2006–2011. Youth offspring/relatives (“Relatives of BD probands;” n = 267; mean age = 16.8 years; ± 2.9 S.D.), identified through a proband family member with DSM-IV BD (Type I or II), were compared to offspring/relatives of control probands (“relatives of control probands;” n = 149; mean age = 17.4 years; ± 2.9 S.D.). Logistic regression with generalized estimating equations was used to compare the groups across a range of substance use and SUD variables. Odds ratios were calculated for lifetime prevalence of substance outcomes. Results Bivariate analyses showed DSM-IV SUDs were more prevalent among relatives of BD probands than among relatives of control probands (29% vs. 18%; p = 0.01). Generalized estimating equation models showed BD mood and childhood-onset externalizing disorders in adolescent and young adult relatives to each significantly increase the odds (OR = 2.80–3.17; p < 0.02) for the development of several substance variables among all relatives, whereas the risk of SUDs in relatives was not increased when the relatives had no mood or externalizing disorders themselves. Conclusion Relatives of BD probands with lifetime mood and externalizing disorders report more substance use/SUDs than relatives of control probands. In contrast, SUD outcomes in relatives of BD probands without mood or externalizing disorders were no different from control relatives without psychopathology. Early recognition and treatment of psychiatric disorders may lead to less substance use in this highly vulnerable population. © 2017 Elsevier Inc.

Document Type: Article
Source: Scopus



Pearson, T.S., Helbig, I.
Epileptic encephalopathy, movement disorder, and the yin and yang of GNAO1 function
(2017) Neurology, 89 (8), pp. 754-755. 

DOI: 10.1212/WNL.0000000000004277

a Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
b Division of Neurology, Children's Hospital of PhiladelphiaPA, United States

Document Type: Editorial
Source: Scopus



Hassanzadeh, C., Rao, Y.J., Chundury, A., Rowe, J., Ponisio, M.R., Sharma, A., Miller-Thomas, M., Tsien, C.I., Ippolito, J.E.
Multiparametric MRI and [18F] fluorodeoxyglucose positron emission tomography imaging is a potential prognostic imaging biomarker in recurrent glioblastoma
(2017) Frontiers in Oncology, 7 (AUG), art. no. 178, . 

DOI: 10.3389/fonc.2017.00178

a Department of Radiation Oncology, Washington University in St. Louis, St. Louis, MO, United States
b Department of Genetics, Washington University in St. Louis, St. Louis, MO, United States
c Mallinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, MO, United States
d Department of Radiology, Mayo Clinic Florida, Jacksonville, FL, United States

Purpose/objectives: Multiparametric advanced MR and [18F]fluorodeoxyglucose (FDG)-positron emission tomography (PET) imaging may be important biomarkers for prognosis as well for distinguishing recurrent glioblastoma multiforme (GBM) from treatment- related changes. Methods/materials: We retrospectively evaluated 30 patients treated with chemoradiation for GBM and underwent advanced MR and FDG-PET for confirmation of tumor progression. Multiparametric MRI and FDG-PET imaging metrics were evaluated for their association with 6-month overall (OS) and progression-free survival (PFS) based on pathological, radiographic, and clinical criteria. results: 17 males and 13 females were treated between 2001 and 2014, and later underwent FDG-PET at suspected recurrence. Baseline FDG-PET and MRI imaging was obtained at a median of 7.5 months [interquartile range (IQR) 3.7-12.4] following completion of chemoradiation. Median follow-up after FDG-PET imaging was 10 months (IQR 7.2-13.0). Receiver-operator characteristic curve analysis identified that lesions characterized by a ratio of the SUVmax to the normal contralateral brain (SUVmax/NB index) &gt; 1.5 and mean apparent diffusion coefficient (ADC) value of =1,400 × 10-6 mm2/s correlated with worse 6-month OS and PFS. We defined three patient groups that predicted the probability of tumor progression: SUVmax/NB index &gt; 1.5 and ADC ≤1,400 × 10-6 mm2/s defined high-risk patients (n = 7), SUVmax/NB index ≤1.5 and ADC &gt; 1,400 × 10-6 mm2/s defined low-risk patients (n = 11), and intermediate-risk (n = 12) defined the remainder of the patients. Median OS following the time of the FDG-PET scan for the low, intermediate, and high-risk groups were 23.5, 10.5, and 3.8 months (p &lt; 0.01). Median PFS were 10.0, 4.4, and 1.9 months (p = 0.03). Rates of progression at 6-months in the low, intermediate, and high-risk groups were 36, 67, and 86% (p = 0.04). conclusion:Recurrent GBM in the molecular era is associated with highly variable outcomes. Multiparametric MR and FDG-PET biomarkers may provide a clinically relevant, non-invasive and cost-effective method of predicting prognosis and improving clinical decision making in the treatment of patients with suspected tumor recurrence. © 2017 Hassanzadeh, Rao, Chundury, Rowe, Ponisio, Sharma, Miller- Thomas, Tsien and Ippolito.

Author Keywords
Apparent diffusion coefficient;  Diffusion;  Glioblastoma;  MRI;  Radiation;  Radionecrosis;  [18F]fluorodeoxyglucose-positron emission tomography

Document Type: Article
Source: Scopus



Brody, D.L., Jiang, H., Wildburger, N., Esparza, T.J.
Non-canonical soluble amyloid-beta aggregates and plaque buffering: Controversies and future directions for target discovery in Alzheimer's disease
(2017) Alzheimer's Research and Therapy, 9 (1), art. no. 62, . 

DOI: 10.1186/s13195-017-0293-3

a Department of Neurology, Washington University School of Medicine, Box 8111 660 South Euclid Avenue, St Louis, MO, United States
b Hope Center for Neurological Disorders, Washington University, School of Medicine, Box 8111 660 South Euclid Avenue, St Louis, MO, United States

The specific amyloid-beta (Aβ) species or other amyloid-precursor protein cleavage products that are most directly related to human neurodegeneration and clinical dementia of the Alzheimer's type have not yet been directly identified. Without a clear understanding of the most relevant species, it is difficult to determine whether therapeutic candidates successfully engaged the correct target(s). Here, we review some of the controversies regarding soluble Aβ aggregates (also termed oligomers, dimers, trimers, Aβ56, amylospheroids, etc.) and propose experiments designed to move forward towards new therapeutic approaches. Specifically, we review the increasing evidence for the relevance of non-canonical forms of Aβ, the much more potent toxicity attributable to native species than to synthetic Aβ, and the evidence implicating the ratio of soluble Aβ aggregates to plaques in differentiating demented patients from non-demented high Aβ plaque pathology controls. To move forward, we propose four related directions. 1) Narrowing the focus to species derived from human Alzheimer's disease (AD) brain tissue, as opposed to synthetic Aβ, cell culture-derived species, or species primarily present in animal models. 2) Careful study of differences between patients with dementia of the Alzheimer's type vs. non-demented controls with high Aβ plaque pathology. This will involve testing the hypothesis that, under some circumstances, plaques may buffer soluble toxic species, but later release them into the surrounding milieu. 3) Investigations of other protein constituents of soluble Aβ aggregates in addition to Aβ itself. Our initial data based on chemical cleavage experiments indicate that other proteins do appear to be part of the human brain soluble Aβ aggregates. 4) Multimodal experimental assessments of toxicity, including longer term effects on synapse loss, related deleterious cellular responses, and degeneration in human-derived neuron-like cells. Overall, the goal is to identify specific Aβ species, other amyloid precursor protein cleavage products, or other key proteins in aggregates present in human AD brains, less abundant in non-demented high pathology control brains, and robustly toxic in a wide variety of relevant assays. These species themselves, the enzymatic or cellular processes involved in their production, and their routes of clearance would be highly relevant therapeutic targets for dementia of the Alzheimer's type. © 2017 The Author(s).

Author Keywords
Alzheimer's disease;  Amyloid-beta;  Buffering;  Chemical cleavage;  Dementia;  Neurotoxicity;  Oligomer;  Plaque

Document Type: Article
Source: Scopus



Ulland, T.K., Song, W.M., Huang, S.C.-C., Ulrich, J.D., Sergushichev, A., Beatty, W.L., Loboda, A.A., Zhou, Y., Cairns, N.J., Kambal, A., Loginicheva, E., Gilfillan, S., Cella, M., Virgin, H.W., Unanue, E.R., Wang, Y., Artyomov, M.N., Holtzman, D.M., Colonna, M.
TREM2 Maintains Microglial Metabolic Fitness in Alzheimer's Disease
(2017) Cell, 170 (4), pp. 649-663.e13. 

DOI: 10.1016/j.cell.2017.07.023

a Department of Pathology and Immunology, 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 Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, United States
d Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, United States
e Computer Technologies Department, ITMO University, Saint Petersburg, Russian Federation
f Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, United States

Elevated risk of developing Alzheimer's disease (AD) is associated with hypomorphic variants of TREM2, a surface receptor required for microglial responses to neurodegeneration, including proliferation, survival, clustering, and phagocytosis. How TREM2 promotes such diverse responses is unknown. Here, we find that microglia in AD patients carrying TREM2 risk variants and TREM2-deficient mice with AD-like pathology have abundant autophagic vesicles, as do TREM2-deficient macrophages under growth-factor limitation or endoplasmic reticulum (ER) stress. Combined metabolomics and RNA sequencing (RNA-seq) linked this anomalous autophagy to defective mammalian target of rapamycin (mTOR) signaling, which affects ATP levels and biosynthetic pathways. Metabolic derailment and autophagy were offset in vitro through Dectin-1, a receptor that elicits TREM2-like intracellular signals, and cyclocreatine, a creatine analog that can supply ATP. Dietary cyclocreatine tempered autophagy, restored microglial clustering around plaques, and decreased plaque-adjacent neuronal dystrophy in TREM2-deficient mice with amyloid-β pathology. Thus, TREM2 enables microglial responses during AD by sustaining cellular energetic and biosynthetic metabolism. © 2017 Elsevier Inc.

Author Keywords
Alzheimer's disease;  immunity;  metabolism;  microglia;  TREM2

Document Type: Article
Source: Scopus



Karimipanah, Y., Ma, Z., Wessel, R.
Criticality predicts maximum irregularity in recurrent networks of excitatory nodes
(2017) PLoS ONE, 12 (8), art. no. e0182501, . 

DOI: 10.1371/journal.pone.0182501

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

A rigorous understanding of brain dynamics and function requires a conceptual bridge between multiple levels of organization, including neural spiking and network-level population activity. Mounting evidence suggests that neural networks of cerebral cortex operate at a critical regime, which is defined as a transition point between two phases of short lasting and chaotic activity. However, despite the fact that criticality brings about certain functional advantages for information processing, its supporting evidence is still far from conclusive, as it has been mostly based on power law scaling of size and durations of cascades of activity. Moreover, to what degree such hypothesis could explain some fundamental features of neural activity is still largely unknown. One of the most prevalent features of cortical activity in vivo is known to be spike irregularity of spike trains, which is measured in terms of the coefficient of variation (CV) larger than one. Here, using a minimal computational model of excitatory nodes, we show that irregular spiking (CV > 1) naturally emerges in a recurrent network operating at criticality. More importantly, we show that even at the presence of other sources of spike irregularity, being at criticality maximizes the mean coefficient of variation of neurons, thereby maximizing their spike irregularity. Furthermore, we also show that such a maximized irregularity results in maximum correlation between neuronal firing rates and their corresponding spike irregularity (measured in terms of CV). On the one hand, using a model in the universality class of directed percolation, we propose new hallmarks of criticality at single-unit level, which could be applicable to any network of excitable nodes. On the other hand, given the controversy of the neural criticality hypothesis, we discuss the limitation of this approach to neural systems and to what degree they support the criticality hypothesis in real neural networks. Finally, we discuss the limitations of applying our results to real networks and to what degree they support the criticality hypothesis. © 2017 Karimipanah et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Document Type: Article
Source: Scopus



Van Engen, K.J.
Clear speech and lexical competition in younger and older adult listeners
(2017) Journal of the Acoustical Society of America, 142 (2), pp. 1067-1077. 

DOI: 10.1121/1.4998708

Department of Psychological and Brain Sciences, Washington University in St. Louis, One Brookings Drive, St. Louis, MO, United States

This study investigated whether clear speech reduces the cognitive demands of lexical competition by crossing speaking style with lexical difficulty. Younger and older adults identified more words in clear versus conversational speech and more easy words than hard words. An initial analysis suggested that the effect of lexical difficulty was reduced in clear speech, but more detailed analyses within each age group showed this interaction was significant only for older adults. The results also showed that both groups improved over the course of the task and that clear speech was particularly helpful for individuals with poorer hearing: for younger adults, clear speech eliminated hearing-related differences that affected performance on conversational speech. For older adults, clear speech was generally more helpful to listeners with poorer hearing. These results suggest that clear speech affords perceptual benefits to all listeners and, for older adults, mitigates the cognitive challenge associated with identifying words with many phonological neighbors. © 2017 Acoustical Society of America.

Document Type: Article
Source: Scopus



Cofield, S.S., Salter, A., Tyry, T., Crowe, C., Cutter, G.R., Fox, R.J., Marrie, R.A.
Perspectives on marijuana use and effectiveness: A survey of NARCOMS participants
(2017) Neurology: Clinical Practice, 7 (4), pp. 333-343. 

DOI: 10.1212/CPJ.0000000000000383

a Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, United States
b Division of Biostatistics, School of Medicine, Washington University, St. Louis, MO, United States
c Dignity Health, St. Joseph's Hospital and Medical Center, Phoenix, AZ, United States
d Mellen Center for Multiple Sclerosis, Cleveland ClinicOH, United States
e Departments of Internal Medicine (Neurology) and Community Health Sciences, University of Manitoba, Winnipeg, Canada

Background: Interest in and use of marijuana by persons with multiple sclerosis (MS) has increased. While potential benefits have been reported, so have concerns about potential risks. Few large studies have been conducted about the perceptions and current usage of marijuana and medical cannabinoids in persons with MS. Methods: Participants in the North American Research Committee on Multiple Sclerosis (NARCOMS) registry were surveyed in 2014 regarding legality and history of marijuana usage, both before and after diagnosis with MS. Results: A total of 5,481 participants responded, with 78.2% female, 90% relapsing disease at onset, and a current mean age of 55.5 (10.2) years. Sixty-four percent had tried marijuana prior to their MS diagnosis, 47% have considered using for their MS, 26% have used for their MS, 20% have spoken with their physician about use, and 16% are currently using marijuana. Ninety-one percent think marijuana should be legal in some form. Men, those with higher disability, current and past nicotine smokers, and younger age were associated with a higher likelihood of current use. Conclusions: The majority of responders favor legalization and report high interest in the use of marijuana for treatment of MS symptoms, but may be reluctant to discuss this with health care providers. Health care providers should systematically inquire about use of marijuana. © 2017 American Academy of Neurology.

Document Type: Article
Source: Scopus



Palanca, B.J.A., Wildes, T.S., Ju, Y.S., Ching, S., Avidan, M.S.
Electroencephalography and delirium in the postoperative period
(2017) British Journal of Anaesthesia, 119 (2), pp. 294-307. Cited 2 times.

DOI: 10.1093/bja/aew475

a Department of Anesthesiology, St Louis, MO, United States
b Department of Neurology, St Louis, MO, United States
c Department of Electrical and Systems Engineering, St Louis, MO, United States
d Department of Biomedical Engineering, Division of Cardiothoracic Surgery, Washington University School of Medicine in St Louis, St Louis, MO, United States
e Department of Surgery, Division of Cardiothoracic Surgery, Washington University School of Medicine in St Louis, St Louis, MO, United States

Delirium commonly manifests in the postoperative period as a clinical syndrome resulting from acute brain dysfunction or encephalopathy. Delirium is characterized by acute and often fluctuating changes in attention and cognition. Emergence delirium typically presents and resolves within minutes to hours after termination of general anaesthesia. Postoperative delirium hours to days after an invasive procedure can herald poor outcomes. Easily recognized when patients are hyperactive or agitated, delirium often evades diagnosis as it most frequently presents with hypoactivity and somnolence. EEG offers objective measurements to complement clinical assessment of this complex fluctuating disorder. Although EEG features of delirium in the postoperative period remain incompletely characterized, a shift of EEG power into low frequencies is a typical finding shared among encephalopathies that manifest with delirium. In aggregate, existing data suggest that serial or continuous EEG in the postoperative period facilitates monitoring of delirium development and severity and assists in detecting epileptic aetiologies. Future studies are needed to clarify the precise EEG features that can reliably predict or diagnose delirium in the postoperative period, and to provide mechanistic insights into this pathologically diverse neurological disorder. © The Author 2017. Published by Oxford University Press.

Author Keywords
delirium;  electroencephalography;  encephalopathy

Document Type: Review
Source: Scopus



Norris, S.A., Pogarcic, A., Hicks, M., Perlmutter, J.S., Shinawi, M.
Adult-onset dystonia with marfanoid features
(2017) Neurology: Clinical Practice, 7 (4), pp. e31-e34. 

DOI: 10.1212/CPJ.0000000000000297

a Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
b Department of Radiology, Washington University School of Medicine, St. Louis, MO, United States
c Department of Neuroscience, Washington University School of Medicine, St. Louis, MO, United States
d Department of Occupational Therapy, Washington University School of Medicine, St. Louis, MO, United States
e Department of Physical Therapy, Washington University School of Medicine, St. Louis, MO, United States
f Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, United States
g Division of Genetics and Genomic Medicine, Washington University School of Medicine, St. Louis, MO, United States

A 43-year-old Asian American man with asthma and hypertension was referred to the movement disorder center with a 5-year history of gradually progressive action-induced ankle inversion followed by trunk tightness and painful neck twisting with right shoulder elevation. He was born in the United States and successfully graduated college as a B/C student with mild learning difficulties. He always had disproportionally long limbs and digits and at age 12 developed ectopia lentis (medial-inferior displacement). Numerous ocular surgeries were performed including intraocular lens exchange with iris fixation. Marfan syndrome was previously diagnosed based on physical findings. There was no family history of Marfan syndrome, marfanoid features, or early death due to aortic dissection. FBN1 mutations were not tested and serial echocardiograms demonstrated no aortic root dilation. Diagnosis was later refined to ectopia lentis syndrome per updated guidelines. At age 29, he required allograft repair of an anterior cruciate ligament following minor impact. Four years later, while walking, he had musculoskeletal trauma in the left foot with subsequent toe extension weakness. Nerve conduction studies confirmed absence of compound motor action potentials in the left peroneal nerve lateral terminal branch. At age 38, he developed left foot pain with tendency for dorsiflexion and ankle inversion when walking. Severity gradually progressed and tightness extended to the trunk within 2 years. At age 41, he developed elevation of the right shoulder and several weeks later rightward rotation of the neck and back. Dystonia gradually progressed. Symptoms were exacerbated by stress but not relieved by alcohol or muscle relaxers. © 2016 American Academy of Neurology.

Document Type: Article
Source: Scopus



Kallogjeri, D., Piccirillo, J.F.
Cognitive training program to treat tinnitus: In reply
(2017) JAMA Otolaryngology - Head and Neck Surgery, 143 (8), pp. 848-849. 

DOI: 10.1001/jamaoto.2017.0523

a Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine in St Louis, 660 S Euclid Ave, St Louis, MO, United States
b JAMA Otolaryngology-Head and Neck Surgery, United States

Document Type: Letter
Source: Scopus



Aranake-Chrisinger, A., Avidan, M.S.
Postoperative delirium portends descent to dementia
(2017) British Journal of Anaesthesia, 119 (2), pp. 285-288. Cited 1 time.

DOI: 10.1093/bja/aex126

Department of Anesthesiology, Washington University School of Medicine, Saint Louis, MO, United States

Document Type: Review
Source: Scopus



Lee, Y., Weihl, C.C.
Regulation of SQSTM1/p62 via UBA domain ubiquitination and its role in disease
(2017) Autophagy, pp. 1-2. Article in Press. 

DOI: 10.1080/15548627.2017.1339845

Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA

Macroautophagy/autophagy can be a selective degradative process via the utilization of various autophagic receptor proteins. Autophagic receptors selectively recognize ubiquitinated cargoes and deliver them to phagophores, the precursors to autophagosomes, for their degradation. For example, SQSTM1/p62 directly binds to ubiquitinated protein aggregates via its UBA domain and sequesters them into inclusion bodies via its PB1 domain. SQSTM1also interacts with phagophores via its LC3-interacting (LIR) motif. However, a regulatory mechanism for autophagic receptors is not yet understood. © 2017 Taylor & Francis

Author Keywords
autophagy;  Keap1-Cullin3-Nrf2 pathway;  neurodegenerative diseases;  p62/SQSTM1;  protein aggregates;  ubiquitination

Document Type: Article in Press
Source: Scopus



Etzel, J.A.
MVPA significance testing when just above chance, and related properties of permutation tests
(2017) 2017 International Workshop on Pattern Recognition in Neuroimaging, PRNI 2017, art. no. 7981498, . 

DOI: 10.1109/PRNI.2017.7981498

Cognitive Control and Psychopathology Lab, Psychological and Brain Sciences, Washington University in St. Louis, Saint Louis, MO, United States

Parametric statistical tests (e.g., t-tests) can sometimes return highly significant results in cases that would be considered uninformative, such as when the individuals' accuracies are just above chance. This paper demonstrates that permutation tests can produce the expected non-significant results in these datasets. The properties of null distributions underlying this difference in significance are illustrated: their relative insensitivity to dataset information content, but sensitivity to dataset characteristics such as number of participants, examples, and runs. © 2017 IEEE.

Author Keywords
classification;  cross-validation;  fMRI;  MVPA;  permutation;  significance

Document Type: Conference Paper
Source: Scopus



Chapuis, J., Flaig, A., Grenier-Boley, B., Eysert, F., Pottiez, V., Deloison, G., Vandeputte, A., Ayral, A.-M., Mendes, T., Desai, S., Goate, A.M., Kauwe, J.S.K., Leroux, F., Herledan, A., Demiautte, F., Bauer, C., Checler, F., Petersen, R.C., Blennow, K., Zetterberg, H., Minthon, L., Van Deerlin, V.M., Lee, V.M.-Y., Shaw, L.M., Trojanowski, J.Q., Albert, M., Moghekar, A., O’Brien, R., Peskind, E.R., Malmanche, N., Schellenberg, G.D., Dourlen, P., Song, O.-R., Cruchaga, C., Amouyel, P., Deprez, B., Brodin, P., Lambert, J.-C., ADGC, Alzheimer's Disease Neuroimaging Initiative
Genome-wide, high-content siRNA screening identifies the Alzheimer’s genetic risk factor FERMT2 as a major modulator of APP metabolism
(2017) Acta Neuropathologica, 133 (6), pp. 955-966. 

DOI: 10.1007/s00401-016-1652-z

a Laboratoire d’Excellence Distalz, Univ. Lille, Unité INSERM 1167, Institut Pasteur de Lille, BP 245, 1 rue du professeur Calmette, Lille cedex, France
b Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, Lille, France
c Univ. Lille, INSERM, Institut Pasteur de Lille, U1177 - Drugs and Molecules for Living Systems, Lille, France
d Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
e Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
f Departments of Biology and Neuroscience, Brigham Young University, Provo, United States
g Laboratoire d’Excellence DistALZ, Université Côte d’Azur, INSERM, CNRS, IPMC, France, 660 route des Lucioles, Sophia-Antipolis, Valbonne, France
h Department of Neurology, Mayo Clinic, Rochester, MN, United States
i Clinical Neurochemistry Laboratory, Department of Neuroscience and Physiology, Sahlgren’s University Hospital, Mölndal, Gothenburg, Sweden
j Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, United Kingdom
k Clinical Memory Research Unit, Dept of Clinical Sciences, Lund University, Lund, Sweden
l Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States
m Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
n Department of Neurology, Duke Medical Center, Box 2900, Durham, NC, United States
o Departments of Psychiatry and Behavioral Sciences, Veterans Affairs Northwest Network Mental Illness Research, Education, and Clinical Center, University of Washington School of Medicine, Seattle, United States
p Stellar-Chance Laboratories, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States

Genome-wide association studies (GWASs) have identified 19 susceptibility loci for Alzheimer’s disease (AD). However, understanding how these genes are involved in the pathophysiology of AD is one of the main challenges of the “post-GWAS” era. At least 123 genes are located within the 19 susceptibility loci; hence, a conventional approach (studying the genes one by one) would not be time- and cost-effective. We therefore developed a genome-wide, high-content siRNA screening approach and used it to assess the functional impact of gene under-expression on APP metabolism. We found that 832 genes modulated APP metabolism. Eight of these genes were located within AD susceptibility loci. Only FERMT2 (a β3-integrin co-activator) was also significantly associated with a variation in cerebrospinal fluid Aβ peptide levels in 2886 AD cases. Lastly, we showed that the under-expression of FERMT2 increases Aβ peptide production by raising levels of mature APP at the cell surface and facilitating its recycling. Taken as a whole, our data suggest that FERMT2 modulates the AD risk by regulating APP metabolism and Aβ peptide production. © 2016, The Author(s).

Document Type: Article
Source: Scopus



Ory, D.S., Ottinger, E.A., Farhat, N.Y., King, K.A., Jiang, X., Weissfeld, L., Berry-Kravis, E., Davidson, C.D., Bianconi, S., Keener, L.A., Rao, R., Soldatos, A., Sidhu, R., Walters, K.A., Xu, X., Thurm, A., Solomon, B., Pavan, W.J., Machielse, B.N., Kao, M., Silber, S.A., McKew, J.C., Brewer, C.C., Vite, C.H., Walkley, S.U., Austin, C.P., Porter, F.D.
Intrathecal 2-hydroxypropyl-β-cyclodextrin decreases neurological disease progression in Niemann-Pick disease, type C1: A non-randomised, open-label, phase 1-2 trial
(2017) The Lancet, . Article in Press. 

DOI: 10.1016/S0140-6736(17)31465-4

a Washington University School of Medicine, St Louis, MO, USA
b National Center for Advancing Translational Sciences, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA
c Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD USA
d National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA
e Statistics Collaborative, Washington, DC, USA
f Rush University Medical Center, Chicago, IL, USA
g Albert Einstein College of Medicine, Bronx, NY, USA
h Vtesse Inc, Gaithersburg, MD, USA
i National Institute of Neurological Disorders and Stroke, National Institutes of Health, Department of Health and Human Services Bethesda, MD, USA
j National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA
k Mark O Hatfield Clinical Research Center, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA
l National Human Genome Research Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA
m Preclinical Development and Safety, Janssen R and D, Raritan, NJ, USA
n Global Public Health, Johnson and Johnson, Philadelphia, PA, USA
o School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA

Background: Niemann-Pick disease, type C1 (NPC1) is a lysosomal storage disorder characterised by progressive neurodegeneration. In preclinical testing, 2-hydroxypropyl-β-cyclodextrins (HPβCD) significantly delayed cerebellar Purkinje cell loss, slowed progression of neurological manifestations, and increased lifespan in mouse and cat models of NPC1. The aim of this study was to assess the safety and efficacy of lumbar intrathecal HPβCD. Methods: In this open-label, dose-escalation phase 1-2a study, we gave monthly intrathecal HPβCD to participants with NPC1 with neurological manifestation at the National Institutes of Health (NIH), Bethesda, MD, USA. To explore the potential effect of 2-week dosing, three additional participants were enrolled in a parallel study at Rush University Medical Center (RUMC), Chicago, IL, USA. Participants from the NIH were non-randomly, sequentially assigned in cohorts of three to receive monthly initial intrathecal HPβCD at doses of 50, 200, 300, or 400 mg per month. A fifth cohort of two participants received initial doses of 900 mg. Participants from RUMC initially received 200 or 400 mg every 2 weeks. The dose was escalated based on tolerance or safety data from higher dose cohorts. Serum and CSF 24(S)-hydroxycholesterol (24[S]-HC), which serves as a biomarker of target engagement, and CSF protein biomarkers were evaluated. NPC Neurological Severity Scores (NNSS) were used to compare disease progression in HPβCD-treated participants relative to a historical comparison cohort of 21 NPC1 participants of similar age range. Findings: Between Sept 21, 2013, and Jan 19, 2015, 32 participants with NPC1 were assessed for eligibility at the National Institutes of Health. 18 patients were excluded due to inclusion criteria not met (six patients), declined to participate (three patients), pursued independent expanded access and obtained the drug outside of the study (three patients), enrolled in the RUMC cohort (one patient), or too late for the trial enrolment (five patients). 14 patients were enrolled and sequentially assigned to receive intrathecal HPβCD at a starting dose of 50 mg per month (three patients), 200 mg per month (three patients), 300 mg per month (three patients), 400 mg per month (three patients), or 900 mg per month (two patients). During the first year, two patients had treatment interrupted for one dose, based on grade 1 ototoxicity. All 14 patients were assessed at 12 months. Between 12 and 18 months, one participant had treatment interrupted at 17 months due to hepatocellular carcinoma, one patient had dose interruption for 2 doses based on caregiver hardship and one patient had treatment interrupted for 1 dose for mastoiditis. 11 patients were assessed at 18 months. Between Dec 11, 2013, and June 25, 2014, three participants were assessed for eligibility and enrolled at RUMC, and were assigned to receive intrathecal HPβCD at a starting dose of 200 mg every 2 weeks (two patients), or 400 mg every two weeks (one patient). There were no dropouts in this group and all 3 patients were assessed at 18 months. Biomarker studies were consistent with improved neuronal cholesterol homoeostasis and decreased neuronal pathology. Post-drug plasma 24(S)-HC area under the curve (AUC8-72) values, an indicator of neuronal cholesterol homoeostasis, were significantly higher than post-saline plasma 24(S)-HC AUC8-72 after doses of 900 mg (p=0·0063) and 1200 mg (p=0·0037). CSF 24(S)-HC concentrations in three participants given either 600 or 900 mg of HPβCD were increased about two fold (p=0·0032) after drug administration. No drug-related serious adverse events were observed. Mid-frequency to high-frequency hearing loss, an expected adverse event, was documented in all participants. When managed with hearing aids, this did not have an appreciable effect on daily communication. The NNSS for the 14 participants treated monthly increased at a rate of 1·22, SEM 0·34 points per year compared with 2·92, SEM 0·27 points per year (p=0·0002) for the 21 patient comparison group. Decreased progression was observed for NNSS domains of ambulation (p=0·0622), cognition (p=0·0040) and speech (p=0·0423). Interpretation: Patients with NPC1 treated with intrathecal HPβCD had slowed disease progression with an acceptable safety profile. These data support the initiation of a multinational, randomised, controlled trial of intrathecal HPβCD. Funding: National Institutes of Health, Dana's Angels Research Trust, Ara Parseghian Medical Research Foundation, Hope for Haley, Samantha's Search for the Cure Foundation, National Niemann-Pick Disease Foundation, Support of Accelerated Research for NPC Disease, Vtesse, Janssen Research and Development, a Johnson &amp; Johnson company, and Johnson &amp; Johnson. © 2017 Elsevier Ltd.

Document Type: Article in Press
Source: Scopus



Doran, K.A., Waldron, M.
Timing of First Alcohol Use and First Sex in Male and Female Adolescents
(2017) Journal of Adolescent Health, . Article in Press. 

DOI: 10.1016/j.jadohealth.2017.05.013

a Department of Counseling and Educational Psychology, School of Education, Indiana University Bloomington, Bloomington, Indiana
b Department of Psychiatry, Midwest Alcoholism Research Center, Washington University, St. Louis, Missouri

Purpose: We examined associations between timing of first alcohol use and first sexual intercourse in adolescent males and potential differences in observed associations between males and females. Methods: Data were drawn from 4,079 male and 4,059 female participants of the National Longitudinal Study of Youth 1997, aged 12-16 years at the first assessment. Cox proportional hazards regression models were estimated predicting age at first sexual intercourse from age at first alcohol use, without and with adjustment for correlated sociodemographic and individual- and family-level risk factors. Analyses were conducted separately for males and females, with interactions between alcohol use and respondent sex (female vs. male) modeled in subsidiary analyses. Results: Onset of first drink was strongly predictive of earlier sexual intercourse for both males and females, with effects of drinking most pronounced for females during early adolescence. Conclusions: Results highlight age at first alcohol use as an important predictor of sexual onset in male as well as female adolescents and suggest that effective prevention efforts focusing on delay of sexual intercourse might also focus on delay on alcohol use. © 2017 Society for Adolescent Health and Medicine.

Author Keywords
Adolescent alcohol use;  Adolescents;  Males;  Sexual intercourse;  Survival analysis

Document Type: Article in Press
Source: Scopus



Keven, N., Kurczek, J., Rosenbaum, R.S., Craver, C.F.
Narrative construction is intact in episodic amnesia
(2017) Neuropsychologia, . Article in Press. 

DOI: 10.1016/j.neuropsychologia.2017.07.028

a Department of Philosophy Bilkent University, Ankara, Turkey
b Loras College, Department of Psychology, Dubuque, Iowa, USA
c Department of Philosophy and Philosophy-Neuroscience-Psychology, Washington University, St. Louis, Missouri, USA
d Cognitive Neuroscience Lab, York University, Toronto, Canada

Autobiographical remembering and future imagining overlap in their underlying psychological and neurological mechanisms. The hippocampus and surrounding regions within the medial temporal lobes (MTL), known for their role in forming and maintaining autobiographical episodic memories, are also thought to play an essential role in fictitious and future constructions. Amnesic individuals with bilateral hippocampal damage cannot reconstruct their past personal experiences and also have severe deficits in the ability to construct coherent fictitious or future narratives. However, it is not known whether this impairment reflects a failure to generate details from autobiographical episodic memory to populate personal narratives or an inability to bind such details into coherent narratives. We show that four individuals with hippocampal damage and episodic amnesia can construct narratives when the relevant details of the story are provided in a picture book and that their narratives maintain overall coherence on several measures. These findings indicate that individuals with hippocampal damage can bind details into coherent narratives when details are available to them. We conclude that the hippocampal system instead likely plays a role in the generation of details from which narratives are constructed. © 2017 Elsevier Ltd.

Author Keywords
Autobiographical remembering;  Episodic memory;  Frog where are you;  Mental time travel;  Narrative construction;  Prospection

Document Type: Article in Press
Source: Scopus



Teng, F., Tsien, C.I., Lawrence, T.S., Cao, Y.
Blood-tumor barrier opening changes in brain metastases from pre to one-month post radiation therapy
(2017) Radiotherapy and Oncology, . Article in Press. 

DOI: 10.1016/j.radonc.2017.08.006

a Department of Radiation Oncology, Ann Arbor, United States
b Department of Radiology, Ann Arbor, United States
c Department of Biomedical Engineering, University of Michigan, Ann Arbor, United States
d Department of Radiation Oncology, Shandong Cancer Hospital, Shandong University, Jinan, China
e Department of Radiation Oncology, Washington University, St. Louis, United States

Purpose: Blood-tumor barrier is a limiting factor for effectiveness of systemic therapy to brain metastases. This study aimed to assess the extent and time course of BTB opening in BM following whole-brain radiotherapy (WBRT) or stereotactic radiosurgery (SRS) to determine optimal timing for systemic therapy. Materials and method: 30 patients received WBRT or SRS and a total of 64 metastatic lesions were analyzed. Dynamic contrast-enhanced MRI were acquired, to quantify a transfer constant (Ktrans), pre-RT, 1-2weeks after starting RT (Wk1-2), and 1-month post-RT (1M post-RT). Lesions were categorized as either low or high permeability based upon the pre-RT percentage volume of a lesion with Ktrans &gt;0.005min-1 (%Vall) less or greater than 50%. Time-course changes of %Vall after RT were analyzed. Results: Fifty-seven lesions had high-permeability and seven had low-permeability at baseline. Intra-patient and inter-lesion heterogeneity was observed in six patients who had both low- (n =7) and high-permeability lesions (n =10). Also, lesion permeability showed a significant size-effect at baseline. For high-permeability lesions, either received WBRT (n =43) or SRS (n =14), %Vall decreased non-significantly following RT (from 85.4% pre-RT to 76.9% 1M post-RT). For low-permeability lesions (n =7, all received WBRT), %Vall increased from 5.6% pre-RT to 30.2% at Wk1-2 and to 52.6% 1M-post (p =0.01). Conclusion: Our preliminary results suggest that 2-4. weeks after RT, when BTB opening is high for both low- and high-permeability brain metastatic lesions, could be optimal time to start systemic therapy. © 2017 Elsevier B.V.

Author Keywords
Blood-tumor barrier;  Brain metastasis;  DCE MRI;  Radiotherapy

Document Type: Article in Press
Source: Scopus



Tye-Murray, N., Spehar, B., Barcroft, J., Sommers, M.
Auditory training for adults who have hearing loss: A comparison of spaced versus massed practice schedules
(2017) Journal of Speech, Language, and Hearing Research, 60 (8), pp. 2337-2345. 

DOI: 10.1044/2017_JSLHR-H-16-0154

a Washington University School of Medicine, St. Louis, MO, United States
b Washington University, St. Louis, MO, United States

Purpose: The spacing effect in human memory research later. In line with transfer appropriate processing theory, refers to situations in which people learn items better when tests assessed both trained tasks and an untrained task. they study items in spaced intervals rather than massed Results: Auditory training improved the speech recognition intervals. This investigation was conducted to compare performance of participants in both groups. Benefits were the efficacy of meaning-oriented auditory training when maintained for 3 months. No effect of practice schedule administered with a spaced versus massed practice was found on overall benefits achieved, on retention of schedule. benefits, nor on generalizability of benefits to nontrained Method: Forty-seven adult hearing aid users received 16 hr tasks. of auditory training. Participants in a spaced group (mean Conclusion: The lack of spacing effect in otherwise age = 64.6 years, SD = 14.7) trained twice per week, and effective auditory training suggests that perceptual participants in a massed group (mean age = 69.6 years, learning may be subject to different influences than are SD = 17.5) trained for 5 consecutive days each week. other types of learning, such as vocabulary learning. Participants completed speech perception tests before Hence, clinicians might have latitude in recommending training, immediately following training, and then 3 months training schedules to accommodate patients’ schedules. © 2017 American Speech-Language-Hearing Association.

Document Type: Article
Source: Scopus



Smith, K.C., Multhaup, K.S., Ihejirika, R.C.
From Eyewitness to Academic Contexts: Examining the Effect of Misinformation in First and Second Languages
(2017) Applied Cognitive Psychology, . Article in Press. 

DOI: 10.1002/acp.3352

a Psychology Department Davidson College Davidson USA
b Department of Psychological and Brain Sciences Washington University in St. Louis St. Louis USA
c NYU-HJD Orthopedic Surgery New York USA

The present study adapts the typical eyewitness misinformation paradigm into an academic context. Unbalanced English-Spanish bilinguals (N = 81) listened to a lecture in English (L1) or Spanish (L2), read notes in L1 or L2, and completed a forced-choice recognition test in the lecture language. Unlike prior studies with proficient bilinguals, unbalanced English-dominant participants showed greater recognition memory accuracy for material presented in English only than did material presented in Spanish only. English misinformation had a greater impact on memory for the Spanish lecture than vice versa. Most importantly, the modified misinformation paradigm is an effective tool to investigate academic misinformation effects and could be used in bilingual and monolingual research. © 2017 John Wiley & Sons, Ltd.

Document Type: Article in Press
Source: Scopus