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Office of Neuroscience Research > Resources and Facilities > WUSTL Neuroscience Publications for the week

WUSTL Neuroscience Publications for the week


The publications below include authors at Washington University and were identified by Scopus search.  These are the most current publications.  For previous lists, visit the WUSTL Neuroscience publications archive.

July 10, 2017 


McAmis, N.E., Prospero, D.A., Standeven, J., Ray, W.Z., Zohny, Z., Engsberg, J.R.
Development of a method to compare microsurgery techniques across different levels of surgical experience
(2017) Interdisciplinary Neurosurgery: Advanced Techniques and Case Management, 10, pp. 52-56. 

DOI: 10.1016/j.inat.2017.06.003

a Department of Occupational Therapy, Washington University in St. Louis School of Medicine, Saint Louis, MO, United States
b Department of Neurosurgery, Washington University in St. Louis School of Medicine, Saint Louis, MO, United States

Object Surgical training is often seen as very timely and cost consuming as it requires multiple interactions with other experienced physicians. Through the use of video motion capture (VMC), novice surgeon's skills will be compared objectively to those of more experienced surgeons. Methods VMC was used to capture the movements of four neurosurgery residents performing five simple tasks: (1) threading the needle through the provided plastic vessel; (2) pulling the needle through the provided plastic vessel; and (3,4,5) tying the suture three times. Results It was concluded that experienced subjects recorded more accurate and precise motions within a shorter amount of time when compared to novice subjects. There was a decrease in time, elapsed path, and thumb tip distance with increasing experience. Conclusions The use of VMC proves to be a successful way to compare the differences between different levels of surgical expertise and we hope that this research will impact training paradigms for future surgical trainees. © 2017

Author Keywords
Human motion;  Medical education;  Motion capture;  Neurology;  Neurosurgery;  Surgical training

Document Type: Article
Source: Scopus


Vélez, A., Kohashi, T., Lu, A., Carlson, B.A.
The cellular and circuit basis for evolutionary change in sensory perception in mormyrid fishes
(2017) Scientific Reports, 7 (1), art. no. 3783, . 

DOI: 10.1038/s41598-017-03951-y

a Department of Biology, Washington University in St. Louis, St. Louis, MO, United States
b Division of Biological Science, Graduate School of Science, Nagoya University, Nagoya, Japan

Species differences in perception have been linked to divergence in gross neuroanatomical features of sensory pathways. The anatomical and physiological basis of evolutionary change in sensory processing at cellular and circuit levels, however, is poorly understood. Here, we show how specific changes to a sensory microcircuit are associated with the evolution of a novel perceptual ability. In mormyrid fishes, the ability to detect variation in electric communication signals is correlated with an enlargement of the midbrain exterolateral nucleus (EL), and a differentiation into separate anterior (ELa) and posterior (ELp) regions. We show that the same cell types and connectivity are found in both EL and ELa/ELp. The evolution of ELa/ELp, and the concomitant ability to detect signal variation, is associated with a lengthening of incoming hindbrain axons to form delay lines, allowing for fine temporal analysis of signals. The enlargement of this brain region is also likely due to an overall increase in cell numbers, which would allow for processing of a wider range of timing information. © 2017 The Author(s).

Document Type: Article
Source: Scopus


Zahn, R., Green, S., Beaumont, H., Burns, A., Moll, J., Caine, D., Gerhard, A., Hoffman, P., Shaw, B., Grafman, J., Lambon Ralph, M.A.
Frontotemporal lobar degeneration and social behaviour: Dissociation between the knowledge of its consequences and its conceptual meaning
(2017) Cortex, 93, pp. 107-118. 

DOI: 10.1016/j.cortex.2017.05.009

a Institute of Psychiatry, Psychology & Neuroscience, Department of Psychological Medicine, King's College London, London, United Kingdom
b Neuroscience and Aphasia Research Unit, Division of Neuroscience and Experimental Psychology, The University of Manchester, Manchester, United Kingdom
c Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
d Division of Neuroscience and Experimental Psychology, The University of Manchester, Manchester, United Kingdom
e Cognitive and Behavioral Neuroscience Unit, D'Or Institute for Research and Education (IDOR), Rio de Janeiro, RJ, Brazil
f National Hospital for Neurology & Neurosurgery, Queen Square, London, United Kingdom
g Department of Nuclear Medicine and Geriatric Medicine, University Hospital Essen, Germany
h Rehabilitation Institute of Chicago, Chicago, IL, United States
i Department of Physical Medicine and Rehabilitation, Northwestern University, Chicago, IL, United States

Inappropriate social behaviour is an early symptom of frontotemporal lobar degeneration (FTLD) in both behavioural variant frontotemporal dementia (bvFTD) and semantic dementia (SD) subtypes. Knowledge of social behaviour is essential for appropriate social conduct. The superior anterior temporal lobe (ATL) has been identified as one key neural component for the conceptual knowledge of social behaviour, but it is unknown whether this is dissociable from knowledge of the consequences of social behaviour. Here, we used a newly-developed test of knowledge about long-term and short-term consequences of social behaviour to investigate its impairment in patients with FTLD relative to a previously-developed test of social conceptual knowledge. We included 19 healthy elderly control participants and 19 consecutive patients with features of bvFTD or SD and defined dissociations as performance differences between tasks for each patient (Bonferroni-corrected p < .05). Knowledge of long-term consequences was selectively impaired relative to short-term consequences in five patients and the reverse dissociation occurred in one patient. Six patients showed a selective impairment of social concepts relative to long-term consequences with the reverse dissociation occurring in one patient. These results corroborate the hypothesis that knowledge of long-term consequences of social behaviour is dissociable from knowledge of short-term consequences, as well as of social conceptual knowledge. Confirming our hypothesis, we found that patients with more marked grey matter (GM) volume loss in frontopolar relative to right superior ATL regions of interest exhibited poorer knowledge of the long-term consequences of social behaviour relative to the knowledge of its conceptual meaning and vice versa (n = 15). These findings support the hypothesis that frontopolar and ATL regions represent distinct aspects of social knowledge. This suggests that rather than being unable to suppress urges to behave inappropriately, FTLD patients often lose the knowledge of what appropriate social behaviour is and can therefore not be expected to behave accordingly. © 2017

Author Keywords
Brodmann Area 10;  Disinhibition;  Frontal lobe;  Impulsivity;  Social behaviour

Document Type: Article
Source: Scopus


Rodebaugh, T.L., Tonge, N.A., Weisman, J.S., Lim, M.H., Fernandez, K.C., Bogdan, R.
The behavioral economics of social anxiety disorder reveal a robust effect for interpersonal traits
(2017) Behaviour Research and Therapy, 95, pp. 139-147. 

DOI: 10.1016/j.brat.2017.06.003

Department of Psychological and Brain Sciences, Washington University in St. Louis, United States

Recent evidence suggests that reduced generosity among individuals with social anxiety disorder (SAD) in behavioral economic tasks may result from constraint in changing behavior according to interpersonal contingencies. That is, people with SAD may be slower to be more generous when the situation warrants. Conversely, more global effects on generosity may be related to interpersonal vindictiveness, a dimension only somewhat related to SAD. A total of 133 participants, 73 with the generalized form of SAD, completed self-report instruments and a behavioral economic task with simulated interpersonal (friend, romantic partner, stranger) interactions. In a separate visit, friends (n = 88) also came to the lab and rated participants on vindictiveness. Interpersonal vindictiveness was associated with reduced initial and overall giving to simulated friends. SAD predicted a lack of increased giving to a simulated friend, and attenuated an increase in giving to simulated known versus unknown players compared to participants without SAD. Friend-reported vindictiveness predicted in the same direction as diagnosis. However, the findings for SAD were less robust than those for vindictiveness. SAD is perhaps weakly related to behavioral constraint in economic tasks that simulate interpersonal interactions, whereas vindictiveness is strongly related to lower overall generosity as well as (via friend report) behavioral constraint. Further study is needed to better characterize the construct of vindictiveness. Our findings dovetail with the suggestion that SAD is related to impairment in the proposed affiliation and attachment system, but further suggest that direct study of that system may be more fruitful than focusing on disorders. © 2017 Elsevier Ltd

Author Keywords
Behavioral economics;  Interpersonal processes;  RDoC;  Social anxiety disorder

Document Type: Article
Source: Scopus


Searles Nielsen, S., Hu, S., Checkoway, H., Negrete, M., Palmández, P., Bordianu, T., Racette, B.A., Simpson, C.D.
Parkinsonism Signs and Symptoms in Agricultural Pesticide Handlers in Washington State
(2017) Journal of Agromedicine, 22 (3), pp. 215-221. 

DOI: 10.1080/1059924X.2017.1317684

a Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
b Department of Neurology, School of Medicine, University of Washington, Seattle, WA, United States
c Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA, United States
d Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, Seattle, WA, United States
e School of Public Health, University of the Witwatersrand, Parktown, South Africa

Objectives: Examine associations between pesticide exposure and signs or symptoms of parkinsonism. Methods: Prior to the 2014 pesticide spray season, the authors examined 38 active pesticide handlers aged 35 to 65 (median: 43.5) who participated in the State of Washington’s cholinesterase monitoring program in the Yakima Valley, where cholinesterase-inhibiting insecticides are applied in fruit orchards. A movement disorder specialist assessed the workers using the Unified Parkinson’s Disease Rating Scale (UPDRS) motor subscore 3 (UPDRS3). Participants also self-reported work and medical histories, including the UPDRS activities of daily living subscore 2 (UPDRS2). The authors explored the relation between these scores and lifetime occupational pesticide exposure while accounting for age. Results: All participants were Hispanic men born in Mexico who had worked in agriculture for 4 to 43 years (median: 21 years, including 11 years applying pesticides, mostly in the United States). Ten participants (26%) reported difficulty with one or more UPDRS2 activities of daily living (maximum = 2), and nine (24%) had a UPDRS3 >0 (maximum = 10). The most common symptom and sign, respectively, were excess saliva (n = 6) and action tremor (n = 5). UPDRS2 and UPDRS3 scores were unrelated to the number of years applying pesticides, but UPDRS3, especially action tremor, was positively associated with living on or by a farm. Conclusions: Symptoms and signs of parkinsonism were absent to mild in this small sample of active workers who apply cholinesterase-inhibiting insecticides in Washington State, USA. Future studies should be larger and examine older, retired workers with greater cumulative exposure to agricultural pesticides at work and home, including other types of agricultural pesticides. © 2017 Taylor & Francis.

Author Keywords
Cholinesterase inhibitors;  occupational health;  parkinsonian disorders;  Parkinson’s disease;  pesticides

Document Type: Article
Source: Scopus


Jonson-Reid, M., Wideman, E.
Trauma and Very Young Children
(2017) Child and Adolescent Psychiatric Clinics of North America, 26 (3), pp. 477-490. 

DOI: 10.1016/j.chc.2017.02.004

George Warren Brown School of Social Work, Washington University, Campus Box 1196, 1 Brookings Drive, St Louis, MO, United States

This article examines the intersection of early childhood mental health and trauma. Working definitions, incidence, and prevalence of trauma events for this population are outlined with an emphasis on children younger than age 4 years. Trauma impacts on early childhood development are reviewed, with attention to clinical consequences, protective factors, and resilience. Best practices for assessment, screening tools, and treatment methods are presented based on the current research. Future implications include clinician and researcher partnerships to increase the number of effective screening and intervention tools for addressing trauma in very young children. © 2017 Elsevier Inc.

Author Keywords
Best practices;  Early childhood;  Screening;  Therapeutic interventions;  Trauma

Document Type: Review
Source: Scopus


Cai, W., Zhang, M., Zhang, Y.
Batch mode active learning for regression with expected model change
(2017) IEEE Transactions on Neural Networks and Learning Systems, 28 (7), art. no. 7454745, pp. 1668-1681. 

DOI: 10.1109/TNNLS.2016.2542184

a Cooperative Medianet Innovation Center, Shanghai Jiao Tong University, Shanghai, China
b Washington University in St. Louis, St. Louis, MO, United States

While active learning (AL) has been widely studied for classification problems, limited efforts have been done on AL for regression. In this paper, we introduce a new AL framework for regression, expected model change maximization (EMCM), which aims at choosing the unlabeled data instances that result in the maximum change of the current model once labeled. The model change is quantified as the difference between the current model parameters and the updated parameters after the inclusion of the newly selected examples. In light of the stochastic gradient descent learning rule, we approximate the change as the gradient of the loss function with respect to each single candidate instance. Under the EMCM framework, we propose novel AL algorithms for the linear and nonlinear regression models. In addition, by simulating the behavior of the sequential AL policy when applied for $k$ iterations, we further extend the algorithms to batch mode AL to simultaneously choose a set of $k$ most informative instances at each query time. Extensive experimental results on both UCI and StatLib benchmark data sets have demonstrated that the proposed algorithms are highly effective and efficient. © 2012 IEEE.

Author Keywords
Active learning (AL);  batch mode;  expected model change;  linear regression;  nonlinear regression

Document Type: Article
Source: Scopus


Constantino, J.N., Marrus, N.
The Early Origins of Autism
(2017) Child and Adolescent Psychiatric Clinics of North America, 26 (3), pp. 555-570. 

DOI: 10.1016/j.chc.2017.02.008

Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8504, St Louis, MO, United States

Autism spectrum disorders (ASDs) are neurodevelopmental disorders whose core features of impaired social communication and atypical repetitive behaviors and/or restrictions in range of interests emerge in toddlerhood and carry significant implications at successive stages of development. The ability to reliably identify most cases of the condition far earlier than the average age of diagnosis presents a novel opportunity for early intervention, but the availability of such an intervention is disparate across US communities, and its impact is imperfectly understood. New research may transform the clinical approach to these conditions in early childhood. © 2017 Elsevier Inc.

Author Keywords
Autism spectrum disorder;  Diagnosis;  Early childhood development;  Genetics

Document Type: Review
Source: Scopus


De Franco, E., Flanagan, S.E., Yagi, T., Abreu, D., Mahadevan, J., Johnson, M.B., Jones, G., Acosta, F., Mulaudzi, M., Lek, N., Oh, V., Petz, O., Caswell, R., Ellard, S., Urano, F., Hattersley, A.T.
Dominant ER stress-inducing WFS1 mutations underlie a genetic syndrome of neonatal/infancy-onset diabetes, congenital sensorineural deafness, and congenital cataracts
(2017) Diabetes, 66 (7), pp. 2044-2053. 

DOI: 10.2337/db16-1296

a Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, United Kingdom
b Department of Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO, United States
c Department of Molecular Genetics, Royal Devon and Exeter NHS Foundation Trust, Exeter, United Kingdom
d Department of Pediatrics, Centro Médico Nacional 20 de Noviembre ISSSTE, Mexico City, Mexico
e Department of Paediatrics and Child Health, University of Pretoria Medical School, Pretoria, South Africa
f KK Women's and Children's Hospital, Singapore, Singapore
g Duke-NUS Medical School, National University of Singapore, Singapore, Singapore
h Praxis für Kinder-und Jugendmedizin, Diabetologische Schwerpunktpraxis, Coesfeld, Germany

Neonatal diabetes is frequently part of a complex syndrome with extrapancreatic features: 18 genes causing syndromic neonatal diabetes have been identified to date. There are still patients with neonatal diabetes who have novel genetic syndromes. We performed exome sequencing in a patient and his unrelated, unaffected parents to identify the genetic etiology of a syndrome characterized by neonatal diabetes, sensorineural deafness, and congenital cataracts. Further testing was performed in 311 patients with diabetes diagnosed before 1 year of age in whom all known genetic causes had been excluded.We identified 5 patients, including the initial case, with three heterozygous missense mutations in WFS1 (4/5 confirmed de novo). They had diabetes diagnosed before 12 months (2 before 6 months) (5/5), sensorineural deafness diagnosed soon after birth (5/5), congenital cataracts (4/5), and hypotonia (4/5). In vitro studies showed that these WFS1 mutations are functionally different from the known recessive Wolfram syndrome-causing mutations, as they tend to aggregate and induce robust endoplasmic reticulum stress. Our results establish specific dominant WFS1 mutations as a cause of a novel syndrome including neonatal/infancy-onset diabetes, congenital cataracts, and sensorineural deafness. This syndrome has a discrete pathophysiology and differs genetically and clinically from recessive Wolfram syndrome. © 2017 by the American Diabetes Association.

Document Type: Article
Source: Scopus


Tandon, M., Pergjika, A.
Attention Deficit Hyperactivity Disorder in Preschool-Age Children
(2017) Child and Adolescent Psychiatric Clinics of North America, 26 (3), pp. 523-538. 

DOI: 10.1016/j.chc.2017.02.007

Division of Child and Adolescent Psychiatry, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8134, St Louis, MO, United States

Attention deficit hyperactivity disorder is a neurodevelopmental disorder marked by age-inappropriate deficits in attention or hyperactivity/impulsivity that interfere with functioning or development. It is highly correlated with other disorders, such as oppositional defiant disorder, conduct disorder, and mood symptoms. The etiology is multifactorial, and neuroimaging findings are nonspecific. Although assessment tools exist, there is variability among them, and historically, parent-teacher agreement has not been consistent. Treatment algorithm for attention deficit hyperactivity disorder in preschoolers includes behavioral interventions first followed by psychopharmacologic treatment when behavioral therapies fail. Other nonpharmacologic and nonbehavioral interventions are discussed including the role of exercise and nutrition. © 2017 Elsevier Inc.

Author Keywords
Assessment;  Attention deficit hyperactivity disorder;  Preschool children;  Treatment

Document Type: Review
Source: Scopus


Marrus, N., Hall, L.
Intellectual Disability and Language Disorder
(2017) Child and Adolescent Psychiatric Clinics of North America, 26 (3), pp. 539-554. 

DOI: 10.1016/j.chc.2017.03.001

a Department of Psychiatry, Division of Child and Adolescent Psychiatry, Washington University in St Louis, 660 South Euclid Avenue, Box 8504, St Louis, MO, United States
b Department of Psychology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, United States

Intellectual disability (ID) and language disorders are neurodevelopmental conditions arising in early childhood. Child psychiatrists are likely to encounter children with ID and language disorders because both are strongly associated with challenging behaviors and mental disorder. Because early intervention is associated with optimal outcomes, child psychiatrists must be aware of their signs and symptoms, particularly as related to delays in cognitive and adaptive function. Optimal management of both ID and language disorders requires a multidisciplinary, team-based, and family centered approach. Child psychiatrists play an important role on this team, given their expertise with contextualizing and treating challenging behaviors. © 2017 Elsevier Inc.

Author Keywords
Early intervention;  Global developmental delay;  Intellectual disability;  Language disorder;  Multidisciplinary care

Document Type: Review
Source: Scopus


Bailey, H.R., Kurby, C.A., Sargent, J.Q., Zacks, J.M.
Attentional focus affects how events are segmented and updated in narrative reading
(2017) Memory and Cognition, pp. 1-16. Article in Press. 

DOI: 10.3758/s13421-017-0707-2

a Kansas State University, 414 Bluemont Hall, Manhattan, KS, United States
b Washington University, St. Louis, MO, United States
c Grand Valley State University, Allendale, MI, United States
d Francis Marion University, Florence, SC, United States

Readers generate situation models representing described events, but the nature of these representations may differ depending on the reading goals. We assessed whether instructions to pay attention to different situational dimensions affect how individuals structure their situation models (Exp. 1) and how they update these models when situations change (Exp. 2). In Experiment 1, participants read and segmented narrative texts into events. Some readers were oriented to pay specific attention to characters or space. Sentences containing character or spatial-location changes were perceived as event boundaries—particularly if the reader was oriented to characters or space, respectively. In Experiment 2, participants read narratives and responded to recognition probes throughout the texts. Readers who were oriented to the spatial dimension were more likely to update their situation models at spatial changes; all readers tracked the character dimension. The results from both experiments indicated that attention to individual situational dimensions influences how readers segment and update their situation models. More broadly, the results provide evidence for a global situation model updating mechanism that serves to set up new models at important narrative changes. © 2017 Psychonomic Society, Inc.

Author Keywords
Event segmentation;  Global updating;  Incremental updating;  Situation model updating;  Text comprehension

Document Type: Article in Press
Source: Scopus


Purtle, J., Lê-Scherban, F., Shattuck, P., Proctor, E.K., Brownson, R.C.
An audience research study to disseminate evidence about comprehensive state mental health parity legislation to US State policymakers: Protocol
(2017) Implementation Science, 12 (1), art. no. 81, . 

DOI: 10.1186/s13012-017-0613-9

a Drexel University, Department of Health Management and Policy, Dornsife School of Public Health, 3215 Market St, Philadelphia, PA, United States
b Drexel University, Department of Epidemiology and Biostatistics, Dornsife School of Public Health, 3215 Market St, Philadelphia, PA, United States
c Drexel University, A.J. Drexel Autism Institute, 3215 Market St, Philadelphia, PA, United States
d Washington University in St. Louis, Center for Mental Health Services Research, Brown School of Social Work, St. Louis, MO, United States
e Washington University in St. Louis, Prevention Research Center in St. Louis, Brown School of Social Work, St. Louis, MO, United States
f Washington University School of Medicine, Washington University in St. Louis, Division of Public Health Sciences and Alvin J. Siteman Cancer Center, St. Louis, MO, United States

Background: A large proportion of the US population has limited access to mental health treatments because insurance providers limit the utilization of mental health services in ways that are more restrictive than for physical health services. Comprehensive state mental health parity legislation (C-SMHPL) is an evidence-based policy intervention that enhances mental health insurance coverage and improves access to care. Implementation of C-SMHPL, however, is limited. State policymakers have the exclusive authority to implement C-SMHPL, but sparse guidance exists to inform the design of strategies to disseminate evidence about C-SMHPL, and more broadly, evidence-based treatments and mental illness, to this audience. The aims of this exploratory audience research study are to (1) characterize US State policymakers' knowledge and attitudes about C-SMHPL and identify individual- and state-level attributes associated with support for C-SMHPL; and (2) integrate quantitative and qualitative data to develop a conceptual framework to disseminate evidence about C-SMHPL, evidence-based treatments, and mental illness to US State policymakers. Methods: The study uses a multi-level (policymaker, state), mixed method (QUAN→qual) approach and is guided by Kingdon's Multiple Streams Framework, adapted to incorporate constructs from Aarons' Model of Evidence-Based Implementation in Public Sectors. A multi-modal survey (telephone, post-mail, e-mail) of 600 US State policymakers (500 legislative, 100 administrative) will be conducted and responses will be linked to state-level variables. The survey will span domains such as support for C-SMHPL, knowledge and attitudes about C-SMHPL and evidence-based treatments, mental illness stigma, and research dissemination preferences. State-level variables will measure factors associated with C-SMHPL implementation, such as economic climate and political environment. Multi-level regression will determine the relative strength of individual- and state-level variables on policymaker support for C-SMHPL. Informed by survey results, semi-structured interviews will be conducted with approximately 50 US State policymakers to elaborate upon quantitative findings. Then, using a systematic process, quantitative and qualitative data will be integrated and a US State policymaker-focused C-SMHPL dissemination framework will be developed. Discussion: Study results will provide the foundation for hypothesis-driven, experimental studies testing the effects of different dissemination strategies on state policymakers' support for, and implementation of, evidence-based mental health policy interventions. © 2017 The Author(s).

Author Keywords
Audience research;  Dissemination;  Parity legislation;  Policy dissemination research;  US State policymakers

Document Type: Article
Source: Scopus


Dai, C., Lehar, M., Sun, D.Q., RVT, L.S., Carey, J.P., MacLachlan, T., Brough, D., Staecker, H., della Santina, A.M., Hullar, T.E., della Santina, C.C.
Rhesus Cochlear and Vestibular Functions Are Preserved After Inner Ear Injection of Saline Volume Sufficient for Gene Therapy Delivery
(2017) JARO - Journal of the Association for Research in Otolaryngology, pp. 1-17. Article in Press. 

DOI: 10.1007/s10162-017-0628-6

a Vestibular NeuroEngineering Lab, Department of Otolaryngology–Head & Neck Surgery, Johns Hopkins University School of Medicine, 720 Rutland Ave., Ross Bldg Rm 830, Baltimore, MD, United States
b Department of Biomedical Engineering, Johns Hopkins University School of Medicine, 720 Rutland Ave., Ross Bldg Rm 830, Baltimore, MD, United States
c Novartis Institutes for Biomedical Research, 250 Massachusetts Ave, Cambridge, MA, United States
d GenVec, 910 Clopper Rd #220n, Gaithersburg, MD, United States
e Dept of Otolaryngology, Head & Neck Surgery, University of Kansas School of Medicine, 3901 Rainbow Blvd, Kansas City, KS, United States
f Department of Otolaryngology, Washington University School of Medicine, 660 S Euclid Ave, St. Louis, MO, United States
g Department of Anatomy and Neurobiology, Washington University School of Medicine, 660 S Euclid Ave, St. Louis, MO, United States
h Department of Audiology and Communication Sciences, Washington University School of Medicine, 660 S Euclid Ave, St. Louis, MO, United States

Sensorineural losses of hearing and vestibular sensation due to hair cell dysfunction are among the most common disabilities. Recent preclinical research demonstrates that treatment of the inner ear with a variety of compounds, including gene therapy agents, may elicit regeneration and/or repair of hair cells in animals exposed to ototoxic medications or other insults to the inner ear. Delivery of gene therapy may also offer a means for treatment of hereditary hearing loss. However, injection of a fluid volume sufficient to deliver an adequate dose of a pharmacologic agent could, in theory, cause inner ear trauma that compromises functional outcome. The primary goal of the present study was to assess that risk in rhesus monkeys, which closely approximates humans with regard to middle and inner ear anatomy. Secondary goals were to identify the best delivery route into the primate ear from among two common surgical approaches (i.e., via an oval window stapedotomy and via the round window) and to determine the relative volumes of rhesus, rodent, and human labyrinths for extrapolation of results to other species. We measured hearing and vestibular functions before and 2, 4, and 8 weeks after unilateral injection of phosphate-buffered saline vehicle (PBSV) into the perilymphatic space of normal rhesus monkeys at volumes sufficient to deliver an atoh1 gene therapy vector. To isolate effects of injection, PBSV without vector was used. Assays included behavioral observation, auditory brainstem responses, distortion product otoacoustic emissions, and scleral coil measurement of vestibulo-ocular reflexes during whole-body rotation in darkness. Three groups (N = 3 each) were studied. Group A received a 10 μL transmastoid/trans-stapes injection via a laser stapedotomy. Group B received a 10 μL transmastoid/trans-round window injection. Group C received a 30 μL transmastoid/trans-round window injection. We also measured inner ear fluid space volume via 3D reconstruction of computed tomography (CT) images of adult C57BL6 mouse, rat, rhesus macaque, and human temporal bones (N = 3 each). Injection was well tolerated by all animals, with eight of nine exhibiting no signs of disequilibrium and one animal exhibiting transient disequilibrium that resolved spontaneously by 24 h after surgery. Physiologic results at the final, 8-week post-injection measurement showed that injection was well tolerated. Compared to its pretreatment values, no treated ear’s ABR threshold had worsened by more than 5 dB at any stimulus frequency; distortion product otoacoustic emissions remained detectable above the noise floor for every treated ear (mean, SD and maximum deviation from baseline: −1.3, 9.0, and −18 dB, respectively); and no animal exhibited a reduction of more than 3 % in vestibulo-ocular reflex gain during high-acceleration, whole-body, passive yaw rotations in darkness toward the treated side. All control ears and all operated ears with definite histologic evidence of injection through the intended site showed similar findings, with intact hair cells in all five inner ear sensory epithelia and intact auditory/vestibular neurons. The relative volumes of mouse, rat, rhesus, and human inner ears as measured by CT were (mean ± SD) 2.5 ± 0.1, 5.5 ± 0.4, 59.4 ± 4.7 and 191.1 ± 4.7 μL. These results indicate that injection of PBSV at volumes sufficient for gene therapy delivery can be accomplished without destruction of inner ear structures required for hearing and vestibular sensation. © 2017 Association for Research in Otolaryngology

Author Keywords
auditory brainstem response;  gene therapy;  inner ear;  otoacoustic emission;  safety;  vestibular ocular reflex;  volume

Document Type: Article in Press
Source: Scopus


Molitoris, J.K., Rao, Y.J., Patel, R.A., Kane, L.T., Badiyan, S.N., Gittleman, H., Barnholtz-Sloan, J.S., Bentzen, S.M., Kruser, T.J., Huang, J., Mehta, M.P.
Multi-institutional external validation of a novel glioblastoma prognostic nomogram incorporating MGMT methylation
(2017) Journal of Neuro-Oncology, pp. 1-8. Article in Press. 

DOI: 10.1007/s11060-017-2529-2

a Radiation Oncology, University of Maryland Medical Center, Baltimore, MD, United States
b Radiation Oncology, Washington University, St. Louis, MO, United States
c Radiation Oncology, Northwestern University, Chicago, IL, United States
d Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, United States
e Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, United States
f Miami Cancer Institute, Radiation Oncology Executive Office, 8900 N. Kendall Drive, 1st Floor, Rm 1RC06, Miami, FL, United States

A recent nomogram for glioblastoma (GBM) was designed to incorporate methylguanine-DNA methyltransferase (MGMT) methylation status in trial patients receiving temozolomide. Since clinical trial patients are strictly selected, compared to the general population, we performed a multi-institutional, external, independent assessment of the nomogram. Consecutive adult patients with supratentorial GBM diagnosed between June 2007 and December 2014 who initiated TMZ-based concurrent chemoradiotherapy (CRT) and were not enrolled on RTOG 0525 or 0825 were eligible. We collected age, gender, MGMT status, performance status, resection extent, race, and tumor site and Cox regression analysis of overall survival (OS) was conducted with the 1-year nomogram-predicted survival (NPS). The predictive accuracy was quantified by the concordance index (c-index) as well as by separating patients into quintile-groups of the population distribution of NPS and comparing mean NPS and observed OS. Of 514 patients with GBM, 309 had all nomogram factors. Median OS was 18.7 months. NPS and observed OS demonstrated a c-index of 0.695. On univariate analysis, the NPS and all included factors except gender were significant. On multivariable analysis (MVA) the only significant factor for worse survival was lower NPS. When separated into quintile-groups of NPS, the observed survival was slightly better than the predicted survival for all but the worst prognostic group. Our multi-institutional cohort provides independent external validation of a novel GBM nomogram incorporating MGMT methylation status. No individual factor included in the nomogram retained significance on MVA after adjusting for NPS. © 2017 Springer Science+Business Media, LLC

Author Keywords
Glioblastoma;  Nomogram;  O6-Methylguanine-DNA methyltransferase;  Survival

Document Type: Article in Press
Source: Scopus


Dhar, R., Misra, H., Diringer, M.N.
SANGUINATE™ (PEGylated Carboxyhemoglobin Bovine) Improves Cerebral Blood Flow to Vulnerable Brain Regions at Risk of Delayed Cerebral Ischemia After Subarachnoid Hemorrhage
(2017) Neurocritical Care, pp. 1-9. Article in Press. 

DOI: 10.1007/s12028-017-0418-3

a Department of Neurology (Division of Neurocritical Care), Washington University School of Medicine in St. Louis, 660 S. Euclid Avenue, Campus Box 8111, St. Louis, MO, United States
b Prolong Pharmaceuticals, 300 Corporate Court, South Plainfield, NJ, United States

Background: Delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) has been linked to focal reductions in cerebral blood flow (CBF) and microvascular impairments in oxygen delivery. Effective therapies that restore flow and oxygen transport to vulnerable brain regions are currently lacking. SANGUINATE is a dual-action carbon monoxide-releasing and hemoglobin-based oxygen transfer agent with efficacy in animal models of focal brain ischemia and tolerability in patients with sickle cell disease. Methods: We performed a safety and proof-of-principle study in 12 SAH patients at risk of DCI across three escalating doses (160, 240, and 320 mg/kg). We used 15O-PET (performed at baseline, after SANGUINATE and at 24 h) to evaluate efficacy for improving CBF and restoring flow–metabolism balance (assessed by oxygen extraction fraction [OEF]) to vulnerable regions (defined as baseline OEF ≥ 0.50). Results: SANGUINATE resulted in a transient rise in mean arterial pressure (116 ± 15–127 ± 13 mm Hg, p = 0.001) that normalized by 24 h and allowed three patients with DCI to be weaned off vasopressors. No adverse events were noted during infusion. Global CBF did not rise (43 ± 8–46 ± 9 ml/100 g/min) although a trend was seen at the highest dose (45 ± 7–51 ± 9, p = 0.044). However, a significant 16% rise in regional CBF associated with reduction in OEF was seen in vulnerable regions, but did not persist at 24 h. Conclusions: We demonstrated that this novel agent can improve regional CBF and may improve oxygen supply–demand balance. Clinical studies (likely with repeat dosing) are required to evaluate whether this effect can prevent DCI or cerebral infarction. © 2017 Springer Science+Business Media New York

Author Keywords
Brain ischemia;  Cerebral blood flow;  Subarachnoid hemorrhage;  Vasospasm

Document Type: Article in Press
Source: Scopus


Sebe, J.Y., Cho, S., Sheets, L., Rutherford, M.A., von Gersdorff, H., Raible, D.W.
Ca2+-permeable AMPARs mediate glutamatergic transmission and excitotoxic damage at the hair cell ribbon synapse
(2017) Journal of Neuroscience, 37 (25), pp. 6162-6175. 

DOI: 10.1523/JNEUROSCI.3644-16.2017

a Departments of Biology and Biological Structure, University of Washington, Seattle, WA, United States
b Center for Sensory Neuroscience, Boys Town National Research Hospital, Omaha, NE, United States
c Eaton-Peabody Laboratories, Massachusetts Eye and Ear, Department of Otolaryngology, Harvard Medical School, Boston, MA, United States
d Department of Otolaryngology, Washington University in St. Louis, St. Louis, MO, United States
e The Vollum Institute, Oregon Health & Science University, Portland, OR, United States

We report functional and structural evidence for GluA2-lacking Ca2+-permeable AMPARs (CP-AMPARs) at the mature hair cell ribbon synapse. By using the methodological advantages of three species (of either sex), we demonstrate that CP-AMPARs are present at the hair cell synapse in an evolutionarily conserved manner. Via a combination of in vivo electrophysiological and Ca2+ imaging approaches in the larval zebrafish, we show that hair cell stimulation leads to robust Ca2+ influx into afferent terminals. Prolonged application of AMPA caused loss of afferent terminal responsiveness, whereas blocking CP-AMPARs protects terminals from excitotoxic swelling. Immuno his to chemical analysis of AMPAR subunits in mature rat cochlea show regions within synapses lacking the GluA2 subunit. Paired recordings from adult bullfrog auditory synapses demonstrate that CP-AMPARs mediate a major component of glutamatergic transmission. Together, our results support the importance of CP-AMPARs in mediating transmission at the hair cell ribbon synapse. Further, excess Ca2+ entry via CP-AMPARs may underlie afferent terminal damage following excitotoxic challenge, suggesting that limiting Ca2+ levels in the afferent terminal may protect against cochlear synaptopathy associated with hearing loss. © 2017 the authors.

Author Keywords
Cochlear synaptopathy;  Excitotoxicity;  GCaMP;  Noise overexposure;  Zebrafish

Document Type: Article
Source: Scopus


Lebois, E.P., Schroeder, J.P., Esparza, T.J., Bridges, T.M., Lindsley, C.W., Conn, P.J., Brody, D.L., Daniels, J.S., Levey, A.I.
Disease-Modifying Effects of M1 Muscarinic Acetylcholine Receptor Activation in an Alzheimer's Disease Mouse Model
(2017) ACS Chemical Neuroscience, 8 (6), pp. 1177-1187. 

DOI: 10.1021/acschemneuro.6b00278

a Department of Neurology, Emory University, Atlanta, GA, United States
b Center for Neurodegenerative Disease, Emory University, Atlanta, GA, United States
c Department of Neurology, Washington University, St. Louis, MO, United States
d Department of Pharmacology, Vanderbilt University, Nashville, TN, United States
e Department of Chemistry, Vanderbilt University, Nashville, TN, United States
f Vanderbilt Center for Neuroscience Drug Discovery, Nashville, TN, United States
g Alzheimer's Disease Research Center, Emory University, Atlanta, GA, United States
h Neuroscience and Pain Research Unit Circuits, Neurotransmitters, and Signaling Division Pfizer, Inc., Cambridge, MA, United States

Alzheimer's disease (AD) is the leading cause of dementia worldwide, and currently no disease-modifying therapy is available to slow or prevent AD, underscoring the urgent need for neuroprotective therapies. Selective M1 muscarinic acetylcholine receptor (mAChR) activation is an attractive mechanism for AD therapy since M1 mediates key effects on memory, cognition, and behavior and has potential for disease-modifying effects on Aβ formation and tau phosphorylation. To validate M1 as a neuroprotective treatment target for AD, the M1-selective agonist, VU0364572, was chronically dosed to 5XFAD mice from a young age preceding Aβ pathology (2 months) to an age where these mice are known to display memory impairments (6 months). Chronic M1 activation prevented mice from becoming memory-impaired, as measured by Morris water maze (MWM) testing at 6 months of age. Additionally, M1 activation significantly reduced levels of soluble and insoluble Aβ40,42 in the cortex and hippocampus of these animals, as measured by ELISA and immunohistochemistry. Moreover, soluble hippocampal Aβ42 levels were strongly correlated with MWM memory impairments and M1 activation with VU0364572 abolished this correlation. Finally, VU0364572 significantly decreased oligomeric (oAβ) levels in the cortex, suggesting one mechanism whereby VU0364572 may be exerting its neuroprotective effects is by reducing the available oAβ pool in the brain. These findings suggest that chronic M1 activation has neuroprotective potential for preventing memory impairments and reducing neuropathology in AD. M1 activation therefore represents a promising avenue for preventative treatment, as well as a promising opportunity to combine symptomatic and disease-modifying effects for early AD treatment. © 2017 American Chemical Society.

Author Keywords
acetylcholine;  Alzheimer's;  amyloid;  hippocampus;  memory;  Muscarinic

Document Type: Article
Source: Scopus


Ross, S.A., Yount, M., Ankarstad, S., Bock, S., Orso, B., Perry, K., Miros, J., Brunstrom-Hernandez, J.E.
Effects of Participation in Sports Programs on Walking Ability and Endurance Over Time in Children With Cerebral Palsy
(2017) American Journal of Physical Medicine and Rehabilitation, . Article in Press. 

DOI: 10.1097/PHM.0000000000000767

From the Maryville University, St. Louis, Missouri (SAR, MY, SA, SB, BO, KP); and Washington University and St. Louis Children's Hospital, St. Louis, Missouri (JM, JEB-H).

OBJECTIVE: Children with cerebral palsy may benefit from maintaining a high level of physical fitness similar to typically developing children especially in terms of long-term physical performance, although in practice this is often difficult. The purpose of this study was to determine the effect of participation in sports programs on walking ability and endurance over time. DESIGN: A retrospective cohort study included participants with cerebral palsy, aged 6 to 20 yrs, who attended a summer sports program from 2004 to 2012. There were 256 participant sessions with pre/post data recorded. The participants consisted of a total of 97 children (mean age [SD] = 11.4 [3.1] yrs), many of whom attended multiple programs throughout the years. Programs were held 6 hrs/d, 5 d/wk for up to 4 wks. Outcome measures included the Timed Up and Go, modified 6-min walk, and 25-ft walk/run. RESULTS: The results showed significant improvements in the Timed Up and Go, modified 6-min walk distance and 25-ft walk/run over time. Children in Gross Motor Classification System level III made the largest gains. CONCLUSIONS: Walking ability and endurance seem to improve after participation in an intensive summer sports programs. Higher frequency of program attendance resulted in significant improvements in the Timed Up and Go. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at CME OBJECTIVES: Upon completion of this article, the reader should be able to: (1) Discuss the importance of physical activity at the participation level (sports programs) for children with cerebral palsy; (2) Contrast the changes in walking ability and endurance for children in Gross Motor Function Classification System level I, II, and III after sports programs; and (3) Identify the impact of higher frequency of sports program attendance over time on walking ability. LEVEL: Advanced ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this activity for a maximum of 1.5 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.

Document Type: Article in Press
Source: Scopus


Estes, A., Munson, J., John, T.S., Dager, S.R., Rodda, A., Botteron, K., Hazlett, H., Schultz, R.T., Zwaigenbaum, L., Piven, J., Guralnick, M.J., The Ibis Network, Piven, J., Hazlett, H.C., Chappell, J.C., Dager, S., Estes, A., Shaw, D., Botteron, K., McKinstry, R., Constantino, J., Pruett, J., Schultz, R., Paterson, S., Zwaigenbaum, L., Evans, A.C., Collins, D.L., Pike, G.B., Kostopolous, P., Das, S., Gerig, G., Styner, M., Gu, H., Sullivan, P., Wright, F.
Parent Support of Preschool Peer Relationships in Younger Siblings of Children with Autism Spectrum Disorder
(2017) Journal of Autism and Developmental Disorders, pp. 1-11. Article in Press. 

DOI: 10.1007/s10803-017-3202-5

a Department of Speech and Hearing Sciences, University of Washington, Seattle, WA, United States
b Department of Psychology, University of Washington, Seattle, WA, United States
c Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, United States
d Department of Radiology, University of Washington, Seattle, WA, United States
e Department of Psychiatry, Washington University, St. Louis, MO, United States
f Carolina Institute for Developmental Disabilities, Chapel Hill, NC, United States
g The Center for Autism Research, Department of Pediatrics, Children’s Hospital of Pennsylvania, University of Pennsylvania, Philadelphia, PA, United States
h Department of Pediatrics, University of Alberta, Edmonton, AB, Canada

Preschool-aged siblings of children with ASD are at high-risk (HR) for ASD and related challenges, but little is known about their emerging peer competence and friendships. Parents are the main providers of peer-relationship opportunities during preschool. Understanding parental challenges supporting early peer relationships is needed for optimal peer competence and friendships in children with ASD. We describe differences in peer relationships among three groups of preschool-aged children (15 HR-ASD, 53 HR-NonASD, 40 low-risk, LR), and examine parent support activities at home and arranging community-based peer activities. Children with ASD demonstrated precursors to poor peer competence and friendship outcomes. Parents in the HR group showed resilience in many areas, but providing peer opportunities for preschool-age children with ASD demanded significant adaptations. © 2017 Springer Science+Business Media, LLC

Author Keywords
Autism;  High risk;  Parent;  Peer relations;  Preschool;  Sibling

Document Type: Article in Press
Source: Scopus


Treiman, R.
Learning to spell: Phonology and beyond
(2017) Cognitive Neuropsychology, pp. 1-11. Article in Press. 

DOI: 10.1080/02643294.2017.1337630

Department of Psychological and Brain Sciences, Washington University, St. Louis, MO, USA

An understanding of the nature of writing systems and of the typical course of spelling development is an essential foundation for understanding the problems of children who have serious difficulties in learning to spell. The present article seeks to provide that foundation. It argues that the dual-route models of spelling that underlie much existing research and practice are based on overly simple assumptions about how writing systems work and about how spelling skills develop. Many writing systems include not only context-free links from phonemes to letters but also context-sensitive phonological patterns, morphological influences, and graphotactic patterns. According to an alternative framework, IMP (integration of multiple patterns), spellers acquire multiple sources of information through use of their statistical-learning skills and through direct instruction. Children learn the spelling of a word most easily when different patterns converge on the spelling, and they have difficulty when patterns conflict. Implications of these ideas for assessment and instruction are considered. © 2017 Informa UK Limited, trading as Taylor & Francis Group

Author Keywords
graphotactics;  morphology;  phonology;  Spelling;  spelling models

Document Type: Article in Press
Source: Scopus


Wang, S., Borschel, W.F., Heyman, S., Hsu, P., Nichols, C.G.
Conformational changes at cytoplasmic intersubunit interactions control Kir channel gating
(2017) Journal of Biological Chemistry, 292 (24), pp. 10087-10096. 

DOI: 10.1074/jbc.M117.785154

Department of Cell Biology and Physiology, Center for the Investigation of Membrane Excitability Diseases, Washington University School of Medicine, 660 South Euclid Ave., St. Louis, MO, United States

The defining structural feature of inward-rectifier potassium (Kir) channels is the unique Kir cytoplasmic domain. Recently we showed that salt bridges located at the cytoplasmic domain subunit interfaces (CD-Is) of eukaryotic Kir channels control channel gating via stability of a novel inactivated closed state. The cytoplasmic domains of prokaryotic and eukaryotic Kir channels show similar conformational rearrangements to the common gating ligand, phosphatidylinositol bisphosphate (PIP2), although these exhibit opposite coupling to opening and closing transitions. In Kir2.1, mutation of one of these CD-I salt bridge residues (R204A) reduces apparent PIP2 sensitivity of channel activity, and here we show that Ala or Cys substitutions of the functionally equivalent residue (Arg-165) in the prokaryotic Kir channel KirBac1.1 also significantly decrease sensitivity of the channel to PIP2 (by 5-30-fold). To further understand the structural basis of CD-I control of Kir channel gating, we examined the effect of the R165A mutation on PIP2-induced changes in channel function and conformation. Single-channel analyses indicated that the R165A mutation disrupts the characteristic long interburst closed state of reconstituted KirBac1.1 in giant liposomes, resulting in a higher open probability due to more frequent opening bursts. Intramolecular FRET measurements indicate that, relative to wild-type channels, the R165A mutation results in splaying of the cytoplasmic domains away from the central axis and that PIP2 essentially induces opposite motions of the major β-sheet in this channel mutant. We conclude that the removal of stabilizing CD-I salt bridges results in a collapsed state of the Kir domain. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Document Type: Article
Source: Scopus


Scherer, S.L., Cain, M.D., Kanai, S.M., Kaltenbronn, K.M., Blumer, K.J.
Regulation of neurite morphogenesis by interaction between R7 regulator of G protein signaling complexes and G protein subunit Gα13
(2017) Journal of Biological Chemistry, 292 (24), pp. 9906-9918. 

DOI: 10.1074/jbc.M116.771923

Department of Cell Biology and Physiology, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO, United States

The R7 regulator of G protein signaling family (R7-RGS) critically regulates nervous system development and function. Mice lacking all R7-RGS subtypes exhibit diverse neurological phenotypes, and humans bearing mutations in the retinal R7-RGS isoform RGS9-1 have vision deficits. Although each R7-RGS subtype forms heterotrimeric complexes with Gβ5 and R7-RGS-binding protein (R7BP) that regulate G protein-coupled receptor signaling by accelerating deactivation of G1/o α-subunits, several neurological phenotypes of R7-RGS knock-out mice are not readily explained by dysregulated G1/o signaling. Accordingly, we used tandem affinity purification and LCMS/MS to search for novel proteins that interact with R7-RGS heterotrimers in the mouse brain. Among several proteins detected, we focused on Gα13 because it had not been linked to R7-RGS complexes before. Split-luciferase complementation assays indicated that Gα13 in its active or inactive state interacts with R7-RGS heterotrimers containing any R7-RGS isoform. LARG (leukemia-associated Rho guanine nucleotide exchange factor (GEF)), PDZ-RhoGEF, and p115RhoGEF augmented interaction between activated Gα13 and R7-RGS heterotrimers, indicating that these effector RhoGEFs can engage Gα13·R7-RGS complexes. Because Gα13/R7-RGS interaction required R7BP, we analyzed phenotypes of neuronal cell lines expressing RGS7 and Gβ5 with or without R7BP. We found that neurite retraction evoked by Gα12/13-dependent lysophosphatidic acid receptors was augmented in R7BP-expressing cells. R7BP expression blunted neurite formation evoked by serum starvation by signaling mechanisms involving Gα12/13 but not G1/o. These findings provide the first evidence that R7-RGS heterotrimers interact with Gα13 to augment signaling pathways that regulate neurite morphogenesis. This mechanism expands the diversity of functions whereby R7-RGS complexes regulate critical aspects of nervous system development and function. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Document Type: Article
Source: Scopus


Kornfield, S.L., Moseley, M., Appleby, D., McMickens, C.L., Sammel, M.D., Epperson, C.N.
Posttraumatic Symptom Reporting and Reported Cigarette Smoking during Pregnancy
(2017) Journal of Women's Health, 26 (6), pp. 662-669. 

DOI: 10.1089/jwh.2016.5928

a Department of Psychiatry, Washington University, School of Medicine, Campus Box 8134, 600 S. Euclid Avenue, St. Louis, MO, United States
b Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
c Penn Center for Women's Behavioral Wellness, Philadelphia, PA, United States
d Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
e Robert Wood Johnson Foundation Clinical Scholars Program, Yale University, School of Medicine, New Haven, CT, United States
f Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States

Introduction: Increased prevalence of nicotine dependence among individuals suffering from posttraumatic stress disorder (PTSD) is well established. However, there are limited studies on the prevalence of smoking during pregnancy in relation to prepregnancy history of trauma exposures and active PTSD symptoms during pregnancy. Prenatal smoking has been implicated in a host of negative outcomes for mother and baby. Given maternal and fetal risk, it is critical to define predictors of continued cigarette smoking during pregnancy. Methods: Pregnant women from an urban perinatal clinic completed an anonymous survey of trauma history using a modified Traumatic Life Events Questionnaire (TLEQ), PTSD symptoms using the PTSD Symptom Checklist - Civilian Version (PCL-C) and current and past smoking behavior. Those who smoked any number of cigarettes per day after pregnancy confirmation were considered to be "pregnant smokers." Results: Of 218 women who completed the survey, 34 (15.6%) reported smoking cigarettes after confirmation of pregnancy. In unadjusted models, trauma exposure that resulted in fear, helplessness, or horror (FHH), as well as current PTSD symptom severity and probable PTSD diagnosis showed statistical significance as predictors of smoking during pregnancy. After adjusting for age only, PTSD symptoms retained their significant association with smoking during pregnancy. When history of smoking at least five cigarettes per day was added to our models, none of the associations remained significant. Conclusions: These findings emphasize the importance of the behavioral response to past traumatic exposures in influencing cigarette smoking behavior before pregnancy. Given such behaviors enhance risk for continued tobacco use during pregnancy, a trauma-informed approach to smoking cessation in preconception care may ultimately reduce the likelihood of smoking during pregnancy and requires further study. © 2017, Mary Ann Liebert, Inc.

Author Keywords
obstetrics;  pregnancy;  PTSD;  smoking

Document Type: Article
Source: Scopus


Lee, H., Park, S.
Gender differences in the trajectory classes of depressive symptoms in Korean older adults
(2017) Aging and Mental Health, pp. 1-8. Article in Press. 

DOI: 10.1080/13607863.2017.1339776

a Department of Social Welfare, Daegu University, Gyeongsan-si, Republic of Korea
b George Warren Brown School of Social Work, Washington University in Saint Louis, St. Louis, MO, USA

Objectives: This study aimed (1) to identify gender-specific heterogeneous longitudinal patterns of depressive symptoms, (2) to explore the effects of economic status and various health conditions as risk factors in depressive symptom trajectories. Method: Data came from the Korean Longitudinal Study of Aging (2006–2012) focuing on older adults aged 65 and older. Latent class growth analysis was used to identify the depressive symptom trajectory groups. Multinomial logistic regression was used to examine the association between economic and health status changes and the depresison trajectories. Results: Among older women, three change groups were identified: stable low, stable high, and moderate but slightly increasing groups. Among older men, four groups were found: stable low, moderate but rapidly increasing, high but decreasing, and moderate but slightly increasing groups. Among women, poverty experience and sustained poor health, particularly constantly low cognition, were significantly associated with the stable high group. Among men, deteriorating economic and health status were significant predictors of membership in the most vulnerable subgroup, the moderate but rapidly increasing group. Conclusion: This study demonstrated among older adults, depressive symptoms change heterogeneously by gender. Identification of the most at risk subgroups among older men and women provides important initial empirical information to target clinical programs and policy development. © 2017 Informa UK Limited, trading as Taylor & Francis Group

Author Keywords
Depressive symptoms;  gender difference;  growth mixture model

Document Type: Article in Press
Source: Scopus


Tang, Y.-Y., Jiang, C., Tang, R.
How mind-body practice works-integration or separation?
(2017) Frontiers in Psychology, 8 (MAY), art. no. 866, . 

DOI: 10.3389/fpsyg.2017.00866

a Department of Psychological Sciences, Texas Tech University, Lubbock, TX, United States
b Beijing Key Lab of Physical Fitness Evaluation and Tech Analysis, Capital University of Physical Education and Sports, Beijing, China
c Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, MO, United States

Author Keywords
Autonomic nervous system;  Central nervous system;  Integrative body-mind training (IBMT);  MBCT;  MBSR;  Mind-body practice;  Mindfulness meditation

Document Type: Note
Source: Scopus


Li, R., Hao, J., Fujiwara, H., Xu, M., Yang, S., Dai, S., Long, Y., Swaroop, M., Li, C., Vu, M., Marugan, J.J., Ory, D.S., Zheng, W.
Analytical Characterization of Methyl-β-Cyclodextrin for Pharmacological Activity to Reduce Lysosomal Cholesterol Accumulation in Niemann-Pick Disease Type C1 Cells
(2017) Assay and Drug Development Technologies, 15 (4), pp. 154-166. 

DOI: 10.1089/adt.2017.774

a National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Bethesda, MD, United States
b Poochon Scientific, Frederick, MD, United States
c Diabetic Cardiovascular Disease Center, Washington University, School of Medicine, St. Louis, MO, United States

Methyl-β-cyclodextrin (MβCD) reduces lysosomal cholesterol accumulation in Niemann-Pick disease type C1 (NPC1) patient fibroblasts. However, the pharmacological activity of MβCD reported by different laboratories varies. To determine the potential causes of this variation, we analyzed the mass spectrum characteristics, pharmacological activity of three preparations of MβCDs, and the protein expression profiles of NPC1 patient fibroblasts after treatment with different sources of MβCDs. Our data revealed varied mass spectrum profiles and pharmacological activities on the reduction of lysosomal cholesterol accumulation in NPC1 fibroblasts for these three preparations of MβCDs obtained from different batches and different sources. Furthermore, a proteomic analysis showed the differences of these three MβCD preparations on amelioration of dysregulated protein expression levels in NPC1 cells. The results demonstrate the importance of prescreening of different cyclodextrin preparations before use as a therapeutic agent. A combination of mass spectrum analysis, measurement of pharmacological activity, and proteomic profiling provides an effective analytical procedure for characterization of cyclodextrins for therapeutic applications. © 2017 Mary Ann Liebert, Inc.

Author Keywords
Lysosomal storage disease;  mass spectrometry;  methyl-b-cyclodextrin;  niemann-pick disease type C1;  proteomics

Document Type: Article
Source: Scopus


Gratton, C., Yousef, S., Aarts, E., Wallace, D.L., D'Esposito, M., Silver, M.A.
Cholinergic, But Not Dopaminergic or Noradrenergic, Enhancement Sharpens Visual Spatial Perception in Humans
(2017) The Journal of neuroscience : the official journal of the Society for Neuroscience, 37 (16), pp. 4405-4415. 

DOI: 10.1523/JNEUROSCI.2405-16.2017

a Neurology Department, Washington University, St. Louis, Missouri 63110,
b School of Optometry, University of California, Berkeley, California 94720
c Vision Science Graduate Group, University of California, Berkeley, California 94720
d Donders Institute, Centre for Cognitive Neuroimaging, Radboud University, Nijmegen 6525 EN, The Netherlands
e Department of Neurosurgery, University of California, San Francisco, California 94122, and
f Helen Wills Neuroscience Institute, University of California, Berkeley, California 94720

The neuromodulator acetylcholine modulates spatial integration in visual cortex by altering the balance of inputs that generate neuronal receptive fields. These cholinergic effects may provide a neurobiological mechanism underlying the modulation of visual representations by visual spatial attention. However, the consequences of cholinergic enhancement on visuospatial perception in humans are unknown. We conducted two experiments to test whether enhancing cholinergic signaling selectively alters perceptual measures of visuospatial interactions in human subjects. In Experiment 1, a double-blind placebo-controlled pharmacology study, we measured how flanking distractors influenced detection of a small contrast decrement of a peripheral target, as a function of target-flanker distance. We found that cholinergic enhancement with the cholinesterase inhibitor donepezil improved target detection, and modeling suggested that this was mainly due to a narrowing of the extent of facilitatory perceptual spatial interactions. In Experiment 2, we tested whether these effects were selective to the cholinergic system or would also be observed following enhancements of related neuromodulators dopamine or norepinephrine. Unlike cholinergic enhancement, dopamine (bromocriptine) and norepinephrine (guanfacine) manipulations did not improve performance or systematically alter the spatial profile of perceptual interactions between targets and distractors. These findings reveal mechanisms by which cholinergic signaling influences visual spatial interactions in perception and improves processing of a visual target among distractors, effects that are notably similar to those of spatial selective attention.SIGNIFICANCE STATEMENT Acetylcholine influences how visual cortical neurons integrate signals across space, perhaps providing a neurobiological mechanism for the effects of visual selective attention. However, the influence of cholinergic enhancement on visuospatial perception remains unknown. Here we demonstrate that cholinergic enhancement improves detection of a target flanked by distractors, consistent with sharpened visuospatial perceptual representations. Furthermore, whereas most pharmacological studies focus on a single neurotransmitter, many neuromodulators can have related effects on cognition and perception. Thus, we also demonstrate that enhancing noradrenergic and dopaminergic systems does not systematically improve visuospatial perception or alter its tuning. Our results link visuospatial tuning effects of acetylcholine at the neuronal and perceptual levels and provide insights into the connection between cholinergic signaling and visual attention. Copyright © 2017 the authors 0270-6474/17/374405-11$15.00/0.

Author Keywords
acetylcholine;  attention;  dopamine;  norepinephrine;  pharmacology;  visuospatial perception

Document Type: Article
Source: Scopus


Papadimitriou, C., White, R.L., 3rd, Snyder, L.H.
Ghosts in the Machine II: Neural Correlates of Memory Interference from the Previous Trial
(2017) Cerebral cortex (New York, N.Y. : 1991), 27 (4), pp. 2513-2527. Cited 1 time.

DOI: 10.1093/cercor/bhw106

a Department of Anatomy and Neurobiology, Washington University in St. Louis, St. Louis, MO 63116, USA
b Department of Psychology, University of California Berkeley, Berkeley, CA 94720, USA

Previous memoranda interfere with working memory. For example, spatial memories are biased toward locations memorized on the previous trial. We predicted, based on attractor network models of memory, that activity in the frontal eye fields (FEFs) encoding a previous target location can persist into the subsequent trial and that this ghost will then bias the readout of the current target. Contrary to this prediction, we find that FEF memory representations appear biased away from (not toward) the previous target location. The behavioral and neural data can be reconciled by a model in which receptive fields of memory neurons converge toward remembered locations, much as receptive fields converge toward attended locations. Convergence increases the resources available to encode the relevant memoranda and decreases overall error in the network, but the residual convergence from the previous trial can give rise to an attractive behavioral bias on the next trial. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail:

Author Keywords
attractor network models;  frontal eye fields;  proactive interference;  receptive field remapping;  spatial working memory

Document Type: Article
Source: Scopus


Adhikari, M.H., Hacker, C.D., Siegel, J.S., Griffa, A., Hagmann, P., Deco, G., Corbetta, M.
Decreased integration and information capacity in stroke measured by whole brain models of resting state activity
(2017) Brain : a journal of neurology, 140 (4), pp. 1068-1085. 

DOI: 10.1093/brain/awx021

a Center for Brain and Cognition, Computational Neuroscience Group, Department of Information and Communication Technologies, Universitat Pompeu Fabra, Ramon Trias Fargas, 25-27, Barcelona, 08005, Spain
b Department of Bioengineering, Washington University Saint Louis, USA
c Department of Neurology, Washington University School of Medicine Saint Louis, USA
d Department of Radiology, Lausanne University Hospital and University of Lausanne (CHUV-UNIL), 1011 Lausanne, Switzerland
e Signal Processing Lab 5, Ecole Polytechnique Federale de Lausanne (EPFL), 1015 Lausanne, Switzerland
f Institucio Catalana de la Recerca I Estudis Avancats (ICREA), University of Pompeu Fabra, Passeig Lluis Companys 23, Barcelona, 08010, Spain
g Departments of Radiology and Neuroscience, Washington University School of Medicine Saint Louis, USA
h Department of Neuroscience, University of Padua, Italy

While several studies have shown that focal lesions affect the communication between structurally normal regions of the brain, and that these changes may correlate with behavioural deficits, their impact on brain's information processing capacity is currently unknown. Here we test the hypothesis that focal lesions decrease the brain's information processing capacity, of which changes in functional connectivity may be a measurable correlate. To measure processing capacity, we turned to whole brain computational modelling to estimate the integration and segregation of information in brain networks. First, we measured functional connectivity between different brain areas with resting state functional magnetic resonance imaging in healthy subjects (n = 26), and subjects who had suffered a cortical stroke (n = 36). We then used a whole-brain network model that coupled average excitatory activities of local regions via anatomical connectivity. Model parameters were optimized in each healthy or stroke participant to maximize correlation between model and empirical functional connectivity, so that the model's effective connectivity was a veridical representation of healthy or lesioned brain networks. Subsequently, we calculated two model-based measures: 'integration', a graph theoretical measure obtained from functional connectivity, which measures the connectedness of brain networks, and 'information capacity', an information theoretical measure that cannot be obtained empirically, representative of the segregative ability of brain networks to encode distinct stimuli. We found that both measures were decreased in stroke patients, as compared to healthy controls, particularly at the level of resting-state networks. Furthermore, we found that these measures, especially information capacity, correlate with measures of behavioural impairment and the segregation of resting-state networks empirically measured. This study shows that focal lesions affect the brain's ability to represent stimuli and task states, and that information capacity measured through whole brain models is a theory-driven measure of processing capacity that could be used as a biomarker of injury for outcome prediction or target for rehabilitation intervention. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email:

Author Keywords
functional connectivity;  information capacity;  integration;  whole-brain modelling

Document Type: Article
Source: Scopus


Gratton, C., Neta, M., Sun, H., Ploran, E.J., Schlaggar, B.L., Wheeler, M.E., Petersen, S.E., Nelson, S.M.
Distinct Stages of Moment-to-Moment Processing in the Cinguloopercular and Frontoparietal Networks
(2017) Cerebral cortex (New York, N.Y. : 1991), 27 (3), pp. 2403-2417. 

DOI: 10.1093/cercor/bhw092

a Department of Neurology
b Department of Psychology, University of Nebraska-Lincoln, Lincoln, NE, USA
c Department of Biomedical Engineering
d Department of Psychology, Hofstra University, Hempstead, NY, USA
e Department of Radiology
f Department of Pediatrics
g Department of Neuroscience
h School of Psychology, Georgia Institute of Technology, Atlanta, GA, USA
i Department of Psychology and
j Department of Neurological Surgery, Washington University in St Louis, St Louis, MO, USA
k VISN 17 Center of Excellence for Research on Returning War Veterans, Waco, TX, USA
l Center for Vital Longevity, School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, TX, USA

Control of goal-directed tasks is putatively carried out via the cinguloopercular (CO) and frontoparietal (FP) systems. However, it remains unclear whether these systems show dissociable moment-to-moment processing during distinct stages of a trial. Here, we characterize dynamics in the CO and FP networks in a meta-analysis of 5 decision-making tasks using fMRI, with a specialized "slow reveal" paradigm which allows us to measure the temporal characteristics of trial responses. We find that activations in left FP, right FP, and CO systems form separate clusters, pointing to distinct roles in decision-making. Left FP shows early "accumulator-like" responses, suggesting a role in pre-decision processing. CO has a late onset and transient response linked to the decision event, suggesting a role in performance reporting. The majority of right FP regions show late onsets with prolonged responses, suggesting a role in post-recognition processing. These findings expand upon past models, arguing that the CO and FP systems relate to distinct stages of processing within a trial. Furthermore, the findings provide evidence for a heterogeneous profile in the FP network, with left and right FP taking on specialized roles. This evidence informs our understanding of how distinct control networks may coordinate moment-to-moment components of complex actions. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail:

Author Keywords
decision-making;  executive control;  fMRI;  networks

Document Type: Article
Source: Scopus


Neta, M., Nelson, S.M., Petersen, S.E.
Dorsal Anterior Cingulate, Medial Superior Frontal Cortex, and Anterior Insula Show Performance Reporting-Related Late Task Control Signals
(2017) Cerebral cortex (New York, N.Y. : 1991), 27 (3), pp. 2154-2165. 

DOI: 10.1093/cercor/bhw053

a Department of Psychology, University of Nebraska-Lincoln, Lincoln, NE68588, USA
b VISN 17 Center of Excellence for Research on Returning War Veterans, Waco, TX 76711, USA
c Center for Vital Longevity, School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, TX 75235, USA
d Department of Neurology
e Department of Psychology
f Department of Radiology
g Department of Anatomy and Neurobiology
h Department of Neurosurgery
i Biomedical Engineering, Washington University, St. Louis, MO 63110, USA

The cingulo-opercular network (including the dorsal anterior cingulate and bilateral anterior insula) shows 3 distinct task-control signals across a wide variety of tasks, including trial-related signals that appear to come online at or near the end of the trial. Previous work suggests that there are separable responses in this network for errors and ambiguity, implicating multiple types of processing units within these regions. Using a unique paradigm, we directly show that these separable responses withhold activity to the end of the trial, in the service of reporting performance back into the task set. Participants performed a slow reveal task where images were presented behind a black mask which was gradually degraded, and they pressed a button when they could recognize the object that was being revealed. A behavioral pilot was used to identify ambiguous stimuli. We found interactive effects of accuracy and ambiguity, which suggests that these regions are computing and utilizing information, at one time, about both types of performance indices. Importantly, we showed a relationship between cingulo-opercular activity and behavioral performance, suggesting a role for these regions in performance reporting, per se. We discuss these results in the context of task control. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail:

Author Keywords
ambiguity;  error;  functional networks;  performance reporting;  task control

Document Type: Article
Source: Scopus


Church, J.A., Bunge, S.A., Petersen, S.E., Schlaggar, B.L.
Preparatory Engagement of Cognitive Control Networks Increases Late in Childhood
(2017) Cerebral cortex (New York, N.Y. : 1991), 27 (3), pp. 2139-2153. 

DOI: 10.1093/cercor/bhw046

a Department of Psychology, The University of Texas at Austin, Austin, TX 78712, USA
b Helen Wills Neuroscience Institute
c Department of Psychology, University of California at Berkeley, Berkeley, CA 94720, USA
d Department of Neurology
e Department of Radiology
f Department of Anatomy and Neurobiology
g Department of Neurosurgery
h Department of Psychology
i Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO 63130, USA
j Department of Pediatrics
k Department of Psychiatry, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA

The ability to engage task control flexibly, especially in anticipation of task demands, is beneficial when juggling different tasks. We investigated whether children in late childhood or early adolescence engaged preparatory task control similar to adults in a trial-wise cued task-switching paradigm. Twenty-eight children (aged 9-15 years) and 30 adults (aged 21-30 years) participated in an fMRI study in which the Cue (preparatory) period across 2 tasks was analyzed separately from the execution of the tasks (the Target period). Children performed more slowly and less accurately than adults, and showed behavioral improvement within the child group age range of 9-15 years. Children exhibited weaker Cue period activation than adults within a number of putative cognitive control regions. In contrast, children exhibited greater activity than adults in several regions, including sensorimotor areas, during the Target period. Children who activated cognitive control-related regions more during the Cue period tended to activate the Target signal age-related regions less, and this correlated with improved accuracy and reaction time on the task, as well as age. The results endorse previous findings that preparatory cognitive control systems are still developing in late childhood, but add new evidence of age-related shifts in activity at the trial level. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail:

Author Keywords
adolescence;  development;  fMRI;  fronto-parietal;  task-switching

Document Type: Article
Source: Scopus


Athiraman, U., Rich, K.M.
CON: Deep brain stimulator insertion for functional neurosurgery under general anesthesia
(2017) Journal of Neurosurgical Anesthesiology, 29 (3), pp. 350-351. 

DOI: 10.1097/01.ana.0000520880.78588.8e

a Department of Anesthesiology, Washington University, St Louis, MO, United States
b Neurological Surgery, Washington University, School of Medicine, St Louis, MO, United States

Document Type: Short Survey
Source: Scopus


He, S., Teagle, H.F.B., Buchman, C.A.
The electrically evoked compound action potential: From laboratory to clinic
(2017) Frontiers in Neuroscience, 11 (JUN), art. no. 339, . 

DOI: 10.3389/fnins.2017.00339

a Center for Hearing Research, Boys Town National Research Hospital, Omaha, NE, United States
b Department of Otolaryngology-Head and Neck Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
c Department of Otolaryngology-Head and Neck Surgery, Washington University, St. Louis, MO, United States

The electrically evoked compound action potential (eCAP) represents the synchronous firing of a population of electrically stimulated auditory nerve fibers. It can be directly recorded on a surgically exposed nerve trunk in animals or from an intra-cochlear electrode of a cochlear implant. In the past two decades, the eCAP has been widely recorded in both animals and clinical patient populations using different testing paradigms. This paper provides an overview of recording methodologies and response characteristics of the eCAP, as well as its potential applications in research and clinical situations. Relevant studies are reviewed and implications for clinicians are discussed. © 2017 He, Teagle and Buchman.

Author Keywords
Auditory nerve;  Clinical application;  Cochlear implant outco;  Electrically evoked compound action potential;  Stimulating paradigm

Document Type: Review
Source: Scopus


Beharie, N., Jessell, L., Osuji, H., McKay, M.M.
The association between shelter rules and psychosocial outcomes among homeless youth residing in family shelters
(2017) Families in Society, 98 (2), pp. 113-120. 

DOI: 10.1606/1044-3894.2017.98.16

a New York University, Behavioral Science Training (BST) Program, NYU Rory Meyers College of Nursing, 10 Chesterwood Ave., Mount Vernon, NY, United States
b New York University, United States
c Brown School, Washington University, St. Louis, United States

Despite growing numbers of homeless youth living in shelters with caregivers, little research has explored the impact of the shelter environment on emotional well-being. As such, this study assesses the relationship between shelter rules and two psychosocial outcomes among youth in New York City family shelters. Additionally, the direct effect of trauma and the moderating effect of difficulty following shelter rules on psychosocial outcomes was assessed. Youth with difficulty following shelter rules reported significantly more depressive symptoms, but less substance use. Trauma was found to be associated with increased depression and substance use. Difficulty following shelter rules was found to moderate the association between trauma and substance use. Recommendations for future interventions and the creation of shelter policies are discussed. © 2017 Alliance for Strong Families and Communities.

Document Type: Article
Source: Scopus


Salloum, N.C., Gott, B.M., Conway, C.R.
Sustained remission in patients with treatment-resistant depression receiving vagal nerve stimulation: A case series
(2017) Brain Stimulation, . Article in Press. 

DOI: 10.1016/j.brs.2017.06.001

Department of Psychiatry, Washington University in St. Louis, 660 S. Euclid Ave, Campus Box #8134, St. Louis, MO, USA

Author Keywords
Major depressive disorder;  Treatment-resistant depression;  Vagus nerve stimulation

Document Type: Article in Press
Source: Scopus


Sutter, E.N., Seidler, K.J., Duncan, R.P., Earhart, G.M., McNeely, M.E.
Low to moderate relationships between gait and postural responses in Parkinson's disease
(2017) Journal of Rehabilitation Medicine, 49 (6), pp. 505-511. 

DOI: 10.2340/16501977-2238

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

Objective: To evaluate the relationship between spatiotemporal parameters of forward and backward gait and quality of compensatory stepping responses in forward and backward directions in people with Parkinson's disease with and without freezing of gait. Design: Cross-sectional analysis. Subjects: A total of 111 individuals with mild to moderate Parkinson's disease. Methods: Forward and backward gait velocity and step length were evaluated using a GAITRite walkway. Forward and backward postural responses were evaluated using items from the Mini Balance Evaluation Systems Test and the Movement Disorders Society Unified Parkinson Disease Rating Scale motor subsection. Relationships between gait and postural responses were examined for the full sample and for sub-groups with and without freezing of gait. Results: There were significant (p < 0.05) low to moderate correlations between postural responses and gait overall. Correlations were similar in the freezer and non-freezer sub-groups. Freezers performed worse than non-freezers on all gait parameters and backward postural response items (p < 0.05). Conclusion: Low to moderate relationships between gait and postural responses indicate the complexity of postural control and the potential involvement of different neural circuitry across these tasks. Better understanding of the relationships between gait and postural deficits in Parkinson's disease may inform the future development of targeted interventions to address these impairments. © 2017 Foundation of Rehabilitation Information.

Author Keywords
Freezing of gait;  Gait;  Parkinson's disease;  Postural balance

Document Type: Article
Source: Scopus


Andelman, S.M., McAnany, S.J., Qureshi, S.A., Hecht, A.C.
Bilateral C5 motor palsy after anterior cervical decompression and fusion: A case report and review of the literature
(2017) International Journal of Spine Surgery, 11 (2), pp. 99-105. 

DOI: 10.14444/4014

a Mount Sinai Icahn School of Medicine, Department of Orthopaedic Surgery, Mount Sinai Hospital, New York, NY, United States
b Washington University, Department of Orthopaedic Surgery, St. Louis, MO, United States

Background Bilateral C5 motor palsy is a rare but potentially debilitating complication after cervical spine decompression with very few reports in the published literature. Purpose To present a case of bilateral C5 motor palsy after anterior cervical decompression and fusion and discuss the incidence and risk factors of this complication. Study Design/Setting We report a case of a 57-year-old male who underwent a three level C3-C6 anterior cervical discectomy and fusion with instrumentation who developed a postoperative bilateral C5 motor palsy. Methods A review of the literature was performed regarding reports on and incidence of post-operative bilateral C5 palsy following either anterior or posterior cervical spine decompression. Results Bilateral C5 motor palsy is a rare complication of cervical spine decompression with an overall incidence of 0.38%. Although a group of risk factors have been suggested no single cause has been identified. Conclusions Bilateral C5 motor palsy is a rare but debilitating complication of cervical decompression.

Author Keywords
Bilateral;  C5 palsy;  Cervical decompression

Document Type: Article
Source: Scopus


Cole, M.W., Patrick, L.M., Meiran, N., Braver, T.S.
A role for proactive control in rapid instructed task learning
(2017) Acta Psychologica, . Article in Press. 

DOI: 10.1016/j.actpsy.2017.06.004

a Psychology Department, Washington University in St. Louis, MO 63130, United States
b Center for Molecular and Behavioral Neuroscience, Rutgers University, NJ 07102, United States
c Department of Psychology and Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel

Humans are often remarkably fast at learning novel tasks from instructions. Such rapid instructed task learning (RITL) likely depends upon the formation of new associations between long-term memory representations, which must then be actively maintained to enable successful task implementation. Consequently, we hypothesized that RITL relies more heavily on a proactive mode of cognitive control, in which goal-relevant information is actively maintained in preparation for anticipated high control demands. We tested this hypothesis using a recently developed cognitive paradigm consisting of 60 novel tasks involving RITL and 4 practiced tasks, with identical task rules and stimuli used across both task types. A robust behavioral cost was found in novel relative to practiced task performance, which was present even when the two were randomly inter-mixed, such that task-switching effects were equated. Novelty costs were most prominent under time-limited preparation conditions. In self-paced conditions, increased preparation time was found for novel trials, and was selectively associated with enhanced performance, suggesting greater proactive control for novel tasks. These results suggest a key role for proactive cognitive control in the ability to rapidly learn novel tasks from instructions. © 2017 Elsevier B.V.

Author Keywords
Cognitive control;  Proactive control;  Rapid instructed task learning

Document Type: Article in Press
Source: Scopus


Zhang, P., Li, L., Lin, L., Hu, P., Shi, J., He, Y., Zhu, L., Zhou, Y., Wang, L.V.
High-resolution deep functional imaging of the whole mouse brain by photoacoustic computed tomography invivo
(2017) Journal of Biophotonics, . Article in Press. 

DOI: 10.1002/jbio.201700024

a Optical Imaging Laboratory, Department of Biomedical Engineering Washington University in St. Louis St. Louis, Missouri 63130 USA
b Department of Medical Engineering California Institute of Technology 1200 E California Blvd. Pasadena, CA 91125
c Department of Electrical Engineering California Institute of Technology 1200 E California Blvd., Pasadena, CA 91125

Photoacoustic computed tomography (PACT) is a non-invasive imaging technique offering high contrast, high resolution, and deep penetration in biological tissues. We report a PACT system equipped with a high frequency linear transducer array for mapping the microvascular network of a whole mouse brain with the skull intact and studying its hemodynamic activities. The linear array was scanned in the coronal plane to collect data from different angles, and full-view images were synthesized from the limited-view images in which vessels were only partially revealed. We investigated spontaneous neural activities in the deep brain by monitoring the concentration of hemoglobin in the blood vessels and observed strong interhemispherical correlations between several chosen functional regions, both in the cortical layer and in the deep regions. We also studied neural activities during an epileptic seizure and observed the epileptic wave spreading around the injection site and the wave propagating in the opposite hemisphere. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Author Keywords
Deep mouse brain;  Functional imaging;  Photoacoustic computed tomography

Document Type: Article in Press
Source: Scopus


Zero, V.H., Barocas, A., Jochimsen, D.M., Pelletier, A., Giroux-Bougard, X., Trumbo, D.R., Castillo, J.A., Mack, D.E., Linnell, M.A., Pigg, R.M., Hoisington-Lopez, J., Spear, S.F., Murphy, M.A., Waits, L.P.
Complementary network-based approaches for exploring genetic structure and functional connectivity in two vulnerable, endemic ground squirrels
(2017) Frontiers in Genetics, 8 (JUN), art. no. 81, . 

DOI: 10.3389/fgene.2017.00081

a Haub School of Environment and Natural Resources, University of Wyoming, Laramie, WY, United States
b Department of Zoology and Physiology, University of Wyoming, Laramie, WY, United States
c University of Wyoming, Laramie, WY, United States
d Department of Biological Sciences, University of Idaho, Moscow, ID, United States
e Department of Environmental Studies and Sciences, University of Winnipeg, Winnipeg, MB, Canada
f Department of Natural Resource Sciences, McGill University, Montreal, QC, Canada
g School of Biological Sciences, Washington State University, Pullman, WA, United States
h Department of Fisheries and Wildlife, Oregon State University, Corvallis, OR, United States
i Idaho Department of Fish and Game, McCall Subregion, McCall, ID, United States
j Division of Biology, Kansas State University, Manhattan, KS, United States
k The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, United States
l The Wilds, Cumberland, OH, United States
m Department of Ecosystem Science and Management, University of Wyoming, Laramie, WY, United States
n Department of Fish and Wildlife Sciences, University of Idaho, Moscow, ID, United States

The persistence of small populations is influenced by genetic structure and functional connectivity. We used two network-based approaches to understand the persistence of the northern Idaho ground squirrel (Urocitellus brunneus) and the southern Idaho ground squirrel (U. endemicus), two congeners of conservation concern. These graph theoretic approaches are conventionally applied to social or transportation networks, but here are used to study population persistence and connectivity. Population graph analyses revealed that local extinction rapidly reduced connectivity for the southern species, while connectivity for the northern species could be maintained following local extinction. Results from gravity models complemented those of population graph analyses, and indicated that potential vegetation productivity and topography drove connectivity in the northern species. For the southern species, development (roads) and small-scale topography reduced connectivity, while greater potential vegetation productivity increased connectivity. Taken together, the results of the two network-based methods (population graph analyses and gravity models) suggest the need for increased conservation action for the southern species, and that management efforts have been effective at maintaining habitat quality throughout the current range of the northern species. To prevent further declines, we encourage the continuation of management efforts for the northern species, whereas conservation of the southern species requires active management and additional measures to curtail habitat fragmentation. Our combination of population graph analyses and gravity models can inform conservation strategies of other species exhibiting patchy distributions. © 2017 Zero, Barocas, Jochimsen, Pelletier, Giroux-Bougard, Trumbo, Castillo, Evans Mack, Linnell, Pigg, Hoisington-Lopez, Spear, Murphy and Waits.

Author Keywords
Functional connectivity;  Gene flow;  Graph theory;  Gravity model;  Landscape genetics;  Sciuridae;  Urocitellus [Spermophilus]

Document Type: Article
Source: Scopus


Bove, R., Elsone, L., Alvarez, E., Borisow, N., Cortez, M.M., Mateen, F.J., Mealy, M.A., Mutch, K., Tobyne, S., Ruprecht, K., Buckle, G., Levy, M., Wingerchuk, D.M., Paul, F., Cross, A.H., Weinshenker, B., Jacob, A., Klawiter, E.C., Chitnis, T.
Female hormonal exposures and neuromyelitis optica symptom onset in a multicenter study
(2017) Neurology: Neuroimmunology and NeuroInflammation, 4 (3), art. no. e339, . 

DOI: 10.1212/NXI.0000000000000339

a Brigham and Women's Hospital, Boston, MA, United States
b Harvard Medical School, Boston, MA, United States
c Walton Centre NHS Foundation Trust, Liverpool, United Kingdom
d Washington University, School of Medicine, St. Louis, MO, United States
e Charité-Universitätsmedizin Berlin, Germany
f University of Utah, Imaging and Neurosciences Center, Salt Lake City, United States
g Massachusetts General Hospital, Boston, United States
h Johns Hopkins Medical Institute, Baltimore, MD, United States
i MS Institute, Shepherd Center, Atlanta, GA, United States
j Mayo Clinic, Rochester, MN, United States
k Mayo Clinic, Scottsdale, AZ, United States

Objective: To study the association between hormonal exposures and disease onset in a cohort of women with neuromyelitis optica spectrum disorder (NMOSD). Methods: Reproductive history and hormone use were assessed using a standardized reproductivesurveyadministered towomen with NMOSD (82% aquaporin-4antibody positive) at 8clinical centers. Using multivariable regression, we examined the association between reproductive exposures and age at first symptom onset (FS). Results: Among 217 respondents, the mean age at menarche was 12.8 years (SD 1.7). The mean number of pregnancies was 2.1 (SD 1.6), including 0.3 (SD 0.7) occurring after onset of NMOSD symptoms. In the 117 participants who were postmenopausal at the time of the questionnaire, 70% reported natural menopause (mean age: 48.9 years [SD 3.9]); fewer than 30% reported systemic hormone therapy (HT) use. Mean FS age was 40.1 years (SD 14.2). Ever-use of systemic hormonal contraceptives (HC) was marginally associated with earlier FS (39 vs 43 years, p 5 0.05). Because HC use may decrease parity, when we included both variables in the model, the association between HC use and FS age became more significant (estimate 5 2.7, p 5 0.007). Among postmenopausal participants, 24% reported NMOSD onset within 2 years of (before or after) menopause. Among these participants, there was no association between age at menopause or HT use and age at NMOSD onset. Conclusions: Overall, age at NMOSD onset did not show a strong relationship with endogenous hormonal exposures. An earlier onset age did appear to be marginally associated with systemic HC exposure, an association that requires confirmation in future studies. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Document Type: Article
Source: Scopus


Tempelhoff, R.
General versus local anesthesia for deep brain stimulator insertion
(2017) Journal of Neurosurgical Anesthesiology, 29 (3), p. 347. 

DOI: 10.1097/ANA.0000000000000394

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

Document Type: Note
Source: Scopus


Hajirezaei, S., Mohammadi, A., Soleimani, M., Rahiminezhad, F., Mohammadi, M.R., Cloninger, C.R.
Comparing the profile of temperament and character dimensions in patients with major depressive disorder and bipolar mood disorder with a control group
(2017) Iranian Journal of Psychiatry, 12 (3), pp. 147-153. 

a Department of Psychiatry, Tehran University of Medical Sciences, Tehran, Iran
b Psychiatric and Psychology Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran
c Center for Psychobiology of Personality, Sansone Center for Well-Being, Washington University St Louis, St Louis, MO, United States

Objective: This study was conducted to compare the profile of temperament and character dimensions in patients with major depressive disorder and bipolar mood disorder with a control group. Method: In this causal-comparative study, the population consisted of 2 clinical groups (major depressive disorder and bipolar mood disorder) and a non-clinical group. The sample was 193 individuals (77 patients with major depressive disorder, 86 patients with bipolar mood disorder, and 30 controls), with an age range of 18 to 65 years and the mean age of 40.1. They were selected from Roozbeh psychiatric hospital using available sampling method. Tools used in this research included Temperament and Character Inventory-140 and General Health Questionnaire-28. Collected data were analyzed by independent t test and one-way analysis of variance using Statistical Package for the Social Sciences-22 software. Results: The results revealed a significant difference among groups in dimensions of novelty seeking, harm avoidance, persistence, self-directedness, and cooperativeness (P < 0.05). The results showed that the mean was different in males and females only in the novelty seeking dimension (P < 0.05). Conclusion: In general, our results revealed that patients with major depressive disorder and bipolar mood disorder have different personality profiles in some dimensions of temperament and character compared with the control group.

Author Keywords
Bipolar mood disorder;  Control group;  Major depressive disorder;  Personality profile;  Temperament and character inventory

Document Type: Article
Source: Scopus


Commean, P.K., Smith, K.E., Hildebolt, C.F., Bohnert, K.L., Sinacore, D.R., Prior, F.W.
A Candidate Imaging Marker for Early Detection of Charcot Neuroarthropathy
(2017) Journal of Clinical Densitometry, . Article in Press. 

DOI: 10.1016/j.jocd.2017.05.008

a Electronic Radiology Laboratory, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, USA
b Department of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
c Applied Kinesiology Laboratory, Program in Physical Therapy, Washington University School of Medicine, St. Louis, MO, USA

Inflammation-mediated foot osteopenia may play a pivotal role in the etiogenesis, pathogenesis, and therapeutic outcomes in individuals with diabetes mellitus (DM), peripheral neuropathy (PN), and Charcot neuroarthropathy (CN). Our objective was to establish a volumetric quantitative computed tomography-derived foot bone measurement as a candidate prognostic imaging marker to identify individuals with DMPN who were at risk of developing CN. We studied 3 groups: 16 young controls (27 ± 5 years), 20 with DMPN (57 ± 11 years), and 20 with DMPN and CN (55 ± 9 years). Computed tomography image analysis was used to measure metatarsal and tarsal bone mineral density in both feet. The mean of 12 right (7 tarsals and 5 metatarsals) and 12 left foot bone mineral densities, maximum percent difference in bone mineral density between paired bones of the right and the left feet, and the mean difference of the 12 right and the 12 left bone mineral density measurements were used as input variables in different classification analysis methods to determine the best classifier. Classification tree analysis produced no misclassification of the young controls and individuals with DMPN and CN. The tree classifier found 7 of 20 (35%) individuals with DMPN to be classified as CN (1 participant developed CN during follow-up) and 13 (65%) to be classified as healthy. These results indicate that a decision tree employing 3 measurements derived from volumetric quantitative computed tomography foot bone mineral density defines a candidate prognostic imaging marker to identify individuals with diabetes and PN who are at risk of developing CN. © 2017 The International Society for Clinical Densitometry.

Author Keywords
Candidate imaging marker;  Charcot neuroarthropathy;  Diabetes mellitus;  Foot bone mineral density;  Peripheral neuropathy

Document Type: Article in Press
Source: Scopus


Gilmore, A.W., Nelson, S.M., Chen, H.-Y., McDermott, K.B.
Task-related and resting-state fMRI identify distinct networks that preferentially support remembering the past and imagining the future
(2016) Neuropsychologia, . Article in Press. 

DOI: 10.1016/j.neuropsychologia.2017.06.016

a Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, MO 63130, USA
b Department of Radiology, Washington University in St. Louis, St. Louis, MO 63110, USA
c VISN 17 Center of Excellence for Research on Returning War Veterans, Waco, TX 76711, USA
d Center for Vital Longevity, School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, TX 75235, USA
e Department of Psychology and Neuroscience, Baylor University, Waco, TX 76789, USA

The relation between episodic memory and episodic future thought (EFT) remains an active target of research. A growing literature suggests that similar cognitive processes and neural substrates tend to support these acts. However, direct comparisons of whole-brain activity reveal clear differences, with numerous regions more active when engaging in EFT than when remembering, and a smaller collection of regions displaying the opposite pattern of activity. Although various network labels have been applied to prior neuroimaging results, to date no formal resting-state functional connectivity analysis has been conducted. In the current experiment, 48 subjects remembered events from their past and engaged in EFT. Resting-state data were collected from all subjects. Task results replicated recent findings, with more activity during EFT in regions across frontal and parietal cortex, and with more activity during remembering in a smaller number of predominantly parahippocampal and retrosplenial regions. Resting-state connectivity analysis, based on seed locations defined using the fMRI task data, indicated that regions preferentially activated during EFT fell primarily within the default mode network, while those more active during remembering fell primarily within the contextual association network. These results suggest that despite their general similarity, the functional network membership of regions showing task differences is dissociable. We discuss our results in light of several hypotheses that attempt to relate remembering and EFT, and suggest that the data speak to differences in the relative contributions of episodic and semantic memory, as well as controlled and automatic processing, during the acts of remembering or engaging in EFT. © 2017.

Author Keywords
Contextual association network;  Default mode network;  Episodic future thought;  Episodic memory;  Resting-state functional connectivity

Document Type: Article in Press
Source: Scopus


Santibáñez-Briones, V., García-Santibáñez, R.
Clinical reasoning: 57 year-old male with pain and proximal muscle weakness [Razonamiento Clínico: Hombre de 57 Años de Edad con Dolor y Debilidad Muscular Proximal]
(2016) Revista Ecuatoriana de Neurologia, 25 (1-3), pp. 76-79. 

a Departamento de Medicina Interna, Icahn School of Medicine at Mount Sinai, Mount Sinai, United States
b Departamento de Medicina Neuromuscular, Washington University, St. Louis, United States

We present a case of a 57-year-old man with a two-month history of shoulder pain and proximal weakness. The history and physical examination are reviewed and a stepwise approach to the differential diagnosis is made to reach the final diagnosis. Keywords: differential diagnosis, proximal weakness, diabetes mellitus.

Document Type: Article
Source: Scopus


Aguirre-Fernández, D., Garcia-Santibanez, R.
Sporadic inclusion body myositis [Miositis Esporádica por Cuerpos de Inclusión]
(2016) Revista Ecuatoriana de Neurologia, 25 (1-3), pp. 44-49. 

a Médico, Universidad Católica de Santiago de Guayaquil, Ecuador
b Departamento de Neurología, Washington University, St. Louis, United States

Sporadic inclusion body myositis is a common acquired inflammatory myopathy in people over 50 years of age. It presents with slowly progressive asymmetric weakness that affects preferentially the quadriceps and deep finger flexors. The pathogenesis is poorly understood. The diagnosis is made with a combination of the clinical history, physical exam, electrodiagnostic tests, imaging, serology and histopathology. There is no treatment for this condition but multiple therapies are currently being investigated.

Author Keywords
Inclusion bodies;  Inflammation;  Myopathy;  Pathogenesis;  Pathology

Document Type: Review
Source: Scopus