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Neuroscience Publications Archive - January 2017


Weekly Scopus Report

 January 20, 2017



Carter, A.R.a , McAvoy, M.P.b , Siegel, J.S.a , Hong, X.a , Astafiev, S.V.b , Rengachary, J.a , Zinn, K.b , Metcalf, N.V.a , Shulman, G.L.a , Corbetta, M.a b c 
Differential white matter involvement associated with distinct visuospatial deficits after right hemisphere stroke
(2017) Cortex, 88, pp. 81-97. 

DOI: 10.1016/j.cortex.2016.12.009

a Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
b Department of Radiology, Washington University School of Medicine, St. Louis, MO, United States
c Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO, United States

Visuospatial attention depends on the integration of multiple processes, and people with right hemisphere lesions after a stroke may exhibit severe or no visuospatial deficits. The anatomy of core components of visuospatial attention is an area of intense interest. Here we examine the relationship between the disruption of core components of attention and lesion distribution in a heterogeneous group (N = 70) of patients with right hemisphere strokes regardless of the presence of clinical neglect. Deficits of lateralized spatial orienting, measured as the difference in reaction times for responding to visual targets in the contralesional or ipsilesional visual field, and deficits in re-orienting attention, as measured by the difference in reaction times for invalidly versus validly cued targets, were measured using a computerized spatial orienting task. Both measures were related through logistic regression and a novel ridge regression method to anatomical damage measured with magnetic resonance imaging. While many regions were common to both deficit maps, a deficit in lateralized spatial orienting was more associated with lesions in the white matter underlying the posterior parietal cortex, and middle and inferior frontal gyri. A deficit in re-orienting of attention toward unattended locations was associated with lesions in the white matter of the posterior parietal cortex, insular cortex and less so with white matter involvement of the anterior frontal lobe. An hodological analysis also supports this partial dissociation between the white matter tracts that are damaged in lateralized spatial biases versus impaired re-orienting. Our results underscore that the integrity of fronto-parietal white matter tracts is crucial for visuospatial attention and that different attention components are mediated by partially distinct neuronal substrates. © 2016 Elsevier Ltd

Author Keywords
Hemispatial neglect;  Logistic regression;  Stroke;  Visuospatial attention;  White matter

Document Type: Article
Source: Scopus



Scherrer, J.F.a b , Salas, J.a b , Schneider, F.D.a , Bucholz, K.K.c , Sullivan, M.D.d , Copeland, L.A.e f g , Ahmedani, B.K.h , Burroughs, T.i , Lustman, P.J.c j 
Characteristics of new depression diagnoses in patients with and without prior chronic opioid use
(2017) Journal of Affective Disorders, 210, pp. 125-129. 

DOI: 10.1016/j.jad.2016.12.027

a Department of Family and Community Medicine, Saint Louis University School of Medicine, St. Louis, MO, United States
b Harry S. Truman Veterans Administration Medical Center, Columbia, MO, United States
c Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
d Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA, United States
e Center for Applied Health Research, Baylor Scott & White Health, Temple, TX, United States
f VA Central Western Massachusetts Healthcare System, Leeds, MA and Central Texas Veterans Health Care System, Temple, TX, United States
g UT Health Science Center, San Antonio, TX, United States
h Henry Ford Health System, Center for Health Policy and Health Services Research and Department of Psychiatry, Detroit, MI, United States
i Saint Louis University Center for Outcomes Research, St. Louis, MO, United States
j The Bell Street Clinic, VA St. Louis Health Care System – John Cochran Division, St. Louis, MO, United States

Chronic use (>90 Days) of opioid analgesics significantly increases the risk of development of new depression episodes (NDE). It is unclear whether depression that develops in this manner is similar to or different from NDE in persons not exposed to opioid analgesic use (OAU). Methods VA patients were classified into two groups, those who did not receive an opioid and developed depression (non-OAU+NDE, n=4314) and those that had >90 days OAU and developed NDE (OAU+NDE, n=444). OAU+NDE patients were compared to non-OAU+NDE in terms of depression severity (PHQ-9 scores), incidence of PTSD, other anxiety disorders and substance use disorders after NDE, receipt of acute phase antidepressant treatment, dual antidepressant treatment, mood stabilizers and atypical antipsychotics. Prior to computing bivariate analysis, the prevalence of pain conditions and average maximum pain scores were equalized between the two groups using propensity scores and inverse probability of treatment weighting. Results Controlling for pain, OAU+NDE patients had more depression symptoms (p=.012), more incident PTSD (p=.04) and opioid abuse/dependence and were more likely to receive 12 weeks of antidepressant treatment (p<.0001). Last, non-OAU+NDE were more likely to have incident diagnoses for any other anxiety disorder (p=.014). Conclusions Within the limitations of electronic medical record data, results indicate OAU+NDE patients have more depression symptoms, greater treatment adherence and different comorbid psychiatric conditions compared to non-OAU+NDE, independent of pain. Overall OAU related depression is as severe as non-OAU related depression and repeated depression screening in chronic opioid therapy may be warranted for pain patients, regardless of pain severity. © 2016

Author Keywords
Depression;  Epidemiology;  Opioids;  Retrospective cohort

Document Type: Article
Source: Scopus



Salas-Wright, C.P.a , Vaughn, M.G.b , Cummings-Vaughn, L.A.c , Holzer, K.J.b , Nelson, E.J.d , AbiNader, M.a , Oh, S.e 
Trends and correlates of marijuana use among late middle-aged and older adults in the United States, 2002–2014
(2017) Drug and Alcohol Dependence, 171, pp. 97-106. 

DOI: 10.1016/j.drugalcdep.2016.11.031

a School of Social Work, Boston University, Boston, MA, United States
b School of Social Work, College for Public Health and Social Justice, Saint Louis University, St. Louis, MO, United States
c School of Medicine, Washington University, St. Louis, MO, United States
d School of Public Health, Indiana University, Bloomington, IN, United States
e School of Social Work, The University of Texas at Austin, Austin, TX, United States

Background Recent trend studies suggest that marijuana use is on the rise among the general population of adults ages 18 and older in the United States. However, little is known about the trends in marijuana use and marijuana-specific risk/protective factors among American adults during the latter part of adulthood. Method Findings are based on repeated, cross-sectional data collected from late middle-aged (ages 50–64) and older adults (ages 65 and older) surveyed as part of the National Survey on Drug Use and Health between 2002 and 2014. Results The prevalence of past-year marijuana use among late middle-aged adults increased significantly from a low of 2.95% in 2003 to a high of 9.08% in 2014. Similarly, the prevalence of marijuana use increased significantly among older adults from a low of 0.15% in 2003 to a high of 2.04% in 2014. Notably, the upward trends in marijuana use remained significant even when accounting for sociodemographic, substance use, behavioral, and health-related factors. We also found that decreases in marijuana-specific protective factors were associated with the observed trend changes in marijuana use among late middle-aged and older adults, and observed a weakening of the association between late-middle aged marijuana use and risk propensity, other illicit drug use, and criminal justice system involvement over the course of the study. Conclusions Findings from the present study provide robust evidence indicating that marijuana use among older Americans has increased markedly in recent years, with the most evident changes observed between 2008 and 2014. © 2016 Elsevier Ireland Ltd

Author Keywords
Adulthood;  Marijuana;  Older adults;  Risk and protective factors;  Trends

Document Type: Article
Source: Scopus



Barceló, J.
National Personality Traits and Regime Type: A Cross-National Study of 47 Countries
(2017) Journal of Cross-Cultural Psychology, 48 (2), pp. 195-216. 

DOI: 10.1177/0022022116678324

Washington University in St. LouisMO, United States

Domestic theories of democratization emphasize the role of values, interests, and mobilization/opportunities as determinants of regime change. This article takes a step back and develops a model of national personality and democratization to ascertain the indirect effect of national personality traits on worldwide variation of regime type. In particular, I theorize that personality traits influence a country’s regime type by shaping citizens’ traditional and self-expression values, which, in turn, influence the establishment and consolidation of democratic institutions. Data from McCrae and Terracciano’s assessment of the five-factor model from 47 countries allow me to assess this hypothesis empirically. Results reveal that countries whose societies are high in Openness to experience tend to have more democratic institutions, even after adjusting for relevant confounders: economic inequalities, economic development, technological advancement, disease stress, climate demands, and methodological characteristics of the national sample. Although the effect of Extraversion on a country’s democratic institutions is also significantly positive, the inclusion of confounders weakens the reliability of this association. In an exploration of the mechanisms of these associations, a mediation analysis shows that the relationship between national Openness and democratic institutions is channeled through secular and especially self-expression national values. The same analysis with the effect of Extraversion on democracy indicates that the association between this trait and democracy is only channeled through national self-expression values but not national secular values. In short, this article constitutes a first step toward a more complete understanding of the cross-cultural psychological roots of political institutions. © 2016, © The Author(s) 2016.

Author Keywords
attitudes;  beliefs;  cultural psychology;  group processes;  national development;  personality;  values

Document Type: Article
Source: Scopus



Corseuil Giehl, M.W.a , Hallal, P.C.b , Brownson, R.C.c , D'Orsi, E.a 
Exploring Associations between Perceived Measures of the Environment and Walking among Brazilian Older Adults
(2017) Journal of Aging and Health, 29 (1), pp. 45-67. 

DOI: 10.1177/0898264315624904

a Federal University of Santa Catarina, Post-Graduation Program in Public Health, 173 Dina Calixto Street, Florianopolis, Santa Catarina, Brazil
b Federal University of Pelotas, Rio Grande do Sul, Brazil
c Washington University, St. Louis, MO, United States

Objective: To investigate the associations between perceived environment features and walking in older adults. Method: A cross-sectional population-based study was performed in Florianopolis, Brazil, including 1,705 older adults (60+ years). Walking was measured by the International Physical Activity Questionnaire (IPAQ), and perceived environment was assessed through the Neighborhood Environment Walkability Scale. We conducted a multinomial logistic regression to examine the association between perceived environment and walking. Results: The presence of sidewalks was related to both walking for transportation and for leisure. Existence of crosswalks in the neighborhood, safety during the day, presence of street lighting, recreational facilities, and having dog were significant predictors of walking for transportation. Safety during the day and social support were significantly associated with walking for leisure. Discussion: The perceived environment may affect walking for specific purposes among older adults. Investments in the environment may increase physical activity levels of older adults in Brazil. © The Author(s) 2016.

Author Keywords
older adults;  perceived environment;  walking

Document Type: Article
Source: Scopus



Holehouse, A.S., Das, R.K., Ahad, J.N., Richardson, M.O.G., Pappu, R.V.
CIDER: Resources to Analyze Sequence-Ensemble Relationships of Intrinsically Disordered Proteins
(2017) Biophysical Journal, 112 (1), pp. 16-21. 

DOI: 10.1016/j.bpj.2016.11.3200

Department of Biomedical Engineering and Center for Biological Systems Engineering, Washington University in St. Louis, St. Louis, Missouri, United States

Intrinsically disordered proteins and regions (IDPs) represent a large class of proteins that are defined by conformational heterogeneity and lack of persistent tertiary/secondary structure. IDPs play important roles in a range of biological functions, and their dysregulation is central to numerous diseases, including neurodegeneration and cancer. The conformational ensembles of IDPs are encoded by their amino acid sequences. Here, we present two computational tools that are designed to enable rapid and high-throughput analyses of a wide range of physicochemical properties encoded by IDP sequences. The first, CIDER, is a user-friendly webserver that enables rapid analysis of IDP sequences. The second, localCIDER, is a high-performance software package that enables a wide range of analyses relevant to IDP sequences. In addition to introducing the two packages, we demonstrate the utility of these resources using examples where sequence analysis offers biophysical insights. © 2017 Biophysical Society

Document Type: Article
Source: Scopus



George, S.C.a , Meyerand, M.E.b , On Behalf Of The Council Of Chairs Of Biomedical Engineeringc 
Challenges and Opportunities: Building a Relationship Between a Department of Biomedical Engineering and a Medical School
(2017) Annals of Biomedical Engineering, pp. 1-4. Article in Press. 

DOI: 10.1007/s10439-016-1785-1

a Washington University in St. Louis, St. Louis, MO, United States
b University of Wisconsin-Madison, Madison, WI, United States

A department of biomedical engineering can significantly enhance the impact of their research and training programs if a productive relationship with a medical school can be established. In order to develop such a relationship, significant hurdles must be overcome. This editorial summarizes some of the major challenges and opportunities for a department of biomedical engineering as they seek to build or enhance a relationship with a medical school. The ideas were formulated by engaging the collective wisdom from the Council of Chairs of the biomedical engineering departments. © 2017 The Author(s)

Author Keywords
Academic department;  Research program;  Teaching program

Document Type: Article in Press
Source: Scopus



López, J.D.a , Shacham, E.a , Brown, T.b 
Suicidal Ideation Persists Among Individuals Engaged in HIV Care in the Era of Antiretroviral Therapy
(2017) AIDS and Behavior, pp. 1-6. Article in Press. 

DOI: 10.1007/s10461-016-1666-5

a Department of Behavioral Sciences and Health Education, College for Public Health and Social Justice, Saint Louis University, 3545 Lafayette Avenue, Saint Louis, MO, United States
b Infectious Diseases Clinic and Project ARK, Washington University School of Medicine, 620 South Taylor Avenue, Suite 100, Saint Louis, MO, United States

Little research has focused on suicidality in the era of successful antiretroviral therapy among those engaged in HIV care. We performed a study of 648 clinic patients who completed a psychological and behavioral annual assessment in 2012. Depressive symptoms were measured using the Patient Health Questionnaire-9 (PHQ-9), suicidal ideation was measured by the last item of the scale. Anxiety symptoms were measured using the Generalized Anxiety Disorder-7 questionnaire (GAD-7). HIV biomedical markers were abstracted from medical records. Suicidal ideation was reported among 13% (n = 81) of the sample. Individuals endorsing suicidality were more likely to have unsuppressed viral loads, moderate to severe anxiety symptoms and consider themselves to be homeless (p < 0.01 for all). After adjusting for confounders, homeless individuals and those endorsing moderate to severe anxiety symptoms had higher odds of reporting suicidality. Results suggest basic needs must be met to complement HIV management efforts. Furthermore, better understanding of how psychological distress symptoms are expressed and how to manage them may better inform barriers to HIV management. © 2017 Springer Science+Business Media New York

Author Keywords
Depression;  HIV;  Psychological distress;  Suicidal ideation

Document Type: Article in Press
Source: Scopus



Carney, R.M., Freedland, K.E.
Reply: NLRP3 inflammasome as a mechanism linking depression and cardiovascular diseases
(2017) Nature Reviews Cardiology, . Article in Press. 

DOI: 10.1038/nrcardio.2016.215

Washington University School of Medicine, 4320 Forest Park Avenue, Suite 301, St. Louis, Missouri 63108, USA.

Document Type: Article in Press
Source: Scopus



Human, T.a , Cook, A.M.b , Anger, B.c , Bledsoe, K.d , Castle, A.e , Deen, D.f , Gibbs, H.g , Lesch, C.h , Liang, N.i , McAllen, K.j , Morrison, C.k , Parker, D., Jrl , Rowe, A.S.m , Rhoney, D.n , Sangha, K.o , Santayana, E.p , Taylor, S.q , Tesoro, E.r , Brophy, G.s 
Treatment of Hyponatremia in Patients with Acute Neurological Injury
(2017) Neurocritical Care, pp. 1-7. Article in Press. 

DOI: 10.1007/s12028-016-0343-x

a Barnes Jewish Hospital, Washington University St. Louis, St. Louis, MO, United States
b University of Kentucky, Lexington, KY, United States
c Saint Louis University Hospital, St. Louis, MO, United States
d University of Virginia Health System, Charlottesville, VA, United States
e Yale-New Haven Hospital, New Haven, CT, United States
f Memorial University Center, Savannah, GA, United States
g Johns Hopkins Hospital, Baltimore, MD, United States
h New York Presbyterian Hospital, New York, NY, United States
i Hartford Hospital, Hartford, CT, United States
j Spectrum Health, Grand Rapids, MI, United States
k Jackson Memorial Hospital, Miami, FL, United States
l Detroit Receiving Hospital, Detroit, MI, United States
m University of Tennessee, Knoxville, TN, United States
n University of North Carolina, Chapel Hill, NC, United States
o University of Cincinnati-University Hospital, Cincinnati, OH, United States
p University of Chicago Medical Center, Chicago, IL, United States
q Via Cristi, Wichita, KS, United States
r University of Illinois-Chicago, Chicago, IL, United States
s Virginia Commonwealth of Virginia, Medical College of Virginia, Richmond, VA, United States

Background: Little data exist regarding the practice of sodium management in acute neurologically injured patients. This study describes the practice variations, thresholds for treatment, and effectiveness of treatment in this population. Methods: This retrospective, multicenter, observational study identified 400 ICU patients, from 17 centers, admitted for ≥48 h with subarachnoid hemorrhage (SAH), traumatic brain injury (TBI), intraparenchymal hemorrhage, or intracranial tumors between January 1, 2011 and July 31, 2012. Data collection included demographics, APACHE II, Glascow Coma Score (GCS), serum sodium (Na+), fluid rate and tonicity, use of sodium-altering therapies, intensive care unit (ICU) and hospital length of stay, and modified Rankin score upon discharge. Data were collected for the first 21 days of ICU admission or ICU discharge, whichever came first. Sodium trigger for treatment defined as the Na+ value prior to treatment with response defined as an increase of ≥4 mEq/L at 24 h. Results: Sodium-altering therapy was initiated in 34 % (137/400) of patients with 23 % (32/137) having Na+ &gt;135 mEq/L at time of treatment initiation. The most common indications for treatment were declining serum Na+ (68/116, 59 %) and cerebral edema with mental status changes (21/116, 18 %). Median Na+ treatment trigger was 133 mEq/L (IQR 129–139) with no difference between diagnoses. Incidence and treatment of hyponatremia was more common in SAH and TBI [SAH (49/106, 46 %), TBI (39/97, 40 %), ICH (27/102, 26 %), tumor (22/95, 23 %); p = 0.001]. The most common initial treatment was hypertonic saline (85/137, 62 %), followed by oral sodium chloride tablets (42/137, 31 %) and fluid restriction (15/137, 11 %). Among treated patients, 60 % had a response at 24 h. Treated patients had lower admission GCS (12 vs. 14, p = 0.02) and higher APACHE II scores (12 vs. 10, p = 0.001). There was no statistically significant difference in outcome when comparing treated and untreated patients. Conclusion: Sodium-altering therapy is commonly employed among neurologically injured patients. Hypertonic saline infusions were used first line in more than half of treated patients with the majority having a positive response at 24 h. Further studies are needed to evaluate the impact of various treatments on patient outcomes. © 2016 Springer Science+Business Media New York

Author Keywords
Hyponatremia;  Intensive care unit;  Intracerebral hemorrhage;  Intracranial tumor;  Neurocritical care;  Subarachnoid hemorrhage;  Traumatic brain injury

Document Type: Article in Press
Source: Scopus



Oreland, L.a , Lagravinese, G.a , Toffoletto, S.a , Nilsson, K.W.b , Harro, J.c d , Robert Cloninger, C.e , Comasco, E.a 
Personality as an intermediate phenotype for genetic dissection of alcohol use disorder
(2017) Journal of Neural Transmission, pp. 1-24. Article in Press. 

DOI: 10.1007/s00702-016-1672-9

a Department of Neuroscience, Uppsala University, BMC, Box 593, Uppsala, Sweden
b Centre for Clinical Research, Uppsala University, Västmanland County Counci, Västerås, Sweden
c Division of Neuropsychopharmacology, Department of Psychology, University of Tartu, Tartu, Estonia
d Psychiatry Clinic, North Estonia Medical Centre, Tallinn, Estonia
e Department of Psychiatry, School of Medicine, Washington University, St. Louis, MO, United States

Genetic and environmental interactive influences on predisposition to develop alcohol use disorder (AUD) account for the high heterogeneity among AUD patients and make research on the risk and resiliency factors complicated. Several attempts have been made to identify the genetic basis of AUD; however, only few genetic polymorphisms have consistently been associated with AUD. Intermediate phenotypes are expected to be in-between proxies of basic neuronal biological processes and nosological symptoms of AUD. Personality is likely to be a top candidate intermediate phenotype for the dissection of the genetic underpinnings of different subtypes of AUD. To date, 38 studies have investigated personality traits, commonly assessed by the Cloninger’s Tridimensional Personality Questionnaire (TPQ) or Temperament and Character Inventory (TCI), in relation to polymorphisms of candidate genes of neurotransmitter systems in alcohol-dependent patients. Particular attention has been given to the functional polymorphism of the serotonin transporter gene (5-HTTLPR), however, leading to contradictory results, whereas results with polymorphisms in other candidate monoaminergic genes (e.g., tryptophan hydroxylase, serotonin receptors, monoamine oxidases, dopamine receptors and transporter) are sparse. Only one genome-wide association study has been performed so far and identified the ABLIM1 gene of relevance for novelty seeking, harm avoidance and reward dependence in alcohol-dependent patients. Studies investigating genetic factors together with personality could help to define more homogenous subgroups of AUD patients and facilitate treatment strategies. This review also urges the scientific community to combine genetic data with psychobiological and environmental data to further dissect the link between personality and AUD. © 2017 The Author(s)

Author Keywords
Alcohol;  AUD;  Gene;  Personality;  Serotonin

Document Type: Article in Press
Source: Scopus



Reid Yates, J.A.a , Wong, A.W.K.b , Strauser, D.R.a , Heft Sears, S.J.a 
The Impact of Type D Personality Traits on the Career Readiness of College Students With and Without Disabilities
(2017) Rehabilitation Counseling Bulletin, 60 (2), pp. 67-76. 

DOI: 10.1177/0034355215610082

a University of Illinois at Urbana–Champaign, United States
b Washington University School of Medicine, St. Louis, MO, United States

The primary purpose of the study was to investigate the relationship of Type D personality and perceived career readiness in a group of college students with and without disabilities. The findings of the study revealed no significant differences in levels of career readiness and Type D personality across disability groups. Results also revealed that Type D traits did have a significant relationship with career readiness variables, and that this relationship is particularly significant for college students with disabilities. Results also indicated that for individuals with disabilities, both Type D traits (negative affect and social inhibition) have an effect on different dimensions of career readiness. Implications of the results are discussed within the context of rehabilitation counselors and professionals. Future directions for research are also offered. © 2015, © Hammill Institute on Disabilities 2015.

Author Keywords
disability(ies);  education;  rehabilitation;  rehabilitation counseling;  transition

Document Type: Article
Source: Scopus



Toonen, J.A., Solga, A.C., Ma, Y., Gutmann, D.H.
Estrogen activation of microglia underlies the sexually dimorphic differences in Nf1 optic glioma-induced retinal pathology
(2017) Journal of Experimental Medicine, 214 (1), pp. 17-25. 

DOI: 10.1084/jem.20160447

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

Children with neurofibromatosis type 1 (NF1) develop low-grade brain tumors throughout the optic pathway. Nearly 50% of children with optic pathway gliomas (OPGs) experience visual impairment, and few regain their vision after chemotherapy. Recent studies have revealed that girls with optic nerve gliomas are five times more likely to lose vision and require treatment than boys. To determine the mechanism underlying this sexually dimorphic difference in clinical outcome, we leveraged Nf1 optic glioma (Nf1-OPG) mice. We demonstrate that female Nf1-OPG mice exhibit greater retinal ganglion cell (RGC) loss and only females have retinal nerve fiber layer (RNFL) thinning, despite mice of both sexes harboring tumors of identical volumes and proliferation. Female gonadal sex hormones are responsible for this sexual dimorphism, as ovariectomy, but not castration, of Nf1-OPG mice normalizes RGC survival and RNFL thickness. In addition, female Nf1-OPG mice have threefold more microglia than their male counterparts, and minocycline inhibition of microglia corrects the retinal pathology. Moreover, pharmacologic inhibition of microglial estrogen receptor-β (ERβ) function corrects the retinal abnormalities in female Nf1-OPG mice. Collectively, these studies establish that female gonadal sex hormones underlie the sexual dimorphic differences in Nf1 optic glioma-induced retinal dysfunction by operating at the level of tumor-associated microglial activation. © 2017 Toonen et al.

Document Type: Article
Source: Scopus



Pop-Busui, R.a , Braffett, B.H.b , Zinman, B.c , Martin, C.a , White, N.H.d , Herman, W.H.a , Genuth, S.e , Gubitosi-Klug, R.e 
Cardiovascular autonomic neuropathy and cardiovascular outcomes in the diabetes control and complications trial/ epidemiology of diabetes interventions and complications (DCCT/EDIC) Study
(2017) Diabetes Care, 40 (1), pp. 94-100. 

DOI: 10.2337/dc16-1397

a Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, United States
b Biostatistics Center, George Washington University, Rockville, MD, United States
c Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada
d Washington University in St. Louis, St. Louis, MO, United States
e Case Western Reserve University, Cleveland, OH, United States

OBJECTIVE To examine whether cardiovascular autonomic neuropathy (CAN) is an independent risk factor of cardiovascular disease (CVD) events during DCCT/EDIC. RESEARCH DESIGN AND METHODS Standardized cardiovascular autonomic reflex tests (R-R response to paced breathing, Valsalva maneuver, postural changes in blood pressure) were performed at DCCT baseline, every 2 years throughout DCCT, and at two time points in EDIC. CVD events were ascertained throughout the study and adjudicated by a review committee. Cox proportional hazards models were used to estimate the effect of CAN at DCCT closeout on subsequent CVD risk. RESULTS There were 299 adjudicated CVD events in 165 participants following the DCCT closeout assessment: 132 of 1,262 subjects (10%) without CAN at DCCT closeout who experienced 244 CVD events versus 33 of 131 subjects (25%) with CAN at DCCT closeout who experienced 55 events (hazard ratio 2.79, 95% CI 1.91-4.09 for time to first CVD event). The cumulative incidence of the first occurrence of any CVD event during EDIC was significantly higher in participants with CAN at DCCT closeout compared with those without CAN. The association remained marginally significant after adjustment for multiple risk factors, including the EDIC updated mean HbA1c. When analyzed as a continuous variable, R-R variation was significantly lower at DCCT closeout in participants who experienced a CVD event compared with those who did not (P = 0.0012). CONCLUSIONS In the DCCT/EDIC cohort, individuals diagnosed with CAN at DCCT closeout experienced a higher long-term risk of CVD events during follow-up in EDIC. This association was not independent of historic glycemic exposure and its metabolic memory effect, the principal determinant of both long-term CVD risk and CAN in type 1 diabetes. © 2017 by the American Diabetes Association.

Document Type: Article
Source: Scopus



Haarbauer-Krupa, J.a , Taylor, C.A.a , Yue, J.K.b c , Winkler, E.A.b c , Pirracchio, R.d , Cooper, S.R.b c e , Burke, J.F.bc , Stein, M.B.f g , Manley, G.T.b c 
Screening for post-traumatic stress disorder in a civilian emergency department population with traumatic brain injury
(2017) Journal of Neurotrauma, 34 (1), pp. 50-58. 

DOI: 10.1089/neu.2015.4158

a Division of Unintentional Injury, National Center for Injury Prevention and Control, Centers for Disease Control and Prevention, Atlanta, Georgia
b Department of Neurological Surgery, University of California, San Francisco, Brain and Spinal Injury Center (B.A.S.I.C.), 1001 Potrero Avenue, San Francisco, CA, United States
c Brain and Spinal Injury Center, San Francisco General Hospital, San Francisco, CA, United States
d Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, CA, United States
e Department of Psychology, Washington University in St. Louis, St. Louis, MO, United States
f Department of Psychiatry, University of California, San Diego, San Diego, CA, United States
g Department of Family and Preventive Medicine, University of California, San Diego, San Diego, CA, United States

Post-traumatic stress disorder (PTSD) is a condition associated with traumatic brain injury (TBI). While the importance of PTSD and TBI among military personnel is widely recognized, there is less awareness of PTSD associated with civilian TBI. We examined the incidence and factors associated with PTSD 6 months post-injury in a civilian emergency department population using measures from the National Institute of Neurological Disorders and Stroke TBI Common Data Elements Outcome Battery. Participants with mild TBI (mTBI) from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot study with complete 6-month outcome batteries (n = 280) were analyzed. Screening for PTSD symptoms was conducted using the PTSD Checklist-Civilian Version. Descriptive measures are summarized and predictors for PTSD were examined using logistic regression. Incidence of screening positive for PTSD was 26.8% at 6 months following mTBI. Screening positive for PTSD was significantly associated with concurrent functional disability, post-concussive and psychiatric symptomatology, decreased satisfaction with life, and decreased performance in visual processing and mental flexibility. Multi-variable regression showed injury mechanism of assault (odds ratio [OR] 3.59; 95% confidence interval [CI] 1.69-7.63; p = 0.001) and prior psychiatric history (OR 2.56; 95% CI 1.42-4.61; p = 0.002) remained significant predictors of screening positive for PTSD, while education (per year OR 0.88; 95% CI 0.79-0.98; p = 0.021) was associated with decreased odds of PTSD. Standardized data collection and review of pre-injury education, psychiatric history, and injury mechanism during initial hospital presentation can aid in identifying patients with mTBI at risk for developing PTSD symptoms who may benefit from closer follow-up after initial injury care. © 2016, Mary Ann Liebert, Inc. 2016.

Author Keywords
emergency department screening;  post-traumatic stress disorder;  traumatic brain injury

Document Type: Article
Source: Scopus



Moran, E.K.a b , Culbreth, A.J.b , Barch, D.M.a c 
Ecological momentary assessment of negative symptoms in schizophrenia: Relationships to effort-based decision making and reinforcement learning
(2017) Journal of Abnormal Psychology, 126 (1), pp. 96-105. 

a Department of Psychiatry, School of Medicine, United States
b Department of Psychological and Brain Sciences, Washington University, St. Louis, United States
c Department of Psychological and Brain Sciences, Department of Radiology, Mallinckrodt Institute of Radiology, School of Medicine, Washington University, St. Louis, United States

Negative symptoms are a core clinical feature of schizophrenia, but conceptual and methodological problems with current instruments can make their assessment challenging. One hypothesis is that current symptom assessments may be influenced by impairments in memory and may not be fully reflective of actual functioning outside of the laboratory. The present study sought to investigate the validity of assessing negative symptoms using ecological momentary assessment (EMA). Participants with schizophrenia (N = 31) completed electronic questionnaires on smartphones 4 times a day for 1 week. Participants also completed effort-based decision making and reinforcement learning (RL) tasks to assess the relationship between EMA and laboratory measures, which tap into negative symptom relevant domains. Hierarchical linear modeling analyses revealed that clinician-rated and self-report measures of negative symptoms were significantly related to negative symptoms assessed via EMA. However, working memory moderated the relationship between EMA and retrospective measures of negative symptoms, such that there was a stronger relationship between EMA and retrospective negative symptom measures among individuals with better working memory. The authors also found that negative symptoms assessed via EMA were related to poor performance on the effort task, whereas clinician-rated symptoms and self-reports were not. Further, they found that negative symptoms were related to poorer performance on learning reward contingencies. The findings suggest that negative symptoms can be assessed through EMA and that working memory impairments frequently seen in schizophrenia may affect recall of symptoms. Moreover, these findings suggest the importance of examining the relationship between laboratory tasks and symptoms assessed during daily life. © 2016 American Psychological Association.

Author Keywords
Ecological momentary assessment;  Motivation;  Negative symptoms;  Pleasure;  Schizophrenia

Document Type: Article
Source: Scopus



Achariyar, T.M.a , Li, B.a d , Peng, W.a , Verghese, P.B.b , Shi, Y.b , McConnell, E.a , Benraiss, A.c , Kasper, T.a , Song, W.a , Takana, T.a , Holtzman, D.M.b , Nedergaard, M.a , Deane, R.a 
Glymphatic distribution of CSF-derived apoE into brain is isoform specific and suppressed during sleep deprivation
(2016) Molecular Neurodegeneration, 11 (1), art. no. 74, . 

DOI: 10.1186/s13024-016-0138-8

a Center for Translational Neuromedicine, Division of Glial Disease and Therapeutics, Department of Neurosurgery, University of Rochester Medical Center, University of Rochester, Rochester, NY, United States
b Department of Neurology, Hope Center for Neurological Disorders, Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University, School of Medicine, St Louis, MO, United States
c Center for Translational Neuromedicine, Division of Cell and Gene Therapy, University of Rochester Medical Center, Rochester, NY, United States
d Laboratory of Brain Metabolic Diseases, Institute of Metabolic Disease Research and Drug Development, China Medical University, Shenyang, China

Background: Apolipoprotein E (apoE) is a major carrier of cholesterol and essential for synaptic plasticity. In brain, it's expressed by many cells but highly expressed by the choroid plexus and the predominant apolipoprotein in cerebrospinal fluid (CSF). The role of apoE in the CSF is unclear. Recently, the glymphatic system was described as a clearance system whereby CSF and ISF (interstitial fluid) is exchanged via the peri-arterial space and convective flow of ISF clearance is mediated by aquaporin 4 (AQP4), a water channel. We reasoned that this system also serves to distribute essential molecules in CSF into brain. The aim was to establish whether apoE in CSF, secreted by the choroid plexus, is distributed into brain, and whether this distribution pattern was altered by sleep deprivation. Methods: We used fluorescently labeled lipidated apoE isoforms, lenti-apoE3 delivered to the choroid plexus, immunohistochemistry to map apoE brain distribution, immunolabeled cells and proteins in brain, Western blot analysis and ELISA to determine apoE levels and radiolabeled molecules to quantify CSF inflow into brain and brain clearance in mice. Data were statistically analyzed using ANOVA or Student's t- test. Results: We show that the glymphatic fluid transporting system contributes to the delivery of choroid plexus/CSF-derived human apoE to neurons. CSF-delivered human apoE entered brain via the perivascular space of penetrating arteries and flows radially around arteries, but not veins, in an isoform specific manner (apoE2 > apoE3 > apoE4). Flow of apoE around arteries was facilitated by AQP4, a characteristic feature of the glymphatic system. ApoE3, delivered by lentivirus to the choroid plexus and ependymal layer but not to the parenchymal cells, was present in the CSF, penetrating arteries and neurons. The inflow of CSF, which contains apoE, into brain and its clearance from the interstitium were severely suppressed by sleep deprivation compared to the sleep state. Conclusions: Thus, choroid plexus/CSF provides an additional source of apoE and the glymphatic fluid transporting system delivers it to brain via the periarterial space. By implication, failure in this essential physiological role of the glymphatic fluid flow and ISF clearance may also contribute to apoE isoform-specific disorders in the long term. © 2016 The Author(s).

Author Keywords
Alzheimer's disease;  AQP4;  Brain clearance;  Glymphatic pathways;  Lymphatic system;  Sleep/wake

Document Type: Article
Source: Scopus



Mattingly, G.W.a b , Anderson, R.H.b 
Optimizing outcomes in ADHD treatment: From clinical targets to novel delivery systems
(2016) CNS Spectrums, 21 (S1), pp. 48-58. 

DOI: 10.1017/S1092852916000808

a Washington University School of Medicine, Department of Psychiatry and Behavioral Neurosciences, 4801Weldon Spring Pkwy, St. Charles, MO, United States
b Midwest Research Group, St. Charles, Missouri, United States

Our knowledge and understanding of the underlying neurobiology and symptomatic expression of ADHD has advanced dramatically over the past decade. Associated with these advances has been a similar explosion of new treatment options to individualize treatment for our patients. This article will: â review strategies to measure ADHD symptoms and functional difficulties while seeking to achieve full symptomatic remission throughout the day â summarize recent findings regarding the management and prioritization of ADHD and comorbid conditions and â discuss the various pharmacologic treatment options with a focus on recently developed molecules and novel delivery systems. © Cambridge University Press 2016.

Author Keywords
attention deficit/hyperactivity disorder;  Key words ADHD;  pharmacology;  rating scales;  review

Document Type: Review
Source: Scopus



Halstead, M.E.a , McAvoy, K.b , Brown, B.E.c 
Expanding concussion laws not necessary for return to learning after concussion
(2016) Pediatrics, 138 (6), art. no. e20163194, . 

DOI: 10.1542/peds.2016-3194

a Department of Orthopaedic Surgery-Sports Medicine, Washington University, 14532 S Outer Forty Dr., Chesterfield, MO, United States
b Center for Concussion, Rocky Mountain Children's Hospital, Denver, CO, United States
c Traumatic Brain Injury Educational Consultant, New Castle, PA, United States

Document Type: Note
Source: Scopus



Glowinski, A.L.a , D'Amelio, G.b 
Depression is a deadly growing threat to our youth: Time to rally
(2016) Pediatrics, 138 (6), art. no. e20162869, . 

DOI: 10.1542/peds.2016-2869

a Division of Child and Adolescent Psychiatry, Department of Psychiatry, Washington University in St. Louis, 4444 Forest Park Ave., St. Louis, MO, United States
b Washington University, School of Medicine, St. Louis, MO, United States

Document Type: Note
Source: Scopus



Carey, C.E.a , Knodt, A.R.b , Conley, E.D.c , Hariri, A.R.b , Bogdan, R.a 
Reward-Related Ventral Striatum Activity Links Polygenic Risk for Attention-Deficit/Hyperactivity Disorder to Problematic Alcohol Use in Young Adulthood
(2016) Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, . Article in Press. 

DOI: 10.1016/j.bpsc.2016.10.003

a Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, Missouri
b Department of Psychology and Neuroscience, Duke University, Durham, North Carolina
c 23andMe, Mountain View, California

Background: Problematic alcohol use in adolescence and adulthood is a common and often debilitating correlate of childhood attention-deficit/hyperactivity disorder (ADHD). Converging evidence suggests that ADHD and problematic alcohol use share a common additive genetic basis, which may be mechanistically related to reward-related brain function. In the current study, we examined whether polygenic risk for childhood ADHD is linked to problematic alcohol use in young adulthood through alterations in reward-related activity of the ventral striatum, a neural hub supporting appetitive behaviors and reinforcement learning. Methods: Genomic, neuroimaging, and self-report data were available for 404 non-Hispanic European American participants who completed the ongoing Duke Neurogenetics Study. Polygenic risk scores for childhood ADHD were calculated based on a genome-wide association study meta-analysis conducted by the Psychiatric Genomics Consortium and tested for association with reward-related ventral striatum activity, measured using a number-guessing functional magnetic resonance imaging paradigm, and self-reported problematic alcohol use. A mediational model tested whether ventral striatum activity indirectly links polygenic risk for ADHD to problematic alcohol use. Results: Despite having no main effect on problematic alcohol use, polygenic risk for childhood ADHD was indirectly associated with problematic alcohol use through increased reward-related ventral striatum activity. Conclusions: Individual differences in reward-related brain function may, at least in part, mechanistically link polygenic risk for childhood ADHD to problematic alcohol use. © 2016 Society of Biological Psychiatry.

Author Keywords
ADHD;  Alcohol;  FMRI;  Polygenic;  Reward;  Ventral striatum

Document Type: Article in Press
Source: Scopus



V. Jain, S.a , Mathur, A.b , Srinivasakumar, P.c , Wallendorf, M.d , Culver, J.P.e f g , Zempel, J.M.a 
Prediction of Neonatal Seizures in Hypoxic-Ischemic Encephalopathy Using Electroencephalograph Power Analyses
(2016) Pediatric Neurology, . Article in Press. 

DOI: 10.1016/j.pediatrneurol.2016.10.019

a Division of Pediatric and Developmental Neurology, Department of Neurology, Washington University School of Medicine, St. Louis, Missouri
b Division of Newborn Medicine, Washington University School of Medicine, St. Louis, Missouri
c MEDNAX Health Solutions Partner, Pediatrix Medical Group of North Carolina, Charlotte, North Carolina
d Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri
e Department of Radiology, Washington University School of Medicine, St. Louis, Missouri
f Department of Biomedical Engineering, Washington University School of Medicine, St. Louis, Missouri
g Department of Physics, Washington University School of Medicine, St. Louis, Missouri

Background: The severity of the initial encephalopathy in neonatal hypoxic-ischemic encephalopathy correlates with seizure burden. Early electroencephalograph (EEG) background activity reflects the severity of encephalopathy. Thus, we hypothesized that early EEG background would be predictive of subsequent seizures in neonatal hypoxic-ischemic encephalopathy. Methods: This study included infants undergoing therapeutic hypothermia at St. Louis Children's Hospital between January 2009 and April 2013. Two pediatric epilepsy specialists independently characterized EEG background qualitatively using amplitude-integrated EEG trends. Total EEG power in the 1-20 Hz frequency band was calculated for quantitative EEG background assessment. Seizures were identified on conventional full montage EEG. Statistical analysis was performed using logistic regression. Results: Seventy-eight of the 93 eligible infants had artifact-free EEG data; 23 of 78 infants (29%) developed seizures, and of these, 11 developed status epilepticus. The best predictors of subsequent seizures during the first hour of EEG recording were a flat tracing pattern on amplitude-integrated EEG (sensitivity 26%, specificity 98%, likelihood ratio 13, positive predictive value 85%) and the total EEG power less than 10 μV2 (sensitivity 52%, specificity 98%, likelihood ratio 30, positive predictive value 92%). Conclusions: Early EEG biomarkers predict subsequent seizures in infants with hypoxic-ischemic encephalopathy. Compared with the qualitative amplitude-integrated EEG background, total EEG power improves our ability to identify high-risk infants from the first hour of EEG recording. Infants with a total EEG power of less than 10 μV2 have a 90% risk of subsequent seizures. Quantitative EEG measures could stratify cohorts while evaluating novel neuroprotective strategies in neonatal hypoxic-ischemic encephalopathy. © 2016 Elsevier Inc.

Author Keywords
AEEG;  Hypoxic-ischemic encephalopathy;  Neonatal EEG;  Neonatal seizures;  Quantitative EEG;  Seizure prediction;  Total EEG power

Document Type: Article in Press
Source: Scopus



Griffanti, L.a , Douaud, G.a , Bijsterbosh, J.a , Evangelisti, S.a b , Alfaro-Almagro, F.a , Glasser, M.F.c , Duff, E.P.a , Fitzgibbon, S.a , Westphal, R.d , Carone, D.e f , Beckmann, C.F.a g , Smith, S.M.a 
Hand classification of fMRI ICA noise components
(2016) NeuroImage, . Article in Press. 

DOI: 10.1016/j.neuroimage.2016.12.036

a Centre for the functional MRI of the Brain (FMRIB), University of Oxford, United Kingdom
b Functional MR Unit, Policlinico S. Orsola - Malpighi, Bologna, Italy - Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy
c Washington University School of Medicine, Washington University, St. Louis, MO, USA
d Department of Psychiatry, University of Oxford, United Kingdom
e Acute Stroke Programme, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom
f Laboratory of Experimental Stroke Research, Department of Surgery and Translational Medicine, University of Milano Bicocca, Milan Center of Neuroscience, Monza, Italy
g Department of Cognitve Neuroscience, Radboudumc and Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands

We present a practical "how-to" guide to help determine whether single-subject fMRI independent components (ICs) characterise structured noise or not. Manual identification of signal and noise after ICA decomposition is required for efficient data denoising: to train supervised algorithms, to check the results of unsupervised ones or to manually clean the data. In this paper we describe the main spatial and temporal features of ICs and provide general guidelines on how to evaluate these. Examples of signal and noise components are provided from a wide range of datasets (3T data, including examples from the UK Biobank and the Human Connectome Project, and 7T data), together with practical guidelines for their identification. Finally, we discuss how the data quality, data type and preprocessing can influence the characteristics of the ICs and present examples of particularly challenging datasets. © 2016 The Authors.

Document Type: Article in Press
Source: Scopus



Bugg, J.M., Diede, N.T.
The effects of awareness and secondary task demands on Stroop performance in the pre-cued lists paradigm
(2016) Acta Psychologica, . Article in Press. 

DOI: 10.1016/j.actpsy.2016.12.013

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

Prior research has demonstrated that explicit pre-cues informing participants of the proportion congruence of an upcoming list of Stroop trials affect performance in mostly congruent lists but not mostly incongruent lists. This pattern suggests a limited role for expectations in influencing Stroop performance. An alternative explanation, however, is that the effects of pre-cues may be masked by a bleed-over of awareness (of the proportion congruence manipulation) from cued to uncued lists given use of a within-subjects manipulation of cueing in prior research. One aim of the current study was to test this explanation by examining patterns of cueing effects when cueing is manipulated between subjects. A second aim was to examine the effects of a secondary, stimulus detection task on expectation and experience-driven effects in the pre-cued lists paradigm. Countering the bleed-over of awareness account, the prior finding of a selective effect of expectations in mostly congruent lists was again observed in the current experiments, and post-experimental assessments of awareness in the uncued condition were unrelated to Stroop performance. Additionally, it was demonstrated that the secondary task did not disrupt experience-driven control but did disrupt the expectation-driven use of pre-cues especially when participants did not know that secondary task stimuli would appear in advance of a list. These findings advance our understanding of the role of awareness in patterns of Stroop performance, and raise interesting questions about the types of advance knowledge that can be integrated in an expectation-driven fashion to optimize Stroop performance. © 2016 Elsevier B.V.

Author Keywords
Awareness;  Explicit versus implicit;  Proportion congruence;  Strategies;  Stroop effect

Document Type: Article in Press
Source: Scopus



Rao, R.a , Trivedi, S.a , Vesoulis, Z.a , Liao, S.M.a , Smyser, C.D.b , Mathur, A.M.a 
Safety and Short-Term Outcomes of Therapeutic Hypothermia in Preterm Neonates 34-35 Weeks Gestational Age with Hypoxic-Ischemic Encephalopathy
(2016) Journal of Pediatrics, . Article in Press. 

DOI: 10.1016/j.jpeds.2016.11.019

a Division of Newborn-Medicine, Department of Pediatrics, Washington University School of Medicine, St Louis, MO
b Division of Pediatric Neurology, Departments of Neurology, Pediatrics, and Radiology, Washington University School of Medicine, St Louis, MO

Objective: To evaluate the safety and short-term outcomes of preterm neonates born at 34-35 weeks gestation with hypoxic-ischemic encephalopathy (HIE) treated with therapeutic hypothermia. Study design: Medical records of preterm neonates born at 34-35 weeks gestational age with HIE treated with therapeutic hypothermia were retrospectively reviewed. Short-term safety outcomes and the presence, severity (mild, moderate, severe), and patterns of brain injury on magnetic resonance imaging were reviewed using a standard scoring system, and compared with a cohort of term neonates with HIE treated with therapeutic hypothermia. Results: Thirty-one preterm and 32 term neonates were identified. Therapeutic hypothermia-associated complications were seen in 90% of preterm infants and 81.3% of term infants (P = .30). In the preterm infants, hyperglycemia (58.1% vs31.3%, P = .03) and rewarming before completion of therapeutic hypothermia (19.4% vs 0.0%, P = .009) were more likely compared with term infants. All deaths occurred in the preterm group (12.9% vs 0%, P = .04). Neuroimaging showed the presence of injury in 80.6% of preterm infants and 59.4% of term infants (P = .07), with no differences in injury severity. Injury to the white matter was more prevalent in preterm infants compared with term infants (66.7% vs 25.0%, P = .001). Conclusions: Therapeutic hypothermia in infants born at 34-35 weeks gestational age appears feasible. Risks of mortality and side effects warrant caution with use of therapeutic hypothermia in preterm infants. © 2016 Elsevier Inc.

Author Keywords
Hypoxic-ischemic encephalopathy;  Magnetic resonance imaging;  Safety;  Therapeutic hypothermia;  White matter injury

Document Type: Article in Press
Source: Scopus



Richmond, L.L.a , Gold, D.A.b , Zacks, J.M.a 
Event Perception: Translations and Applications
(2016) Journal of Applied Research in Memory and Cognition, . Article in Press. 

DOI: 10.1016/j.jarmac.2016.11.002

a Washington University in St. Louis, United States
b University Health Network, Canada

Event segmentation is the parsing of ongoing activity into meaningful events. Segmenting in a normative fashion-identifying event boundaries similar to others' boundaries-is associated with better memory for and better performance of naturalistic actions. Given this, a reasonable hypothesis is that interventions that improve memory and attention for everyday events could lead to improvement in domains that are important for independent living, particularly in older populations. Event segmentation and memory measures may also be effective diagnostic tools for estimating people's ability to carry out tasks of daily living. Such measures preserve the rich, naturalistic character of everyday activity, but are easy to quantify in a laboratory or clinical setting. Therefore, event segmentation and memory measures may be useful proxies for clinicians to assess everyday functioning in patient populations and an appropriate target for interventions aimed at improving everyday memory and tasks of daily living. © 2016 Society for Applied Research in Memory and Cognition.

Author Keywords
Activities of daily living;  Event perception;  Everyday memory;  Intervention;  Rehabilitation;  Remediation

Document Type: Article in Press
Source: Scopus



Kinser, H.E.a , Pincus, Z.b 
High-throughput screening in the C. elegans nervous system
(2016) Molecular and Cellular Neuroscience, . Article in Press. 

DOI: 10.1016/j.mcn.2016.06.001

a Department of Biomedical Engineering, Washington University in St. Louis, United States
b Department of Developmental Biology, Department of Genetics, Washington University, St. Louis, United States

The nematode . Caenorhabditis elegans is widely used as a model organism in the field of neurobiology. The wiring of the . C. elegans nervous system has been entirely mapped, and the animal's optical transparency allows for in vivo observation of neuronal activity. The nematode is also small in size, self-fertilizing, and inexpensive to cultivate and maintain, greatly lending to its utility as a whole-animal model for high-throughput screening (HTS) in the nervous system. However, the use of this organism in large-scale screens presents unique technical challenges, including reversible immobilization of the animal, parallel single-animal culture and containment, automation of laser surgery, and high-throughput image acquisition and phenotyping. These obstacles require significant modification of existing techniques and the creation of new . C. elegans-based HTS platforms. In this review, we outline these challenges in detail and survey the novel technologies and methods that have been developed to address them. © 2016 Elsevier Inc.

Author Keywords
Caenorhabditis elegans;  High-throughput screening;  Nervous system;  Whole-animal model

Document Type: Article in Press
Source: Scopus



Weiner, M.W.a b c d e , Veitch, D.P.a , Aisen, P.S.f , Beckett, L.A.g , Cairns, N.J.h i , Green, R.C.j , Harvey, D.g , Jack, C.R.k , Jagust, W.l , Morris, J.C.f , Petersen, R.C.m , Salazar, J.f , Saykin, A.J.n o , Shaw, L.M.p , Toga, A.W.q , Trojanowski, J.Q.r s t u 
The Alzheimer's Disease Neuroimaging Initiative 3: Continued innovation for clinical trial improvement
(2016) Alzheimer's and Dementia, . Article in Press. 

DOI: 10.1016/j.jalz.2016.10.006

a Department of Veterans Affairs Medical Center, Center for Imaging of Neurodegenerative Diseases, San Francisco, CA, USA
b Department of Radiology, University of California, San Francisco, CA, USA
c Department of Medicine, University of California, San Francisco, CA, USA
d Department of Psychiatry, University of California, San Francisco, CA, USA
e Department of Neurology, University of California, San Francisco, CA, USA
f Alzheimer's Therapeutic Research Institute, University of Southern California, San Diego, CA, USA
g Division of Biostatistics, Department of Public Health Sciences, University of California, Davis, CA, USA
h Knight Alzheimer's Disease Research Center, Washington University School of Medicine, Saint Louis, MO, USA
i Department of Neurology, Washington University School of Medicine, Saint Louis, MO, USA
j Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
k Department of Radiology, Mayo Clinic, Rochester, MN, USA
l Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, CA, USA
m Department of Neurology, Mayo Clinic, Rochester, MN, USA
n Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA
o Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA
p Tailored Therapeutics, Eli Lilly and Company, Indianapolis, IN, USA
q Laboratory of Neuroimaging, Institute of Neuroimaging and Informatics, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA
r Institute on Aging, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
s Alzheimer's Disease Core Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
t Udall Parkinson's Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
u Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

Introduction: The overall goal of the Alzheimer's Disease Neuroimaging Initiative (ADNI) is to validate biomarkers for Alzheimer's disease (AD) clinical trials. ADNI-3, which began on August 1, 2016, is a 5-year renewal of the current ADNI-2 study. Methods: ADNI-3 will follow current and additional subjects with normal cognition, mild cognitive impairment, and AD using innovative technologies such as tau imaging, magnetic resonance imaging sequences for connectivity analyses, and a highly automated immunoassay platform and mass spectroscopy approach for cerebrospinal fluid biomarker analysis. A Systems Biology/pathway approach will be used to identify genetic factors for subject selection/enrichment. Amyloid positron emission tomography scanning will be standardized using the Centiloid method. The Brain Health Registry will help recruit subjects and monitor subject cognition. Results: Multimodal analyses will provide insight into AD pathophysiology and disease progression. Discussion: ADNI-3 will aim to inform AD treatment trials and facilitate development of AD disease-modifying treatments. © 2016 The Alzheimer's Association.

Author Keywords
Alzheimer's disease;  Amyloid phenotyping;  Brain Health Registry;  Centiloid method;  Clinical trial biomarkers;  Functional connectivity;  Tau imaging

Document Type: Article in Press
Source: Scopus



Khaligh-Razavi, S.-M.a b , Henriksson, L.a c , Kay, K.d , Kriegeskorte, N.a 
Fixed versus mixed RSA: Explaining visual representations by fixed and mixed feature sets from shallow and deep computational models
(2016) Journal of Mathematical Psychology, . Article in Press. 

DOI: 10.1016/

a MRC Cognition and Brain Sciences Unit, Cambridge, UK
b Computer Science and Artificial intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA, USA
c Department of Neuroscience and Biomedical Engineering, Aalto University, Espoo, Finland
d Department of Psychology, Washington University in St. Louis, St. Louis, MO, USA

Studies of the primate visual system have begun to test a wide range of complex computational object-vision models. Realistic models have many parameters, which in practice cannot be fitted using the limited amounts of brain-activity data typically available. Task performance optimization (e.g. using backpropagation to train neural networks) provides major constraints for fitting parameters and discovering nonlinear representational features appropriate for the task (e.g. object classification). Model representations can be compared to brain representations in terms of the representational dissimilarities they predict for an image set. This method, called representational similarity analysis (RSA), enables us to test the representational feature space as is (fixed RSA) or to fit a linear transformation that mixes the nonlinear model features so as to best explain a cortical area's representational space (mixed RSA). Like voxel/population-receptive-field modelling, mixed RSA uses a training set (different stimuli) to fit one weight per model feature and response channel (voxels here), so as to best predict the response profile across images for each response channel. We analysed response patterns elicited by natural images, which were measured with functional magnetic resonance imaging (fMRI). We found that early visual areas were best accounted for by shallow models, such as a Gabor wavelet pyramid (GWP). The GWP model performed similarly with and without mixing, suggesting that the original features already approximated the representational space, obviating the need for mixing. However, a higher ventral-stream visual representation (lateral occipital region) was best explained by the higher layers of a deep convolutional network and mixing of its feature set was essential for this model to explain the representation. We suspect that mixing was essential because the convolutional network had been trained to discriminate a set of 1000 categories, whose frequencies in the training set did not match their frequencies in natural experience or their behavioural importance. The latter factors might determine the representational prominence of semantic dimensions in higher-level ventral-stream areas. Our results demonstrate the benefits of testing both the specific representational hypothesis expressed by a model's original feature space and the hypothesis space generated by linear transformations of that feature space. © 2016 The Author(s).

Author Keywords
Deep convolutional networks;  Mixed RSA;  Object-vision models;  Representational similarity analysis;  Voxel-receptive-field modelling

Document Type: Article in Press
Source: Scopus



Thanh Vu, A.a b c f , Jamison, K.a , Glasser, M.F.d , Smith, S.M.e , Coalson, T.d , Moeller, S.a , Auerbach, E.J.a , Ugurbil, K.a , Yacoub, E.a 
Tradeoffs in pushing the spatial resolution of fMRI for the 7T Human Connectome Project
(2016) NeuroImage, . Article in Press. 

DOI: 10.1016/j.neuroimage.2016.11.049

a Center for Magnetic Resonance Research, University of Minnesota Medical School, Minneapolis, MN, USA
b Helen Wills Institute for Neuroscience, University of California, Berkeley, CA, USA
c Advanced MRI Technologies, Sebastopol, CA, USA
d Washington University School of Medicine, Washington University, St. Louis, MO, USA
e FMRIB (Oxford Centre for Functional MRI of the Brain), Oxford University, Oxford, UK
f San Francisco VA Medical Center, Center for Imaging of Neurodegenerative Diseases (CIND), 4150 Clement Street - 114M, San Francisco, CA 94121

Whole-brain functional magnetic resonance imaging (fMRI), in conjunction with multiband acceleration, has played an important role in mapping the functional connectivity throughout the entire brain with both high temporal and spatial resolution. Ultrahigh magnetic field strengths (7. T and above) allow functional imaging with even higher functional contrast-to-noise ratios for improved spatial resolution and specificity compared to traditional field strengths (1.5. T and 3. T). High-resolution 7. T fMRI, however, has primarily been constrained to smaller brain regions given the amount of time it takes to acquire the number of slices necessary for high resolution whole brain imaging. Here we evaluate a range of whole-brain high-resolution resting state fMRI protocols (0.9, 1.25, 1.5, 1.6 and 2. mm isotropic voxels) at 7. T, obtained with both in-plane and slice acceleration parallel imaging techniques to maintain the temporal resolution and brain coverage typically acquired at 3. T. Using the processing pipeline developed by the Human Connectome Project, we demonstrate that high resolution images acquired at 7. T provide increased functional contrast to noise ratios with significantly less partial volume effects and more distinct spatial features, potentially allowing for robust individual subject parcellations and descriptions of fine-scaled patterns, such as visuotopic organization. © 2016.

Author Keywords
7T;  Connectome;  FMRI;  High-resolution;  Resting state;  Whole brain

Document Type: Article in Press
Source: Scopus