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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.

June 19, 2017  


Xue, Y.a f , Sato, S.a , Razafsky, D.a g , Sahu, B.b , Shen, S.Q.c , Potter, C.a , Sandell, L.L.d , Corbo, J.C.c , Palczewski, K.e , Maeda, A.b e , Hodzic, D.a , Kefalov, V.J.a
The role of retinol dehydrogenase 10 in the cone visual cycle
(2017) Scientific Reports, 7 (1), art. no. 2390, . 

DOI: 10.1038/s41598-017-02549-8

a Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO, United States
b Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, OH, United States
c Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States
d Department of Oral Immunology and Infectious Diseases, University of Louisville, Louisville, KY, United States
e Department of Pharmacology and Cleveland Center for Membrane and Structural Biology, Case Western Reserve University, Cleveland, OH, United States
f Department of Genetics, Harvard Medical School, Boston, MA, United States
g MilliporeSigma, St. Louis, MO, United States

Pigment regeneration is critical for the function of cone photoreceptors in bright and rapidly-changing light conditions. This process is facilitated by the recently-characterized retina visual cycle, in which Müller cells recycle spent all-Trans-retinol visual chromophore back to 11-cis-retinol. This 11-cis-retinol is oxidized selectively in cones to the 11-cis-retinal used for pigment regeneration. However, the enzyme responsible for the oxidation of 11-cis-retinol remains unknown. Here, we sought to determine whether retinol dehydrogenase 10 (RDH10), upregulated in rod/cone hybrid retinas and expressed abundantly in Müller cells, is the enzyme that drives this reaction. We created mice lacking RDH10 either in cone photoreceptors, Müller cells, or the entire retina. In vivo electroretinography and transretinal recordings revealed normal cone photoresponses in all RDH10-deficient mouse lines. Notably, their cone-driven dark adaptation both in vivo and in isolated retina was unaffected, indicating that RDH10 is not required for the function of the retina visual cycle. We also generated transgenic mice expressing RDH10 ectopically in rod cells. However, rod dark adaptation was unaffected by the expression of RDH10 and transgenic rods were unable to use cis-retinol for pigment regeneration. We conclude that RDH10 is not the dominant retina 11-cis-RDH, leaving its primary function in the retina unknown. © 2017 The Author(s).

Document Type: Article
Source: Scopus


Cicero, T.J., Ellis, M.S., Kasper, Z.A.
Increased use of heroin as an initiating opioid of abuse
(2017) Addictive Behaviors, 74, pp. 63-66. 

DOI: 10.1016/j.addbeh.2017.05.030

Washington University in St. Louis, Department of Psychiatry, Campus Box 8134, 660 S. Euclid Avenue, St. Louis, MO, United States

Introduction Given the relatively recent growth in access to heroin and a more permissive atmosphere surrounding its use, we hypothesized that an increasing number of persons with limited experience and tolerance to opioids would experiment with heroin as their first opioid rather than more common prescription opioid analgesics. Methods Individuals entering substance abuse treatment for an opioid use disorder in the period 2010–2016 (N = 5885) were asked about the specific opioid they first regularly used to get high. To limit long-term recall and survival bias, analyses was restricted to opioid initiation that occurred in the past ten years (2005–2015). Results In 2005, only 8.7% of opioid initiators started with heroin, but this sharply increased to 33.3% (p < 0.001) in 2015, with no evidence of stabilization. The use of commonly prescribed opioids, oxycodone and hydrocodone, dropped from 42.4% and 42.3% of opioid initiators, respectively, to 24.1% and 27.8% in 2015, such that heroin as an initiating opioid was now more frequently endorsed than prescription opioid analgesics. Conclusions Our data document that, as the most commonly prescribed opioids – hydrocodone and oxycodone – became less accessible due to supply-side interventions, the use of heroin as an initiating opioid has grown at an alarming rate. Given that opioid novices have limited tolerance to opioids, a slight imprecision in dosing inherent in heroin use is likely to be an important factor contributing to the growth in heroin-related over dose fatalities in recent years. © 2017

Author Keywords
Heroin;  Heroin overdose;  Opioid abuse;  Opioid initiation;  Prescription opioid abuse

Document Type: Article
Source: Scopus


Wright, P.W.a , Archambault, A.S.b , Peek, S.c , Bauer, A.Q.a , Culican, S.M.c , Ances, B.M.a b , Culver, J.P.a , Wu, G.F.b d
Functional connectivity alterations in a murine model of optic neuritis
(2017) Experimental Neurology, 295, pp. 18-22. 

DOI: 10.1016/j.expneurol.2017.05.004

a Department of Radiology, Washington University in St. Louis School of Medicine, United States
b Department of Neurology, Washington University in St. Louis School of Medicine, United States
c Department of Ophthalmology, Washington University in St. Louis School of Medicine, United States
d Department of Pathology & Immunology, Washington University in St. Louis School of Medicine, United States

The basis for neuronal dysfunction following inflammatory demyelination of the central nervous system (CNS) remains poorly understood. We characterized the network response to white matter injury in the anterior visual pathway using an experimental model of optic neuritis (ON), as ON is often an early manifestation of immune-mediated CNS demyelination in multiple sclerosis (MS). Optical intrinsic signal imaging was performed before and after the induction of ON in mice to measure changes in cortical network functional connectivity. We observed a greater loss of connectivity between homotopic visual cortices in ON mice compared to controls. Further, decreases in homotopic visual cortex connectivity were associated with visual acuity loss in ON mice. These results demonstrate that network connectivity changes resulting from ON can be modeled in an experimental murine system. Future studies will identify the mechanisms that cause neuronal dysfunction due to white matter injury seen in MS. © 2017 Elsevier Inc.

Author Keywords
Demyelination;  Functional connectivity;  Multiple sclerosis;  Optic neuritis;  Optical imaging;  Visual cortex

Document Type: Article
Source: Scopus


Adam, E.K.a , Quinn, M.E.b c , Tavernier, R.d , McQuillan, M.T.a , Dahlke, K.A.e , Gilbert, K.E.f
Diurnal cortisol slopes and mental and physical health outcomes: A systematic review and meta-analysis
(2017) Psychoneuroendocrinology, 83, pp. 25-41. 

DOI: 10.1016/j.psyneuen.2017.05.018

a School of Education and Social Policy and Institute for Policy Research, Northwestern University, 2120 Campus Drive, Evanston, IL, United States
b Department of Psychology, Northwestern University, 2029 Sheridan Rd., Evanston, IL, United States
c Department of Psychiatry, University of Illinois at Chicago, 912 S. Wood St., Chicago, IL, United States
d Department of Psychology, Wesleyan University, 207 High Street, Middletown, CT, United States
e American Institutes for Research, 1120 E. Diehl Road, Suite 200, Naperville, IL, United States
f Department of Psychiatry, Washington University in St. Louis, 4444 Forest Park Parkway, Suite 2100, St. Louis, MO, United States

Changes in levels of the stress-sensitive hormone cortisol from morning to evening are referred to as diurnal cortisol slopes. Flatter diurnal cortisol slopes have been proposed as a mediator between chronic psychosocial stress and poor mental and physical health outcomes in past theory and research. Surprisingly, neither a systematic nor a meta-analytic review of associations between diurnal cortisol slopes and health has been conducted to date, despite extensive literature on the topic. The current systematic review and meta-analysis examined associations between diurnal cortisol slopes and physical and mental health outcomes. Analyses were based on 179 associations from 80 studies for the time period up to January 31, 2015. Results indicated a significant association between flatter diurnal cortisol slopes and poorer health across all studies (average effect size, r = 0.147). Further, flatter diurnal cortisol slopes were associated with poorer health in 10 out of 12 subtypes of emotional and physical health outcomes examined. Among these subtypes, the effect size was largest for immune/inflammation outcomes (r = 0.288). Potential moderators of the associations between diurnal cortisol slopes and health outcomes were examined, including type of slope measure and study quality indices. The possible roles of flatter slopes as either a marker or a mechanism for disease etiology are discussed. We argue that flatter diurnal cortisol slopes may both reflect and contribute to stress-related dysregulation of central and peripheral circadian mechanisms, with corresponding downstream effects on multiple aspects of biology, behavior, and health. © 2017 Elsevier Ltd

Author Keywords
Circadian rhythms;  Diurnal cortisol slopes;  Hypothalamic pituitary adrenal (HPA) axis;  Mental health;  Physical health

Document Type: Review
Source: Scopus


Cicero, T.J., Ellis, M.S., Kasper, Z.A.
Increases in self-reported fentanyl use among a population entering drug treatment: The need for systematic surveillance of illicitly manufactured opioids
(2017) Drug and Alcohol Dependence, 177, pp. 101-103. 

DOI: 10.1016/j.drugalcdep.2017.04.004

Department of Psychiatry, Washington University, Campus Box 8134, 660 S. Euclid Avenue, St. Louis, MO, United States

Background/purpose Recent reports indicate a sharp increase in fentanyl-related overdose deaths across the United States, much of which is likely related to the introduction of cheap, illicitly manufactured fentanyl derivatives. In this study, we sought to estimate the magnitude of illicit fentanyl use from 2012 to 2016 using a national opioid abuse surveillance system. Methods The study program surveyed 10,900 individuals entering substance abuse treatment for opioid use disorder, with participants asked to endorse past month ‘use to get high’ of fentanyl drugs, stratified by identifiable (i.e., branded) fentanyl formulations or a ‘type unknown’ drug alleged to contain fentanyl. Main findings Total past-month fentanyl-use rose modestly from 2012 to 2016. While use of known fentanyl products remained relatively stable (mean = 10.9%; P = 0.25), endorsements of ‘unknown’ fentanyl products nearly doubled from 9% in 2013 to 15.1% by 2016 (P < 0.001). Data show no discernable indication that this increase is diminishing or stabilizing. Conclusions This first attempt to assess the prevalence of illicit fentanyl use shows that recent increases in fentanyl use seem to be due almost entirely to ‘unknown’ fentanyl presumed to be illicitly manufactured. Given that it is difficult to assess the extent to which fentanyl may have been substituted for another drug (i.e., oxycodone, alprazolam, etc.) or was used as a heroin admixture, our data likely represent an underestimation of the full magnitude of illicit fentanyl abuse. As such, this growing public health problem requires immediate attention and more systematic efforts to identify and track its abuse. © 2017

Author Keywords
Epidemiology;  Fentanyl;  Illicit fentanyl;  Opioid abuse;  Synthetic opioids

Document Type: Article
Source: Scopus


Wysocki, T.
Arguments over Intuitions?
(2017) Review of Philosophy and Psychology, 8 (2), pp. 477-499. 

DOI: 10.1007/s13164-016-0301-8

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

Deutsch 2010 (The Review of Philosophy and Psychology 1: 447–460) claims that hypothetical scenarios are evaluated using arguments, not intuitions, and therefore experiments on intuitions are philosophically inconsequential. Using the Gettier case as an example, he identifies three arguments that are supposed to point to the right response to the case. In the paper, I present the results of studies ran on Polish, Indian, Spanish, and American participants that suggest that there’s no deep difference between evaluating the Gettier case with intuitions and evaluating it with Deutsch’s arguments. Specifically, I argue that one would find these arguments persuasive if and only if one is already disposed to exhibit the relevant intuition. © 2016, Springer Science+Business Media Dordrecht.

Document Type: Article
Source: Scopus


Welch, R.D.a b , Ellis, M.a , Lewis, L.M.c , Ayaz, S.I.a , Mika, V.H.a , Millis, S.a d , Papa, L.e
Modeling the Kinetics of Serum Glial Fibrillary Acidic Protein, Ubiquitin Carboxyl-Terminal Hydrolase-L1, and S100B Concentrations in Patients with Traumatic Brain Injury
(2017) Journal of Neurotrauma, 34 (11), pp. 1957-1971. 

DOI: 10.1089/neu.2016.4772

a Department of Emergency Medicine, Wayne State University School of Medicine, Cardiovascular Research Institute, 4201 St. Antoine, Detroit, MI, United States
b Cardiovascular Research Institute, Wayne State University School of Medicine, Detroit, MI, United States
c Department of Emergency Medicine, Washington University School of Medicine, St. Louis, MO, United States
d Department of Physical Medicine and Rehabilitation, Wayne State University School of Medicine, Detroit, MI, United States
e Department of Emergency Medicine, Orlando Regional Medical Center, Orlando, FL, United States

Glial fibrillary acidic protein (GFAP), ubiquitin carboxyl-terminal hydrolase-L1 (UCH-L1), and S100B have been shown to be predictive of patients with brain injury. Kinetics of these biomarkers in injured humans have not been extensively examined. This prospective multi-center study included patients with mild-to-moderate traumatic brain injury. Blood samples obtained at enrollment and every 6 h up to 24 h post-injury were assayed for GFAP, UCH-L1, and S100B. Random effects models examined changes in the biomarkers' level over time. A total of 167 patients were enrolled; mean age was 46.0 ± 17.8, 61.1% were male, 143 (85.6%) had a Glasgow Coma Scale score of 15, and 33 (19.8%) had a positive head computed tomography (CT) scan. Baseline median biomarker concentrations for all three were higher among CT-positive patients (p < 0.0001) but GFAP was the only biomarker that significantly increased over time among CT-positive patients relative to CT-negative patients (log transformed values 0.037; 95% confidence interval 0.02, 0.05; p < 0.001), indicating a 3.7% per hour rise in GFAP concentration. There was no significant increase in either UCH-L1 or S100B in CT-positive patients (p = 0.15 and p = 0.47, respectively). GFAP concentrations increased 3.7% per hour among CT-positive patients whereas neither UCH-L1 nor S100B increased, compared with CT-negative patients. The kinetics and temporal profile of GFAP suggest it may be a more robust biomarker to detect patients with positive CT findings, particularly at later post-injury times. Further study is needed to determine if GFAP is a useful test to follow throughout a patient's clinical course. © 2017, Mary Ann Liebert, Inc.

Author Keywords
biomarkers;  glia cell response to injury;  neural injury;  traumatic brain injury

Document Type: Article
Source: Scopus


Kwon, E.a , Park, S.b
Heterogeneous trajectories of physical and mental health in late middle age: Importance of life-course socioeconomic positions
(2017) International Journal of Environmental Research and Public Health, 14 (6), art. no. 582, . 

DOI: 10.3390/ijerph14060582

a Center for Social Science, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, South Korea
b George Warren Brown School of Social Work, Washington University, One Brookings Drive, Saint Louis, MO, United States

Drawing on life course and cumulative disadvantage theory, this study examines heterogeneous trajectories of functional limitations and depressive symptoms among late middle-aged individuals. This study used prospective data from 6010 adults, 51 to 64 years old, collected over a 12-year-period from the Health and Retirement Study. Considering the empirical proposition that several physical and mental trajectories may exist, Latent Class Growth Modeling was used. Five heterogeneous patterns of joint trajectories (Relatively healthy, Moderately improving, Steadily deteriorating, Steeply deteriorating, and Persistently high comorbid) were identified. Early life adversity was related to an increasing risk of declines in physical and mental health. The Persistently high comorbid class was characterized by a concentration of disadvantages over the life course. The development of public health interventions could help reduce co-existing physical and mental health problems, especially during late middle-age. © 2017 by the authors. Licensee MDPI, Basel, Switzerland.

Author Keywords
Cumulative disadvantage;  Health disparities;  Heterogeneous trajectories of physical and mental health;  Late middle age;  Life course

Document Type: Article
Source: Scopus


Lean, R.E.a , Melzer, T.R.b c , Bora, S.d , Watts, R.e , Woodward, L.J.f g
Attention and Regional Gray Matter Development in Very Preterm Children at Age 12 Years
(2017) Journal of the International Neuropsychological Society, pp. 1-12. Article in Press. 

DOI: 10.1017/S1355617717000388

a Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri
b Department of Medicine, University of Otago, Christchurch, New Zealand
c New Zealand Brain Research Institute, Christchurch, New Zealand
d Mothers, Babies and Women’s Health Program, Mater Research Institute, The University of Queensland, Brisbane, QLD, Australia
e Department of Radiology, University of Vermont, Burlington, Vermont
f Department of Pediatric Newborn Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
g Department of Psychology, University of Canterbury, Christchurch, New Zealand

Objectives: This study examines the selective, sustained, and executive attention abilities of very preterm (VPT) born children in relation to concurrent structural magnetic resonance imaging (MRI) measures of regional gray matter development at age 12 years. Methods: A regional cohort of 110 VPT (≤32 weeks gestation) and 113 full term (FT) born children were assessed at corrected age 12 years on the Test of Everyday Attention-Children. They also had a structural MRI scan that was subsequently analyzed using voxel-based morphometry to quantify regional between-group differences in cerebral gray matter development, which were then related to attention measures using multivariate methods. Results: VPT children obtained similar selective (p=.85), but poorer sustained (p=.02) and executive attention (p=.01) scores than FT children. VPT children were also characterized by reduced gray matter in the bilateral parietal, temporal, prefrontal and posterior cingulate cortices, bilateral thalami, and left hippocampus; and increased gray matter in the occipital and anterior cingulate cortices (family-wise error–corrected p<.05). Poorer sustained auditory attention was associated with increased gray matter in the anterior cingulate cortex (p=.04). Poor executive shifting attention was associated with reduced gray matter in the right superior temporal cortex (p=.04) and bilateral thalami (p=.05). Poorer executive divided attention was associated with reduced gray matter in the occipital (p=.001), posterior cingulate (p=.02), and left temporal (p=.01) cortices; and increased gray matter in the anterior cingulate cortex (p=.001). Conclusions: Disturbances in regional gray matter development appear to contribute, at least in part, to the poorer attentional performance of VPT children at school age. (JINS, 2017, 23, 1–12) Copyright © The International Neuropsychological Society 2017

Author Keywords
Attention;  Brain;  Gray matter;  MRI;  Outcome;  Very preterm

Document Type: Article in Press
Source: Scopus


Hoye, M.L.a , Koval, E.D.a , Wegener, A.J.a , Hyman, T.S.a , Yang, C.b , O’Brien, D.R.b , Miller, R.L.a , Cole, T.c , Schoch, K.M.a , Shen, T.a , Kunikata, T.a , Richard, J.-P.d , Gutmann, D.H.a , Maragakis, N.J.d , Kordasiewicz, H.B.c , Dougherty, J.D.b , Miller, T.M.a
MicroRNA profiling reveals marker of motor neuron disease in ALS models
(2017) Journal of Neuroscience, 37 (22), pp. 5574-5586. 

DOI: 10.1523/JNEUROSCI.3582-16.2017

a Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
b Department of Genetics, Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
c Ionis Pharmaceuticals, Carlsbad, CA, United States
d Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MO, United States

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder marked by the loss of motor neurons (MNs) in the brain and spinal cord, leading to fatally debilitating weakness. Because this disease predominantly affects MNs, we aimed to characterize the distinct expression profile of that cell type to elucidate underlying disease mechanisms and to identify novel targets that inform on MN health during ALS disease time course. Micron RNAs (miRNAs) are short, noncoding RNAs that can shape the expression profile of a cell and thus often exhibit cell-type-enriched expression. To determine MN-enriched miRNA expression, we used Cre recombinase-dependent miRNA tagging and affinity purification in mice. By defining the in vivo miRNA expression of MNs, all neurons, astrocytes, and microglia, we then focused on MN-enriched miRNAs via a comparative analysis and found that they may functionally distinguish MNs postnatally from other spinal neurons. Characterizing the levels of the MN-enriched miRNAs in CSF harvested from ALS models of MN disease demonstrated that one miRNA (miR-218) tracked with MN loss and was responsive to an ALS therapy in rodent models. Therefore, we have used cellular expression profiling tools to define the distinct miRNA expression of MNs, which is likely to enrich future studies of MN disease. This approach enabled the development of a novel, drug-responsive marker of MN disease in ALS rodents. © 2017 the authors.

Author Keywords
ALS;  MicroRNAs;  MiRAP;  Motor neuron;  Motor neuron disease;  TRAP

Document Type: Article
Source: Scopus


Duan, C.a , Kallehauge, J.F.b c , Pérez-Torres, C.J.d e , Bretthorst, G.L.f , Beeman, S.C.d , Tanderup, K.c f g , Ackerman, J.J.H.a d h i , Garbow, J.R.d i
Modeling Dynamic Contrast-Enhanced MRI Data with a Constrained Local AIF
(2017) Molecular Imaging and Biology, pp. 1-10. Article in Press. 

DOI: 10.1007/s11307-017-1090-x

a Department of Chemistry, Washington University, Saint Louis, MO, United States
b Department of Medical Physics, Aarhus University, Aarhus, Denmark
c Department of Oncology, Aarhus University, Aarhus, Denmark
d Department of Radiology, Washington University, Saint Louis, MO, United States
e School of Health Sciences, Purdue University, West Lafayette, IN, United States
f Department of Radiation Oncology, Washington University, Saint Louis, MO, United States
g Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark
h Department of Medicine, Washington University, Saint Louis, MO, United States
i Alvin J Siteman Cancer Center, Washington University, Saint Louis, MO, United States

Purpose: This study aims to develop a constrained local arterial input function (cL-AIF) to improve quantitative analysis of dynamic contrast-enhanced (DCE)-magnetic resonance imaging (MRI) data by accounting for the contrast-agent bolus amplitude error in the voxel-specific AIF. Procedures: Bayesian probability theory-based parameter estimation and model selection were used to compare tracer kinetic modeling employing either the measured remote-AIF (R-AIF, i.e., the traditional approach) or an inferred cL-AIF against both in silico DCE-MRI data and clinical, cervical cancer DCE-MRI data. Results: When the data model included the cL-AIF, tracer kinetic parameters were correctly estimated from in silico data under contrast-to-noise conditions typical of clinical DCE-MRI experiments. Considering the clinical cervical cancer data, Bayesian model selection was performed for all tumor voxels of the 16 patients (35,602 voxels in total). Among those voxels, a tracer kinetic model that employed the voxel-specific cL-AIF was preferred (i.e., had a higher posterior probability) in 80 % of the voxels compared to the direct use of a single R-AIF. Maps of spatial variation in voxel-specific AIF bolus amplitude and arrival time for heterogeneous tissues, such as cervical cancer, are accessible with the cL-AIF approach. Conclusions: The cL-AIF method, which estimates unique local-AIF amplitude and arrival time for each voxel within the tissue of interest, provides better modeling of DCE-MRI data than the use of a single, measured R-AIF. The Bayesian-based data analysis described herein affords estimates of uncertainties for each model parameter, via posterior probability density functions, and voxel-wise comparison across methods/models, via model selection in data modeling. © 2017 World Molecular Imaging Society

Document Type: Article in Press
Source: Scopus


Saha, D., Sun, W., Li, C., Nizampatnam, S., Padovano, W., Chen, Z., Chen, A., Altan, E., Lo, R., Barbour, D.L., Raman, B.
Engaging and disengaging recurrent inhibition coincides with sensing and unsensing of a sensory stimulus
(2017) Nature Communications, 8, art. no. 15413, . 

DOI: 10.1038/ncomms15413

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

Even simple sensory stimuli evoke neural responses that are dynamic and complex. Are the temporally patterned neural activities important for controlling the behavioral output? Here, we investigated this issue. Our results reveal that in the insect antennal lobe, due to circuit interactions, distinct neural ensembles are activated during and immediately following the termination of every odorant. Such non-overlapping response patterns are not observed even when the stimulus intensity or identities were changed. In addition, we find that ON and OFF ensemble neural activities differ in their ability to recruit recurrent inhibition, entrain field-potential oscillations and more importantly in their relevance to behaviour (initiate versus reset conditioned responses). Notably, we find that a strikingly similar strategy is also used for encoding sound onsets and offsets in the marmoset auditory cortex. In sum, our results suggest a general approach where recurrent inhibition is associated with stimulus 'recognition' and 'derecognition'. © The Author(s) 2017.

Document Type: Article
Source: Scopus


Jaeger, A.a , Dobbins, I.G.b
Revising recognition judgments during noisy recognition evidence accumulation: The dynamics of losses versus gains
(2017) Memory and Cognition, pp. 1-15. Article in Press. 

DOI: 10.3758/s13421-017-0715-2

a Department of Psychology, Federal University of Minas Gerais, Antonio Carlos Avenue, 6627, Belo Horizonte, MG, Brazil
b Department of Psychology, Washington University, St. Louis, MO, United States

Outside the laboratory, we sometimes revise our recognition judgments of others—realizing, for example, that we have accidentally failed to greet an acquaintance we just passed in the hallway. These recognition reversals have rarely been studied. Here, using a basic noisy-accumulation framework, we simulated recognition response reversals in which initial speeded recognition judgments were followed by an opportunity to revise the initial judgment. The simulation predictions were compared to empirical data from two experiments in which we gave participants the opportunity to revise each of their initial speeded recognition judgments. The speeded old–new responses were restricted to either 300–800 ms (Exp. 1) or 200–600 ms (Exp. 2) after each probe’s onset, and the second response was self-paced in both experiments. The noisy-accumulation framework correctly anticipated three findings. First, gain rates (incorrect followed by correct responses) always exceeded loss rates (correct followed by incorrect responses). Second, despite being corrective, the raw gain rates exhibited a modest negative correlation with overall recognition skill. Third, when gain rates were conditioned on the opportunity to correct an initial error (conditional gain rate), they were then positively correlated with recognition skill but were less diagnostic than the conditional loss rates. Thus, the mechanics of noisy accumulation naturally predict that skilled recognizers will demonstrate infrequent corrective behavior but a high probability of correction, should an initial error occur. © 2017 Psychonomic Society, Inc.

Author Keywords
Accumulation;  Memory;  Recognition;  Simulation

Document Type: Article in Press
Source: Scopus


Nemanich, S.T.a , McNeely, M.E.a b , Earhart, G.M.a b c , Norris, S.A.b , Black, K.J.b c d e
A case of apparent upper-body freezing in parkinsonism while using a wheelchair
(2017) Frontiers in Neurology, 8 (MAY), art. no. 205, . 

DOI: 10.3389/fneur.2017.00205

a Program in Physical Therapy, Washington University School of Medicine in St. Louis, 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
d Department of Radiology, Washington University School of Medicine in St. Louis, St. Louis, MO, United States
e Department of Psychiatry, Washington University School of Medicine in St. Louis, St. Louis, MO, United States

Freezing of gait (FOG) is a common, disabling gait disturbance in Parkinson's disease (PD) and other Parkinsonian syndromes. Freezing also occurs during non-gait movements involving the upper limbs. The mechanisms underlying freezing are complex, likely involving motor, cognitive, and sensory systems that contribute to the episodes. Here, we reported a 60-year-old female with a 24-year history of parkinsonism who experienced significant FOG when ambulatory. Disease progression resulted in her permanent use of a powered wheelchair. While using the power chair, the patient experiences apparent paroxysmal freezing in the hand and arm used to steer and propel the chair. These episodes, some lasting up to several minutes, occur only in circumstances (e.g., entering and leaving an elevator) that are similar to environments known to elicit and exacerbate FOG. Episodes are transient and can be volitionally interrupted by the patient but sometimes require external assistance. Therapeutic intervention for this type of potential freezing has yet to be determined. This case may provide insight into the complex nature of freezing behavior and suggests a need for new approaches to treating non-traditional freezing behavior. © 2017 Nemanich, McNeely, Earhart, Norris and Black.

Author Keywords
Akinesia;  Freezing;  Hypokinesia;  Parkinson's disease;  Upper-limb freezing

Document Type: Article
Source: Scopus


Richardson, S.P.a , Altenmüller, E.b , Alter, K.c , Alterman, R.L.d , Chen, R.e , Frucht, S.f , Furuya, S.g , Jankovic, J.h , Jinnah, H.A.i j k , Kimberley, T.J.l , Lungu, C.m , Perlmutter, J.S.n o p q r , Prudente, C.N.l , Hallett, M.s
Research priorities in limb and task-specific dystonias
(2017) Frontiers in Neurology, 8 (MAY), art. no. 170, . 

DOI: 10.3389/fneur.2017.00170

a Department of Neurology, University of New Mexico Health Sciences Center, Albuquerque, NM, United States
b Institute for Music Physiology and Musicians' Medicine (IMMM), Hannover University of Music, Drama and Media, Hannover, Germany
c Functional and Applied Biomechanics Section, Rehabilitation Medicine, National Institute of Child Health and Development, National Institutes of Health, Bethesda, MD, United States
d Division of Neurosurgery, Beth Israel Deaconess Medical Center, Boston, MA, United States
e Division of Neurology, Department of Medicine (Neurology), Krembil Research Institute, University of Toronto, Toronto, ON, Canada
f Robert and John M. Bendheim Parkinson and Movement Disorders Center, Mount Sinai Hospital, New York, NY, United States
g Musical Skill and Injury Center (MuSIC), Sophia University, Tokyo, Japan
h Department of Neurology, Baylor College of Medicine, Houston, TX, United States
i Department of Neurology, Emory University School of Medicine, Atlanta, GA, United States
j Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, United States
k Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, United States
l Department of Rehabilitation Medicine, Division of Physical Therapy and Rehabilitation Science, University of Minnesota, Minneapolis, MN, United States
m Division of Clinical Research, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States
n Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
o Department of Radiology, Washington University School of Medicine, St. Louis, MO, United States
p Department of Neurosciences, Washington University School of Medicine, St. Louis, MO, United States
q Department of Physical Therapy, Washington University School of Medicine, St. Louis, MO, United States
r Department of Occupational Therapy, Washington University School of Medicine, St. Louis, MO, United States
s Human Motor Control Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States

Dystonia, which causes intermittent or sustained abnormal postures and movements, can present in a focal or a generalized manner. In the limbs, focal dystonia can occur in either the upper or lower limbs and may be task-specific causing abnormal motor performance for only a specific task, such as in writer's cramp, runner's dystonia, or musician's dystonia. Focal limb dystonia can be non-task-specific and may, in some circumstances, be associated with parkinsonian disorders. The true prevalence of focal limb dystonia is not known and is likely currently underestimated, leaving a knowledge gap and an opportunity for future research. The pathophysiology of focal limb dystonia shares some commonalities with other dystonias with a loss of inhibition in the central nervous system and a loss of the normal regulation of plasticity, called homeostatic plasticity. Functional imaging studies revealed abnormalities in several anatomical networks that involve the cortex, basal ganglia, and cerebellum. Further studies should focus on distinguishing cause from effect in both physiology and imaging studies to permit focus on most relevant biological correlates of dystonia. There is no specific therapy for the treatment of limb dystonia given the variability in presentation, but off-label botulinum toxin therapy is often applied to focal limb and task-specific dystonia. Various rehabilitation techniques have been applied and rehabilitation interventions may improve outcomes, but small sample size and lack of direct comparisons between methods to evaluate comparative efficacy limit conclusions. Finally, non-invasive and invasive therapeutic modalities have been explored in small studies with design limitations that do not yet clearly provide direction for larger clinical trials that could support new clinical therapies. Given these gaps in our clinical, pathophysiologic, and therapeutic knowledge, we have identified priorities for future research including: the development of diagnostic criteria for limb dystonia, more precise phenotypic characterization and innovative clinical trial design that considers clinical heterogeneity, and limited available number of participants. © 2017 Pirio Richardson, Altenmüller, Alter, Alterman, Chen, Frucht, Furuya, Jankovic, Jinnah, Kimberley, Lungu, Perlmutter, Prudente and Hallett.

Author Keywords
Botulinum toxin;  Deep brain stimulation;  Dystonia;  Inhibition;  Limb;  Research priorities;  Task-specific

Document Type: Review
Source: Scopus


Kallogjeri, D.a c , Piccirillo, J.F.a , Spitznagel, E., Jr.b , Hale, S.c , Nicklaus, J.E.d , Hardin, F.M.e , Shimony, J.S.f , Coalson, R.S.f g , Schlaggar, B.L.f g h i j
Cognitive training for adults with bothersome tinnitus a randomized clinical trial
(2017) JAMA Otolaryngology - Head and Neck Surgery, 143 (5), pp. 443-451. 

DOI: 10.1001/jamaoto.2016.3779

a Department of Otolaryngology-Head and Neck Surgery, Washington University, School of Medicine in St. Louis, 660 S Euclid Ave, St. Louis, MO, United States
b Department of Mathematics, Washington University in St. Louis, St. Louis, MO, United States
c Department of Psychology, Washington University in St. Louis, St. Louis, MO, United States
d AbbVie Clinical Pharmacology Research Unit, Global Pharmaceutical R and D, Grayslake, IL, United States
e Case Western Reserve University, School of Medicine, Cleveland, OH, United States
f Mallinckrodt Institute of Radiology, Washington University, School of Medicine in St. Louis, St. Louis, MO, United States
g Department of Neurology, Washington University, School of Medicine in St. Louis, St. Louis, MO, United States
h Department of Pediatrics, Washington University, School of Medicine in St. Louis, St. Louis, MO, United States
i Department of Neuroscience, Washington University, School of Medicine in St. Louis, St. Louis, MO, United States
j Department of Psychiatry, Washington University, School of Medicine in St. Louis, St. Louis, MO, United States

IMPORTANCE: Individuals with tinnitus have poorer working memory, slower processing speeds and reaction times, and deficiencies in selective attention, all of which interfere with readiness and performance. Brain Fitness Program-Tinnitus (BFP-T) is a cognitive training program specially designed to exploit neuroplasticity for preservation and expansion of cognitive health in adults with tinnitus. OBJECTIVE: To evaluate the effect of the BFP-T on tinnitus. DESIGN, SETTING, AND PARTICIPANTS: This open-label, intention-to-treat randomized clinical trial prescreened 191 patients with tinnitus and 64 healthy controls (HCs) from June 1, 2012, through October 31, 2013. Participants were 40 adults with bothersome tinnitus for more than 6 months and 20 age-matched HCs. Patients with tinnitus were randomized to a BFP-T or non-BFP-T control group. The BFP-T was completed online, and assessments were completed at Washington University School of Medicine. INTERVENTIONS: Participants in the intervention group were required to complete the BFP-T online 1 hour per day 5 days per week for 8 weeks. Tinnitus assessment, neuroimaging, and cognitive testing were completed at baseline and 8 weeks later. The HCs underwent neuroimaging and cognitive assessments. MAIN OUTCOMES AND MEASURES: The primary outcome measure was the change in Tinnitus Handicap Inventory (THI) score. Behavioral measures, neuroimaging, and cognitive tests were performed before and after the intervention. RESULTS: A total of 40 patients with tinnitus and 20 HCs participated in the study (median [range] age, 56 [35-64] years in the BFP-T group, 52 [24-64] years in the non-BFP-T group, and 50 [30-64] years in the HC group; 13 [65%] in the BFP-T group, 14 [70%] in the non-BFP-T group, and 13 [65%] in the HC group were males; and 16 [80%] in the BFP-T group, 16 [80%] in the non-BFP-T group, and 15 [75%] in the HC group were white). There was a reduction in the THI score in the BFP-T group (median, 7; range,-16 to 64) and non-BFP-T group (median, 11; range, -6 to 26), but this reduction was not significantly different between the 2 groups (median difference, 0; 95% CI, -10 to 8). There was no difference in cognitive test scores and other behavioral measures. There was a significant difference between baseline and follow-up in functional connectivity in cognitive control regions in the BFP-T group but not in HCs or individuals with untreated tinnitus. Of the 20 patients in the BFP-T group, 10(50%) self-reported improvement attributable to the intervention, and 6 (30%) reported to be much improved in the domains of tinnitus, memory, attention, and concentration. CONCLUSIONS AND RELEVANCE: These findings suggest that the computer-based cognitive training program is associated with self-reported changes in attention, memory, and perception of tinnitus. A possible mechanistic explanation for these changes could be neuroplastic changes in key brain systems involved in cognitive control. Cognitive training programs might have a role in the future treatment of patients with tinnitus. © 2017 American Medical Association. All rights reserved.

Document Type: Article
Source: Scopus


Huff, J.S.a , Naunheim, R.b , Ghosh Dastidar, S.c , Bazarian, J.d , Michelson, E.A.e
Referrals for CT scans in mild TBI patients can be aided by the use of a brain electrical activity biomarker
(2017) American Journal of Emergency Medicine, . Article in Press. 

DOI: 10.1016/j.ajem.2017.05.027

a University of Virginia Health System, Charlottesville, VA, United States
b Washington University Barnes Jewish Medical Center, St. Louis, MO, United States
c BrainScope Company, Inc., Bethesda, MD, United States
d University of Rochester Medical Center, Rochester, NY, United States
e Department of Emergency Medicine, Texas Tech Univ. Health Sciences Center, El Paso, TX, United States

Author Keywords
Brain function;  Classification;  CT;  EEG Biomarker;  MTBI

Document Type: Article in Press
Source: Scopus


Pearson, T.S.b g , Pons, R.b h , Engelstad, K.a , Kane, S.A.c , Goldberg, M.E.d e f i j , De Vivo, D.C.a
Paroxysmal eye-head movements in Glut1 deficiency syndrome
(2017) Neurology, 88 (17), pp. 1666-1673. 

DOI: 10.1212/WNL.0000000000003867

a Colleen Giblin Research Laboratory, United States
b Division of Pediatric Neurology, Department of Neurology, United States
c Department of Ophthalmology, Edward S. Harkness Eye Institute, United States
d Mahoney-Keck Center for Brain and Behavior Research, United States
e Department of Neuroscience, United States
f Department of Neurology, Psychiatry, and Ophthalmology, Columbia University, CPS, New York, NY, United States
g Department of Neurology, Washington University, School of Medicine, St. Louis, MO, United States
h First Department of Pediatrics, National and Kapodistrian University of Athens, Aghia Sofia Hospital, Greece
i Kavli Institute for Neuroscience, Columbia University, United States
j Division of Neurobiology and Behavior, New York State Psychiatric Institute, New York, United States

Objective: To describe a characteristic paroxysmal eye-head movement disorder that occurs in infants with Glut1 deficiency syndrome (Glut1 DS). Methods: We retrospectively reviewed the medical charts of 101 patients with Glut1 DS to obtain clinical data about episodic abnormal eye movements and analyzed video recordings of 18 eye movement episodes from 10 patients. Results: A documented history of paroxysmal abnormal eye movements was found in 32/101 patients (32%), and a detailed description was available in 18 patients, presented here. Episodes started before age 6 months in 15/18 patients (83%), and preceded the onset of seiz ures in10/16 patients (63%) who experienced both types of episodes. Eye movement episodes resolved, with or without treatment, by 6 years of age in 7/8 patients with documented longtermcourse. Episodes were brief (usually ,5 minutes). Video analysis revealed that the eye movements were rapid, multidirectional, and often accompanied by a head movement in the same direction. Eye movements were separated by clear intervals of fixation, usually ranging from 200to 800 ms. The movements were consistent with eye-head gaze saccades. These movements can be distinguished from opsoclonus by the presence of a clear intermovement fixation interval and the association of a same-direction head movement. Conclusions: Paroxysmal eye-head movements, for which we suggest the term aberrant gaze saccades, are an early symptom of Glut1 DS in infancy. Recognition of the episodes will facilitate prompt diagnosis of this treatable neurodevelopmental disorder. © 2017 American Academy of Neurology.

Document Type: Article
Source: Scopus


Lieu, J.E.C.
Role of qualitative research in shared decision making for treatment of sleep-disordered breathing: Patients, preferences, and personal factors
(2017) JAMA Otolaryngology - Head and Neck Surgery, 143 (3), pp. 213-214. 

DOI: 10.1001/jamaoto.2016.3364

Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St Louis, MO, United States

Document Type: Short Survey
Source: Scopus


Zipfel, G.J.
Dural arteriovenous fistula: A clinical model of thalamic dementia?: Response
(2017) Journal of Neurosurgery, 126 (3), p. 1022. 

DOI: 10.3171/2016.7.JNS161826

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

Document Type: Letter
Source: Scopus


Liang, X., Holy, T.E., Taghert, P.H.
A Series of Suppressive Signals within the Drosophila Circadian Neural Circuit Generates Sequential Daily Outputs
(2017) Neuron, . Article in Press. 

DOI: 10.1016/j.neuron.2017.05.007

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

We studied the Drosophila circadian neural circuit using whole-brain imaging in vivo. Five major groups of pacemaker neurons display synchronized molecular clocks, yet each exhibits a distinct phase of daily Ca2+ activation. Light and neuropeptide pigment dispersing factor (PDF) from morning cells (s-LNv) together delay the phase of the evening (LNd) group by
12 hr; PDF alone delays the phase of the DN3 group by 17 hr. Neuropeptide sNPF, released from s-LNv and LNd pacemakers, produces Ca2+ activation in the DN1 group late in the night. The circuit also features negative feedback by PDF to truncate the s-LNv Ca2+ wave and terminate PDF release. Both PDF and sNPF suppress basal Ca2+ levels in target pacemakers with long durations by cell-autonomous actions. Thus, light and neuropeptides act dynamically at distinct hubs of the circuit to produce multiple suppressive events that create the proper tempo and sequence of circadian pacemaker neuronal activities. Liang et al. record 24-hr Ca2+ activity patterns in all the major circadian pacemaker neurons of the Drosophila brain in vivo. Their results reveal a series of suppressive signals that creates a dynamic and patterned sequence of temporal outputs. © 2017 Elsevier Inc.

Author Keywords
Calcium;  Circadian physiology;  Drosophila;  Modulation;  Neuropeptide

Document Type: Article in Press
Source: Scopus


Hayes, J.F.a , Eichen, D.M.b , Barch, D.M.a , Wilfley, D.E.a
Executive function in childhood obesity: Promising intervention strategies to optimize treatment outcomes
(2017) Appetite, . Article in Press. 

DOI: 10.1016/j.appet.2017.05.040

a Washington University in St. Louis, 1 Brookings Drive, St. Louis, MO 63130, United States
b University of California, San Diego, 9500 Gilman Drive #0874, La Jolla, CA 92093, United States

Executive functions (EFs) are hypothesized to play a role in the development and maintenance of obesity due to their role in self-regulatory processes that manage energy-balance behaviors. Children with obesity have well-documented deficits in EF, which may impede effectiveness of current, evidence-based treatments. This review examines top-down EF processes (e.g., inhibitory control, working memory, cognitive flexibility), as well as bottom-up automatic processes that interact with EFs (e.g., attentional bias, delay discounting) and their relation to weight-loss treatment success in children. It then evaluates EF-related interventions that may improve treatment response. Empirical studies that included an intervention purported to affect EF processes as well as pre-post measurements of EF and/or relative weight in populations ages 19 or younger with overweight/obesity were reviewed. Findings indicate that poorer EF may hinder treatment response. Moreover, there is preliminary evidence that behavioral weight loss intervention and physical activity may positively affect EF and that improvements in EF are related to enhanced weight loss. Finally, novel intervention strategies, such as computer training of core EFs, attention modification programs, and episodic future thinking, show promise in influencing both EFs and EF-related skills and weight. Further research is needed to provide more conclusive evidence of the efficacy of these interventions and additional applications and settings should be considered. © 2017 Elsevier Ltd.

Document Type: Article in Press
Source: Scopus


Lu, P.G.a , Kung, N.H.b , Van Stavern, G.P.b
Ethambutol optic neuropathy associated with enhancement at the optic chiasm
(2017) Canadian Journal of Ophthalmology, . Article in Press. 

DOI: 10.1016/j.jcjo.2017.03.001

a Washington University School of Medicine, St. Louis, Missouri
b Department of Ophthalmology and Visual Sciences, Washington University, St. Louis, Missouri

Document Type: Article in Press
Source: Scopus


Sadler, B.E.a , Grant, J.D.a , Duncan, A.E.a b , Sartor, C.E.c , Waldron, M.d , Heath, A.C.a , Bucholz, K.K.a
The influence of paternal separation, paternal history of alcohol use disorder risk, and early substance use on offspring educational attainment by young adulthood
(2017) Journal of Studies on Alcohol and Drugs, 78 (3), pp. 426-434. 

DOI: 10.15288/jsad.2017.78.426

a Washington University School of Medicine, St. Louis, MO, United States
b George Warren Brown School of Social Work, Washington University in St. Louis, St. Louis, MO, United States
c Yale School of Medicine, New Haven, CT, United States
d Indiana University Bloomington, Bloomington, IN, United States

Objective: This study aimed to determine the associations among paternal alcohol problems, separation, and educational attainment in European American and African American offspring and whether offspring early alcohol/tobacco/marijuana use influenced these associations. Method: Families with offspring ages 13–19 years at intake were selected from state birth records and screened by telephone to determine high-risk or low-risk status (with/without paternal heavy drinking). Families of men with two or more driving-under-the-influence offenses were added as a very-high-risk group. Data from 340 African American and 288 European American offspring who were not enrolled in school at their last interview were analyzed. Educational attainment was modeled as less than high school, high school only (reference category), and some college or higher. Separation was defined as offspring report of not having lived continuously in the same household with their biological father from birth to age 14. Analyses were stratified by race. Results: In European Americans, neither family risk status nor early alcohol/ tobacco/marijuana use was associated with educational outcomes. However, paternal separation significantly elevated the likelihood of not completing high school in all models (relative risk ratios [RRRs] = 6.0–8.1, p <.001). For African American offspring, likelihoods of high school noncompletion were elevated marginally for paternal separation in only one model, but significantly for early marijuana use (RRRs = 2.8–3.2, p <.05). Very-high-risk status significantly reduced the likelihood of post–high school education in an adjusted model (RRR = 0.4, p <.05). Conclusions: High school noncompletion was significantly associated with paternal separation in European Americans and with early marijuana use in African American offspring. In addition, very-high-risk status reduced the likelihood of post–high school education in African American offspring only, suggesting that research with ethnically diverse samples yields important differences when examining outcomes of both separation and substance use on offspring education. © 2017, Alcohol Research Documentation Inc. All rights reserved.

Document Type: Article
Source: Scopus


Avidan, M.S.a , Maybrier, H.R.a , Abdallah, A.B.a , Jacobsohn, E.b , Vlisides, P.E.d , Pryor, K.O.e , Veselis, R.A.f , Grocott, H.P.c , Emmert, D.A.a , Rogers, E.M.e , Downey, R.J.g , Yulico, H.h , Noh, G.-J.i , Lee, Y.H.i , Waszynski, C.M.j , Arya, V.K.k , Pagel, P.S.l , Hudetz, J.A.l , Muench, M.R.a , Fritz, B.A.a , Waberski, W.m , Inouye, S.K.n , Mashour, G.A.d
Intraoperative ketamine for prevention of postoperative delirium or pain after major surgery in older adults: An international, multicentre, double-blind, randomised clinical trial
(2017) The Lancet, . Article in Press. 

DOI: 10.1016/S0140-6736(17)31467-8

a Department of Anesthesiology, Washington University School of Medicine, Saint Louis, MO, USA
b Department of Anesthesiology and Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada
c Department of Anesthesia and Perioperative Medicine, University of Manitoba, Winnipeg, MB, Canada
d Department of Anesthesiology, University of Michigan, Ann Arbor, MI, USA
e Department of Anesthesiology, Weill Cornell Medicine, New York City, NY, US
f Department of Neuroanesthesiology, Memorial Sloan Kettering Cancer Center, New York City, NY, USA
g Department of Surgery, Memorial Sloan Kettering Cancer Center, New York City, NY, USA
h Department of Anesthesiology, Memorial Sloan Kettering Cancer Center, New York City, NY, USA
i Department of Anesthesiology, Asan Medical Center, Seoul, South Korea
j Department of Medicine, Hartford Hospital, Hartford, CT, USA
k Department of Anaesthesiology and Intensive Care, Postgraduate Institute of Medical Education and Research, Chandigarh, India
l Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI, USA
m Department of Anesthesiology, Hartford Hospital, Hartford, Connecticut, USA
n Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, and Institute for Aging Research, Hebrew SeniorLife, Boston, MA, USA

Background: Delirium is a common and serious postoperative complication. Subanaesthetic ketamine is often administered intraoperatively for postoperative analgesia, and some evidence suggests that ketamine prevents delirium. The primary purpose of this trial was to assess the effectiveness of ketamine for prevention of postoperative delirium in older adults. Methods: The Prevention of Delirium and Complications Associated with Surgical Treatments [PODCAST] study is a multicentre, international randomised trial that enrolled adults older than 60 years undergoing major cardiac and non-cardiac surgery under general anaesthesia. Using a computer-generated randomisation sequence we randomly assigned patients to one of three groups in blocks of 15 to receive placebo (normal saline), low-dose ketamine (0·5 mg/kg), or high dose ketamine (1·0 mg/kg) after induction of anaesthesia, before surgical incision. Participants, clinicians, and investigators were blinded to group assignment. Delirium was assessed twice daily in the first 3 postoperative days using the Confusion Assessment Method. We did analyses by intention-to-treat and assessed adverse events. This trial is registered with, number NCT01690988. Findings: Between Feb 6, 2014, and June 26, 2016, 1360 patients were assessed, and 672 were randomly assigned, with 222 in the placebo group, 227 in the 0·5 mg/kg ketamine group, and 223 in the 1·0 mg/kg ketamine group. There was no difference in delirium incidence between patients in the combined ketamine groups and the placebo group (19·45% vs 19·82%, respectively; absolute difference 0·36%, 95% CI -6·07 to 7·38, p=0·92). There were more postoperative hallucinations (p=0·01) and nightmares (p=0·03) with increasing ketamine doses compared with placebo. Adverse events (cardiovascular, renal, infectious, gastrointestinal, and bleeding), whether viewed individually (p value for each >0·40) or collectively (36·9% in placebo, 39·6% in 0·5 mg/kg ketamine, and 40·8% in 1·0 mg/kg ketamine groups, p=0·69), did not differ significantly across groups. Interpretation: A single subanaesthetic dose of ketamine did not decrease delirium in older adults after major surgery, and might cause harm by inducing negative experiences. Funding: National Institutes of Health and Cancer Center Support. © 2017 Elsevier Ltd.

Document Type: Article in Press
Source: Scopus


Stein, L.R.a , Zorumski, C.F.a b c , Izumi, Y.a b c
Hippocampal slice preparation in rats acutely suppresses immunoreactivity of microtubule-associated protein (Map2) and glycogen levels without affecting numbers of glia or levels of the glutamate transporter VGlut1
(2017) Brain and Behavior, . Article in Press. 

DOI: 10.1002/brb3.736

a Department of Psychiatry Washington University School of Medicine St. Louis, MO USA
b The Taylor Family Institute for Innovative Psychiatric Research Washington University School of Medicine St. Louis, MO USA
c Center for Brain Research in Mood Disorders Washington University School of Medicine St. Louis, MO USA

Introduction: With its preservation of cytoarchitecture and synaptic circuitry, the hippocampal slice preparation has been a critical tool for studying the electrophysiological effects of pharmacological and genetic manipulations. To analyze the maximum number of slices or readouts per dissection, long incubation times postslice preparation are commonly used. We were interested in how slice integrity is affected by incubation postslice preparation. Methods: Hippocampal slices were prepared by three different methods: a chopper, a vibratome, and a rotary slicer. To test slice integrity, we compared glycogen levels and immunohistochemistry of selected proteins in rat hippocampal slices immediately after dissection and following 2 and 4 hr of incubation. Results: We found that immunoreactivity of the dendritic marker microtubule-associated protein 2 (Map2) drastically decreased during this incubation period, whereas immunoreactivity of the glutamate transporter VGlut1 did not significantly change with incubation time. Astrocytic and microglial cell numbers also did not significantly change with incubation time whereas glycogen levels markedly increased during incubation. Conclusion: Immunoreactivity of the dendritic marker Map2 quickly decreased after dissection with all the slicing methods. This work highlights a need for caution when using long incubation periods following slice preparation. © 2017 Published by Wiley Periodicals, Inc.

Author Keywords
Glycogen;  Hippocampus;  Map2;  Slice preparation;  VGlut1

Document Type: Article in Press
Source: Scopus


Bahr, N.C.a , Trotman, R.L.b , Samman, H.c , Jung, R.S.d , Rosterman, L.R.c , Weil, G.J.e , Hinthorn, D.R.a
Eosinophilic meningitis due to infection with Paragonimus kellicotti
(2017) Clinical Infectious Diseases, 64 (9), pp. 1271-1274. 

DOI: 10.1093/cid/cix102

a Division of Infectious Diseases, Department of Medicine, University of Kansas, MS 1028, 3901 Rainbow Blvd, Kansas City, KS, United States
b Infectious Diseases Specialty Clinic, CoxHealth, Springfield, MO, United States
c Department of Neurology, University of Kansas, Kansas City, United States
d Vascular Neurology and Neurointerventional Surgery, CoxHealth, Springfield, United States
e Infectious Diseases Division, Department of Medicine, Washington University School of Medicine, St Louis, MO, United States

Paragonimus kellicotti is an emerging pathogen in the United States with 19 previously reported cases, most in Missouri. Pulmonary symptoms with eosinophilia are most common, though 1 case did involve the central nervous system with few symptoms. We describe the first 2 cases of eosinophilic meningitis due to Paragonimus kellicotti. © The Author 2017.

Author Keywords
Eosinophilia;  Meningitis;  Paragonimus;  Trematoda

Document Type: Article
Source: Scopus


Wolf, T.J.a , Spiers, M.J.a , Doherty, M.b , Leary, E.V.c
The effect of self-management education following mild stroke: An exploratory randomized controlled trial*
(2017) Topics in Stroke Rehabilitation, 24 (5), pp. 345-352. 

DOI: 10.1080/10749357.2017.1289687

a Department of Occupational Therapy, University of Missouri, Columbia, MO, United States
b Washington University in St. Louis, St. Louis, MO, United States
c Biostatistics and Research Design Unit, School of Medicine, University of Missouri, Columbia, MO, United States

Background: Mild stroke comprises 53% of stroke hospital admissions; however, the majority of those with mild stroke patients receive little support to address chronic symptoms following stroke. Objectives: To evaluate the feasibility and preliminary effect of the Chronic Disease Self-Management Program (CDSMP) for use with individuals immediately post mild-stroke. Methods: Single-blind, exploratory, randomized controlled trial with participants who sustained a mild stroke (NIHSS <6). Participants were randomized to either receive the CDSMP intervention or to an inactive control group. Primary outcomes were self-reported health and self-efficacy and were obtained at baseline, post-intervention (treatment group only), and at six months post-baseline. Wilcoxon Signed Rank Tests were used to compare change score differences for all participants and effect size was computed using effect size r for non-parametric data. Results: There were no differences between groups in demographics or baseline data with the exception of how participants felt they are able to manage their health in general (p = 0.05). At follow-up, effect sizes ranged from 0 to 0.35 (no effect to medium effect); however, while the treatment group reported improvements in several areas of health at follow-up, the results are not compelling when compared to the control group over the same time period. Conclusions: The results did not identify a positive effect that would support the use of the CDSMP with individual’s post-mild stroke; however, the generalizability of these results is limited secondary to several limitations in this exploratory study. © 2017 Informa UK Limited, trading as Taylor & Francis Group.

Author Keywords
Chronic disease;  Occupational therapy;  Rehabilitation;  Stroke;  Stroke management

Document Type: Article
Source: Scopus


Schuckit, M.A.a , Smith, T.L.a , Danko, G.a , Anthenelli, R.a , Schoen, L.a , Kawamura, M.a , Kramer, J.b , Dick, D.M.c , Neale, Z.d , Kuperman, S.e , Mccutcheon, V.f , Anokhin, A.P.g , Hesselbrock, V.h , Hesselbrock, M.i , Bucholz, K.g
A Prospective Comparison of How the Level of Response to Alcohol and Impulsivity Relate to Future DSM-IV Alcohol Problems in the COGA Youth Panel
(2017) Alcoholism: Clinical and Experimental Research, . Article in Press. 

DOI: 10.1111/acer.13407

a Department of Psychiatry University of California, San Diego La Jolla, California
b Department of Psychiatry The University of Iowa Iowa City, Iowa
c Department of Psychiatry Virginia Commonwealth University Richmond, Virginia
d Department of Psychology Virginia Commonwealth University Richmond, Virginia
e Child Psychiatry Clinic The University of Iowa Iowa City, Iowa
f Department of Psychiatry Washington University St. Louis Missouri
g Washington University in Saint Louis School of Medicine St. Louis, Missouri
h Department of Psychiatry University of Connecticut Farmington, Connecticut
i Department of PsychiatrySchool of Medicine University of Connecticut Farmington, Connecticut

Background: Alcohol problems reflect both environmental and genetic characteristics that often operate through endophenotypes like low levels of response (low LRs) to alcohol and higher impulsivity. Relationships of these preexisting characteristics to alcohol problems have been studied, but few analyses have included both low LR and impulsivity in the same model. Methods: We extracted prospective data from 1,028 participants in the Prospective Youth Sample of the Collaborative Study on the Genetics of Alcoholism (COGA). At Time 1 (age 18), these drinking but non-alcohol-dependent males and females completed the Barratt Impulsivity Scale and the Self-Report of the Effects of Alcohol questionnaire regarding drinks required for effects the first 5 times of drinking (SRE5-LR). Two years later, they reported perceived drinking patterns of peers (PEER), their own alcohol expectancies (EXPECT), and their drinking to cope with stress (COPE). Subsequently, at Time 3, participants reported numbers of up to 11 DSM-IV alcohol criterion items experienced in the 2 years since Time 2 (ALC PROBS). Data were analyzed using structural equation modeling (SEM). Results: In the SEM, Baseline SRE5-LR and impulsivity were weakly related and did not interact in predicting later ALC PROBS. LR was directly linked to Time 3 ALC PROBS and to PEER, but had no direct path to EXPECT, with partial mediation to ALC PROBS through PEER to EXPECT and via COPE. Impulsivity did not relate directly to ALC PROBS or PEER, but was directly related to EXPECT and COPE, with effects on ALC PROBS also operating through EXPECT and COPE. Conclusions: Low LRs and impulsivity related to Time 3 ALC PROBS through somewhat different paths. Education- and counseling-based approaches to mitigate future alcohol problems may benefit from emphasizing different potential mediators of adverse alcohol outcomes for youth with low LRs versus those with high impulsivity or both characteristics. © 2017 Research Society on Alcoholism.

Author Keywords
Alcohol Problems;  Impulsivity;  Levels of Response to Alcohol;  Structural Equation Models

Document Type: Article in Press
Source: Scopus


Franco, M.J., Phillips, B.Z., Lalchandani, G.R., Mackinnon, S.E.
Decompression of the superficial peroneal nerve: Clinical outcomes and anatomical study
(2017) Journal of Neurosurgery, 126 (1), pp. 330-335. 

DOI: 10.3171/2016.1.JNS152454

Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, MO, United States

OBJECTIVE: The authors of this study sought to determine the outcomes of patients undergoing superficial peroneal nerve (SPN) release to treat lower-extremity pain and describe consistent anatomical landmarks to direct surgical planning. METHODS: This retrospective cohort study examined 54 patients with pain in the SPN distribution who were treated with decompression between 2011 and 2014. Patients rated pain and the effect of pain on quality of life (QOL) on the visual analog scale (VAS) from 0 to 10. Scores were then converted to percentages. Linear regression analysis was performed to assess the impact of the preoperative effect of pain on QOL, age, body mass index (BMI), and preoperative duration of pain on the postoperative effect of pain on QOL. Measurements were made intraoperatively in 13 patients to determine the landmarks for identifying the SPN. RESULTS A higher BMI was a negative predictor for improvement in the effect of pain on QOL. A decrease in pain compared with the initial level of pain suggested a nonlinear relationship between these variables. A minority of patients (7 of 16) with a preoperative pain VAS score ≤ 60 reported less pain after surgery. A large majority (30 of 36 patients) of those with a preoperative pain VAS score > 60 reported improvement. Intraoperative measurements demonstrated that the SPN was consistently found to be 5 ± 1.1, 5 ± 1.1, and 6 ± 1.2 cm lateral to the tibia at 10, 15, and 20 cm proximal to the lateral malleolus, respectively. CONCLUSIONS: A majority of patients with a preoperative pain VAS score > 60 showed a decrease in postoperative pain. A higher BMI was associated with less improvement in the effect of pain on QOL. This information can be useful when counseling patients on treatment options. Based on the intraoperative data, the authors found that the SPN can be located at reliable points in reference to the tibia and lateral malleolus. ©AANS, 2017.

Author Keywords
Peripheral nerve compression;  Peripheral nerve pain;  Superficial peroneal nerve anatomy

Document Type: Article
Source: Scopus


Kennedy, R.E.a , Cutter, G.R.b , Wang, G.c , Schneider, L.S.d
Challenging Assumptions About African American Participation in Alzheimer Disease Trials
(2016) American Journal of Geriatric Psychiatry, . Article in Press. 

DOI: 10.1016/j.jagp.2017.04.013

a Department of Medicine, University of Alabama at Birmingham, Birmingham, AL
b Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL
c Department of Biostatistics, Washington University School of Medicine, St. Louis, MO
d Departments of Psychiatry, Neurology, and Gerontology, University of Southern California Keck School of Medicine, Los Angeles, CA

Objective: The authors investigated potential effects of increased African American participation in Alzheimer disease (AD) and mild cognitive impairment (MCI) clinical trials by examining differences in comorbid conditions and treatment outcome affecting trial design. Methods: Using a meta-database of 18 studies from the Alzheimer's Disease Cooperative Study and the Alzheimer's Disease Neuroimaging Initiative, a cohort of 5,164 subjects were included for whom there were baseline demographic data and information on comorbid disorders, grouped by organ system. Meta-analysis was used to compare prevalence of comorbidities, dropouts, and rates of change on the cognitive subscale of the Alzheimer's Disease Assessment Scale by race. Clinical trial scenarios similar to recent therapeutic trials were simulated to determine effects of increased African American participation on statistical power. Results: Approximately 7% of AD, 4% of MCI, and 11% of normal participants were African American. African American subjects had higher prevalence of cardiovascular disorders (odds ratio: 2.10; 95% confidence interval [CI]: 1.71-2.57) and higher rate of dropouts (odds ratio: 1.60; 95% CI: 1.15-2.21) compared with whites but lower rates of other disorders. There were no significant differences in rate of progression (-0.862 points/year; 95% CI: -1.89 to 0.162) by race and little effect on power in simulated trials with sample sizes similar to current AD trial designs. Conclusion: Increasing African American participation in AD clinical trials will require adaptation of trial protocols to address comorbidities and dropouts. However, increased diversity is unlikely to negatively affect trial outcomes and should be encouraged to promote generalizability of trial results. © 2017 American Association for Geriatric Psychiatry.

Author Keywords
Alzheimer disease;  Clinical trial design;  Diversity;  Mild cognitive impairment;  Racial differences

Document Type: Article in Press
Source: Scopus