Arts & Sciences Brown School McKelvey School of Engineering School of Law School of Medicine Weekly Publications

WashU weekly Neuroscience publications

“Ocular and brain imaging findings in Peters’ anomaly: A case report and literature review” (2020) Radiology Case Reports

Ocular and brain imaging findings in Peters’ anomaly: A case report and literature review
(2020) Radiology Case Reports, 15 (7), pp. 863-866. 

Samara, A.a , Eldaya, R.W.b

a Department of Psychiatry, Washington University School of Medicine, 4525 Scott Ave, St. Louis, MO 63110, United States
b Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, United States

Abstract
Peters’ anomaly is a rare congenital eye condition characterized by anterior segment dysgenesis and commonly presents as unilateral or bilateral corneal opacity in the early neonatal period. Peters’ anomaly is often associated with congenital brain and skull abnormalities, which are frequently overlooked. In this paper, we present a case of a 5-day-old female neonate with Peters’ anomaly, and review the literature for similar reports that describe associated brain imaging findings. In our case, imaging studies show abnormalities involving the anterior segments of both globes with absent intracranial manifestations. Although Peters’ anomaly is a condition of interest for ophthalmologists, radiological studies should be performed, and neuroradiologists should be aware of the imaging findings associated with this rare entity. © 2020 The Authors

Author Keywords
Anterior eye segment;  Magnetic resonance imaging;  Peters’ anomaly

Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access

“Antidepressant use in patients with heart failure” (2020) General Hospital Psychiatry

Antidepressant use in patients with heart failure
(2020) General Hospital Psychiatry, 65, pp. 1-8. 

Freedland, K.E.a , Steinmeyer, B.C.a , Carney, R.M.a , Skala, J.A.a , Rich, M.W.b

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

Abstract
Objective: There is little evidence that antidepressants are efficacious for depression in patients with heart failure (HF), and equivocal evidence that they are safe. This study identified characteristics that are associated with antidepressant use in hospitalized patients with HF. Method: Logistic regression models were used to identify independent correlates of antidepressant use in 400 patients hospitalized with HF between 2014 and 2016. The measure of depression in the primary analysis was a DSM-5 diagnosis based on a structured interview; this was replaced by a PHQ-9 depression score in a secondary analysis. Results: In the primary analysis, there were positive associations between antidepressant use and white race, younger age, unemployment, non-ischemic HF, number of other prescribed medications, current minor depression, history of major depression, and functional impairment. In the secondary analysis, there were positive associations with white race, unemployment, number of other prescribed medications, and functional impairment; the effect of current severity of depression differed between patients with vs. without a history of major depression. Conclusions: Current depression is only one of several factors that influence the use of antidepressant medications in patients with HF. Further research is needed to ensure that these agents are being used appropriately in this patient population. © 2020

Author Keywords
Antidepressive agents;  Depression;  Depressive disorder;  Drug utilization;  Heart failure

Document Type: Article
Publication Stage: Final
Source: Scopus

“Examining delay of gratification in healthy aging” (2020) Behavioural Processes

Examining delay of gratification in healthy aging
(2020) Behavioural Processes, 176, art. no. 104125, . 

Lamichhane, B., Di Rosa, E., Green, L., Myerson, J., Braver, T.S.

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

Abstract
Delay of gratification (DofG) refers to the capacity to forego an immediate reward in order to receive a more desirable reward later. As a core executive function, it might be expected that DofG would follow the standard pattern of age-related decline observed in older adults for other executive tasks. However, there actually have been few studies of aging and DofG, and even these have shown mixed results, suggesting the need for further investigation and new approaches. The present study tested a novel reward-based decision-making paradigm enabling examination of age-related DofG effects in adult humans. Results showed that older adults earned fewer overall rewards than young adults, both before and after instruction regarding the optimal DofG strategy. Prior to instruction, learning this strategy was challenging for all participants, regardless of age. The finding of age-related impairments even after strategy instruction indicated that these impairments were not due to a failure to understand the task or follow the optimal strategy, but instead were related to self-reported difficulty in waiting for delayed rewards. These results suggest the presence of age-related changes in DofG capacity and highlight the advantages of this new experimental paradigm for use in future investigations, including both behavioral and neuroimaging studies. © 2020 Elsevier B.V.

Document Type: Article
Publication Stage: Final
Source: Scopus

“Inhibitors of cellular stress overcome acute effects of ethanol on hippocampal plasticity and learning” (2020) Neurobiology of Disease

Inhibitors of cellular stress overcome acute effects of ethanol on hippocampal plasticity and learning
(2020) Neurobiology of Disease, 141, art. no. 104875, . 

Izumi, Y., Zorumski, C.F.

Department of Psychiatry and Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine, St. Louis, MO, United States

Abstract
Ethanol intoxication can produce marked changes in cognitive function including states in which the ability to learn and remember new information is completely disrupted. These defects likely reflect changes in the synaptic plasticity thought to underlie memory formation. We have studied mechanisms contributing to the adverse effects of ethanol on hippocampal long-term potentiation (LTP) and provided evidence that ethanol-mediated LTP inhibition involves a form of metaplasticity resulting from local metabolism of ethanol to acetaldehyde and untimely activation of N-methyl-D-aspartate receptors (NMDARs), both of which are neuronal stressors. In the present studies, we sought to understand the role of cellular stress in LTP defects, and demonstrate that ethanol’s effects on LTP in the CA1 hippocampal region are overcome by agents that inhibit cellular stress responses, including ISRIB, a specific inhibitor of integrated stress responses, and GW3965, an agonist that acts at liver X receptors (LXRs) and dampens cellular stress. The agents that alter LTP inhibition also prevent the adverse effects of acute ethanol on one trial inhibitory avoidance learning. Unexpectedly, we found that the LXR agonist but not ISRIB overcomes effects of ethanol on synaptic responses mediated by N-methyl-D-aspartate receptors (NMDARs). These results have implications for understanding the adverse effects of ethanol and possibly for identifying novel paths to treatments that can prevent or overcome ethanol-induced cognitive dysfunction. © 2020 The Author(s)

Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access

“Plasticity of the adult auditory system based on corticocortical and corticofugal modulations” (2020) Neuroscience and Biobehavioral Reviews

Plasticity of the adult auditory system based on corticocortical and corticofugal modulations
(2020) Neuroscience and Biobehavioral Reviews, 113, pp. 461-478. 

Suga, N.

Department of Biology, Washington University, One Brookings Drive, St. Louis, MO 63130, United States

Abstract
Suga, N. Plasticity of the adult auditory system based on corticocortical and corticofugal modulations. NEUROSCI. BIOBEHAV. REV. XXX-XXX, 2020. Corticocortical and corticofugal modulations mediated by neurons in the lemniscal pathway are based on positive feedback associated with lateral inhibition and play an essential role not only in auditory signal processing, but also sound-specific plastic changes (e.g., frequency-tuning shifts) for the reorganization of the adult auditory system based on auditory experiences. The modulations evoke the facilitation of auditory responses of “tuning-matched” neurons and the tuning shifts of “tuning-unmatched” neurons in the auditory cortex and subcortical auditory nuclei. Here, “tuning-matched” means that the tuning properties of a recorded neuron are the same as those of an electrically stimulated cortical neuron or the frequency of tone burst stimuli. Tuning shifts, corticocortical and corticofugal modulations, evoked by focal cortical electric stimulation or tone burst stimulation are augmented by electric stimulation of the somatosensory cortex, acetylcholine application to the auditory cortex and associative learning such as auditory fear conditioning. Tuning shifts occur not only in the frequency domain, but also in the time, amplitude and spatial domains. © 2020

Author Keywords
Centripetal and centrifugal tuning shifts;  Focal activation and inactivation;  Multi-parametric modulations;  Plasticity in the frequency, amplitude, time and spatial domains;  Positive feedback associated with lateral inhibition

Document Type: Review
Publication Stage: Final
Source: Scopus

“Neural circuit dynamics for sensory detection” (2020) Journal of Neuroscience

Neural circuit dynamics for sensory detection
(2020) Journal of Neuroscience, 40 (17), pp. 3408-3423. 

Mallik, S.a , Nizampatnam, S.a , Nandi, A.b , Saha, D.c , Raman, B.d , Ching, S.a d

a Department of Electrical and Systems Engineering, Washington University in St. Louis, St. Louis, MO 63130, United States
b Allen Institute of Brain Science, Seattle, WA 98109, United States
c Department of Biomedical Engineering, Michigan State University, East Lansing, MI 48824, United States
d Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO 63130, United States

Abstract
We consider the question of how sensory networks enable the detection of sensory stimuli in a combinatorial coding space. We are specifically interested in the olfactory system, wherein recent experimental studies have reported the existence of rich, enigmatic response patterns associated with stimulus onset and offset. This study aims to identify the functional relevance of such response patterns (i.e., what benefits does such neural activity provide in the context of detecting stimuli in a natural environment). We study this problem through the lens of normative, optimization-based modeling. Here, we define the notion of a low-dimensional latent representation of stimulus identity, which is generated through action of the sensory network. The objective of our optimization framework is to ensure high-fidelity tracking of a nominal representation in this latent space in an energy-efficient manner. It turns out that the optimal motifs emerging from this framework possess morphologic similarity with prototypical onset and offset responses observed in vivo in locusts (Schistocerca americana) of either sex. Furthermore, this objective can be exactly achieved by a network with reciprocal excitatory–inhibitory competitive dynamics, similar to interactions between projection neurons and local neurons in the early olfactory system of insects. The derived model also makes several predictions regarding maintenance of robust latent representations in the presence of confounding background information and trade-offs between the energy of sensory activity and resultant behavioral measures such as speed and accuracy of stimulus detection. Copyright © 2020 the authors.

Document Type: Article
Publication Stage: Final
Source: Scopus

“Design of the WHIP-PD study: a phase II, twelve-month, dual-site, randomized controlled trial evaluating the effects of a cognitive-behavioral approach for promoting enhanced walking activity using mobile health technology in people with Parkinson-disease” (2020) BMC Neurology

Design of the WHIP-PD study: a phase II, twelve-month, dual-site, randomized controlled trial evaluating the effects of a cognitive-behavioral approach for promoting enhanced walking activity using mobile health technology in people with Parkinson-disease
(2020) BMC Neurology, 20 (1), p. 146. 

Rawson, K.S.a , Cavanaugh, J.T.b , Colon-Semenza, C.c , DeAngelis, T.c , Duncan, R.P.a d , Fulford, D.e , LaValley, M.P.f , Mazzoni, P.d , Nordahl, T.c , Quintiliani, L.M.g , Saint-Hilaire, M.h , Thomas, C.A.h , Earhart, G.M.a d i , Ellis, T.D.c

a Program in Physical Therapy, Washington University in St. Louis School of Medicine, St. Louis, MO, USA
b Department of Physical Therapy, University of New England, MEPortland, United States
c Department of Physical Therapy and Athletic Training, Sargent College of Health and Rehabilitation Sciences, Boston University, MA, Boston, United States
d Department of Neurology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA
e Department of Occupational Therapy, Sargent College of Health and Rehabilitation Sciences, Boston University, MA, Boston, United States
f School of Public Health, Boston University, MA, Boston, United States
g Department of Medicine, Section of General Internal Medicine, Boston University, MA, Boston, United States
h Department of Neurology, Parkinson’s Disease and Movement Disorders Center, Boston University, MA, Boston, United States
i Department of Neuroscience, Washington University in St. Louis School of Medicine, St. Louis, MO, USA

Abstract
BACKGROUND: Parkinson disease (PD) is a debilitating and chronic neurodegenerative disease resulting in ambulation difficulties. Natural walking activity often declines early in disease progression despite the relative stability of motor impairments. In this study, we propose a paradigm shift with a “connected behavioral approach” that targets real-world walking using cognitive-behavioral training and mobile health (mHealth) technology. METHODS/DESIGN: The Walking and mHealth to Increase Participation in Parkinson Disease (WHIP-PD) study is a twelve-month, dual site, two-arm, randomized controlled trial recruiting 148 participants with early to mid-stage PD. Participants will be randomly assigned to connected behavioral or active control conditions. Both conditions will include a customized program of goal-oriented walking, walking-enhancing strengthening exercises, and eight in-person visits with a physical therapist. Participants in the connected behavioral condition also will (1) receive cognitive-behavioral training to promote self-efficacy for routine walking behavior and (2) use a mHealth software application to manage their program and communicate remotely with their physical therapist. Active control participants will receive no cognitive-behavioral training and manage their program on paper. Evaluations will occur at baseline, three-, six-, and twelve-months and include walking assessments, self-efficacy questionnaires, and seven days of activity monitoring. Primary outcomes will include the change between baseline and twelve months in overall amount of walking activity (mean number of steps per day) and amount of moderate intensity walking activity (mean number of minutes per day in which > 100 steps were accumulated). Secondary outcomes will include change in walking capacity as measured by the six-minute walk test and ten-meter walk test. We also will examine if self-efficacy mediates change in amount of walking activity and if change in amount of walking activity mediates change in walking capacity. DISCUSSION: We expect this study to show the connected behavioral approach will be more effective than the active control condition in increasing the amount and intensity of real-world walking activity and improving walking capacity. Determining effective physical activity interventions for persons with PD is important for preserving mobility and essential for maintaining quality of life. Clinical trials registration NCT03517371, May 7, 2018. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03517371. Date of registration: May 7, 2018. Protocol version: Original.

Author Keywords
Cognitive behavioral training;  Exercise;  Mobile health;  Parkinson disease;  RCT;  Self-efficacy;  Walking

Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access

“Editorial. Pediatric neurosurgery along with Children’s Hospitals’ innovations are rapid and uniform in response to the COVID-19 pandemic” (2020) Journal of Neurosurgery. Pediatrics

Editorial. Pediatric neurosurgery along with Children’s Hospitals’ innovations are rapid and uniform in response to the COVID-19 pandemic
(2020) Journal of Neurosurgery. Pediatrics, pp. 1-3. 

Weiner, H.L.a , Adelson, P.D.b , Brockmeyer, D.L.c , Maher, C.O.d , Gupta, N.e , Smyth, M.D.f , Jea, A.g , Blount, J.P.h , Riva-Cambrin, J.i , Lam, S.K.j , Ahn, E.S.k , Albert, G.W.l , Leonard, J.R.m

a Department of Neurosurgery, Division of Pediatric Neurosurgery, Texas Children’s Hospital, Baylor College of Medicine, Houston, TX
b Department of Neurosurgery, Barrow Neurological Institute at Phoenix Children’s Hospital, University of Arizona College of Medicine, Phoenix, AZ, United States
c Department of Neurosurgery, Division of Pediatric Neurosurgery, Primary Children’s Hospital, University of Utah, Salt Lake City, UT, United States
d Department of Neurosurgery, Division of Pediatric Neurosurgery, Mott Children’s Hospital, University of Michigan, Ann Arbor, MI, United States
e Department of Neurological Surgery, Division of Pediatric Neurosurgery, UCSF Benioff Children’s Hospital, University of California, San Francisco, CA, Mexico
f Department of Neurological Surgery, Division of Pediatric Neurological Surgery, St. Louis Children’s Hospital, Washington University School of Medicine in St. LouisMO
g Department of Neurosurgery, Division of Pediatric Neurosurgery, Riley Hospital for Children at IU Health, Indiana University School of Medicine, Indianapolis, IN, United States
h Department of Neurosurgery, Division of Pediatric Neurosurgery, Children’s of Alabama, University of Alabama at Birmingham School of Medicine, Birmingham, AL
i Department of Clinical Neurosciences, Section of Neurosurgery, University of CalgaryAB, Canada
j 10Department of Neurological Surgery, Division of Pediatric Neurosurgery, Ann and Robert H. Lurie Children’s Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL, Mexico
k 11Department of Neurosurgery, Division of Pediatric Neurosurgery, Children’s Center, Mayo Clinic College of Medicine and Science, Rochester, MN
l 12Department of Neurosurgery, Division of Pediatric Neurosurgery, Arkansas Children’s Hospital, University of Arkansas for Medical Sciences, Little Rock, Arkansas; and
m 13Department of Neurological Surgery, Section of Neurosurgery, Ohio State University College of Medicine, Nationwide Children’s Hospital, Columbus, OH, United States

Document Type: Editorial
Publication Stage: Article in Press
Source: Scopus
Access Type: Open Access

“Wide-field ophthalmic space-division multiplexing optical coherence tomography” (2020) Photonics Research

Wide-field ophthalmic space-division multiplexing optical coherence tomography
(2020) Photonics Research, 8 (4), pp. 539-547. 

Jerwick, J.a b , Huang, Y.a , Dong, Z.a b , Slaudades, A.c , Brucker, A.J.c , Zhou, C.a b d

a Department of Electrical and Computer Engineering, Lehigh University, Bethlehem, PA 18015, United States
b Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO 63130, United States
c Scheie Eye Institute, Penn Presbyterian Medical Center, University of Pennsylvania, Philadelphia, PA 19104, United States
d Department of Bioengineering, Lehigh University, Bethlehem, PA 18015, United States

Abstract
High-speed ophthalmic optical coherence tomography (OCT) systems are of interest because they allow rapid, motion-free, and wide-field retinal imaging. Space-division multiplexing optical coherence tomography (SDM-OCT) is a high-speed imaging technology that takes advantage of the long coherence length of microelectromechanical vertical cavity surface emitting laser sources to multiplex multiple images along a single imaging depth. We demonstrate wide-field retinal OCT imaging, acquired at an effective A-scan rate of 800,000 A-scans/s with volumetric images covering up to 12.5 mm × 7.4 mm on the retina and captured in less than 1 s. A clinical feasibility study was conducted to compare the ophthalmic SDM-OCT with commercial OCT systems, illustrating the high-speed capability of SDM-OCT in a clinical setting. © 2020 Chinese Laser Press

Document Type: Article
Publication Stage: Final
Source: Scopus

“Identification and characterization of novel TRPM1 autoantibodies from serum of patients with melanoma-associated retinopathy” (2020) PLoS ONE

Identification and characterization of novel TRPM1 autoantibodies from serum of patients with melanoma-associated retinopathy
(2020) PLoS ONE, 15 (4), art. no. e0231750, . 

Varin, J.a , Reynolds, M.M.b , Bouzidi, N.a , Tick, S.c , Wohlschlegel, J.a , Becquart, O.d , Michiels, C.a , Dereure, O.d , Duvoisin, R.M.e , Morgans, C.W.e , Sahe, J.-A.a c f g h , Samaran, Q.d , Guillot, B.d , Pulido, J.S.i j , Audo, I.a c k , Zeitz, C.a

a Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, France
b Department of Ophthalmology, Washington University, Saint Louis, MO, United States
c CHNO des Quinze- Vingts, DHU Sight Restore, INSERM-DGOS CIC 1423, Paris, France
d Department of Dermatology, INSERM U1058 Pathogenesis and Control of Chronic Infections, University of Montpellier, Montpellier, France
e Department of Chemical Physiology & Biochemistry, Oregon Health & Science University, Portland, OR, United States
f Fondation Ophtalmologique Adolphe de Rothschild, Paris, France
g Académie des Sciences, Institut de France, Paris, France
h Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
i Department of Ophthalmology, Mayo Clinic, Rochester, MN, United States
j Department of Molecular Medicine, Mayo Clinic, Rochester, MN, United States
k Institute of Ophthalmology, University College of London, London, United Kingdom

Abstract
Melanoma-associated retinopathy (MAR) is a rare paraneoplastic retinal disorder usually occurring in the context of metastatic melanoma. Patients present with night blindness, photopsias and a constriction of the visual field. MAR is an auto-immune disorder characterized by the production of autoantibodies targeting retinal proteins, especially autoantibodies reacting to the cation channel TRPM1 produced in melanocytes and ON-bipolar cells. TRPM1 has at least three different isoforms which vary in the N-terminal region of the protein. In this study, we report the case of three new MAR patients presenting different anti- TRPM1 autoantibodies reacting to the three isoforms of TRPM1 with variable binding affinity. Two sera recognized all isoforms of TRPM1, while one recognized only the two longest isoforms upon immunolocalization studies on overexpressing cells. Similarly, the former two sera reacted with all TRPM1 isoforms on western blot, but an immunoprecipitation enrichment step was necessary to detect all isoforms with the latter serum. In contrast, all sera labelled ON-bipolar cells on Tprm1+/+ but not on Trpm1-/- mouse retina as shown by coimmunolocalization. This confirms that the MAR sera specifically detect TRPM1. Most likely, the anti-TRPM1 autoantibodies of different patients vary in affinity and concentration. In addition, the binding of autoantibodies to TRPM1 may be conformation-dependent, with epitopes being inaccessible in some constructs (truncated polypeptides versus full-length TRPM1) or applications (western blotting versus immunohistochemistry). Therefore, we propose that a combination of different methods should be used to test for the presence of anti-TRPM1 autoantibodies in the sera of MAR patients. © 2020 Varin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access

“Political psychophysiology” (2020) Politics and the Life Sciences

Political psychophysiology
(2020) Politics and the Life Sciences, 39 (1), pp. 101-117. 

Settle, J.E.a , Hibbing, M.V.b , Anspach, N.M.c , Carlson, T.N.d , Coe, C.M.b , Hernandez, E.a , Peterson, J.e , Stuart, J.a , Arceneaux, K.f

a College of William and Mary Government, Tyler Hall, 300 James Blair Drive, Williamsburg, VA 23187, United States
b University of California, Merced, United States
c York College, Pennsylvania, United States
d Washington University, St. Louis, United States
e Palo Alto College, United States
f Temple University, United States

Abstract
The past decade has seen a rapid increase in the number of studies employing psychophysiological methods to explain variation in political attitudes and behavior. However, the collection, analysis, and interpretation of physiological data present novel challenges for political scientists unfamiliar with the underlying biological concepts and technical skills necessary for utilizing this approach. Our objective in this article is to maximize the effectiveness of future work utilizing psychophysiological measurement by providing guidance on how the techniques can be employed most fruitfully as a complement to, not a replacement for, existing methods. We develop clear, step-by-step instructions for how physiological research should be conducted and provide a discussion of the issues commonly faced by scholars working with these measures. Our hope is that this article will be a useful resource for both neophytes and experienced scholars in lowering the start-up costs to doing this work and assessing it as part of the peer review process. More broadly, in the spirit of the open science framework, we aim to foster increased communication, collaboration, and replication of findings across political science labs utilizing psychophysiological methods. © Association for Politics and the Life Sciences 2020.

Author Keywords
Psychophysiology;  Research Tool Report;  Skin conductance

Document Type: Article
Publication Stage: Final
Source: Scopus

“Resting State Functional Connectivity Signature Differentiates Cognitively Normal from Individuals Who Convert to Symptomatic Alzheimer’s Disease” (2020) Journal of Alzheimer’s Disease

Resting State Functional Connectivity Signature Differentiates Cognitively Normal from Individuals Who Convert to Symptomatic Alzheimer’s Disease
(2020) Journal of Alzheimer’s Disease, 74 (4), pp. 1085-1095. 

Wisch, J.K.a , Roe, C.M.a d , Babulal, G.M.a d , Schindler, S.E.a d , Fagan, A.M.c d d , Benzinger, T.L.b d d , Morris, J.C.a d b d , Ances, B.M.a d b c d

a Department of Neurology, Washington University in Saint Louis, School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, United States
b Department of Radiology, Washington University in St. Louis, St. Louis, MO, United States
c Hope Center, Washington University in Saint Louis, St. Louis, MO, United States
d Knight Alzheimer Disease Research Center, Washington University, School of Medicine, St. Louis, MO, United States

Abstract
Background: Changes in resting state functional connectivity (rs-fc) occur in Alzheimer’s disease (AD), but few longitudinal rs-fc studies have been performed. Most studies focus on single networks and not a global measure of rs-fc. Although the amyloid tau neurodegeneration (AT(N)) framework is increasingly utilized by the AD community, few studies investigated when global rs-fc signature changes occur within this model. Objective: 1) Identify a global rs-fc signature that differentiates cognitively normal (CN) individuals from symptomatic AD. 2) Assess when longitudinal changes in rs-fc occur relative to conversion to symptomatic AD. 3) Compare rs-fc with amyloid, tau, and neurodegeneration biomarkers. Methods: A global rs-fc signature composed of intra-network connections was longitudinally evaluated in a cohort of cognitively normal participants at baseline (n=335). Biomarkers, including cerebrospinal fluid (Aβ42 and tau), structural magnetic resonance imaging, and positron emission tomography were obtained. Results: Global rs-fc signature distinguished CN individuals from individuals who developed symptomatic AD. Changes occurred nearly four years before conversion to symptomatic AD. The global rs-fc signature most strongly correlated with markers of neurodegeneration. Conclusion: The global rs-fc signature changes near symptomatic onset and is likely a neurodegenerative biomarker. Rs-fc changes could serve as a biomarker for evaluating potential therapies for symptomatic conversion to AD. © 2020 – IOS Press and the authors. All rights reserved.

Author Keywords
Alzheimer’s disease;  biomarkers;  neuroimaging;  observational studies

Document Type: Article
Publication Stage: Final
Source: Scopus

“Depression is Associated with Tau and Not Amyloid Positron Emission Tomography in Cognitively Normal Adults” (2020) Journal of Alzheimer’s Disease

Depression is Associated with Tau and Not Amyloid Positron Emission Tomography in Cognitively Normal Adults
(2020) Journal of Alzheimer’s Disease, 74 (4), pp. 1045-1055. 

Babulal, G.M.a b , Roe, C.M.a b , Stout, S.H.a b , Rajasekar, G.a b , Wisch, J.K.b , Benzinger, T.L.S.a c d h , Morris, J.C.a b c d e f g , Ances, B.M.a b c

a Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University, St. Louis, MO, United States
b Department of Neurology, Washington University, School of Medicine, 660 S. Euclid Ave., St. Louis, MO, United States
c Hope Center for Neurological Disorders, Washington University, School of Medicine, St. Louis, MO, United States
d Department of Radiology, Washington University, School of Medicine, St. Louis, MO, United States
e Department of Pathology and Immunology, Washington University, School of Medicine, St. Louis, MO, United States
f Department of Physical Therapy, Washington University, School of Medicine, St. Louis, MO, United States
g Department of Occupational Therapy, Washington University, School of Medicine, St. Louis, MO, United States
h Department of Neurosurgery, Washington University, School of Medicine, St. Louis, MO, United States

Abstract
Background: Depression is also common with older age. Alzheimer’s disease (AD) studies suggest that both cerebrospinal fluid and positron emission tomography (PET) amyloid biomarkers are associated with more depressive symptoms in cognitively normal older adults. The recent availability of tau radiotracers offers the ability to examine in vivo tauopathy. It is unclear if the tau biomarker is associated with depression diagnosis. Objective: We examined if tau and amyloid imaging were associated with a depression diagnosis among cognitively normal adults (Clinical Dementia Rating=0) and whether antidepressants modified this relationship. Methods: Among 301 participants, logistic regression models evaluated whether in vivo PET tau was associated with depression, while another model tested the interaction between PET tau and antidepressant use. A second set of models substituted PET amyloid for PET tau. A diagnosis of depression (yes/no) was made during an annual clinical assessment by a clinician. Antidepressant use (yes/no) was determined by comparing medications the participants used to a list of 30 commonly used antidepressants. All models adjusted for age, sex, education, race, and apolipoprotein ϵ4. Similar models explored the association between the biomarkers and depressive symptoms. Results: Participants with elevated tau were twice as likely to be depressed. Antidepressant use modified this relationship where participants with elevated tau who were taking antidepressants had greater odds of being depressed. Relatedly, elevated amyloid was not associated with depression. Conclusions: Our results demonstrate that tau, not amyloid, was associated with a depression diagnosis. Additionally, antidepressant use interacts with tau to increase the odds of depression among cognitively normal adults. © 2020 – IOS Press and the authors. All rights reserved.

Author Keywords
Alzheimer’s disease;  antidepressants;  biomarkers;  depression;  older adults

Document Type: Article
Publication Stage: Final
Source: Scopus

“Practical training of anesthesia clinicians in electroencephalogram-based determination of hypnotic depth of general anesthesia” (2020) Anesthesia and Analgesia

Practical training of anesthesia clinicians in electroencephalogram-based determination of hypnotic depth of general anesthesia
(2020) Anesthesia and Analgesia, pp. 777-786. 

Bombardieri, A.M.a , Wildes, T.S.a , Stevens, T.a , Wolfson, M.a , Steinhorn, R.b , Ben Abdallah, A.a , Sleigh, J.c , Avidan, M.S.a

a Department of Anesthesiology, Washington University School of Medicine, 660 S Euclid Ave, St Louis, MO 63110, United States
b Department of Anesthesiology, Massachusetts General Hospital, Boston, MA, United States
c Department of Anesthesiology, Waikato Clinical School, University of Auckland, Hamilton, New Zealand

Abstract
BACKGROUND: Electroencephalographic (EEG) brain monitoring during general anesthesia provides information on hypnotic depth. We hypothesized that anesthesia clinicians could be trained rapidly to recognize typical EEG waveforms occurring with volatile-based general anesthesia. METHODS: This was a substudy of a trial testing the hypothesis that EEG-guided anesthesia prevents postoperative delirium. The intervention was a 35-minute training session, summarizing typical EEG changes with volatile-based anesthesia. Participants completed a preeducational test, underwent training, and completed a posteducational test. For each question, participants indicated whether the EEG was consistent with (1) wakefulness, (2) non–slow-wave anesthesia, (3) slow-wave anesthesia, or (4) burst suppression. They also indicated whether the processed EEG (pEEG) index was discordant with the EEG waveforms. Four clinicians, experienced in intraoperative EEG interpretation, independently evaluated the EEG waveforms, resolved disagreements, and provided reference answers. Ten questions were assessed in the preeducational test and 9 in the posteducational test. RESULTS: There were 71 participants; 13 had previous anesthetic-associated EEG interpretation training. After training, the 58 participants without prior training improved at identifying dominant EEG waveforms (median 60% with interquartile range [IQR], 50%–70% vs 78% with IQR, 67%–89%; difference: 18%; 95% confidence interval [CI], 8–27; P < .001). In contrast, there was no significant improvement following the training for the 13 participants who reported previous training (median 70% with IQR, 60%–80% vs 67% with IQR, 67%–78%; difference: −3%; 95% CI, −18 to 11; P = .88). The difference in the change between the pre- and posteducational session for the previously untrained versus previously trained was statistically significant (difference in medians: 21%; 95% CI, 2–28; P = .005). Clinicians without prior training also improved in identifying discordance between the pEEG index and the EEG waveform (median 60% with IQR, 40%–60% vs median 100% with IQR, 75%–100%; difference: 40%; 95% CI, 30–50; P < .001). Clinicians with prior training showed no significant improvement (median 60% with IQR, 60%–80% vs 75% with IQR, 75%–100%; difference: 15%; 95% CI, −16 to 46; P = .16). Regarding the identification of discordance, the difference in the change between the pre- and posteducational session for the previously untrained versus previously trained was statistically significant (difference in medians: 25%; 95% CI, 5–45; P = .012). CONCLUSIONS: A brief training session was associated with improvements in clinicians without prior EEG training in (1) identifying EEG waveforms corresponding to different hypnotic depths and (2) recognizing when the hypnotic depth suggested by the EEG was discordant with the pEEG index. Copyright © 2019 International Anesthesia Research Society

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

“Opioid prescribing and use patterns in postsurgical facial trauma patients” (2020) Plastic and Reconstructive Surgery

Opioid prescribing and use patterns in postsurgical facial trauma patients
(2020) Plastic and Reconstructive Surgery, pp. 780-789. 

Lapidus, J.B.b , Santosa, K.B.b , Skolnick, G.B.b , Som, A.b , Cho, G.J.b , Waljee, J.F.b , Aubuchon, J.D.b , Patel, K.B.a

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

Abstract
Background: Facial fractures are painful injuries routinely managed by opioids after surgical repair. Studies have identified patient risk factors and prescribing patterns associated with opioid use in medicine and general surgery; however, little is known about these entities in the facial trauma population. Methods: A retrospective cohort study of opioid-naive patients undergoing surgical repair of facial fractures was conducted using the Truven Health MarketScan Commercial Claims and Encounters (2006 to 2015) and Medicaid Multi-State Databases (2011 to 2015). Eligible procedures included nasal, nasoorbitoethmoid, orbital, mandible, and Le Fort fracture repair. Opioid type, daily dosage, and prescription duration were analyzed. Multivariable logistic regression was performed to determine independent predictors of prescription refill. Results: A total of 20,191 patients undergoing surgical repair of facial fractures were identified. Of these, 15,861 patients (78.6 percent) filled a perioperative opioid prescription. Refill (58.7 percent) and potentially inappropriate prescribing (39.4 percent) were common among this population. Patient factors including prior substance use (adjusted OR, 1.84; 95 percent CI, 1.63 to 2.07) and history of mental health disorder (adjusted OR, 1.43; 95 percent CI, 1.06 to 1.91) were independent predictors of refill. Increased odds of refill were seen in patients prescribed tramadol (OR, 1.98; 95 percent CI, 1.48 to 2.66) and those who underwent multiple surgical repairs (OR, 3.38; 95 percent CI, 2.54 to 4.50). Conclusions: Refill and potentially inappropriate prescribing occurred at high rates in facial trauma patients undergoing surgical repair. Additional studies are needed to develop guidelines for proper opioid prescribing in this population. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III. © 2019 by the American Society of Plastic Surgeons.

Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Access Type: Open Access

“Neurofilament Light Predicts Decline in Attention but Not Episodic Memory in Preclinical Alzheimer’s Disease” (2020) Journal of Alzheimer’s Disease

Neurofilament Light Predicts Decline in Attention but Not Episodic Memory in Preclinical Alzheimer’s Disease
(2020) Journal of Alzheimer’s Disease, 74 (4), pp. 1119-1129. 

Aschenbrenner, A.J.a , Gordon, B.A.b , Fagan, A.M.a , Schindler, S.E.a , Balota, D.A.c , Morris, J.C.a , Hassenstab, J.J.a c , Tales, A.d

a Charles F. and Joanne Knight Alzheimer’s Disease Research Center, Department of Neurology, Washington University, School of Medicine, 4488 Forest Park Parkway, St. Louis, MO 63108, United States
b Department of Radiology, Washington University, School of Medicine, St. Louis, MO, United States
c Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, MO, United States

Abstract
Background: Cerebrospinal fluid tau and neurofilament light (NfL) are two biomarkers of neurodegeneration in Alzheimer’s disease. Previous reports have shown that the influence of tau on cognitive decline depends on levels of amyloid burden whereas NfL predicts decline independently of amyloid. Most studies use a global cognitive composite as the primary outcome, and it is unknown if critical cognitive domain scores are similarly sensitive to rates of decline due to neurodegeneration. Objective: To examine the unique contribution of amyloid, tau, and NfL to rates of cognitive decline in multiple cognitive composites in a cognitively healthy, middle-aged to older adult cohort. Methods: A total of 255 participants (55% female; mean age=66.2 years, range=42.5-86.7 years) completed CSF studies and serial cognitive assessments to measure global cognition, episodic memory, and attentional control. Linear mixed effects models were used to examine rates of change on each composite score as a function of baseline biomarker levels. Results: Total tau predicted decline in attention regardless of amyloid status, but the relationship to global cognition and episodic memory was dependent on amyloid, replicating prior literature. NfL predicted decline in attention and global cognition, but not memory, and this effect was independent of amyloid status. Conclusions: These findings suggest that NfL can be used to monitor cognitive decline in aging and Alzheimer’s disease and that an attentional control composite may be a better outcome for tracking general neurodegenerative effects on cognition. © 2020 – IOS Press and the authors. All rights reserved.

Author Keywords
Alzheimer’s disease;  attention;  cerebrospinal fluid;  memory;  neurofilament light

Document Type: Article
Publication Stage: Final
Source: Scopus

“The trajectory of gait development in mice” (2020) Brain and Behavior

The trajectory of gait development in mice
(2020) Brain and Behavior, . 

Akula, S.K.a b c , McCullough, K.B.a b , Weichselbaum, C.a b , Dougherty, J.D.a b d , Maloney, S.E.a d

a Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
b Department of Genetics, Washington University School of Medicine, St. Louis, MO, United States
c Harvard-MIT MD/PhD Program, Harvard Medical School, Boston, MA, United States
d Intellectual and Developmental Disabilities Research Center, Washington University School of Medicine, St. Louis, MO, United States

Abstract
Objective: Gait irregularities are prevalent in neurodevelopmental disorders (NDDs). However, there is a paucity of information on gait phenotypes in NDD experimental models. This is in part due to the lack of understanding of the normal developmental trajectory of gait maturation in the mouse. Materials and methods: Using the DigiGait system, we have developed a quantitative, standardized, and reproducible assay of developmental gait metrics in commonly used mouse strains that can be added to the battery of mouse model phenotyping. With this assay, we characterized the trajectory of gait in the developing C57BL/6J and FVB/AntJ mouse lines. Results: In both lines, a mature stride consisted of 40% swing and 60% stance in the forelimbs, which mirrors the mature human stride. In C57BL/6J mice, developmental trajectories were observed for stance width, paw overlap distance, braking and propulsion time, rate of stance loading, peak paw area, and metrics of intraindividual variability. In FVB/AntJ mice, developmental trajectories were observed for percent shared stance, paw overlap distance, rate of stance loading, and peak paw area, although in different directions than C57 mice. By accounting for the impact of body length on stride measurements, we demonstrate the importance of considering body length when interpreting gait metrics. Conclusion: Overall, our results show that aspects of mouse gait development parallel a timeline of normal human gait development, such as the percent of stride that is stance phase and swing phase. This study may be used as a standard reference for developmental gait phenotyping of murine models, such as models of neurodevelopmental disease. © 2020 The Authors. Brain and Behavior published by Wiley Periodicals, LLC.

Author Keywords
development;  DigiGait;  gait;  motor function;  mouse;  mouse strains

Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Access Type: Open Access

“Examining Specificity of Neural Correlates of Childhood Psychotic-like Experiences During an Emotional n-Back Task” (2020) Biological Psychiatry: Cognitive Neuroscience and Neuroimaging

Examining Specificity of Neural Correlates of Childhood Psychotic-like Experiences During an Emotional n-Back Task
(2020) Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, . 

O’Brien, K.J.a , Barch, D.M.a b , Kandala, S.a , Karcher, N.R.a

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

Abstract
Background: Psychotic-like experiences (PLEs) during childhood are associated with greater risk of developing a psychotic disorder in adulthood, highlighting the importance of identifying neural correlates of childhood PLEs. Furthermore, impairment of cognitive functions, such as working memory and emotion regulation, has also been linked to psychosis risk as well as to disruptions in several brain regions. However, impairments in these domains have also been linked to other disorders, including depression. Therefore, the aim of the current study was to examine whether neural impairments in regions associated with working memory and implicit emotion regulation impairments are specific to PLEs versus depression. Methods: The current study used an emotional n-back task to examine the relationship between childhood PLEs and neural activation of regions involved in both working memory and implicit emotion regulation using data from 8805 9- to 11-year-olds in the Adolescent Brain Cognitive Development (ABCD) Study 2.0 release. To examine specificity, we also analyzed associations with depressive symptoms. Results: Our results indicated that increased PLEs during middle childhood were associated with decreased activation of the dorsolateral prefrontal cortex, striatum, and pallidum during trials requiring working memory. In contrast, increased activation of the parahippocampus, caudate, nucleus accumbens, and rostral anterior cingulate during face-viewing trials was associated with increased depressive symptoms. Conclusions: These results support the dimensional view of psychosis across the lifespan, providing evidence that neural correlates of PLEs, such as decreased activation during working memory, are present during middle childhood. Furthermore, these correlates are specific to psychotic-like symptoms as compared with depressive symptoms. © 2020 Society of Biological Psychiatry

Author Keywords
Depression;  Emotional n-back;  Implicit emotion regulation;  Neuroimaging;  Psychotic-like experiences;  Working memory

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

“Metabolic changes in human brain evolution” (2020) Evolutionary Anthropology

Metabolic changes in human brain evolution
(2020) Evolutionary Anthropology, . 

Bauernfeind, A.L.a b , Babbitt, C.C.c

a Department of Neuroscience, Washington University Medical School, St. Louis, MO, United States
b Department of Anthropology, Washington University in St. Louis, St. Louis, MO, United States
c Department of Biology, University of Massachusetts Amherst, Amherst, MA, United States

Abstract
Because the human brain is considerably larger than those of other primates, it is not surprising that its energy requirements would far exceed that of any of the species within the order. Recently, the development of stem cell technologies and single-cell transcriptomics provides novel ways to address the question of what specific genomic changes underlie the human brain’s unique phenotype. In this review, we consider what is currently known about human brain metabolism using a variety of methods from brain imaging and stereology to transcriptomics. Next, we examine novel opportunities that stem cell technologies and single-cell transcriptomics provide to further our knowledge of human brain energetics. These new experimental approaches provide the ability to elucidate the functional effects of changes in genetic sequence and expression levels that potentially had a profound impact on the evolution of the human brain. © 2020 Wiley Periodicals, Inc.

Author Keywords
chimpanzee;  energy;  gene expression;  genomics;  glucose metabolism;  neuron;  primate

Document Type: Review
Publication Stage: Article in Press
Source: Scopus

“Effort, Avolition, and Motivational Experience in Schizophrenia: Analysis of Behavioral and Neuroimaging Data With Relationships to Daily Motivational Experience” (2020) Clinical Psychological Science

Effort, Avolition, and Motivational Experience in Schizophrenia: Analysis of Behavioral and Neuroimaging Data With Relationships to Daily Motivational Experience
(2020) Clinical Psychological Science, . 

Culbreth, A.J.a , Moran, E.K.b , Kandala, S.b , Westbrook, A.c d , Barch, D.M.a b e

a Department of Psychological and Brain Sciences, Washington University in St. Louis, United States
b Department of Psychiatry, Washington University School of Medicine, United States
c Department of Cognitive, Linguistics, and Psychological Sciences, Brown University, United States
d Donders Institute for Brain, Cognition and Behaviour, Radboud University, Netherlands
e Department of Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, United States

Abstract
Recent research suggests that schizophrenia is associated with reduced effort allocation. We examined the willingness to expend effort, neural correlates of effort allocation, and the relationship of effort to daily motivational experience in individuals with schizophrenia. We recruited 28 individuals with schizophrenia and 30 control participants to perform an effort task during functional MRI. Individuals with schizophrenia also completed a protocol involving ecological momentary assessment (EMA). Individuals with schizophrenia with severe negative symptoms were less willing to expend effort for rewards. Daily EMAs of motivation were positively associated with effort allocation on a trend level. Individuals with schizophrenia and control participants displayed similar increases in blood-oxygen-level-dependent (BOLD) activation in frontal, cingulate, parietal, and insular regions during effort-based decision making. However, negative symptoms were associated with reduced BOLD activation in the bilateral ventral striatum. These results replicate previous reports of reduced effort allocation in patients with severe negative symptoms and provide evidence for the role of the ventral striatum in effort impairments. © The Author(s) 2020.

Author Keywords
affective neuroscience;  cognitive neuroscience;  decision making;  neuroimaging;  schizophrenia

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

“Editorial: Several Roads Lead to Anxiety” (2020) Journal of the American Academy of Child and Adolescent Psychiatry

Editorial: Several Roads Lead to Anxiety
(2020) Journal of the American Academy of Child and Adolescent Psychiatry, . 

Sylvester, C.M.

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

Abstract
Traditional attempts to characterize the brain pathophysiology associated with mental illnesses have relied on relating symptoms to a static snapshot of abnormal brain structure or function. Over the last few decades, however, it has become increasingly clear that many or most psychiatric disorders are the consequence of atypical brain development.1 As such, the pathophysiology of mental illnesses may be better understood by characterizing the dynamic changes in brain structure or function that unfold over time and ultimately result in psychiatric symptoms. One important concept that has emerged out of studies that have examined longitudinal trajectories resulting in mental illnesses is the concept of equifinality—that multiple different trajectories can result in the same symptoms in adolescence or adulthood.2 If proved to be true, equifinality is a fundamentally important principle because it suggests that even if two patients have the same symptoms, the cascade of brain changes that ultimately resulted in these symptoms differed. Potentially diverse monitoring and treatment strategies would be required to detect and treat patients with the same set of symptoms. There would be no “one-size fits all” approach to screening and treating patients, and clinicians would ultimately have to learn to identify and alter multiple different risk trajectories. © 2019 American Academy of Child and Adolescent Psychiatry

Document Type: Editorial
Publication Stage: Article in Press
Source: Scopus

“MRI Volumetric Quantification in Persons with a History of Traumatic Brain Injury and Cognitive Impairment” (2020) Advances in Alzheimer’s Disease

MRI Volumetric Quantification in Persons with a History of Traumatic Brain Injury and Cognitive Impairment
(2020) Advances in Alzheimer’s Disease, 7, pp. 441-448. 

Meysami, S.a , Raji, C.A.b , Merrill, D.A.c d , Porter, V.R.a d , Mendez, M.F.a c e

a Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States
b Mallinckrodt Institute of Radiology, Division of Neuroradiology, Washington University, St. Louis, MO, United States
c Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States
d John Wayne Cancer Institute and Pacific Neuroscience Institute, Providence and St. Johns Health Center, Santa Monica, CA, United States
e V.A. Greater Los Angeles Healthcare System, Los Angeles, CA, United States

Abstract
Background: While traumatic brain injury (TBI) is recognized as a risk factor for dementia, there is lack of clinical tools to identify brain changes that may confer such vulnerability. Brain MRI volumetric quantification can sensitively identify brain atrophy. Objective: To characterize regional brain volume loss in persons with TBI presenting with cognitive impairment. Methods: IRB approved review of medical records in patients with cognitive decline focused on those who had documented TBI histories and brain MRI scans after TBI (n = 40, 67.7 ± 14.5 years) with volumetric quantification by applying an FDA cleared software program. TBI documentation included head trauma mechanism. Brain volumes were compared to a normative database to determine the extent of atrophy. Correlations between these regions and global tests of cognition (MMSE in n = 17, MoCA in n = 27, n = 14 in both) were performed. Results: Multiple regions demonstrated volume loss in TBI, particularly ventral diencephalon, putamen, and pallidum with smaller magnitude of atrophy in temporal lobes and brainstem. Lobar structures showed strongest correlations between atrophy and lower scores on MMSE and MoCA. The hippocampus, while correlated to tests of cognitive function, was the least atrophic region as a function of TBI history. Conclusion: Persons with TBI history exhibit show regional brain atrophy. Several of these areas, such as thalamus and temporal lobes, also correlate with cognitive function. Alzheimer’s disease atrophy was less likely given relative sparing of the hippocampi. Volumetric quantification of brain MRI in TBI warrants further investigation to further determine its clinical potential in TBI and differentiating causes of cognitive impairment. © 2020 The authors and IOS Press. All rights reserved.

Author Keywords
Magnetic resonance imaging;  traumatic brain injury;  volumetric quantification

Document Type: Book Chapter
Publication Stage: Final
Source: Scopus

“The ENIGMA Stroke Recovery Working Group: Big data neuroimaging to study brain–behavior relationships after stroke” (2020) Human Brain Mapping

The ENIGMA Stroke Recovery Working Group: Big data neuroimaging to study brain–behavior relationships after stroke
(2020) Human Brain Mapping, . 

Liew, S.-L.a b c d , Zavaliangos-Petropulu, A.b d e , Jahanshad, N.b e , Lang, C.E.f , Hayward, K.S.g h , Lohse, K.R.i j , Juliano, J.M.d , Assogna, F.k , Baugh, L.A.l m , Bhattacharya, A.K.n , Bigjahan, B.b o , Borich, M.R.p , Boyd, L.A.q r , Brodtmann, A.s , Buetefisch, C.M.p t , Byblow, W.D.u , Cassidy, J.M.v , Conforto, A.B.w x , Craddock, R.C.y , Dimyan, M.A.z aa , Dula, A.N.y ab , Ermer, E.z , Etherton, M.R.ac ad , Fercho, K.A.l ae , Gregory, C.M.af , Hadidchi, S.ag ah , Holguin, J.A.a , Hwang, D.H.o , Jung, S.ai , Kautz, S.A.af aj , Khlif, M.S.s , Khoshab, N.ak , Kim, B.al am , Kim, H.b , Kuceyeski, A.an ao , Lotze, M.ap , MacIntosh, B.J.aq ar , Margetis, J.L.a , Mohamed, F.B.as , Piras, F.k , Ramos-Murguialday, A.at au , Richard, G.av aw ax , Roberts, P.ay , Robertson, A.D.az ba , Rondina, J.M.bb , Rost, N.S.bc , Sanossian, N.bd , Schweighofer, N.be , Seo, N.J.af aj bf , Shiroishi, M.S.bg , Soekadar, S.R.bh bi , Spalletta, G.k bj , Stinear, C.M.bk , Suri, A.bl , Tang, W.K.W.bm , Thielman, G.T.bn bo , Vecchio, D.k , Villringer, A.bp bq br , Ward, N.S.bs , Werden, E.s , Westlye, L.T.av aw , Winstein, C.be bt , Wittenberg, G.F.bu bv , Wong, K.A.bw , Yu, C.bx by , Cramer, S.C.bz , Thompson, P.M.b e

a Chan Division of Occupational Science and Occupational Therapy, University of Southern California, Los Angeles, CA, United States
b Department of Neurology, USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
c Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, United States
d Neuroscience Graduate Program, University of Southern California, Los Angeles, CA, United States
e Imaging Genetics Center, USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
f Program in Physical Therapy, Washington University School of Medicine, St. Louis, MO, United States
g Department of Physiotherapy, and Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia
h NHMRC Centre of Research Excellence in Stroke Rehabilitation and Brain Recovery, University of Melbourne, Parkville, VIC, Australia
i Department of Health, Kinesiology, and Recreation, University of Utah, Salt Lake City, UT, United States
j Department of Physical Therapy and Athletic Training, University of Utah, Salt Lake City, UT, United States
k Laboratory of Neuropsychiatry, Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, Italy
l Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD, United States
m Sioux Falls VA Health Care System, Sioux Falls, SD, United States
n Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, United States
o Department of Radiology, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
p Department of Rehabilitation Medicine, Emory University, Atlanta, GA, United States
q Department of Physical Therapy, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
r Djavad Mowafaghian Centre for Brain Health, Vancouver, BC, Canada
s Florey Institute for Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia
t Department of Neurology, Emory University, Atlanta, GA, United States
u Department of Exercise Sciences, Centre for Brain Research, University of Auckland, Auckland, New Zealand
v Division of Physical Therapy, Department Allied Health Sciences, University of North Carolina, Chapel Hill, Chapel Hill, NC, United States
w Neurology Clinical Division, Hospital das Clínicas/São Paulo University, São Paulo, Brazil
x Hospital Israelita Albert Einstein, São Paulo, Brazil
y Department of Diagnostic Medicine, The University of Texas at Austin Dell Medical School, Austin, TX, United States
z Department of Neurology and Neurorehabilitation, School of Medicine, University of Maryland, Baltimore, Baltimore, MD, United States
aa VA Maryland Health Care System, Baltimore, MD, United States
ab Department of Neurology, Dell Medical School at University of Texas at Austin, Austin, TX, United States
ac Department of Neurology, Massachusetts General Hospital, Boston, MA, United States
ad J. Philip Kistler Stroke Research Center, Harvard Medical School, Boston, MA, United States
ae Federal Aviation Administration, Civil Aerospace Medical Institute, Oklahoma City, OK, United States
af Department of Health Sciences and Research, Medical University of South Carolina, Charleston, SC, United States
ag Department of Radiology, Wayne State University/Detroit Medical Center, Detroit, MI, United States
ah Department of Internal Medicine, Wayne State University/Detroit Medical Center, Detroit, MI, United States
ai Department of Neurology, University of Bern, Bern, Switzerland
aj Ralph H Johnson VA Medical Center, Charleston, SC, United States
ak Department of Anatomy and Neurobiology, University of California, Irvine, CA, United States
al Department of Physical Therapy Education, State University of New York Upstate Medical University, Syracuse, NY, United States
am Division of Biokinesiology and Physical Therapy, University of Southern California, Los Angeles, CA, United States
an Department of Radiology, Weill Cornell Medicine, New York, NY, United States
ao Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, United States
ap Functional Imaging Unit, Center for Diagnostic Radiology, School of Medicine, University of Greifswald, Greifswald, Germany
aq Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada
ar Physical Sciences Platform, Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada
as Department of Radiology, Thomas Jefferson University, Philadelphia, PA, United States
at TECNALIA, Basque Research and Technology Alliance (BRTA), Neurotechnology Laboratory, Derio, Spain
au Institute of Medical Psychology and Behavioural Neurobiology, University of Tubingen, Tübingen, Germany
av Department of Psychology, University of Oslo, Oslo, Norway
aw NORMENT, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
ax Institute of Clinical Medicine, University of Oslo, Oslo, Norway
ay Department of Physical Medicine and Rehabilitation, Cedars-Sinai, Los Angeles, CA, United States
az Department of Kinesiology, University of Waterloo, Waterloo, ON, Canada
ba Schlegel-UW Research Institute for Aging, University of Waterloo, Waterloo, ON, Canada
bb Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom
bc Stroke Division, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
bd Division of Neurocritical Care and Stroke, Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
be Division of Biokinesiology and Physical Therapy, University of Southern California, Los Angeles, CA, United States
bf Division of Occupational Therapy, Department of Health Professions, Medical University of South Carolina, Charleston, SC, United States
bg Division of Neuroradiology, Department of Radiology, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
bh Department of Psychiatry and Psychotherapy, Clinical Neurotechnology Laboratory, Charité – University Medicine Berlin, Berlin, Germany
bi Applied Neurotechnology Laboratory, Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany
bj Division of Neuropsychiatry, Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, United States
bk Department of Medicine, University of Auckland, Auckland, New Zealand
bl Department of Electrical and Computer Engineering, University of Pittsburgh, Pittsburgh, PA, United States
bm Department of Psychiatry, The Chinese University of Hong Kong, Hong Kong
bn Physical Therapy and Neuroscience, University of the Sciences, Philadelphia, PA, United States
bo Samson College, Quezon City, Philippines
bp Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany
bq Department of Cognitive Neurology, University Hospital Leipzig, Leipzig, Germany
br Center for Stroke Research, Charité-Universitätsmedizin Berlin, Berlin, Germany
bs UCL Queen Square Institute of Neurology, University College London, London, United Kingdom
bt Department of Neurology, University of Southern California, Los Angeles, CA, United States
bu Department of Neurology, University of Pittsburgh, Pittsburgh, PA, United States
bv Department of Veterans Affairs, University Drive Campus, Pittsburgh, PA, United States
bw Department of Physical Medicine and Rehabilitation, Dell Medical School, University of Texas Austin, Austin, TX, United States
bx Department of Radiology, Tianjin Medical University General Hospital, Tianjin, China
by Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin, China
bz Department of Neurology, UCLA and California Rehabilitation Institute, Los Angeles, CA, United States

Abstract
The goal of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Stroke Recovery working group is to understand brain and behavior relationships using well-powered meta- and mega-analytic approaches. ENIGMA Stroke Recovery has data from over 2,100 stroke patients collected across 39 research studies and 10 countries around the world, comprising the largest multisite retrospective stroke data collaboration to date. This article outlines the efforts taken by the ENIGMA Stroke Recovery working group to develop neuroinformatics protocols and methods to manage multisite stroke brain magnetic resonance imaging, behavioral and demographics data. Specifically, the processes for scalable data intake and preprocessing, multisite data harmonization, and large-scale stroke lesion analysis are described, and challenges unique to this type of big data collaboration in stroke research are discussed. Finally, future directions and limitations, as well as recommendations for improved data harmonization through prospective data collection and data management, are provided. © 2020 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.

Author Keywords
big data;  lesions;  MRI;  neuroinformatics;  stroke

Document Type: Review
Publication Stage: Article in Press
Source: Scopus
Access Type: Open Access

“Select Atrophied Regions in Alzheimer disease (SARA): An improved volumetric model for identifying Alzheimer disease dementia” (2020) NeuroImage: Clinical

Select Atrophied Regions in Alzheimer disease (SARA): An improved volumetric model for identifying Alzheimer disease dementia
(2020) NeuroImage: Clinical, 26, art. no. 102248, . 

Koenig, L.N.a , Day, G.S.a b , Salter, A.a , Keefe, S.a , Marple, L.M.a , Long, J.a b , LaMontagne, P.a , Massoumazada, P.a b , Snider, B.J.a b , Kanthamneni, M.c , Raji, C.A.a b , Ghoshal, N.a b , Gordon, B.A.a b , Miller-Thomas, M.a , Morris, J.C.a b , Shimony, J.S.a , Benzinger, T.L.S.a b , for the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and the Dominantly Inherited Alzheimer Network (DIAN)d

a Washington University in St. Louis School of Medicine, 660 S Euclid Ave, St. Louis, MO 63110, United States
b Knight Alzheimer Disease Research Center, 4488 Forest Park Pkwy, St. Louis, MO 63108, United States
c St. George’s University School of Medicine, University Centre Grenada, West Indies, Grenada

Abstract
Introduction: Volumetric biomarkers for Alzheimer disease (AD) are attractive due to their wide availability and ease of administration, but have traditionally shown lower diagnostic accuracy than measures of neuropathological contributors to AD. Our purpose was to optimize the diagnostic specificity of structural MRIs for AD using quantitative, data-driven techniques. Methods: This retrospective study assembled several non-overlapping cohorts (total n = 1287) with publicly available data and clinical patients from Barnes–Jewish Hospital (data gathered 1990–2018). The Normal Aging Cohort (n = 383) contained amyloid biomarker negative, cognitively normal (CN) participants, and provided a basis for determining age-related atrophy in other cohorts. The Training (n = 216) and Test (n = 109) Cohorts contained participants with symptomatic AD and CN controls. Classification models were developed in the Training Cohort and compared in the Test Cohort using the receiver operating characteristics areas under curve (AUCs). Additional model comparisons were done in the Clinical Cohort (n = 579), which contained patients who were diagnosed with dementia due to various etiologies in a tertiary care outpatient memory clinic. Results: While the Normal Aging Cohort showed regional age-related atrophy, classification models were not improved by including age as a predictor or by using volumetrics adjusted for age-related atrophy. The optimal model used multiple regions (hippocampal volume, inferior lateral ventricle volume, amygdala volume, entorhinal thickness, and inferior parietal thickness) and was able to separate AD and CN controls in the Test Cohort with an AUC of 0.961. In the Clinical Cohort, this model separated AD from non-AD diagnoses with an AUC 0.820, an incrementally greater separation of the cohort than by hippocampal volume alone (AUC of 0.801, p = 0.06). Greatest separation was seen for AD vs. frontotemporal dementia and for AD vs. non-neurodegenerative diagnoses. Conclusions: Volumetric biomarkers distinguished individuals with symptomatic AD from CN controls and other dementia types but were not improved by controlling for normal aging. © 2020

Author Keywords
Aging;  Alzheimer disease;  Diagnostic biomarkers;  MRI;  Volumetrics

Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access

“The Association Between Parental Age and Autism-Related Outcomes in Children at High Familial Risk for Autism” (2020) Autism Research

The Association Between Parental Age and Autism-Related Outcomes in Children at High Familial Risk for Autism
(2020) Autism Research, . 

Lyall, K.a , Song, L.b , Botteron, K.c , Croen, L.A.d , Dager, S.R.e , Fallin, M.D.b , Hazlett, H.C.f , Kauffman, E.a , Landa, R.g , Ladd-Acosta, C.h , Messinger, D.S.i , Ozonoff, S.j , Pandey, J.k , Piven, J.f , Schmidt, R.J.l m , Schultz, R.T.k , Stone, W.L.n , Newschaffer, C.J.o , Volk, H.E.b

a AJ Drexel Autism Institute, Drexel University, Philadelphia, PA, United States
b Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, United States
c Department of Psychiatry, Washington University, St Louis, MO, United States
d Kaiser Permanente Division of Research, Oakland, CA, United States
e Department of Radiology, University of Washington, Seattle, WA, United States
f Department of Psychiatry, University of North Carolina, Chapel Hill, NC, United States
g Department of Psychiatry and Behavioral Sciences, Center for Autism and Related Disorders, Kennedy Krieger Institute, Johns Hopkins University, Baltimore, MD, United States
h Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States
i Department of Psychology, University of Miami, Miami, FL, United States
j MIND Institute, Department of Psychiatry and Behavioral Sciences, University of California Davis, Sacramento, CA, United States
k Center for Autism Research, Children’s Hospital of Philadelphia, Philadelphia, PA, United States
l Department of Public Health, University of California Davis, Davis, CA, United States
m MIND Institute, University of California Davis, Sacramento, CA, United States
n Department of Psychology, University of Washington, Seattle, WA, United States
o College of Health and Human Development, Pennsylvania State University, State College, PA, United States

Abstract
Advanced parental age is a well-replicated risk factor for autism spectrum disorder (ASD), a neurodevelopmental condition with a complex and not well-defined etiology. We sought to determine parental age associations with ASD-related outcomes in subjects at high familial risk for ASD. A total of 397 younger siblings of a child with ASD, drawn from existing prospective high familial risk cohorts, were included in these analyses. Overall, we did not observe significant associations of advanced parental age with clinical ASD diagnosis, Social Responsiveness Scale, or Vineland Adaptive Behavior Scales scores. Instead, increased odds of ASD were found with paternal age < 30 years (adjusted odds ratio [AOR] = 2.83 and 95% confidence intervals [CI] = 1.14–7.02). Likewise, younger age (<30 years) for both parents was associated with decreases in Mullen Scales of Early Learning early learning composite (MSEL-ELC) scores (adjusted β = −9.62, 95% CI = −17.1 to −2.15). We also found significant increases in cognitive functioning based on MSEL-ELC scores with increasing paternal age (adjusted β associated with a 10-year increase in paternal age = 5.51, 95% CI = 0.70–10.3). Results suggest the potential for a different relationship between parental age and ASD-related outcomes in families with elevated ASD risk than has been observed in general population samples. Autism Res 2020. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary: Previous work suggests that older parents have a greater likelihood of having a child with autism. We investigated this relationship in the younger siblings of families who already had a child with autism. In this setting, we found a higher likelihood of autism, as well as poorer cognitive scores, in the siblings with younger fathers, and higher cognitive scores in the siblings with older parents. These results suggest that parental age associations may differ based on children’s familial risk for autism. © 2020 International Society for Autism Research, Wiley Periodicals, Inc.

Author Keywords
autism;  autism-related traits;  high familial risk;  parental age

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

“The impact of happy and sad affective states on biases in ethical decision making” (2020) Ethics and Behavior

The impact of happy and sad affective states on biases in ethical decision making
(2020) Ethics and Behavior, . 

Rainone, N.A.a , Watts, L.L.a , Mulhearn, T.J.b , McIntosh, T.J.c , Medeiros, K.E.d

a Department of Psychology, Baruch College & The Graduate Center, CUNY, United States
b Neurostat Analytical Solutions, LLC, United States
c Washington University School of Medicine in St. Louis, United States
d College of Business Administration, University of Nebraska at Omaha, United States

Abstract
Researchers have increasingly acknowledged that affect plays a role in ethical decision making. However, the impact that specific affective states may have on the expression of decision biases in the context of ethical dilemmas has received limited empirical attention. To address this, the present effort examined the impact of happy and sad affective states on biases in ethical decision making. In an online experiment, undergraduate students read short stories that either induced happy, sad, or relaxed (neutral) affective states, followed by a covert measure of three types of biases (i.e., simplification, verification, and regulation) held to inhibit ethical decision making. Results demonstrated that happy affective states increased the expression of regulation biases, and sad affective states increased the expression of simplification biases, compared to relaxed (neutral) affective states. Implications are discussed for advancing research on ethical decision making and reducing unethical behavior in organizations. © 2020, © 2020 Taylor & Francis Group, LLC.

Author Keywords
Affect;  biases;  ethical decision making;  ethics;  stories

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

“Utility of Motor and Somatosensory Evoked Potentials for Neural Thermoprotection in Ablations of Musculoskeletal Tumors” (2020) Journal of Vascular and Interventional Radiology

Utility of Motor and Somatosensory Evoked Potentials for Neural Thermoprotection in Ablations of Musculoskeletal Tumors
(2020) Journal of Vascular and Interventional Radiology, . 

Yoon, J.T.a , Nesbitt, J.a , Raynor, B.L.b , Roth, M.b , Zertan, C.C.b , Jennings, J.W.a

a Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 S. Kingshighway Blvd., St. Louis, MO 63110, United States
b Department of Electrophysiology, Barnes–Jewish Hospital, St. Louis, MO, United States

Abstract
Purpose: To characterize the utility of monitoring transcranial electrical motor evoked potentials (TCeMEPs) and somatosensory evoked potentials (SSEPs) for neural thermoprotection during musculoskeletal tumor ablations. Materials and Methods: Retrospective review of 29 patients (16 male; median age, 46 y; range, 7–77 y) who underwent musculoskeletal tumor radiofrequency ablation (n = 8) or cryoablation (n = 22) with intraprocedural TCeMEP and SSEP monitoring was performed. The most common tumor histologies were osteoid osteoma (n = 6), venous malformation (n = 5), sarcoma (n = 5), renal cell carcinoma (n = 4), and non–small-cell lung cancer (n = 3). The most common tumor sites were spine (n = 22) and lower extremities (n = 4). Abnormal TCeMEP change was defined by 100-V increase above baseline threshold activation for a given myotome; abnormal SSEP change was defined by 60% reduction in baseline amplitude and/or 10% increase in latency. Results: Abnormal changes in TCeMEP (n = 9; 30%) and/or SSEP (n = 5; 17%) occurred in 12 procedures (40%) and did not recover in 5 patients. Patients with unchanged TCeMEP/SSEP activities throughout the procedure (n = 18) did not have motor or sensory symptoms after the procedure; 3 (60%) with unrecovered activity changes and 2 (29%) with transient activity changes had new motor (n = 1) or sensory (n = 4) symptoms. Relative risk for neurologic sequelae for patients with unrecovered TCeMEP/SSEP changes vs those with transient or no changes was 7.50 (95% confidence interval, 1.66–33.9; P = .009). Conclusions: Abnormal activity changes of TCeMEP or SSEP during percutaneous ablative procedures correlate with postprocedural neurologic sequelae. © 2020 SIR

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

“Executive Functions and Impulsivity Are Genetically Distinct and Independently Predict Psychopathology: Results From Two Adult Twin Studies” (2020) Clinical Psychological Science

Executive Functions and Impulsivity Are Genetically Distinct and Independently Predict Psychopathology: Results From Two Adult Twin Studies
(2020) Clinical Psychological Science, . 

Friedman, N.P.a b , Hatoum, A.S.b c , Gustavson, D.E.d , Corley, R.P.a , Hewitt, J.K.a b , Young, S.E.e

a Institute for Behavioral Genetics, University of Colorado Boulder, United States
b Department of Psychology and Neuroscience, University of Colorado Boulder, United States
c Department of Psychiatry, Washington University in St. Louis Medical School, United States
d Department of Psychiatry, Center for Behavior Genetics of Aging, University of California, San Diego, United States
e Division of Substance Dependence, Psychiatry Department, University of Colorado Denver, United States

Abstract
Laboratory executive function (EF) constructs, such as response inhibition, are often conceptually linked with self-report measures of impulsivity, yet their empirical correlations are low. We examined, in two twin studies (ns = 749 and 761 individuals with EF data), the phenotypic and genetic overlap of three EF latent variables (a Common EF factor predicting response inhibition, working memory updating, and mental set-shifting tasks and Updating- and Shifting-Specific factors) with five impulsivity dimensions (negative and positive urgency, lack of premeditation and perseverance, and sensation seeking). In both samples, impulsivity dimensions were only modestly correlated phenotypically (rs = −.20–.11) and genetically (rAs = −.44–.04) with Common EF. In both samples, Common EF and multiple impulsivity dimensions, particularly negative urgency, independently predicted Externalizing psychopathology, and multiple impulsivity dimensions but not Common EF predicted Internalizing psychopathology. These results suggest that EFs and self-reported impulsivity tap different aspects of control that are both relevant for psychopathology. © The Author(s) 2020.

Author Keywords
cognitive control;  executive control;  self-control;  UPPS-P

Document Type: Article
Publication Stage: Article in Press
Source: Scopus