WashU weekly Neuroscience publications

New guidance to seekers of autism biomarkers: an update from studies of identical twins
(2021) Molecular Autism, 12 (1), art. no. 28, . 

Constantino, J.N.

Department of Psychiatry, Washington University in St. Louis, 660 S Euclid Ave, Campus Box 8504, St. Louis, MO 63110, United States

Abstract
Background: The autism spectrum disorders (ASD) are common neuropsychiatric conditions of childhood for which the vast proportion of population risk is attributable to inheritance, and for which there exist few if any replicated biomarkers. Main body: This commentary summarizes a set of recent studies involving identical (monozygotic, MZ) twins which, taken together, have significant implications for the search for biomarkers of inherited susceptibility to autism. A first is that variation-in-severity of the condition (above the threshold for clinical diagnosis) appears more strongly influenced by stochastic/non-shared environmental influences than by heredity. Second is that there exist disparate early behavioral predictors of the familial recurrence of autism, which are themselves strongly genetically influenced but largely independent from one another. The nature of these postnatal predictors is that they are trait-like, continuously distributed in the general population, and largely independent from variation in general cognition, thereby reflecting a developmental substructure for familial autism. A corollary of these findings is that autism may arise as a developmental consequence of an allostatic load of earlier-occurring liabilities, indexed by early behavioral endophenotypes, in varying permutations and combinations. The clinical threshold can be viewed as a “tipping point” at which stochastic influences and/or other non-shared environmental influences assert much stronger influence on variation-in-severity (a) than do the genetic factors which contributed to the condition in the first place, and (b) than is observed in typical development. Conclusion: Biomarkers identified on the basis of association with clinical symptom severity in ASD may reflect effects rather than causes of autism. The search for biomarkers of pathogenesis may benefit from a greater focus on traits that predict autism recurrence, among both clinical and general populations. In case–control studies, salient developmental liabilities should be systematically measured in both cases and controls, to avoid the erosion in statistical power (i.e., to detect differences) that can occur if control subjects carry sub-clinical aggregations of the same unmeasured traits that exert causal influences on the development of autism. © 2021, The Author(s).

Funding details
Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNICHD
National Institutes of HealthNIHP50 HD103525
University of WashingtonUW

Brain network mechanisms of visual shape completion
(2021) NeuroImage, 236, art. no. 118069, . 

Keane, B.P.^a b , Barch, D.M.^c , Mill, R.D.^d , Silverstein, S.M.^a b e , Krekelberg, B.^d , Cole, M.W.^d

^a University Behavioral Health Care, Department of Psychiatry, and Center for Cognitive Science, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, United States
^b Departments of Psychiatry and Neuroscience, University of Rochester Medical Center, 601 Elmwood Ave, Rochester, NY 14642, United States
^c Departments of Psychological & Brain Sciences, Psychiatry, and Radiology, Washington University in St. Louis, One Brookings Drive, St. Louis, MO 63130, United States
^d Center for Molecular and Behavioral Neuroscience, Rutgers, The State University of New Jersey, 197 University Ave07102, United States
^e Department of Ophthalmology, University of Rochester Medical Center, 601 Elmwood Ave, Rochester, NY, United States

Abstract
Visual shape completion recovers object shape, size, and number from spatially segregated edges. Despite being extensively investigated, the process’s underlying brain regions, networks, and functional connections are still not well understood. To shed light on the topic, we scanned (fMRI) healthy adults during rest and during a task in which they discriminated pac-man configurations that formed or failed to form completed shapes (illusory and fragmented condition, respectively). Task activation differences (illusory-fragmented), resting-state functional connectivity, and multivariate patterns were identified on the cortical surface using 360 predefined parcels and 12 functional networks composed of such parcels. Brain activity flow mapping (ActFlow) was used to evaluate the likely involvement of resting-state connections for shape completion. We identified 36 differentially-active parcels including a posterior temporal region, PH, whose activity was consistent across 95% of observers. Significant task regions primarily occupied the secondary visual network but also incorporated the frontoparietal, dorsal attention, default mode, and cingulo-opercular networks. Each parcel’s task activation difference could be modeled via its resting-state connections with the remaining parcels (r=.62, p<10−9), suggesting that such connections undergird shape completion. Functional connections from the dorsal attention network were key in modelling task activation differences in the secondary visual network. Dorsal attention and frontoparietal connections could also model activations in the remaining networks. Taken together, these results suggest that shape completion relies upon a sparsely distributed but densely interconnected network coalition that is centered in the secondary visual network, coordinated by the dorsal attention network, and inclusive of at least three other networks. © 2021

Author Keywords
Area PH;  Dorsal attention network;  Frontoparietal network;  Kanizsa shapes;  Resting-state functional connectivity;  Secondary visual network;  Subjective contours

Funding details
National Institutes of HealthNIHK01MH108783

Contributions from resting state functional connectivity and familial risk to early adolescent-onset MDD: Results from the Adolescent Brain Cognitive Development study
(2021) Journal of Affective Disorders, 287, pp. 229-239. 

Cai, Y.^a , Elsayed, N.M.^a , Barch, D.M.^a b c

^a Department of Psychological & Brain Sciences, Washington University, Campus Box 1125, 1 Brookings Drive, St. Louis, MO 63130, United States
^b Department of Psychiatry, Washington University, St. Louis, MO, United States
^c Department of Radiology, Washington University, St. Louis, MO, United States

Abstract
Background: Family history of Major Depressive Disorder (MDD) is a robust predictor of MDD onset, especially in early adolescence. We examined the relationships between familial risk for depression and alterations to resting state functional connectivity (rsFC) within the default mode network (wDMN) and between the DMN and the left/right hippocampus (DMN-LHIPP/DMN-RHIPP) to the risk for early adolescent MDD onset. Methods: We examined 9403 youth aged nine to eleven from the Adolescent Brain Cognitive Development study. Depressive symptoms were measured with the parent-reported Child Behavior Checklist. Both youth and their parents completed the Kiddie Schedule for Affective Disorders and Schizophrenia, which provided MDD diagnoses. A family history screen was administered to determine familial risk for depression. Youth underwent a resting state functional magnetic resonance imaging scan, providing us with rsFC data. Results: Negative wDMN rsFC was associated with child-reported current depression, both child- and parent-reported past depression, and parent-reported current depressive symptoms. No difference was found in wDMN, DMN-LHIPP or DMN-RHIPP rsFC in children with or without familial risk for depression. Familial risk for depression interacted with wDMN rsFC in association with child-reported past MDD diagnosis and parent-reported current depressive symptoms. Limitations: Information such as length of depressive episodes and age of onset of depression was not collected. Conclusions: Altered wDMN rsFC in youth at familial risk for depression may be associated with increased risk for MDD onset in adolescence, but longitudinal studies are needed to test this hypothesis. © 2021

Author Keywords
Adolescence;  Depression;  Familial risk;  Functional Connectivity

Funding details
National Institutes of HealthNIHU01DA041022, U01DA041028, U01DA050988, U01DA041174, U01DA041025, U01DA041156, U01DA041093, U01DA041048, U01DA041106, U01DA041148, U01DA051038, U01DA041134, U01DA050989, U01DA041117, U01DA051018, U01DA051039, U01DA041089, U01DA041147, U01DA041120, U01DA051016, U01DA051037, U01DA050987, U01DA041123

Human cells and networks of pain: Transforming pain target identification and therapeutic development
(2021) Neuron, 109 (9), pp. 1426-1429. 

Renthal, W.^a , Chamessian, A.^b , Curatolo, M.^c , Davidson, S.^d , Burton, M.^e , Dib-Hajj, S.^f g , Dougherty, P.M.^h , Ebert, A.D.ⁱ , Gereau, R.W., IV^b , Ghetti, A.^j , Gold, M.S.^k , Hoben, G.^l , Menichella, D.M.^m , Mercier, P.ⁿ , Ray, W.Z.^o , Salvemini, D.^p , Seal, R.P.^k , Waxman, S.^f g , Woolf, C.J.^q , Stucky, C.L.ⁱ , Price, T.J.^e

^a Department of Neurology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, United States
^b Department of Anesthesiology, Washington University Pain Center, Washington University School of Medicine, St LouisMO 63110, United States
^c Department of Anesthesiology and Pain Medicine, CLEAR Center for Musculoskeletal Disorder, Harborview Injury Prevention and Research Center, University of Washington, Seattle, WA 98195, United States
^d Department of Anesthesiology, University of Cincinnati, College of Medicine, Cincinnati, OH 45267, United States
^e Department of Neuroscience and Center for Advanced Pain Studies, University of Texas at Dallas, Richardson, TX 75080, United States
^f Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT 06510, United States
^g Center for Rehabilitation Research, VA Connecticut Healthcare System, West HavenCT 06516, United States
^h Department of Pain Medicine, Division of Anesthesiology and Critical Care, The University of Texas MD Anderson Cancer Center, Houston, TX 78712, United States
ⁱ Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, United States
^j AnaBios Corporation, San Diego, CA 92109, United States
^k Department of Neurobiology, Pittsburgh Center for Pain Research, University of Pittsburgh, Pittsburgh, PA 15260, United States
^l Department of Plastic Surgery, Medical College of Wisconsin, Milwaukee, WI 53226, United States
^m Department of Neurology and Pharmacology, Northwestern University Feinberg Medical School, Chicago, IL 60611, United States
ⁿ Department of Neurosurgery and Henry and Amelia Nasrallah Center for Neuroscience, Saint Louis University, St. Louis, MO 63117, United States
^o Department of Neurosurgery, Washington University School of Medicine, St. Louis, MO 63110, United States
^p Department of Pharmacology and Physiology and Henry and Amelia Nasrallah Center for Neuroscience, Saint Louis University, St. Louis, MO 63103, United States
^q F.M. Kirby Neurobiology Center, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, United States

Abstract
Chronic pain is a disabling disease with limited treatment options. While animal models have revealed important aspects of pain neurobiology, therapeutic translation of this knowledge requires our understanding of these cells and networks of pain in humans. We propose a multi-institutional collaboration to rigorously and ethically address this challenge. © 2021 Elsevier Inc.

Funding details
National Center for Advancing Translational SciencesNCATSUG3TR003090
National Institute of Mental HealthNIMHR01AT011447
National Institute of Arthritis and Musculoskeletal and Skin DiseasesNIAMSR01AR077691
National Institute of General Medical SciencesNIGMSR01AR063772
National Institute of Neurological Disorders and StrokeNINDSR01NS107364, R35NS105076, RF1NS113881, R01NS070711, R01NS065926, K08NS101064, R21NS109792, K22NS096030, R37NS108278, R01NS104295
Burroughs Wellcome FundBWF
Migraine Research FoundationMRF
National Institute of Diabetes and Digestive and Kidney DiseasesNIDDKR01DK107966
Merck

Cell-type-specific binocular vision guides predation in mice
(2021) Neuron, 109 (9), pp. 1527-1539.e4. Cited 1 time.

Johnson, K.P.^a b , Fitzpatrick, M.J.^a b c , Zhao, L.^a , Wang, B.^a , McCracken, S.^a , Williams, P.R.^a d e , Kerschensteiner, D.^a d e f

^a John F. Hardesty, MD Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, United States
^b Graduate Program in Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, United States
^c Medical Scientist Training Program, Washington University School of Medicine, St. Louis, MO 63110, United States
^d Department of Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, United States
^e Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, United States
^f Department of Biomedical Engineering, Washington University School of Medicine, St. Louis, MO 63110, United States

Abstract
Predators use vision to hunt, and hunting success is one of evolution’s main selection pressures. However, how viewing strategies and visual systems are adapted to predation is unclear. Tracking predator-prey interactions of mice and crickets in 3D, we find that mice trace crickets with their binocular visual fields and that monocular mice are poor hunters. Mammalian binocular vision requires ipsi- and contralateral projections of retinal ganglion cells (RGCs) to the brain. Large-scale single-cell recordings and morphological reconstructions reveal that only a small subset (9 of 40+) of RGC types in the ventrotemporal mouse retina innervate ipsilateral brain areas (ipsi-RGCs). Selective ablation of ipsi-RGCs (<2% of RGCs) in the adult retina drastically reduces the hunting success of mice. Stimuli based on ethological observations indicate that five ipsi-RGC types reliably signal prey. Thus, viewing strategies align with a spatially restricted and cell-type-specific set of ipsi-RGCs that supports binocular vision to guide predation. © 2021 Elsevier Inc.

Author Keywords
depth perception;  ganglion cell;  hunting;  ipsilateral projection;  prey capture;  retina;  stereopsis

Funding details
Research to Prevent BlindnessRPB
National Institutes of HealthNIHEY030623, EY023341, EY027411, EY026978, EY0268, EY029975

Increase in trigeminal ganglion neurons that respond to both calcitonin gene-related peptide and pituitary adenylate cyclase-activating polypeptide in mouse models of chronic migraine and posttraumatic headache
(2021) Pain, 162 (5), pp. 1483-1499. 

Guo, Z., Czerpaniak, K., Zhang, J., Cao, Y.-Q.

Department of Anesthesiology and Washington University Pain Center, Washington University School of Medicine, St. Louis, MO, United States. Dr. Zhang is now with the Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, China

Abstract
A large body of animal and human studies indicates that blocking peripheral calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating polypeptide (PACAP) signaling pathways may prevent migraine episodes and reduce headache frequency. To investigate whether recurring migraine episodes alter the strength of CGRP and PACAP signaling in trigeminal ganglion (TG) neurons, we compared the number of TG neurons that respond to CGRP and to PACAP (CGRP-R and PACAP-R, respectively) under normal and chronic migraine-like conditions. In a mouse model of chronic migraine, repeated nitroglycerin (NTG) administration significantly increased the number of CGRP-R and PACAP-R neurons in TG but not dorsal root ganglia. In TG neurons that express endogenous αCGRP, repeated NTG led to a 7-fold increase in the number of neurons that respond to both CGRP and PACAP (CGRP-R&PACAP-R). Most of these neurons were unmyelinated C-fiber nociceptors. This suggests that a larger fraction of CGRP signaling in TG nociceptors may be mediated through the autocrine mechanism, and the release of endogenous αCGRP can be enhanced by both CGRP and PACAP signaling pathways under chronic migraine condition. The number of CGRP-R&PACAP-R TG neurons was also increased in a mouse model of posttraumatic headache (PTH). Interestingly, low-dose interleukin-2 treatment, which completely reverses chronic migraine-related and PTH-related behaviors in mouse models, also blocked the increase in both CGRP-R and PACAP-R TG neurons. Together, these results suggest that inhibition of both CGRP and PACAP signaling in TG neurons may be more effective in treating chronic migraine and PTH than targeting individual signaling pathways. Copyright © 2020 International Association for the Study of Pain.

Evidence to inform occupational therapy interventionwith adultswith intellectual disability: A scoping review
(2021) American Journal of Occupational Therapy, 75 (3), art. no. 7503180010, . 

Blaskowitz, M.G.^a , Johnson, K.R.^b , Bergfelt, T.^c , Mahoney, W.J.^d

^a Department of Occupational Therapy, Duquesne University, Pittsburgh, PA, United States
^b Division of Occupational Science and Occupational Therapy, University of North Carolina, School of Medicine, Chapel Hill, United States
^c Gumberg Library, Duquesne University, Pittsburgh, PA, United States
^d Program in Occupational Therapy, Washington University, School of Medicine, St. Louis, MO, United States

Abstract
Importance: Occupational therapy practitioners use a range of habilitative and compensatory approaches to teach new skills or modify tasks and environments to address occupational performance among adults with intellectual disability (ID); therefore, they must identify and use available evidence to guide intervention planning. Objective: To summarize the scope of evidence that can inform occupational therapy intervention with adults with primary or comorbid ID. Data Sources: Articles published in peer-reviewed journals between January 2002 and January 2018 and indexed in PubMed, CINAHL, PsycINFO, and Scopus. Study Selection and Data Collection: A total of 159 articles met inclusion criteria and contained information on occupational therapy intervention with adults ages 18 yr or older with primary or coexisting ID. Findings: Fifty-seven of the 159 articles focused on intervention to address occupational performance outcomes (i.e., employment, self-care, leisure and social interaction, community participation). Conclusions and Relevance: A wide range of literature is available to support occupational therapy intervention with adults with ID. Occupational therapy practitioners may be less knowledgeable about this evidence because much of it is located in non-occupational therapy or international journals. © 2021 American Occupational Therapy Association, Inc. All rights reserved.

Occupational therapy interventions for instrumental activities of daily living for adultswith parkinson’s disease: A systematic review
(2021) American Journal of Occupational Therapy, 75 (3), art. no. 7503190030, . Cited 1 time.

Foster, E.R.^a , Carson, L.G.^a , Archer, J.^a , Hunter, E.G.^b

^a Program in Occupational Therapy, Washington University, School of Medicine in St. Louis, St. Louis, MO, United States
^b Graduate Center for Gerontology, University of Kentucky, Lexington, United States

Abstract
Importance: Instrumental activities of daily living (IADLs) are important for independence, safety, and productivity, and people with Parkinson’s disease (PD) can experience IADL limitations. Occupational therapy practitioners should address IADLs with their clients with PD. Objective: To systematically review the evidence for the effectiveness of occupational therapy interventions to improve or maintain IADL function in adults with PD. Data Sources: MEDLINE, CINAHL, PsycINFO, OTseeker, and Cochrane databases from January 2011 to December 2018. Study Selection and Data Collection: Primary inclusion criteria were peer-reviewed journal articles describing Level 1-3 studies that tested the effect of an intervention within the scope of occupational therapy on an IADL outcome in people with PD. Three reviewers assessed records for inclusion, quality, and validity following Cochrane Collaboration and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Findings: Twenty-two studies met the inclusion criteria and were categorized into four themes on the basis of primary focus or type of intervention: Physical activity, specific IADL-focused, cognitive rehabilitation, and individualized occupational therapy interventions. There were 9 Level 1b, 9 Level 2b, and 4 Level 3b studies. Strong strength of evidence was found for the beneficial effect of occupational therapy-related interventions for physical activity levels and handwriting, moderate strength of evidence for IADL participation and medication adherence, and low strength of evidence for cognitive rehabilitation. Conclusions and Relevance: Occupational therapy interventions can improve health management and maintenance (i.e., physical activity levels, medication management), handwriting, and IADL participation for people with PD. Further research is needed on cognitive rehabilitation. This review is limited by the small number of studies that specifically addressed IADL function in treatment and as an outcome. © 2021 American Occupational Therapy Association, Inc. All rights reserved.

Funding details
Asia and Oceania Thyroid AssociationAOTA
National Institute on AgingNIA
National Institutes of HealthNIH
American Parkinson Disease AssociationAPDA
National Institute of Diabetes and Digestive and Kidney DiseasesNIDDKR01DK064832
National Institute on AgingNIAR01AG065214, R21AG063974

Occupational therapy-related assessments for adultswith intellectual disability: A scoping review
(2021) American Journal of Occupational Therapy, 75 (3), art. no. 7503180100, . 

Mahoney, W.J.^a , Blaskowitz, M.G.^b , Johnson, K.R.^c

^a Program in Occupational Therapy, Washington University, School of Medicine, St. Louis, MO, United States
^b Department of Occupational Therapy, Duquesne University, Pittsburgh, PA, United States
^c Division of Occupational Science and Occupational Therapy, University of North Carolina, School of Medicine, Chapel Hill, United States

Abstract
Importance: Occupational therapy practitioners use structured assessment tools to gather information from adults with intellectual disability (ID) in order to develop the occupational profile, guide occupational therapy intervention, and assess change over time. Objective: To identify occupational therapy-related tools in the peer-reviewed literature for use in practice with adults with ID. Data Sources: Peer-reviewed literature published between January 2002 and January 2018 included in CINAHL, PsycINFO, PubMed, and Scopus. Study Selection and Data Collection: The review included articles that had information on occupational therapy-related assessment with adults 18 yr or older who had primary or co-occurring ID. Findings: Fifty-eight articles identified 73 occupational therapy-related assessment tools. Conclusions and Relevance: This scoping review identified a broad range of assessment tools in the occupational therapy domain that are appropriate for adults with ID, some of which may be unfamiliar to occupational therapy practitioners. © 2021 American Occupational Therapy Association, Inc. All rights reserved.

Association of Infection-Related Hospitalization with Cognitive Impairment among Nursing Home Residents
(2021) JAMA Network Open

Gracner, T.^a b , Agarwal, M.^c d , Murali, K.P.^c , Stone, P.W.^c , Larson, E.L.^e f , Furuya, E.Y.^g , Harrison, J.M.^h , Dick, A.W.ⁱ

^a RAND Corporation, Arlington, VA, United States
^b RAND Corporation, 1776 Main Street, Santa Monica, CA 90401, United States
^c Center for Health Policy, Columbia University, School of Nursing, New York, NY, United States
^d Washington University, School of Medicine, St Louis, MO, United States
^e Columbia University, School of Nursing, New York, NY, United States
^f Columbia University, Mailman School of Public Health, New York, NY, United States
^g Department of Medicine, Columbia University, Irving Medical Center, New York, NY, United States
^h RAND Corporation, Pittsburgh, PA, United States
ⁱ RAND Corporation, Boston, MA, United States

Abstract
Importance: Hospitalizations for infections among nursing home (NH) residents remain common despite national initiatives to reduce them. Cognitive impairment, which markedly affects quality of life and caregiving needs, has been associated with hospitalizations, but the association between infection-related hospitalizations and long-term cognitive function among NH residents is unknown. Objective: To examine whether there are changes in cognitive function before vs after infection-related hospitalizations among NH residents. Design, Setting, and Participants: This cohort study used data from the Minimum Data Set 3.0 linked to Medicare hospitalization data from 2011 to 2017 for US nursing home residents aged 65 years or older who had experienced an infection-related hospitalization and had at least 2 quarterly Minimum Data Set assessments before and 4 or more after the infection-related hospitalization. Analyses were performed from September 1, 2019, to December 21, 2020. Exposure: Infection-related hospitalization lasting 1 to 14 days. Main Outcomes and Measures: Using an event study approach, associations between infection-related hospitalizations and quarterly changes in cognitive function among NH residents were examined overall and by sex, age, Alzheimer disease and related dementias (ADRD) diagnosis, and sepsis vs other infection-related diagnoses. Resident-level cognitive function was measured using the Cognitive Function Scale (CFS), with scores ranging from 1 (intact) to 4 (severe cognitive impairment). Results: Of the sample of 20698 NH residents, 71.0% were women and 82.6% were non-Hispanic White individuals; the mean (SD) age at the time of transfer to the hospital was 82 (8.5) years. The mean CFS score was 2.17, and the prevalence of severe cognitive impairment (CFS score, 4) was 9.0%. During the first quarter after an infection-related hospitalization, residents experienced a mean increase of 0.06 points in CFS score (95% CI, 0.05-0.07 points; P <.001), or 3%. The increase in scores was greatest among residents aged 85 years or older vs younger residents by approximately 0.022 CFS points (95% CI, 0.004-0.040 points; P <.05). The prevalence of severe cognitive impairment increased by 1.6 percentage points (95% CI, 1.2-2.0 percentage points; P <.001), or 18%; the increases were observed among individuals with ADRD but not among those without it. After an infection-related hospitalization, cognition among residents who had experienced sepsis declined more than for residents who had not by about 0.02 CFS points (95% CI, 0.00-0.04 points; P <.05). All observed differences persisted without an accelerated rate of decline for at least 6 quarters after infection-related hospitalization. No differences were observed by sex. Conclusions and Relevance: In this cohort study, infection-related hospitalization was associated with immediate and persistent cognitive decline among nursing home residents, with the largest increase in CFS scores among older residents, those with ADRD, and those who had experienced sepsis. Identification of NH residents at risk of worsened cognition after an infection-related hospitalization may help to ensure that their care needs are addressed to prevent further cognitive decline. © 2021 American Medical Association. All rights reserved.

Myosin V Regulates Spatial Localization of Different Forms of Neurotransmitter Release in Central Synapses
(2021) Frontiers in Synaptic Neuroscience, 13, art. no. 650334, . 

Maschi, D.^a , Gramlich, M.W.^b , Klyachko, V.A.^a

^a Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, United States
^b Physics Department, Auburn University, Auburn, AL, United States

Abstract
Synaptic active zone (AZ) contains multiple specialized release sites for vesicle fusion. The utilization of release sites is regulated to determine spatiotemporal organization of the two main forms of synchronous release, uni-vesicular (UVR) and multi-vesicular (MVR). We previously found that the vesicle-associated molecular motor myosin V regulates temporal utilization of release sites by controlling vesicle anchoring at release sites in an activity-dependent manner. Here we show that acute inhibition of myosin V shifts preferential location of vesicle docking away from AZ center toward periphery, and results in a corresponding spatial shift in utilization of release sites during UVR. Similarly, inhibition of myosin V also reduces preferential utilization of central release sites during MVR, leading to more spatially distributed and temporally uniform MVR that occurs farther away from the AZ center. Using a modeling approach, we provide a conceptual framework that unites spatial and temporal functions of myosin V in vesicle release by controlling the gradient of release site release probability across the AZ, which in turn determines the spatiotemporal organization of both UVR and MVR. Thus myosin V regulates both temporal and spatial utilization of release sites during two main forms of synchronous release. © Copyright © 2021 Maschi, Gramlich and Klyachko.

Author Keywords
active zone;  myosin V;  neurotransmitter release;  release probability;  release site;  synaptic transmission;  vesicle docking

Funding details
National Institute of Neurological Disorders and StrokeNINDSR35 NS111596
Center for Cellular Imaging, Washington UniversityWUCCI

Trends in antimicrobial resistance amongst pathogens isolated from blood and cerebrospinal fluid cultures in Pakistan (2011-2015): A retrospective cross-sectional study
(2021) PLoS ONE, 16 (4 April), art. no. e0250226, . 

Javaid, N.^a , Sultana, Q.^b , Rasool, K.^b , Gandra, S.^c , Ahmad, F.^d , Chaudhary, S.U.^e , Mirza, S.^a

^a Department of Biology, School of Science and Engineering, Lahore University of Management Science, Lahore, Pakistan
^b Department of Microbiology, Chughtai Lab/Chughtai Institute of Pathology, Lahore, Pakistan
^c Division of Infectious Diseases, Washington University School of Medicine in St. Louis, St. Louis, MI, United States
^d Department of Statistics, University of Gujrat, Gujrat, Pakistan
^e Biomedical Informatics Research Laboratory, Department of Biology, Lahore University of Management Sciences, Lahore, Pakistan

Abstract
While antimicrobial resistance (AMR) continues to be a major public health problem in Pakistan, data regarding trends of resistance among pathogenic bacteria remains scarce, with few studies presenting long-term trends in AMR. This study was therefore designed to analyze long-term AMR trends at a national level in Pakistan. We report here results of a comprehensive analysis of resistance, among pathogens isolated from blood and cerebrospinal fluid (CSF), between 2011 and 2015. Susceptibility data was obtained from a local laboratory with collection points all across Pakistan (Chughtai Laboratory). Resistance proportions to most commonly used antimicrobials were calculated for each pathogen over a period of five years. While Acinetobacter species demonstrated highest resistance rates to all tested antimicrobials, a sharp increase in carbapenem resistance was the most noticeable (50%-95%) between 2011–2015. Our results also highlight the presence of third and fourth generation cephalosporins resistance in Salmonella enterica serovar Typhi in Pakistan. Interestingly, where rise in AMR was being observed in some major invasive pathogens, decreasing resistance trends were observed in Staphylococcus aureus, against commonly used antimicrobials. Overall pathogens isolated from blood and CSF between 2011–2015, showed an increase in resistance towards commonly used antimicrobials. © 2021 Javaid 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.

Sequential Transfer Learning via Segment after Cue Enhances the Motor Imagery-based Brain-Computer Interface
(2021) 9th IEEE International Winter Conference on Brain-Computer Interface, BCI 2021, art. no. 9385340, . 

Kim, D.-K.^a , Kim, Y.-T.^a , Jung, H.-R.^b , Kim, H.^a , Kim, D.-J.^a

^a Korea University, Department of Brain and Cognitive Engineering, Seoul, South Korea
^b Washington University in St. Louis, Department of Psychological and Brain Sciences, St. Louis, MO, United States

Abstract
Brain-computer interface (BCI) based on electroencephalogram (EEG) is a promising technology, allowing computers to estimate human intentions. Intention recognition tool such as motor imagery (MI) with high reliability is one of the major challenges in the BCI field. Recently, researchers have attempted to use transfer learning for various BCI datasets, but the studies showed low classification accuracy. This study aimed to increase the classification accuracy of the MI through sequential transfer learning for a single dataset. EEG-MI data with 9 subjects from the dataset 2a of BCI competition IV were used. EEGNet was used for MI classification. The pre-trained model was constructed by first learning whether the data were MI or not. The model was then sequentially fine-tuned through transfer learning for four MI tasks (i.e., left hand, right hand, both feet and tongue). The model was able to classify MI with 91.34% accuracy. In the meantime, the baseline model without transfer learning showed an accuracy of 61.62%, whereas the fine-tuned model presented an improved accuracy of 63.82%. Consequently, the sequential transfer learning was able to improve the performance of MI-BCI. © 2021 IEEE.

Author Keywords
brain-computer interface;  deep learning;  electroencephalography;  motor-imagery;  transfer learning

Funding details
Ministry of Science and ICT, South KoreaMSIT
Institute for Information and Communications Technology PromotionIITP
Ministry of Science, ICT and Future PlanningMSIPIITP-2020-2016-0-00464
National Research Foundation of KoreaNRF2019R1A2C1003399, 2020R1C1C1006773

Balancing serendipity and reproducibility: Pluripotent stem cells as experimental systems for intellectual and developmental disorders
(2021) Stem Cell Reports, . 

Anderson, N.C.^a , Chen, P.-F.^a , Meganathan, K.^b , Afshar Saber, W.^a , Petersen, A.J.^c , Bhattacharyya, A.^c d , Kroll, K.L.^b , Sahin, M.^a

^a Department of Neurology, Rosamund Stone Zander Translational Neuroscience Center, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, United States
^b Department of Developmental Biology, Washington University School of Medicine, Saint Louis, MO 63110, United States
^c Waisman Center, University of Wisconsin, Madison, WI 53705, United States
^d Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53705, United States

Abstract
Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) and their differentiation into neural lineages is a revolutionary experimental system for studying neurological disorders, including intellectual and developmental disabilities (IDDs). However, issues related to variability and reproducibility have hindered translating preclinical findings into drug discovery. Here, we identify areas for improvement by conducting a comprehensive review of 58 research articles that utilized iPSC-derived neural cells to investigate genetically defined IDDs. Based upon these findings, we propose recommendations for best practices that can be adopted by research scientists as well as journal editors. © 2021 The Authors

Funding details
Novartis
Ipsen Biopharmaceuticals
Pfizer
LAM Therapeutics
Roche
John Merck FundJMF
Tommy Fuss Fund
National Institutes of HealthNIHR01MH124808, P50HD129966, R01NS114551
University of WashingtonUWU54HD090256
R01NS113591, T32MH112510, U54NS092090
National Institute of Neurological Disorders and StrokeNINDS
CDI-LI-2019-819
Intellectual and Developmental Disabilities Research CenterIDDRCU54HD087011, U54HD090255
Institute of Clinical and Translational SciencesICTSR03HD092640, R21NS105339
Fondation Jérôme Lejeune
U01HG007530

Longitudinal intravital imaging nerve degeneration and sprouting in the toes of spared nerve injured mice
(2021) Journal of Comparative Neurology, . 

Yeh, H.-Y.^a , Lee, J.-C.^b , Chi, H.-H.^a , Chen, C.-C.^c , Liu, Q.^d , Yen, C.-T.^a

^a Department of Life Science, National Taiwan University, Taipei, Taiwan
^b Graduate Institute of Pharmacology, National Taiwan University College of Medicine, Taipei, Taiwan
^c Institute of Biomedical Science, Academia Sinica, Taipei, Taiwan
^d Department of Anesthesiology and the Center for the Study of Itch, Washington University School of Medicine, St. Louis, MO, United States

Abstract
Neuropathic pain is pain caused by damage to the somatosensory nervous system. Both degenerating injured nerves and neighboring sprouting nerves can contribute to neuropathic pain. However, the mesoscale changes in cutaneous nerve fibers over time after the loss of the parent nerve has not been investigated in detail. In this study, we followed the changes in nerve fibers longitudinally in the toe tips of mice that had undergone spared nerve injury (SNI). Nav1.8-tdTomato, Thy1-GFP and MrgD-GFP mice were used to observe the small and large cutaneous nerve fibers. We found that peripheral nerve plexuses degenerated within 3 days of nerve injury, and free nerve endings in the epidermis degenerated within 2 days. The timing of degeneration paralleled the initiation of mechanical hypersensitivity. We also found that some of the Nav1.8-positive nerve plexuses and free nerve endings in the fifth toe survived, and sprouting occurred mostly from 7 to 28 days. The timing of the sprouting of nerve fibers in the fifth toe paralleled the maintenance phase of mechanical hypersensitivity. Our results support the hypotheses that both injured and intact nerve fibers participate in neuropathic pain, and that, specifically, nerve degeneration is related to the initiation of evoked pain and nerve sprouting is related to the maintenance of evoked pain. © 2021 Wiley Periodicals LLC.

Author Keywords
cutaneous nerve fibers;  intravital imaging;  MrgD-GFP;  Nav1.8-tdTomato;  neuropathic pain;  Thy1-GFP

Funding details
National Science CouncilNSC
National Taiwan UniversityNTU
Ministry of Science and Technology, TaiwanMOSTMOST‐109‐2321‐B‐002‐028

Selective removal of astrocytic APOE4 strongly protects against tau-mediated neurodegeneration and decreases synaptic phagocytosis by microglia
(2021) Neuron, . 

Wang, C.^a , Xiong, M.^a , Gratuze, M.^a , Bao, X.^a , Shi, Y.^a , Andhey, P.S.^b , Manis, M.^a , Schroeder, C.^c , Yin, Z.^c , Madore, C.^c , Butovsky, O.^c d , Artyomov, M.^b , Ulrich, J.D.^a , Holtzman, D.M.^a

^a Department of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer Disease, Research Center, Washington University, St. Louis, MO 63110, United States
^b Department of Pathology and Immunology, Washington University, St. Louis, MO 63110, United States
^c Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, United States
^d Evergrande Center for Immunologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, United States

Abstract
The apolipoprotein E (APOE) gene is the strongest genetic risk factor for Alzheimer’s disease and directly influences tauopathy and tau-mediated neurodegeneration. ApoE4 has strong deleterious effects on both parameters. In the brain, apoE is produced and secreted primarily by astrocytes and by activated microglia. The cell-specific role of each form of apoE in the setting of neurodegeneration has not been determined. We generated P301S Tau/Aldh1l1-CreERT2/apoE3flox/flox or Tau/Aldh1l1-CreERT2/apoE4flox/flox mice. At 5.5 months of age, after the onset of tau pathology, we administered tamoxifen or vehicle and compared mice at 9.5 months of age. Removing astrocytic APOE4 markedly reduced tau-mediated neurodegeneration and decreased phosphorylated tau (pTau) pathology. Single-nucleus RNA sequencing analysis revealed striking gene expression changes in all cell types, with astrocytic APOE4 removal decreasing disease-associated gene signatures in neurons, oligodendrocytes, astrocytes, and microglia. Removal of astrocytic APOE4 decreased tau-induced synaptic loss and microglial phagocytosis of synaptic elements, suggesting a key role for astrocytic apoE in synaptic degeneration. © 2021 Elsevier Inc.

Author Keywords
APOE;  astrocyte;  microglia;  neurodegeneration;  tau

Funding details
Foundation for Barnes-Jewish Hospital3770, 4642
Office of Research Infrastructure Programs, National Institutes of HealthORIP, NIH
Office of Research Infrastructure Programs, National Institutes of HealthORIP, NIHOD021629
Cure Alzheimer’s FundCAF
Alvin J. Siteman Cancer Center
JPB Foundation
CDI-CORE-2019-813, CDI-CORE-2015-505
National Institutes of HealthNIHNS090934, AG054672, NS088137, AG051812, AG047644
National Center for Research ResourcesNCRR
Institute of Clinical and Translational SciencesICTS
Center for Cellular Imaging, Washington UniversityWUCCI
National Cancer InstituteNCIP30 CA91842
Georgia Clinical and Translational Science AllianceGaCTSAUL1TR002345

Perioperative sleep in geriatric cardiac surgical patients: a feasibility study using a wireless wearable device
(2021) British Journal of Anaesthesia, . 

Kafashan, M.^a , Hyche, O.^a , Nguyen, T.^a , Smith, S.K.^a , Guay, C.S.^a , Wilson, E.^a , Labonte, A.K.^a , Guan, M.J.^a f , Lucey, B.P.^b , Ju, Y.-E.S.^b , Palanca, B.J.A.^a c d e

^a Department of Anesthesiology, 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 Psychiatry, Washington University School of Medicine in St Louis, St Louis, MO, United States
^d Division of Biology and Biomedical Sciences, Washington University School of Medicine in St Louis, St Louis, MO, United States
^e Department of Biomedical Engineering, Washington University in St Louis, St Louis, MO, United States
^f Kansas City University of Medicine and Biosciences, Kansas City, MO, United States

Author Keywords
cardiac surgery;  electroencephalography;  geriatric;  mobile technology;  non-REM sleep;  perioperative sleep;  REM sleep

Funding details
National Institute on AgingNIA
National Institutes of HealthNIHR01AG057901

Opioid use and social disadvantage in patients with chronic musculoskeletal pain
(2021) PM and R, . 

Cheng, A.L.^a , Brady, B.K.^b , Bradley, E.C.^c , Calfee, R.P.^d , Klesges, L.M.^e , Colditz, G.A.^e , Prather, H.^a

^a Division of Physical Medicine and Rehabilitation, Department of Orthopaedic Surgery, Washington University in St. Louis School of Medicine, St. Louis, MO, United States
^b Washington University in St. Louis School of Medicine, St. Louis, MO, United States
^c The Brown School of Social Work, Washington University in St. Louis, St. Louis, MO, United States
^d Division of Hand and Microsurgery, Department of Orthopaedic Surgery, Washington University in St. Louis School of Medicine, St. Louis, MO, United States
^e Division of Public Health Sciences, Department of Surgery, Washington University in St. Louis School of Medicine, St. Louis, MO, United States

Abstract
Background: Historically, marginalized patients were prescribed less opioid medication than affluent, white patients. However, because of persistent differential access to nonopioid pain treatments, this direction of disparity in opioid prescribing may have reversed. Objective: To compare social disadvantage and health in patients with chronic pain who were managed with versus without chronic opioid therapy. It was hypothesized that patients routinely prescribed opioids would be more likely to live in socially disadvantaged communities and report worse health. Design: Cross-sectional analysis of a retrospective cohort defined from medical records from 2000 to 2019. Setting: Single tertiary safety net medical center. Patients: Adult patients with chronic musculoskeletal pain who were managed longitudinally by a physiatric group practice from at least 2011 to 2015 (n = 1173), subgrouped by chronic (≥4 years) adherent opioid usage (n = 356) versus no chronic opioid usage (n = 817). Intervention: Not applicable. Main Outcome Measures: The primary outcome was the unadjusted between-group difference in social disadvantage, defined by living in the worst national quartile of the Area Deprivation Index (ADI). An adjusted effect size was also calculated using logistic regression, with age, sex, race, and Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference and Physical Function scores as covariates. Secondary outcomes included adjusted differences in health by chronic opioid use (measured by PROMIS). Results: Patients managed with chronic opioid therapy were more likely to live in a zip code within the most socially disadvantaged national quartile (34.9%; 95% confidence interval [CI] 29.9–39.9%; vs. 24.9%; 95% CI 21.9–28.0%; P <.001), and social disadvantage was independently associated with chronic opioid use (odds ratio [OR] 1.01 per ADI percentile [1.01–1.02]). Opioid use was also associated with meaningfully worse PROMIS Depression (3.8 points [2.4–5.1]), Anxiety (3.0 [1.4–4.5]), and Pain Interference (2.6 [1.7–3.5]) scores. Conclusions: Patients prescribed chronic opioid treatment were more likely to live in socially disadvantaged neighborhoods, and chronic opioid use was independently associated with worse behavioral health. Improving access to multidisciplinary, nonopioid treatments for chronic pain may be key to successfully overcoming the opioid crisis. null

Funding details
National Institute of Arthritis and Musculoskeletal and Skin DiseasesNIAMSK23AR074520
Doris Duke Charitable FoundationDDCF
Doris Duke Charitable FoundationDDCFK23AR074520
National Institute of Arthritis and Musculoskeletal and Skin DiseasesNIAMS

Ischaemic stroke on anticoagulation therapy and early recurrence in acute cardioembolic stroke: The IAC study
(2021) Journal of Neurology, Neurosurgery and Psychiatry, . 

Yaghi, S.^a , Henninger, N.^b c , Giles, J.A.^d , Leon Guerrero, C.^e , Mistry, E.^f , Liberman, A.L.^g , Asad, D.^h , Liu, A.^d , Nagy, M.^b , Kaushal, A.ⁱ , Azher, I.^f i , Mac Grory, B.ⁱ , Fakhri, H.^f , Brown Espaillat, K.^f , Pasupuleti, H.^j , Martin, H.^j , Tan, J.^j , Veerasamy, M.^j , Esenwa, C.^g , Cheng, N.^g , Moncrieffe, K.^g , Moeini-Naghani, I.^e , Siddu, M.^e , Scher, E.^k , Trivedi, T.^k , Furie, K.L.ⁱ , Keyrouz, S.G.^d , Nouh, A.^h , de Havenon, A.^l , Khan, M.^j m , Smith, E.E.ⁿ , Gurol, M.E.^o p

^a Dpeartment of Neurology, Brown University, Providence, RI, United States
^b Neurology, University of Massachusetts Medical School, Worcester, MA, United States
^c Department of Psychiatry, University of Massachusetts, Worcester, MA, United States
^d Neurology, Washington University in Saint Louis, St Louis, MO, United States
^e The George Washington University School of Medicine and Health Sciences, Washington, DC, United States
^f Neurology, Vanderbilt University, Nashville, TN, United States
^g Neurology, Montefiore Hospital and Medical Center, Bronx, NY, United States
^h Neurology, Hartford Hospital, Hartford, CT, United States
ⁱ Neurology, Brown University Warren Alpert Medical School, Providence, RI, United States
^j Neuroscience Institute, Spectrum Health, Grand Rapids, MI, United States
^k Neurology, NYU Langone Health, New York, NY, United States
^l Neurology, University of Utah Health Hospitals and Clinics, Salt Lake City, UT, United States
^m Neurology, Michigan State University College of Human Medicine, Grand Rapids, MI, United States
ⁿ Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada
^o Neurology, Massachusetts General Hospital, Boston, MA, United States
^p Neurology, Harvard Medical School, Boston, MA, United States

Abstract
A subset of ischaemic stroke patients with atrial fibrillation (AF) have ischaemic stroke despite anticoagulation. We sought to determine the association between prestroke anticoagulant therapy and recurrent ischaemic events and symptomatic intracranial haemorrhage (sICH). We included consecutive patients with acute ischaemic stroke and AF from the Initiation of Anticoagulation after Cardioembolic stroke (IAC) study from eight comprehensive stroke centres in the USA. We compared recurrent ischaemic events and delayed sICH risk using adjusted Cox regression analyses between patients who were prescribed anticoagulation (ACp) versus patients who were naïve to anticoagulation therapy prior to the ischaemic stroke (anticoagulation naïve). Among 2084 patients in IAC, 1518 had prior anticoagulation status recorded and were followed for 90 days. In adjusted Cox hazard models, ACp was associated with some evidence of a higher risk higher risk of 90-day recurrent ischaemic events only in the fully adjusted model (adjusted HR 1.50, 95% CI 0.99 to 2.28, p=0.058) but not increased risk of 90-day sICH (adjusted HR 1.08, 95% CI 0.46 to 2.51, p=0.862). In addition, switching anticoagulation class was not associated with reduced risk of recurrent ischaemic events (adjusted HR 0.41, 95% CI 0.12 to 1.33, p=0.136) nor sICH (adjusted HR 1.47, 95% CI 0.29 to 7.50, p=0.641). AF patients with ischaemic stroke despite anticoagulation may have higher recurrent ischaemic event risk compared with anticoagulation-naïve patients. This suggests differing underlying pathomechanisms requiring different stroke prevention measures and identifying these mechanisms may improve secondary prevention strategies. © Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Acellular Nerve Allografts in Major Peripheral Nerve Repairs: An Analysis of Cases Presenting With Limited Recovery
(2021) Hand, . 

Peters, B.R.^a b , Wood, M.D.^a , Hunter, D.A.^a , Mackinnon, S.E.^a

^a Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, MO, United States
^b Division of Plastic and Reconstructive Surgery, Department of Surgery, Oregon Health Science Univeristy, Portland, OR, United States

Abstract
Background: Acellular nerve allografts have been used successfully and with increasing frequency to reconstruct nerve injuries. As their use has been expanded to treat longer gap, larger diameter nerve injuries, some failed cases have been reported. We present the histomorphometry of 5 such cases illustrating these limitations and review the current literature of acellular nerve allografts. Methods: Between 2014 and 2019, 5 patients with iatrogenic nerve injuries to the median or ulnar nerve reconstructed with an AxoGen AVANCE nerve allograft at an outside hospital were treated in our center with allograft excision and alternative reconstruction. These patients had no clinical or electrophysiological evidence of recovery, and allograft specimens at the time of surgery were sent for histomorphological examination. Results: Three patients with a median and 2 with ulnar nerve injury were included. Histology demonstrated myelinated axons present in all proximal native nerve specimens. In 2 cases, axons failed to regenerate into the allograft and in 3 cases, axonal regeneration diminished or terminated within the allograft. Conclusions: The reported cases demonstrate the importance of evaluating the length and the function of nerves undergoing acellular nerve allograft repair. In long length, large-diameter nerves, the use of acellular nerve allografts should be carefully considered. © The Author(s) 2021.

Author Keywords
allograft;  autograft;  basic science;  diagnosis;  nerve;  nerve injury;  nerve reconstruction;  nerve regeneration

Pipeline embolization of distal posterior inferior cerebellar artery aneurysms
(2021) Interventional Neuroradiology, . 

Lauzier, D.C.^a , Root, B.K.^a , Kayan, Y.^b , Almandoz, J.E.D.^b , Osbun, J.W.^a c d , Chatterjee, A.R.^a c d , Whaley, K.L.^e , Tipps, M.E.^e , Moran, C.J.^a d , Kansagra, A.P.^a c d

^a Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, United States
^b Division of Neurointerventional Radiology, Neuroscience Institute, Abbott Northwestern Hospital, Minneapolis, MN, United States
^c Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
^d Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO, United States
^e Neuroscience Institute, Abbott Northwestern Hospital, Minneapolis, MN, United States

Abstract
Background and purpose: Flow diversion is commonly used to treat intracranial aneurysms in various regions of the cerebral vasculature, but is only approved for use in the internal carotid arteries. Treatment of distal PICA aneurysms with PED is sometimes performed but has not been well studied. Here, we report our experience with flow diversion of distal PICA aneurysms with PED. Materials and methods: Clinical and angiographic data of eligible patients was retrospectively obtained and assessed for key demographic characteristics and clinical and angiographic outcomes. Principal outcomes included rates of aneurysm occlusion, ischemic or hemorrhagic complication, technical complication, and in-stent stenosis. Results: Three female and 2 male patients underwent placement of PED in the PICA for treatment of 5 distal PICA aneurysms. Clinical and angiographic follow-up was obtained for all patients. Complete aneurysm occlusion was observed in 100% (5/5) of treated aneurysms at 6 month and longest angiographic follow-up. While there were no ischemic or device-related complications, delayed hemorrhagic complications occurred in 20% (1/5) of patients. Conclusion: Pipeline embolization of distal PICA aneurysms can be performed in select patients. Further study is necessary in larger cohorts to better define clinical scenarios in which flow diversion in the distal PICA should be considered. © The Author(s) 2021.

Author Keywords
Aneurysm;  endovascular;  pipeline embolization device;  posterior inferior cerebellar artery

Presleep Arousal and Sleep in Early Childhood
(2021) Journal of Genetic Psychology, . 

Hoyniak, C.P.^a , McQuillan, M.M.^b , Bates, J.E.^c , Staples, A.D.^d , Schwichtenberg, A.J.^e , Honaker, S.M.^b

^a Department of Psychiatry, Washington University School of Medicine in St. Louis, St Louis, MO, United States
^b Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, United States
^c Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, United States
^d Department of Psychology, Eastern Michigan University, Ypsilanti, MI, United States
^e Department of Psychological and Brain Sciences, Purdue University, West Lafayette, IN, United States

Abstract
Research suggests that arousal during the transition to sleep—presleep arousal—is associated with sleep disturbances. Although a robust literature has examined the role of presleep arousal in conferring risk for sleep disturbances in adults, substantially less research has examined the developmental origins of presleep arousal in early childhood. The authors examined presleep arousal using parent report and psychophysiological measures in a sample of preschoolers to explore the association between different measures of presleep arousal, and to examine how nightly presleep arousal is associated with sleep. Participants included 29 children assessed at 54 months of age. Presleep arousal was measured using parent reports of child arousal each night at bedtime and using a wearable device that took minute-by-minute recordings of heart rate, peripheral skin temperature, and electrodermal activity each night during the child’s bedtime routine. This yielded a dataset with 4,550 min of ambulatory recordings across an average of 3.52 nights per child (SD = 1.84 nights per child; range = 1–8 nights). Sleep was estimated using actigraphy. Findings demonstrated an association between parent-reported and psychophysiological arousal, including heart rate, peripheral skin temperature, and skin conductance responses during the child’s bedtime routine. Both the parent report and psychophysiological measures of presleep arousal showed some associations with poorer sleep, with the most robust associations occurring between presleep arousal and sleep onset latency. Behavioral and biological measures of hyperarousal at bedtime are associated with poorer sleep in young children. Findings provide early evidence of the utility of wearable devices for assessing individual differences in presleep arousal in early childhood. © 2021 Taylor & Francis Group, LLC.

Author Keywords
Early childhood;  hyperarousal;  pre-sleep arousal;  sleep

Central vein sign and other radiographic features distinguishing myelin oligodendrocyte glycoprotein antibody disease from multiple sclerosis and aquaporin-4 antibody-positive neuromyelitis optica
(2021) Multiple Sclerosis Journal, . 

Ciotti, J.R., Eby, N.S., Brier, M.R., Wu, G.F., Chahin, S., Cross, A.H., Naismith, R.T.

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

Abstract
Background: Myelin oligodendrocyte glycoprotein antibody disease (MOGAD) can radiographically mimic multiple sclerosis (MS) and aquaporin-4 (AQP4) antibody-positive neuromyelitis optica spectrum disorder (NMOSD). Central vein sign (CVS) prevalence has not yet been well-established in MOGAD. Objective: Characterize the magnetic resonance imaging (MRI) appearance and CVS prevalence of MOGAD patients in comparison to matched cohorts of MS and AQP4+ NMOSD. Methods: Clinical MRIs from 26 MOGAD patients were compared to matched cohorts of MS and AQP4+ NMOSD. Brain MRIs were assessed for involvement within predefined regions of interest. CVS was assessed by overlaying fluid-attenuated inversion recovery (FLAIR) and susceptibility-weighted sequences. Topographic analyses were performed on spinal cord and orbital MRIs when available. Results: MOGAD patients had fewer brain lesions and average CVS+ rate of 12.1%, compared to 44.4% in MS patients (p = 0.0008). MOGAD spinal cord and optic nerve involvement was lengthier than MS (5.8 vs 1.0 vertebral segments, p = 0.020; 3.0 vs 0.5 cm, p < 0.0001). MOGAD patients tended to have bilateral/anterior optic nerve pathology with perineural contrast enhancement, contrasting with posterior optic nerve involvement in NMOSD. Conclusion: CVS+ rate and longer segments of involvement in the spinal cord and optic nerve can differentiate MOGAD from MS, but do not discriminate as well between MOGAD and AQP4+ NMOSD. © The Author(s), 2021.

Author Keywords
central vein sign;  magnetic resonance imaging;  multiple sclerosis;  Myelin oligodendrocyte glycoprotein antibody disease;  neuromyelitis optica spectrum disorder

Funding details
Biogen
National Multiple Sclerosis Society
National Institutes of HealthNIH
Roche

Looking around and looking ahead: forecasting and moral intensity in ethical decision-making
(2021) Ethics and Behavior, . 

Fichtel, M.^a , Gujar, Y.^a , Sanders, C.^a , Higgs, C.^a , McIntosh, T.^b , Connelly, S.^a , Mumford, M.D.^a

^a Department of Psychology, The University of Oklahoma, United States
^b Department of Medicine, Washington University in St. Louis, United States

Abstract
Prior studies have examined the impacts of sensemaking processes, such as forecasting, on ethical decision making (EDM) but only a few have considered how aspects of the ethical issue itself, such as social consensus and magnitude of consequences, might interact with sensemaking processes to influence EDM. The present effort examines both forecasting and moral intensity, as well as their interactions, during the EDM process. Participants in this study were given an ethical scenario with either a high or low degree of social consensus as well as a greater or smaller magnitude of consequences. They were then asked to forecast either many or few potential outcomes stemming from their actions before coming up with a final plan of action. Responses were rated for quality of forecasting, use of metacognitive reasoning strategies, perceived moral intensity, and ethicality. Results indicate that social consensus may not be beneficial for EDM if the magnitude of consequences is low or individuals are not engaged in extensive forecasting. Implications of these findings are discussed. © 2021 Taylor & Francis Group, LLC.

Author Keywords
Ethical decision-making;  forecasting;  moral intensity;  sensemaking

MS can be considered a primary progressive disease in all cases, but some patients have superimposed relapses – No
(2021) Multiple Sclerosis Journal, . 

Cross, A.H., Naismith, R.T.

Department of Neurology, Washington University School of Medicine, Saint LouisMO, United States

Changes in Sedation Practices in Association with Delirium Screening in Infants After Cardiopulmonary Bypass
(2021) Pediatric Cardiology, . 

Chomat, M.R.^a b , Said, A.S.^b , Mann, J.L.^c , Wallendorf, M.^d , Bickhaus, A.^c , Figueroa, M.^a b e

^a Division of Pediatric Cardiology, Washington University in St. Louis, St. Louis, United States
^b Division of Pediatric Critical Care Medicine, Washington University in St. Louis, St. Louis, United States
^c St. Louis Children’s Hospital, Washington University in St. Louis, St. Louis, United States
^d Division of Biostatistics, Washington University in St. Louis, St. Louis, United States
^e Washington University in St. Louis School of Medicine, 660 S. Euclid Ave., Campus Box 8116, St. Louis, MO 63110-1093, United States

Abstract
Sedation in the cardiac intensive care unit (CICU) is necessary to keep critically ill infants safe and comfortable. However, long-term use of sedatives may be associated with adverse neurodevelopmental outcomes. We aimed to examine sedation practices in the CICU after the implementation of the Cornell Assessment of Pediatric Delirium (CAPD). We hypothesize the use of the CAPD would be associated with a decrease in sedative weans at CICU discharge. This is a single institution, retrospective cohort study. The study inclusion criteria were term infants, birthweight > 2.5 kg, cardiopulmonary bypass (CPB), and mechanical ventilation (MV) on postoperative day zero. During the study period, 50 and 35 patients respectively, met criteria pre- and post-implementation of CAPD screening. Our results showed a statistically significant increase in the incidence of sedative habituation wean at CICU discharge after CAPD implementation (24% vs. 45.7%, p = 0.036). There was a statistically significant increase in exposure to opiate (56% vs. 88.6%, p = 0.001) and dexmedetomidine infusions (52% vs 80%, p = 0.008), increased likelihood of clonidine use at CICU discharge (OR 9.25, CI 2.39–35.84), and increase in the duration of intravenous sedative infusions (8.1 days vs. 5.1 days, p = 0.04) No statistical difference was found in exposure to fentanyl (42% vs. 58.8%, p = 0.13) or midazolam infusions (22% vs. 25.7%, p = 0.691); and there was no change in benzodiazepine or opiate use at CICU discharge or dosage. The prevalence of delirium in the CAPD cohort was 92%. CAPD implementation in the CICU was associated with changes in sedation practices, specifically an increase in the use of dexmedetomidine, which possibly explains the increased clonidine weans at CICU discharge. This is the first report of the association between CAPD monitoring and changes in sedative practices. Multi-center prospective studies are recommended to evaluate sedative practices, delirium, and its effects on neurodevelopment. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Author Keywords
Cornell Assessment of Pediatric Delirium;  Dexmedetomidine;  Pediatric cardiac surgery;  Pediatric delirium;  Sedation;  Sedation wean

How are expectancies and values cognitively combined to determine behavioral intentions? The role of expectancy-value theory, information integration and behavioral outcomes in dietary intentions
(2021) Applied Cognitive Psychology, . 

Fowler, L.A.^a , Moore, P.J.^b , Macura, Z.^b , Singh, M.A.^b , Cooke, F.P.R.^c , Charmak, W.D.^d

^a Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
^b Department of Psychological & Brain Sciences, The George Washington University, Washington, DC, United States
^c Department of Allergy & Immunology, Children’s National Hospital, Washington, DC, United States
^d United States Department of Defense Medical Activity, Ft Meade, MD, United States

Abstract
The expectancy-value (EV) framework is among the most prominent psychological approaches to predicting behavioral intentions. However, how expectancies and values are cognitively integrated (e.g., multiplicatively, additively or averaging) to produce intentions has yet to be tested. This research combined EV and Information Integration Theory methodologies to identify how EV integration determined dietary intentions among 80 participants (Meanage = 19.4 years, 61 females). Participants were presented with scenarios depicting three potential outcomes of junk-food consumption (weight gain, increased disease risk, and time savings). Expectancies (no information/low/medium/high) were varied within-subjects, and between-subject values were trichotomized for each outcome. Participants indicated their dietary intentions in this 3×4 mixed design for all three outcomes. Expectancies and values were integrated additively to produce dietary intentions in the context of weight gain and disease-risk, but the integration rule for time savings could not be determined. Theoretical implications and practical applications of these results are also discussed. © 2021 John Wiley & Sons Ltd.

Author Keywords
behavioral intentions;  behavioral outcomes;  diet;  expectancy-value;  information integration theory

Funding details
National Heart, Lung, and Blood InstituteNHLBI
National Heart, Lung, and Blood InstituteNHLBI

The Energetic Brain Club in Life and Death
(2021) Anthropology and Humanism, . 

Hames, A.

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

Abstract
Japan’s aging society leaves many of its eldest residents to encounter loneliness and social isolation. However, the elderly in Japan and elsewhere are rarely passive vessels to fate and often use available tools to meet their needs. Exploring loneliness and its remedy, this essay presents an ethnographic account of a single Energetic Brain Club meeting in the Tokyo sprawl. While, on paper, the club is aimed at preventing dementia, cognitive declines frequently remain a peripheral topic. Elderly members partake in hospitality rituals and engage in long, meandering conversations about family, memories, struggles, and politics. In the process, they find commiseration, connection, and a salve for loneliness. © 2021 by the American Anthropological Association. All rights reserved

Author Keywords
dementia;  ethnography;  Japan;  loneliness;  memories

Measures of resting state EEG rhythms for clinical trials in Alzheimer’s disease: Recommendations of an expert panel
(2021) Alzheimer’s and Dementia, . 

Babiloni, C.^a b , Arakaki, X.^c , Azami, H.^d , Bennys, K.^e , Blinowska, K.^f g , Bonanni, L.^h , Bujan, A.ⁱ , Carrillo, M.C.^j , Cichocki, A.^k l m , de Frutos-Lucas, J.ⁿ , Del Percio, C.^a , Dubois, B.^o p , Edelmayer, R.^j , Egan, G.^q , Epelbaum, S.^o p , Escudero, J.^r , Evans, A.^s , Farina, F.^t , Fargo, K.^j , Fernández, A.ⁿ , Ferri, R.^u , Frisoni, G.^v w , Hampel, H.^x , Harrington, M.G.^c , Jelic, V.^y , Jeong, J.^z , Jiang, Y.^aa , Kaminski, M.^g , Kavcic, V.^ab , Kilborn, K.^ac , Kumar, S.^ad , Lam, A.^ae , Lim, L.^af , Lizio, R.^ag , Lopez, D.ⁿ , Lopez, S.^a , Lucey, B.^ah , Maestú, F.ⁿ , McGeown, W.J.^ai , McKeith, I.^aj , Moretti, D.V.^v , Nobili, F.^ak al , Noce, G.^ag , Olichney, J.^am , Onofrj, M.^h , Osorio, R.^an , Parra-Rodriguez, M.^ai , Rajji, T.^ad , Ritter, P.^ao ap , Soricelli, A.^ag aq , Stocchi, F.^ar , Tarnanas, I.^as at , Taylor, J.P.^aj , Teipel, S.^au av , Tucci, F.^a , Valdes-Sosa, M.^aw , Valdes-Sosa, P.^aw ax , Weiergräber, M.^ay , Yener, G.^az , Guntekin, B.^ba bb

^a Department of Physiology and Pharmacology “Vittorio Erspamer”, Sapienza University of Rome, Rome, Italy
^b San Raffaele of Cassino, Cassino (FR), Italy
^c Huntington Medical Research Institutes, Pasadena, CA, United States
^d Department of Neurology and Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States
^e Centre Mémoire de Ressources et de Recherche (CMRR), Centre Hospitalier, Universitaire de Montpellier, Montpellier, France
^f Institute of BiocyberneticsWarsaw, Poland
^g Faculty of Physics University of Warsaw and Nalecz, Warsaw, Poland
^h Department of Neuroscience Imaging and Clinical Sciences and CESI, University “G. D’Annunzio” of Chieti-Pescara, Chieti, Italy
ⁱ Psychological Neuroscience Lab, School of Psychology, University of Minho, Minho, Portugal
^j Division of Medical & Scientific Relations, Alzheimer’s Association, Chicago, IL, United States
^k Skolkowo Institute of Science and Technology (SKOLTECH)Moscow, Russian Federation
^l Systems Research Institute PASWarsaw, Poland
^m Nicolaus Copernicus University (UMK), Torun, Poland
ⁿ Laboratory of Cognitive and Computational Neuroscience, Center for Biomedical Technology, Universidad Complutense and Universidad Politécnica de Madrid, Madrid, Spain
^o Department of Neurology, Pitié-Salpêtrière Hospital, AP-HP, Boulevard de l’hôpital, Institute of Memory and Alzheimer’s Disease (IM2A), Paris, France
^p ICM, INSERM U1127, CNRS UMR 7225, Sorbonne Université, Institut du Cerveau et de la Moelle épinière, Paris, France
^q Foundation Director of the Monash Biomedical Imaging (MBI) Research Facilities, Monash University, Clayton, Australia
^r School of Engineering, Institute for Digital Communications, The University of Edinburgh, Edinburgh, United Kingdom
^s Department of Neurology and Neurosurgery, McGill University, Montreal, Canada
^t Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland
^u Oasi Research Institute – IRCCS, Troina, Italy
^v IRCCS San Giovanni di Dio Fatebenefratelli, Brescia, Italy
^w Memory Clinic and LANVIE – Laboratory of Neuroimaging of Aging, University Hospitals and University of Geneva, Geneva, Switzerland
^x GRC n° 21, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Boulevard de l’hôpital, Sorbonne University, Paris, France
^y Division of Clinical Geriatrics, NVS Department, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
^z Department of Bio and Brain Engineering/Program of Brain and Cognitive Engineering Korea Advanced Institute of Science and Technology (KAIST), Daejeon, South Korea
^aa Department of Behavioral Science, College of Medicine, University of Kentucky, Lexington, KY, United States
^ab Institute of Gerontology, Wayne State University, Detroit, MI, United States
^ac School of Psychology, University of Glasgow, Glasgow, United Kingdom
^ad Geriatric Psychiatry Division, Centre for Addiction and Mental Health, Toronto, ON, Canada
^ae MGH Epilepsy Service, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
^af Vielight Inc., Toronto, ON, Canada
^ag IRCCS SDN, Napoli, Italy
^ah Washington University School of Medicine in St. Louis, St. Louis, MO, United States
^ai School of Psychological Sciences and Health, University of Strathclyde, Glasgow, United Kingdom
^aj Newcastle upon Tyne, Translational and Clinical Research Institute, Newcastle University, United Kingdom
^ak Department of Neuroscience (DINOGMI), University of Genoa, Genoa, Italy
^al Clinica Neurologica, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
^am UC Davis Department of Neurology and Center for Mind and Brain, Davis, CA, United States
^an Center for Brain Health, Department of Psychiatry, NYU Langone Medical Center, New York, NY, United States
^ao Brain Simulation Section, Department of Neurology, Charité Universitätsmedizin and Berlin Institute of Health, Berlin, Germany
^ap Bernstein Center for Computational Neuroscience, Berlin, Germany
^aq Department of Motor Sciences and Healthiness, University of Naples Parthenope, Naples, Italy
^ar IRCCS San Raffaele Pisana, Rome, Italy
^as Global Brain Health Institute, University of California San Francisco, San Francisco, United States
^at Global Brain Health Institute, Trinity College Dublin, Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland
^au Department of Psychosomatic Medicine, University of Rostock, Rostock, Germany
^av German Center for Neurodegenerative Diseases (DZNE) – Rostock/Greifswald, Rostock, Germany
^aw Cuban Neuroscience Center, Havana, Cuba
^ax Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, China
^ay Experimental Neuropsychopharmacology, BfArM), Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte, Bonn, Germany
^az Departments of Neurosciences and Department of Neurology, Dokuz Eylül University Medical School, Izmir, Turkey
^ba Department of Biophysics, School of Medicine, Istanbul Medipol University, Istanbul, Turkey
^bb REMER, Clinical Electrophysiology, Neuroimaging and Neuromodulation Lab, Istanbul Medipol University, Istanbul, Turkey

Abstract
The Electrophysiology Professional Interest Area (EPIA) and Global Brain Consortium endorsed recommendations on candidate electroencephalography (EEG) measures for Alzheimer’s disease (AD) clinical trials. The Panel reviewed the field literature. As most consistent findings, AD patients with mild cognitive impairment and dementia showed abnormalities in peak frequency, power, and “interrelatedness” at posterior alpha (8-12 Hz) and widespread delta (< 4 Hz) and theta (4-8 Hz) rhythms in relation to disease progression and interventions. The following consensus statements were subscribed: (1) Standardization of instructions to patients, resting state EEG (rsEEG) recording methods, and selection of artifact-free rsEEG periods are needed; (2) power density and “interrelatedness” rsEEG measures (e.g., directed transfer function, phase lag index, linear lagged connectivity, etc.) at delta, theta, and alpha frequency bands may be use for stratification of AD patients and monitoring of disease progression and intervention; and (3) international multisectoral initiatives are mandatory for regulatory purposes. © 2021 the Alzheimer’s Association

Author Keywords
Alzheimer’s disease;  biomarkers;  clinical trials;  dementia;  electroencephalography (EEG);  eyes-closed resting state condition;  The Alzheimer’s Association International Society to Advance Alzheimer’s Research and Treatment (ISTAART)

Funding details
European CommissionEC
785907, 945539, 826421, ERC 683049
Deutsche ForschungsgemeinschaftDFGCRC 1315, RI 2073/6‐1, CRC 936
National Institute on AgingNIAK76 AG054863

Effects of age, word frequency, and noise on the time course of spoken word recognition
(2020) Collabra: Psychology, 6 (1), art. no. 11, . 

Van Engen, K.J.^a , Dey, A.^b c , Runge, N.^a , Spehar, B.^d , Sommers, M.S.^a , Peelle, J.E.^d

^a Department of Psychological and Brain Sciences, Washington University, St. Louis, MO, United States
^b Department of Psychological and Brain Sciences, Washington University, St. Louis, MO, United States
^c Center for Vital Longevity, University of Texas, Dallas, TX, United States
^d Department of Otolaryngology, Washington University, St. Louis, MO, United States

Abstract
This study assessed the effects of age, word frequency, and background noise on the time course of lexical activation during spoken word recognition. Participants (41 young adults and 39 older adults) performed a visual world word recognition task while we monitored their gaze position. On each trial, four phonologically unrelated pictures appeared on the screen. A target word was presented auditorily following a carrier phrase (“Click on “), at which point participants were instructed to use the mouse to click on the picture that corresponded to the target word. High- and low-frequency words were presented in quiet to half of the participants. The other half heard the words in a low level of noise in which the words were still readily identifiable. Results showed that, even in the absence of phonological competitors in the visual array, high-frequency words were fixated more quickly than low-frequency words by both listener groups. Young adults were generally faster to fixate on targets compared to older adults, but the pattern of interactions among noise, word frequency, and listener age showed that older adults’ lexical activation largely matches that of young adults in a modest amount of noise. © 2020 University of California Press. All rights reserved.

Author Keywords
Aging;  Eyetracking;  Lexical frequency;  Noise;  Word recognition