The basolateral amygdala-anterior cingulate pathway contributes to depression-like behaviors and comorbidity with chronic pain behaviors in male mice
(2023) Nature Communications, 14 (1), art. no. 2198, .
Becker, L.J.a i , Fillinger, C.a , Waegaert, R.a , Journée, S.H.a , Hener, P.a , Ayazgok, B.a b , Humo, M.a , Karatas, M.a c , Thouaye, M.a , Gaikwad, M.a d , Degiorgis, L.c , Santin, M.N.c , Mondino, M.c , Barrot, M.a , Ibrahim, E.C.e , Turecki, G.f , Belzeaux, R.e g , Veinante, P.a , Harsan, L.A.c , Hugel, S.a , Lutz, P.-E.a h , Yalcin, I.a d
a Centre National de la Recherche Scientifique, Université de Strasbourg, Institut des Neurosciences Cellulaires et Intégratives, Strasbourg, France
b Department of Biochemistry, Faculty of Pharmacy, University of Hacettepe, Ankara, Turkey
c Laboratory of Engineering, Informatics and Imaging (ICube), Integrative multimodal imaging in healthcare (IMIS), CNRS, UMR 7357, University of Strasbourg, Strasbourg, France
d Department of Psychiatry and Neuroscience, Université Laval, Québec, QC G1V 0A6, Canada
e Aix-Marseille Univ, CNRS, INT, Inst Neurosci Timone, Marseille, France
f Department of Psychiatry, McGill University and Douglas Mental Health University Institute, Montreal, QC, Canada
g Department of Psychiatry, CHU de Montpellier, Montpellier, France
h Douglas Mental Health University Institute, Montreal, QC, Canada
i Department of Anesthesiology, Center for Clinical Pharmacology Washington University in St. Louis, St. Louis, MO, United States
Abstract
While depression and chronic pain are frequently comorbid, underlying neuronal circuits and their psychopathological relevance remain poorly defined. Here we show in mice that hyperactivity of the neuronal pathway linking the basolateral amygdala to the anterior cingulate cortex is essential for chronic pain-induced depression. Moreover, activation of this pathway in naive male mice, in the absence of on-going pain, is sufficient to trigger depressive-like behaviors, as well as transcriptomic alterations that recapitulate core molecular features of depression in the human brain. These alterations notably impact gene modules related to myelination and the oligodendrocyte lineage. Among these, we show that Sema4a, which was significantly upregulated in both male mice and humans in the context of altered mood, is necessary for the emergence of emotional dysfunction. Overall, these results place the amygdalo-cingulate pathway at the core of pain and depression comorbidity, and unravel the role of Sema4a and impaired myelination in mood control. © 2023, The Author(s).
Funding details
ANR-10-INBS-0009
Brain and Behavior Research FoundationBBRF24736
National Alliance for Research on Schizophrenia and DepressionNARSAD
Horizon 2020 Framework ProgrammeH2020
H2020 Marie Skłodowska-Curie ActionsMSCA955684
Agence Nationale de la RechercheANRANR-17- EURE-0022, ANR-18-CE19-0006-03, ANR-18-CE37-0004, ANR-19-CE37-0010
Fondation pour la Recherche MédicaleFRMFDT201805005527, FDT202012010622
Université de Strasbourg
Türkiye Bilimsel ve Teknolojik Araştırma KurumuTÜBİTAK
Fondation de France
Centre National de la Recherche ScientifiqueCNRSUPR3212
Hacettepe ÜniversitesiTBI-2018-17569
Document Type: Article
Publication Stage: Final
Source: Scopus
Comparison between gradients and parcellations for functional connectivity prediction of behavior
(2023) NeuroImage, 273, art. no. 120044, .
Kong, R.a b c d , Tan, Y.R.b , Wulan, N.a b c d , Ooi, L.Q.R.a b c d , Farahibozorg, S.-R.e , Harrison, S.e , Bijsterbosch, J.D.f , Bernhardt, B.C.g , Eickhoff, S.h i , Thomas Yeo, B.T.a b c d j
a Centre for Sleep and Cognition (CSC) & Centre for Translational Magnetic Resonance Research (TMR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore
b Department of Electrical and Computer Engineering, National University of Singapore, Singapore
c N.1 Institute for Health and Institute for Digital Medicine (WisDM), National University of Singapore, Singapore
d Integrative Sciences and Engineering Programme (ISEP), National University of Singapore, Singapore
e Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
f Department of Radiology, Washington University School of Medicine, St Louis, MO, United States
g McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada
h Institute for Systems Neuroscience, Medical Faculty, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany
i Institute of Neuroscience and Medicine, Brain & Behaviour (INM-7), Research Center Jülich, Jülich, Germany
j Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States
Abstract
Resting-state functional connectivity (RSFC) is widely used to predict behavioral measures. To predict behavioral measures, representing RSFC with parcellations and gradients are the two most popular approaches. Here, we compare parcellation and gradient approaches for RSFC-based prediction of a broad range of behavioral measures in the Human Connectome Project (HCP) and Adolescent Brain Cognitive Development (ABCD) datasets. Among the parcellation approaches, we consider group-average “hard” parcellations (Schaefer et al., 2018), individual-specific “hard” parcellations (Kong et al., 2021a), and an individual-specific “soft” parcellation (spatial independent component analysis with dual regression; Beckmann et al., 2009). For gradient approaches, we consider the well-known principal gradients (Margulies et al., 2016) and the local gradient approach that detects local RSFC changes (Laumann et al., 2015). Across two regression algorithms, individual-specific hard-parcellation performs the best in the HCP dataset, while the principal gradients, spatial independent component analysis and group-average “hard” parcellations exhibit similar performance. On the other hand, principal gradients and all parcellation approaches perform similarly in the ABCD dataset. Across both datasets, local gradients perform the worst. Finally, we find that the principal gradient approach requires at least 40 to 60 gradients to perform as well as parcellation approaches. While most principal gradient studies utilize a single gradient, our results suggest that incorporating higher order gradients can provide significant behaviorally relevant information. Future work will consider the inclusion of additional parcellation and gradient approaches for comparison. © 2023
Funding details
NUHSRO/2020/124/TMR/LOA
National Institutes of HealthNIHR01MH120080, U01DA041022, U01DA041025, U01DA041028, U01DA041048, U01DA041089, U01DA041093, U01DA041106, U01DA041117, U01DA041120, U01DA041134, U01DA041148, U01DA041156, U01DA041174, U01DA050987, U01DA050988, U01DA050989, U01DA051016, U01DA051018, U01DA051037, U01DA051038, U01DA051039, U24DA041123, U24DA041147
National Institute of Mental HealthNIMH
NIH Blueprint for Neuroscience Research
McDonnell Center for Systems Neuroscience
Wellcome TrustWT1U54MH091657, 203139/Z/16/Z
National Medical Research CouncilNMRCOFLCG19May-0035, STaR20nov-0003
Ministry of Health -SingaporeMOHCG21APR1009
National Research Foundation SingaporeNRF
Document Type: Article
Publication Stage: Final
Source: Scopus
Associations of environmental and lifestyle factors with spatial navigation in younger and older adults
(2023) Journal of the International Neuropsychological Society, 29 (4), pp. 377-387.
Maybrier, H.a , Palanca, B.J.A.b c d e , Head, D.a f
a Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, MO 63130, United States
b Center on Biological Rhythms and Sleep, Washington University in St. Louis, St. Louis, MO 63130, United States
c Department of Anesthesiology, Washington University in St. Louis, St. Louis, MO 63130, United States
d Department of Psychiatry, Washington University in St. Louis, St. Louis, MO 63130, United States
e Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO 63130, United States
f Department of Radiology, Washington University in St. Louis, St. Louis, MO 63130, United States
Abstract
Objective: Advanced age is associated with prominent impairment in allocentric navigation dependent on the hippocampus. This study examined whether age-related impairment in allocentric navigation and strategy selection was associated with sleep disruption or circadian rest-activity fragmentation. Further, we examined whether associations with navigation were moderated by perceived stress and physical activity. Method: Sleep fragmentation and total sleep time over the course of 1 week were assayed in younger (n = 42) and older (n = 37) adults via wrist actigraphy. Subsequently, participants completed cognitive mapping and route learning tasks, as well a measure of spontaneous navigation strategy selection. Measurements of perceived stress and an actigraphy-based index of physical activity were also obtained. Circadian rest-activity fragmentation was estimated via actigraphy post-hoc. Results: Age was associated with reduced cognitive mapping, route learning, allocentric strategy use, and total sleep time (ps <.01), replicating prior findings. Novel findings included that sleep fragmentation increased with advancing age (p =.009) and was associated with lower cognitive mapping (p =.022) within the older adult cohort. Total sleep time was not linearly associated with the navigation tasks (ps >.087). Post-hoc analyses revealed that circadian rest-activity fragmentation increased with advancing age within the older adults (p =.026) and was associated with lower cognitive mapping across the lifespan (p =.001) and within older adults (p =.005). Neither stress nor physical activity were robust moderators of sleep fragmentation associations with the navigation tasks (ps >.113). Conclusion: Sleep fragmentation and circadian rest-activity fragmentation are potential contributing factors to age effects on cognitive mapping within older adults. © 2022 INS. Published by Cambridge University Press.
Author Keywords
circadian rhythms; cognitive mapping; physical activity; route learning; sleep fragmentation
Funding details
National Institutes of HealthNIHR01AG057901
McDonnell Center for Systems Neuroscience
Document Type: Article
Publication Stage: Final
Source: Scopus
Distinct effects of two hearing loss–associated mutations in the sarcomeric myosin MYH7b
(2023) Journal of Biological Chemistry, 299 (5), art. no. 104631, .
Lee, L.A.a b , Barrick, S.K.c , Buvoli, A.E.a b , Walklate, J.d , Stump, W.T.c , Geeves, M.d , Greenberg, M.J.c , Leinwand, L.A.a b
a Molecular, Cellular, Developmental Biology Department, Boulder, CO, United States
b BioFrontiers Institute, Boulder, CO, United States
c Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, MO, United States
d School of Biosciences, University of Kent, Canterbury, United Kingdom
Abstract
For decades, sarcomeric myosin heavy chain proteins were assumed to be restricted to striated muscle where they function as molecular motors that contract muscle. However, MYH7b, an evolutionarily ancient member of this myosin family, has been detected in mammalian nonmuscle tissues, and mutations in MYH7b are linked to hereditary hearing loss in compound heterozygous patients. These mutations are the first associated with hearing loss rather than a muscle pathology, and because there are no homologous mutations in other myosin isoforms, their functional effects were unknown. We generated recombinant human MYH7b harboring the D515N or R1651Q hearing loss–associated mutation and studied their effects on motor activity and structural and assembly properties, respectively. The D515N mutation had no effect on steady-state actin-activated ATPase rate or load-dependent detachment kinetics but increased actin sliding velocity because of an increased displacement during the myosin working stroke. Furthermore, we found that the D515N mutation caused an increase in the proportion of myosin heads that occupy the disordered-relaxed state, meaning more myosin heads are available to interact with actin. Although we found no impact of the R1651Q mutation on myosin rod secondary structure or solubility, we observed a striking aggregation phenotype when this mutation was introduced into nonmuscle cells. Our results suggest that each mutation independently affects MYH7b function and structure. Together, these results provide the foundation for further study of a role for MYH7b outside the sarcomere. © 2023 The Authors
Author Keywords
actin; coiled-coil; kinetics; molecular motor; myopathy; myosin; SRX (super-relaxed state)
Funding details
National Institutes of HealthNIHF31DC017927, R01GM029090, R01HL141086
European CommissionEC
Horizon 2020777204
Document Type: Article
Publication Stage: Final
Source: Scopus
MEK Inhibition Synergizes with TYK2 Inhibitors in NF1-Associated Malignant Peripheral Nerve Sheath Tumors
(2023) Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 29 (8), pp. 1592-1604.
Borcherding, D.C.a , Amin, N.V.a , He, K.a , Zhang, X.a , Lyu, Y.a , Dehner, C.b , Bhatia, H.a , Gothra, A.a , Daud, L.a , Ruminski, P.a , Pratilas, C.A.c , Pollard, K.c , Sundby, T.d , Widemann, B.C.d , Hirbe, A.C.a e
a Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, United States
b Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States
c Division of Pediatric Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, Liberia
d Pediatric Oncology Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD, Liberia
e Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, United States
Abstract
PURPOSE: Malignant peripheral nerve sheath tumors (MPNST) are aggressive sarcomas with limited treatment options and poor survival rates. About half of MPNST cases are associated with the neurofibromatosis type 1 (NF1) cancer predisposition syndrome. Overexpression of TYK2 occurs in the majority of MPNST, implicating TYK2 as a therapeutic target. EXPERIMENTAL DESIGN: The effects of pharmacologic TYK2 inhibition on MPNST cell proliferation and survival were examined using IncuCyte live cell assays in vitro, and downstream actions were analyzed using RNA-sequencing (RNA-seq), qPCR arrays, and validation of protein changes with the WES automated Western system. Inhibition of TYK2 alone and in combination with MEK inhibition was evaluated in vivo using both murine and human MPNST cell lines, as well as MPNST PDX. RESULTS: Pharmacologic inhibition of TYK2 dose-dependently decreased proliferation and induced apoptosis over time. RNA-seq pathway analysis on TYK2 inhibitor-treated MPNST demonstrated decreased expression of cell cycle, mitotic, and glycolysis pathways. TYK2 inhibition resulted in upregulation of the MEK/ERK pathway gene expression, by both RNA-seq and qPCR array, as well as increased pERK1/2 levels by the WES Western system. The compensatory response was tested with dual treatment with TYK2 and MEK inhibitors, which synergistically decreased proliferation and increased apoptosis in vitro. Finally, combination therapy was shown to inhibit growth of MPNST in multiple in vivo models. CONCLUSIONS: These data provide the preclinical rationale for the development of a phase I clinical trial of deucravacitinib and mirdametinib in NF1-assosciated MPNST. ©2023 The Authors; Published by the American Association for Cancer Research.
Document Type: Article
Publication Stage: Final
Source: Scopus
Median Nerve Stimulation for Treatment of Tics: Randomized, Controlled, Crossover Trial
(2023) Journal of Clinical Medicine, 12 (7), art. no. 2514, . Cited 1 time.
Iverson, A.M.a , Arbuckle, A.L.b , Ueda, K.c , Song, D.Y.d , Bihun, E.C.b , Koller, J.M.b , Wallendorf, M.e , Black, K.J.f
a Washington University School of Medicine, Washington University in St. Louis, St. Louis, MO 63110, United States
b Department of Psychiatry, Washington University in St. Louis, St. Louis, MO 63110, United States
c Department of Neurology, Washington University in St. Louis, St. Louis, MO 63110, United States
d University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, United States
e Division of Biostatistics, Institute for Informatics, Washington University in St. Louis, St. Louis, MO 63110, United States
f Departments of Psychiatry, Neurology, Radiology, and Neuroscience, Washington University in St. Louis, St. Louis, MO 63110, United States
Abstract
A prior study showed that rhythmic, but not arrhythmic, 12 Hz stimulation of the median nerve (MNS) entrained the sensorimotor cortex EEG signal and found that 10 Hz MNS improved tics in Tourette syndrome (TS). However, no control condition was tested, and stimulation blocks lasted only 1 min. We set out to replicate the TS results and to test whether tic improvement occurs by the proposed cortical entrainment mechanism. Preregistration was completed at ClinicalTrials.gov, under number NCT04731714. Thirty-two people with TS, age 15–64, completed two study visits with repeated MNS on and off blocks in random order, one visit for rhythmic and one for arrhythmic MNS. Subjects and staff were blind to order; a video rater was additionally blind to stimulation and to the order of visits and blocks. Rhythmic MNS at 10 Hz improved tics. Both rhythmic and arrhythmic 12 Hz MNS improved tic frequency, intensity, and urges, but the two treatments did not differ significantly. Participant masking was effective, and there was no carryover effect. Several participants described a dramatic benefit. Discomfort was minimal. There was no evidence that the MNS benefit persisted after stimulation ended. These results replicate the tic benefit from MNS but show that the EEG entrainment hypothesis cannot explain that benefit. Another electrophysiological mechanism may explain the benefit; alternatively, these data do not exclude a placebo effect. © 2023 by the authors.
Author Keywords
crossover studies; randomized controlled trial; tic disorders/therapy; Tourette syndrome/therapy; transcutaneous electric nerve stimulation
Funding details
National Institutes of HealthNIHUL1TR002345
National Cancer InstituteNCIP30CA091842
University of WashingtonUW
Institute of Clinical and Translational SciencesICTS
Alvin J. Siteman Cancer Center
Document Type: Article
Publication Stage: Final
Source: Scopus
Median Nerve Stimulation for Treatment of Tics: A 4-Week Open Trial with Ecological Momentary Assessment
(2023) Journal of Clinical Medicine, 12 (7), art. no. 2545, .
Iverson, A.M.a , Arbuckle, A.L.b , Song, D.Y.c , Bihun, E.C.b , Black, K.J.d
a Washington University School of Medicine, Washington University in St. Louis, St. Louis, MO 63110, United States
b Department of Psychiatry, Washington University in St. Louis, St. Louis, MO 63110, United States
c University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, United States
d Departments of Psychiatry, Neurology, Radiology and Neuroscience, Washington University in St. Louis, St. Louis, MO 63110, United States
Abstract
Median nerve stimulation (MNS) at 10–12 Hz was recently proposed as a treatment for Tourette syndrome and other chronic tic disorders (TS/CTD). We report on 31 participants ages 15–64 with TS/CTD in an open-label, comparative (within-group, several time points) study of MNS (ClinicalTrials.gov registration number NCT05016765). Participants were recruited from completers of a randomized controlled trial (RCT) of MNS and were given a transcutaneous electrical nerve stimulation (TENS) unit to use as desired for 12 Hz MNS for 4 weeks. Participants were instructed to complete surveys regarding tic symptoms and stimulation discomfort before and after stimulation, as well as twice daily when randomly prompted by text message. Participants also completed an extensive final survey. Twenty-seven participants completed the study. Median device use was 1.5 days per week and 50 min per day used. Tic frequency improved during MNS (mean improvement: 1.0 on a 0–5 scale, p < 0.001), as did tic intensity (mean improvement: 0.9, p < 0.001). Mean discomfort was mild (1.2 on a 3-point scale). In total, 21 participants (78%) planned to continue using the device. Participants’ results in this study did not correlate significantly with their results in the blinded RCT. We found MNS to improve tic frequency and intensity with minimal side effects. © 2023 by the authors.
Author Keywords
clinical trial; median nerve stimulation; open label; persistent motor tic disorder; tic disorders; Tourette syndrome
Funding details
National Institutes of HealthNIHUL1 TR002345
National Cancer InstituteNCIP30 CA091842
Washington University in St. LouisWUSTL
University of WashingtonUW
Alvin J. Siteman Cancer Center
Document Type: Article
Publication Stage: Final
Source: Scopus
Bayesian Inference of Tissue Heterogeneity for Individualized Prediction of Glioma Growth
(2023) IEEE Transactions on Medical Imaging, pp. 1-1.
Liang, B.a , Tan, J.a , Lozenski, L.b , Hormuth II, D.A.c , Yankeelov, T.E.c , Villa, U.d , Faghihi, D.a
a Mechanical and Aerospace Engineering Department, University at Buffalo, Buffalo, NY, USA
b Electrical and Systems Engineering Department, Washington University in St. Louis, St. Louis, MO, USA
c Livestrong Cancer Institutes, Oden Institute for Computational Engineering and Sciences, The University of Texas at Austin, Austin, TX, USA
d Oden Institute for Computational Engineering and Sciences, The University of Texas at Austin, Austin, TX, USA
Abstract
Reliably predicting the future spread of brain tumors using imaging data and on a subject-specific basis requires quantifying uncertainties in data, biophysical models of tumor growth, and spatial heterogeneity of tumor and host tissue. This work introduces a Bayesian framework to calibrate the two-/three-dimensional spatial distribution of the parameters within a tumor growth model to quantitative magnetic resonance imaging (MRI) data and demonstrates its implementation in a pre-clinical model of glioma. The framework leverages an atlas-based brain segmentation of grey and white matter to establish subject-specific priors and tunable spatial dependencies of the model parameters in each region. Using this framework, the tumor-specific parameters are calibrated from quantitative MRI measurements early in the course of tumor development in four rats and used to predict the spatial development of the tumor at later times. The results suggest that the tumor model, calibrated by animal-specific imaging data at one time point, can accurately predict tumor shapes with a Dice coefficient > 0.89. However, the reliability of the predicted volume and shape of tumors strongly relies on the number of earlier imaging time points used for calibrating the model. This study demonstrates, for the first time, the ability to determine the uncertainty in the inferred tissue heterogeneity and the model-predicted tumor shape. IEEE
Author Keywords
biophysical tumor model; Brain modeling; Computational modeling; Computational oncology; Data models; Magnetic resonance imaging; Predictive models; quantitative MRI; Rats; tumor shape prediction; Tumors; uncertainty quantification
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Cognitive fusion accounts for the relation of anxiety sensitivity cognitive concerns and rumination
(2023) Current Psychology, .
Anderberg, J.L.a , Baker, L.D.b , Kalantar, E.A.a , Berghoff, C.R.c
a Department of Psychology, University of South Dakota, Vermillion, SD, United States
b Department of Mental Health Service, George E. Wahlen VA Medical Center, Salt Lake City, UT, United States
c School of Medicine, Division of Gastroenterology, Washington University in St. Louis, Saint Louis, MO, United States
Abstract
Rumination is a transdiagnostic construct associated with poor outcomes broadly. Though extant research indicates anxiety sensitivity (AS) cognitive concerns is associated with, and a risk factor for, excessive rumination, behavioral constructs that may account for this relation have not been specified. Cognitive fusion may be one such construct, in that individuals with high AS cognitive concerns may become overly entangled in and influenced by unwanted cognition, leading to rumination. However, relations of AS cognitive concerns, cognitive fusion, and rumination have not been identified. The present study aimed to identify the variance accounted for by cognitive fusion in the AS cognitive concerns-rumination relation using conditional process analysis on cross-sectional data provided by college students (N = 368). All variables were positively correlated, and bootstrapped analyses indicated cognitive fusion accounted for significant variance in the relation of AS cognitive concerns and rumination, ab = 1.03, SE = 0.11, 95% CI [0.82, 1.26]. Additional research evaluating the applicability of cognitive fusion as an intervention strategy for individuals struggling with high AS cognitive concerns and rumination appears warranted. © 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Author Keywords
Anxiety sensitivity; Anxiety sensitivity cognitive concerns; Cognitive fusion; Conditional process analysis; Mediation; Rumination
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Plasma amyloid-β42/40 and apolipoprotein E for amyloid PET pre-screening in secondary prevention trials of Alzheimer’s disease
(2023) Brain Communications, 5 (2), art. no. fcad015, .
Cullen, N.C.a , Janelidze, S.a , Stomrud, E.a b , Bateman, R.J.c , Palmqvist, S.a b , Hansson, O.a b , Mattsson-Carlgren, N.a d e
a Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Faculty of Medicine, Lund University, Lund, 202 13, Sweden
b Memory Clinic, Skane University Hospital, Malmö, 205 02, Sweden
c Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, United States
d Department of Neurology, Skane University Hospital, Lund, 221 85, Sweden
e Wallenberg Center for Molecular Medicine, Lund University, Lund, 221 84, Sweden
Abstract
The extent to which newly developed blood-based biomarkers could reduce screening costs in secondary prevention trials of Alzheimer’s disease is mostly unexplored. We collected plasma amyloid-β42/40, apolipoprotein E ϵ4 status and amyloid PET at baseline in 181 cognitively unimpaired participants [the age of 72.9 (5.3) years; 61.9% female; education of 11.9 (3.4) years] from the Swedish BioFINDER-1 study. We tested whether a model predicting amyloid PET status from plasma amyloid-β42/40, apolipoprotein E status and age (combined) reduced cost of recruiting amyloid PET + cognitively unimpaired participants into a theoretical trial. We found that the percentage of cognitively unimpaired participants with an amyloid PET + scan rose from 29% in an unscreened population to 64% [(49, 79); P < 0.0001] when using the biomarker model to screen for high risk for amyloid PET + status. In simulations, plasma screening also resulted in a 54% reduction of the total number of amyloid PET scans required and reduced total recruitment costs by 43% [(31, 56), P < 0.001] compared to no pre-screening when assuming a 16× PET-to-plasma cost ratio. Total savings remained significant when the PET-to-plasma cost ratio was assumed to be 8× or 4×. This suggests that a simple plasma biomarker model could lower recruitment costs in Alzheimer’s trials requiring amyloid PET positivity for inclusion. © 2023 The Author(s). Published by Oxford University Press on behalf of the Guarantors of Brain.
Author Keywords
Alzheimer’s disease; amyloid; clinical trials; PET; plasma biomarkers
Document Type: Article
Publication Stage: Final
Source: Scopus
The separate and joint effects of recent interpersonal abuse and cannabis use on psychotic experiences: findings from students in higher education in the United States
(2023) Social Psychiatry and Psychiatric Epidemiology, .
Oh, H.a , Du, J.b , Karcher, N.R.c , van der Ven, E.d , DeVylder, J.E.e , Smith, L.f , Koyanagi, A.g h
a Suzanne Dworak Peck School of Social Work, University of Southern California, Los Angeles, United States
b Southern Methodist University, Dallas, United States
c Department of Psychiatry, Washington University in St. Louis School of Medicine, St. Louis, United States
d Department of Clinical, Neuro- and Developmental Psychology, Vrije Universiteit Amsterdam, Amsterdam, Netherlands
e School of Social Service, Fordham University, New York, United States
f Centre for Health, Performance and Wellbeing, Anglia Ruskin University, Cambridge, United Kingdom
g Research and Development Unit, Parc Sanitari Sant Joan de Déu, CIBERSAM, ISCIII, Barcelona, Spain
h ICREA, Barcelona, Spain
Abstract
Background: Various forms of interpersonal abuse (e.g., physical, emotional, sexual) and cannabis use across the lifespan have both been known to increase odds of psychotic experiences; however, there have been few studies examining their separate and joint effects in the United States. Methods: We analyzed data from the Healthy Minds Study (2020–2021) and used multivariable logistic regression and interaction contrast ratios to assess separate and joint effects of interpersonal abuse (past 12 months) and cannabis use (past 30 days) on psychotic experiences (past 12 months). Results: Students who only used cannabis had significantly greater odds of psychotic experiences (aOR: 1.70; 95% CI 1.58–1.82), as well as those who only experienced interpersonal abuse (aOR: 2.40; 95% CI 2.25–2.56). However, those who reported both cannabis use and interpersonal abuse had the greatest odds, exceeding the sum of these individual effects (the combined effect aOR: 3.46; 95% CI 3.19–3.76). Conclusions: Recent interpersonal abuse and recent cannabis use both separately and jointly increase odds of having recent psychotic experiences. Future research should continue to examine the potential interactive and additive impact of multiple known exposures to better inform primary and secondary prevention efforts. © 2023, The Author(s).
Author Keywords
Adversity; Cannabis; Interpersonal abuse; Psychosis; Trauma
Funding details
National Institute of Mental HealthNIMHK23MH121792
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
QuNex—An integrative platform for reproducible neuroimaging analytics
(2023) Frontiers in Neuroinformatics, 17, art. no. 1104508, .
Ji, J.L.a b , Demšar, J.c d , Fonteneau, C.a , Tamayo, Z.a , Pan, L.a , Kraljič, A.d , Matkovič, A.d , Purg, N.d , Helmer, M.a b , Warrington, S.e , Winkler, A.f , Zerbi, V.g h , Coalson, T.S.i , Glasser, M.F.i j , Harms, M.P.k , Sotiropoulos, S.N.e l , Murray, J.D.a m , Anticevic, A.a n , Repovš, G.d
a Department of Psychiatry, Yale University School of Medicine, New Haven, CT, United States
b Manifest Technologies, North Haven, CT, United States
c Faculty of Computer and Information Science, University of Ljubljana, Ljubljana, Slovenia
d Department of Psychology, Faculty of Arts, University of Ljubljana, Ljubljana, Slovenia
e Sir Peter Mansfield Imaging Centre, School of Medicine, University of Nottingham, Nottingham, United Kingdom
f Department of Human Genetics, The University of Texas Rio Grande Valley, Brownsville, TX, United States
g Centre for Biomedical Imaging (CIBM), Lausanne, Switzerland
h Neuro-X Institute, School of Engineering (STI), EPFL, Lausanne, Switzerland
i Department of Neuroscience, Washington University in St. Louis, St. Louis, MO, United States
j Department of Radiology, Washington University in St. Louis, St. Louis, MO, United States
k Department of Psychiatry, Washington University in St. Louis, St. Louis, MO, United States
l Nottingham NIHR Biomedical Research Centre, Queen’s Medical Centre, University of Nottingham, Nottingham, United Kingdom
m Department of Physics, Yale University, New Haven, CT, United States
n Department of Psychology, Yale University School of Medicine, New Haven, CT, United States
Abstract
Introduction: Neuroimaging technology has experienced explosive growth and transformed the study of neural mechanisms across health and disease. However, given the diversity of sophisticated tools for handling neuroimaging data, the field faces challenges in method integration, particularly across multiple modalities and species. Specifically, researchers often have to rely on siloed approaches which limit reproducibility, with idiosyncratic data organization and limited software interoperability. Methods: To address these challenges, we have developed Quantitative Neuroimaging Environment & Toolbox (QuNex), a platform for consistent end-to-end processing and analytics. QuNex provides several novel functionalities for neuroimaging analyses, including a “turnkey” command for the reproducible deployment of custom workflows, from onboarding raw data to generating analytic features. Results: The platform enables interoperable integration of multi-modal, community-developed neuroimaging software through an extension framework with a software development kit (SDK) for seamless integration of community tools. Critically, it supports high-throughput, parallel processing in high-performance compute environments, either locally or in the cloud. Notably, QuNex has successfully processed over 10,000 scans across neuroimaging consortia, including multiple clinical datasets. Moreover, QuNex enables integration of human and non-human workflows via a cohesive translational platform. Discussion: Collectively, this effort stands to significantly impact neuroimaging method integration across acquisition approaches, pipelines, datasets, computational environments, and species. Building on this platform will enable more rapid, scalable, and reproducible impact of neuroimaging technology across health and disease. Copyright © 2023 Ji, Demšar, Fonteneau, Tamayo, Pan, Kraljič, Matkovič, Purg, Helmer, Warrington, Winkler, Zerbi, Coalson, Glasser, Harms, Sotiropoulos, Murray, Anticevic and Repovš.
Author Keywords
cloud integration; containerization; data processing; diffusion MRI; functional MRI; high-performance computing; multi-modal analyses; neuroimaging
Funding details
National Science FoundationNSF2015276
National Institutes of HealthNIH1U01MH121766, 5R01MH108590, 5R01MH112189, DP5OD012109-01, R01MH112746
National Institute on Alcohol Abuse and AlcoholismNIAAA2P50AA012870-11, 5R24MH122820, AG052564, MH109589, R24MH108315
Brain and Behavior Research FoundationBBRF
American Roentgen Ray SocietyARRSJ7-6829, J7-8275, P3-0338
Wellcome TrustWT217266/Z/19/Z
Simons Foundation Autism Research InitiativeSFARI
European Research CouncilERC101000969
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungSNFPCEFP3_203005
Javna Agencija za Raziskovalno Dejavnost RSARRS
Document Type: Article
Publication Stage: Final
Source: Scopus
A somato-cognitive action network alternates with effector regions in motor cortex
(2023) Nature, .
Gordon, E.M.a , Chauvin, R.J.b , Van, A.N.b c , Rajesh, A.a , Nielsen, A.b , Newbold, D.J.b d , Lynch, C.J.e , Seider, N.A.b f , Krimmel, S.R.b , Scheidter, K.M.b , Monk, J.b , Miller, R.L.b f , Metoki, A.b , Montez, D.F.b , Zheng, A.b , Elbau, I.e , Madison, T.g , Nishino, T.f , Myers, M.J.f , Kaplan, S.b , Badke D’Andrea, C.a f h , Demeter, D.V.h , Feigelis, M.h , Ramirez, J.S.B.i , Xu, T.i , Barch, D.M.a f j , Smyser, C.D.a b k , Rogers, C.E.e k , Zimmermann, J.l , Botteron, K.N.f , Pruett, J.R.f , Willie, J.T.b e m , Brunner, P.c m , Shimony, J.S.a , Kay, B.P.b , Marek, S.a , Norris, S.A.a b , Gratton, C.n , Sylvester, C.M.f , Power, J.D.e , Liston, C.e , Greene, D.J.h , Roland, J.L.m , Petersen, S.E.a b c j o , Raichle, M.E.a b c j o , Laumann, T.O.f , Fair, D.A.g p q , Dosenbach, N.U.F.a b c j k r
a Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, MO, United States
b Department of Neurology, Washington University School of Medicine, St Louis, MO, United States
c Department of Biomedical Engineering, Washington University in St. Louis, St Louis, MO, United States
d Department of Neurology, New York University Langone Medical Center, New York, NY, United States
e Department of Psychiatry, Weill Cornell Medicine, New York, NY, United States
f Department of Psychiatry, Washington University School of Medicine, St Louis, MO, United States
g Department of Pediatrics, University of Minnesota, Minneapolis, MN, United States
h Department of Cognitive Science, University of California San Diego, La Jolla, CA, United States
i Center for the Developing Brain, Child Mind Institute, New York, NY, United States
j Department of Psychological and Brain Sciences, Washington University in St. Louis, St Louis, MO, United States
k Department of Pediatrics, Washington University School of Medicine, St Louis, MO, United States
l Department of Neuroscience, University of Minnesota, Minneapolis, MN, United States
m Department of Neurosurgery, Washington University School of Medicine, St Louis, MO, United States
n Department of Psychology, Florida State University, Tallahassee, FL, United States
o Department of Neuroscience, Washington University School of Medicine, St Louis, MO, United States
p Masonic Institute for the Developing Brain, University of Minnesota, Minneapolis, MN, United States
q Institute of Child Development, University of Minnesota, Minneapolis, MN 55455, United States
r Program in Occupational Therapy, Washington University in St. Louis, St Louis, MO, United States
Abstract
Motor cortex (M1) has been thought to form a continuous somatotopic homunculus extending down the precentral gyrus from foot to face representations1,2, despite evidence for concentric functional zones3 and maps of complex actions4. Here, using precision functional magnetic resonance imaging (fMRI) methods, we find that the classic homunculus is interrupted by regions with distinct connectivity, structure and function, alternating with effector-specific (foot, hand and mouth) areas. These inter-effector regions exhibit decreased cortical thickness and strong functional connectivity to each other, as well as to the cingulo-opercular network (CON), critical for action5 and physiological control6, arousal7, errors8 and pain9. This interdigitation of action control-linked and motor effector regions was verified in the three largest fMRI datasets. Macaque and pediatric (newborn, infant and child) precision fMRI suggested cross-species homologues and developmental precursors of the inter-effector system. A battery of motor and action fMRI tasks documented concentric effector somatotopies, separated by the CON-linked inter-effector regions. The inter-effectors lacked movement specificity and co-activated during action planning (coordination of hands and feet) and axial body movement (such as of the abdomen or eyebrows). These results, together with previous studies demonstrating stimulation-evoked complex actions4 and connectivity to internal organs10 such as the adrenal medulla, suggest that M1 is punctuated by a system for whole-body action planning, the somato-cognitive action network (SCAN). In M1, two parallel systems intertwine, forming an integrate–isolate pattern: effector-specific regions (foot, hand and mouth) for isolating fine motor control and the SCAN for integrating goals, physiology and body movement. © 2023, The Author(s).
Funding details
National Science FoundationNSFBCS-2048066
National Institutes of HealthNIHDA04112, DA041148, DA047851, DA048742, EB031765, HD055741, HD088125, HD103525, MH096773, MH100019, MH113883, MH114976, MH115357, MH116961, MH118362, MH118370, MH118388, MH120194, MH120989, MH121276, MH121462, MH121518, MH122066, MH122389, MH124567, MH128177, MH128696, MH129426, MH129493, MH129616, NS088590, NS098482, NS110332, NS123345, NS124789, NS129521
Dystonia Medical Research FoundationDMRF
Intellectual and Developmental Disabilities Research CenterIDDRC
Dysphonia InternationalNSDA
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
A Phenome-Wide Association Study (PheWAS) of Late Onset Alzheimer Disease Genetic Risk in Children of European Ancestry at Middle Childhood: Results from the ABCD Study
(2023) Behavior Genetics, .
Gorelik, A.J.a , Paul, S.E.a , Karcher, N.R.b , Johnson, E.C.b , Nagella, I.a , Blaydon, L.a , Modi, H.a , Hansen, I.S.b , Colbert, S.M.C.b , Baranger, D.A.A.a , Norton, S.A.a , Spears, I.a , Gordon, B.c d , Zhang, W.c , Hill, P.L.a , Oltmanns, T.F.a , Bijsterbosch, J.D.c , Agrawal, A.b , Hatoum, A.S.a , Bogdan, R.a
a Department of Psychological and Brain Sciences, Washington University in Saint Louis, One Booking Drive, St. Louis, MO 63130, United States
b Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
c Department of Radiology, Washington University in Saint Louis, 660 South Euclid Ave, Box 8225, St. Louis, MO 63110, United States
d Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University, St Louis, MO, United States
Abstract
Genetic risk for Late Onset Alzheimer Disease (AD) has been associated with lower cognition and smaller hippocampal volume in healthy young adults. However, whether these and other associations are present during childhood remains unclear. Using data from 5556 genomically-confirmed European ancestry youth who completed the baseline session of the ongoing the Adolescent Brain Cognitive DevelopmentSM Study (ABCD Study®), our phenome-wide association study estimating associations between four indices of genetic risk for late-onset AD (i.e., AD polygenic risk scores (PRS), APOE rs429358 genotype, AD PRS with the APOE region removed (ADPRS-APOE), and an interaction between ADPRS-APOE and APOE genotype) and 1687 psychosocial, behavioral, and neural phenotypes revealed no significant associations after correction for multiple testing (all ps > 0.0002; all pfdr > 0.07). These data suggest that AD genetic risk may not phenotypically manifest during middle-childhood or that effects are smaller than this sample is powered to detect. © 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Author Keywords
Alzheimer disease; APOE; Imaging; Middle childhood; Phenome-wide association study; Polygenic risk scores
Funding details
National Science FoundationNSFDGE-213989, F31AA029934, K01AA030083, K01DA051759, K23MH12179201
National Institutes of HealthNIHU01DA041022, U01DA041025, U01DA041028, U01DA041048, U01DA041089, U01DA041093, U01DA041106, U01DA041117, U01DA041120, U01DA041134, U01DA041148, U01DA041156, U01DA041174, U24DA041123, U24DA041147
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Cerebral revascularization surgery reduces cerebrovascular events in children with sickle cell disease and moyamoya syndrome: Results of the stroke in sickle cell revascularization surgery retrospective study
(2023) Pediatric Blood and Cancer, .
Aldana, P.R.a , Hanel, R.A.b , Piatt, J.c , Han, S.H.d , Bansal, M.M.e , Schultz, C.f , Gauger, C.e , Pederson, J.M.g h , Iii, J.C.W.i , Hulbert, M.L.j , Jordan, L.C.k , Qureshi, A.l , Garrity, K.a , Robert, A.P.a , Hatem, A.a , Stein, J.d , Beydler, E.d , Adelson, P.D.m , Greene, S.n , Grabb, P.o , Johnston, J.p , Lang, S.-S.q , Leonard, J.r , Magge, S.N.s , Scott, A.t , Shah, S.u , Smith, E.R.v , Smith, J.w , Strahle, J.t , Vadivelu, S.x , Webb, J.y , Wrubel, D.z
a Department of Neurosurgery, University of Florida College of Medicine – Jacksonville and Wolfson Children’s Hospital, Jacksonville, FL, United States
b Lyerly Neurosurgery, Baptist Neurological Institute, Jacksonville, FL, United States
c Division of Neurosurgery, Nemours Neuroscience Center, A.I. duPont Hospital for Children, Wilmington, DE, United States
d University of Florida College of Medicine, Gainesville, FL, United States
e Department of Pediatric Hematology/Oncology, Nemours Children’s Health System and Wolfson Children’s Hospital, Jacksonville, FL, United States
f Department of Pediatrics, Nemours Center for Cancer and Blood Disorders, Nemours Children’s Hospital, Wilmington, DE, United States
g Superior Medical Experts, St. Paul, MN, United States
h Nested Knowledge, St. Paul, MN, United States
i Division of Pediatric Neurological Surgery, Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, TN, United States
j Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, United States
k Division of Pediatric Neurology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, United States
l Department of Neurology, Zeenat Qureshi Stroke Institute, University of Missouri, Columbia, MO, United States
m Barrow Neurological Institute, Phoenix Children’s Hospital, Phoenix, AZ, United States
n Department of Neurosurgery, Children’s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
o Department of Neurosurgery, Children’s Mercy Hospital, Kansas, MO, United States
p Department of Neurosurgery, Children’s Hospital of Alabama, Birmingham, AL, United States
q Department of Neurosurgery and Pediatric Neurosurgery, University of Pennsylvania School of Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA, United States
r Department of Neurosurgery, Nationwide Children’s Hospital, Columbus, OH, United States
s Department of Neurosurgery, CHOC Neuroscience Institute, Children’s Health of Orange County, Orange, CA, United States
t Department of Neurosurgery, Washington University School of Medicine, Washington University in Saint Louis, St Louis, MO, United States
u Department of Pediatric Hematology/Oncology, Phoenix Children’s Hospital, Phoenix, AZ, United States
v Department of Neurosurgery, Children’s Hospital Boston, and Harvard Medical School, Boston, MA, United States
w Department of Pediatric Neurosurgery, Goodman Campbell Brain and Spine, Peyton Manning Children’s Hospital, Indianapolis, IN, United States
x Division of Neurosurgery, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United States
y Department of Hematology/Oncology, Children’s National Hospital, Washington, DC, United States
z Department of Neurosurgery, Children’s Healthcare of Atlanta, Egleston Hospital, Atlanta, GA, United States
Abstract
Background: Recent studies suggest that cerebral revascularization surgery may be a safe and effective therapy to reduce stroke risk in patients with sickle cell disease and moyamoya syndrome (SCD–MMS). Methods: We performed a multicenter, retrospective study of children with SCD–MMS treated with conservative management alone (conservative group)—chronic blood transfusion and/or hydroxyurea—versus conservative management plus surgical revascularization (surgery group). We monitored cerebrovascular event (CVE) rates—a composite of strokes and transient ischemic attacks. Multivariable logistic regression was used to compare CVE occurrence and multivariable Poisson regression was used to compare incidence rates between groups. Covariates in multivariable models included age at treatment start, age at moyamoya diagnosis, antiplatelet use, CVE history, and the risk period length. Results: We identified 141 patients with SCD–MMS, 78 (55.3%) in the surgery group and 63 (44.7%) in the conservative group. Compared with the conservative group, preoperatively the surgery group had a younger age at moyamoya diagnosis, worse baseline modified Rankin scale scores, and increased prevalence of CVEs. Despite more severe pretreatment disease, the surgery group had reduced odds of new CVEs after surgery (odds ratio = 0.27, 95% confidence interval [CI] = 0.08–0.94, p =.040). Furthermore, comparing surgery group patients during presurgical versus postsurgical periods, CVEs odds were significantly reduced after surgery (odds ratio = 0.22, 95% CI = 0.08–0.58, p =.002). Conclusions: When added to conservative management, cerebral revascularization surgery appears to reduce the risk of CVEs in patients with SCD–MMS. A prospective study will be needed to validate these findings. © 2023 Wiley Periodicals LLC.
Author Keywords
cerebrovascular event; encephalo-duro-arterio-synangiosis; moyamoya syndrome; revascularization surgery; sickle cell disease; stroke
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Prior Sexual Trauma Exposure Impacts Posttraumatic Dysfunction and Neural Circuitry Following a Recent Traumatic Event in the AURORA Study
(2023) Biological Psychiatry Global Open Science, .
Rowland, G.E.a , Roeckner, A.b , Ely, T.D.b , Lebois, L.A.M.a c , van Rooij, S.J.H.b , Bruce, S.E.d , Jovanovic, T.e , House, S.L.f , Beaudoin, F.L.g h , An, X.i , Neylan, T.C.j k , Clifford, G.D.l m , Linnstaedt, S.D.i , Germine, L.T.c n o , Rauch, S.L.c n p , Haran, J.P.q , Storrow, A.B.r , Lewandowski, C.s , Musey, P.I., Jr.t , Hendry, P.L.u , Sheikh, S.u , Jones, C.W.v , Punches, B.E.w x , Kurz, M.C.y z aa , Gentile, N.T.ab , Hudak, L.A.ac , Pascual, J.L.ad ae af , Seamon, M.J.af ag , Harris, E.ah , Pearson, C.ai , Merchant, R.C.aj , Domeier, R.M.ak , Rathlev, N.K.al , Sergot, P.am , Sanchez, L.D.aj an , Miller, M.W.ao ap , Pietrzak, R.H.aq ar , Joormann, J.as , Pizzagalli, D.A.a c , Sheridan, J.F.at au , Smoller, J.W.av aw , Harte, S.E.ax ay , Elliott, J.M.az ba bb , Kessler, R.C.bc , Koenen, K.C.bd , McLean, S.A.be bf , Ressler, K.J.a c , Stevens, J.S.b , Harnett, N.G.a c
a Division of Depression and Anxiety, McLean Hospital, Belmont, Massachusetts, United States
b Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Georgia, Atlanta, Georgia
c Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, United States
d Department of Psychological Sciences, University of Missouri – St. Louis, St. Louis, Missouri, United States
e Department of Psychiatry and Behavioral Neurosciences, Wayne State University, Detroit, MI, United States
f Department of Emergency Medicine, Washington University School of Medicine, St. Louis, Missouri, United States
g Department of Epidemiology, Brown University, Providence, Rhode Island, United States
h Department of Emergency Medicine, Brown University, Providence, Rhode Island, United States
i Institute for Trauma Recovery, Department of Anesthesiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
j Department of Psychiatry, University of California, San Francisco, San Francisco, California, United States
k Department of Neurology, University of California, San Francisco, San Francisco, California, United States
l Department of Biomedical Informatics, Emory University School of Medicine, Georgia, Atlanta, Georgia
m Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Georgia, Atlanta, Georgia
n Institute for Technology in Psychiatry, McLean Hospital, Belmont, Massachusetts, United States
o TheMany Brains Project, Belmont, Massachusetts, United States
p Department of Psychiatry, McLean Hospital, Belmont, Massachusetts, United States
q Department of Emergency Medicine, University of Massachusetts Chan Medical School, Worcester, Massachusetts, United States
r Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, TN, United States
s Department of Emergency Medicine, Henry Ford Health System, Detroit, MI, United States
t Department of Emergency Medicine, Indiana University School of Medicine, Indianapolis, IN, United States
u Department of Emergency Medicine, University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, United States
v Department of Emergency Medicine, Cooper Medical School of Rowan University, Camden, New Jersey, United States
w Department of Emergency Medicine, Ohio State University College of Medicine, Columbus, OH, United States
x Ohio State University College of Nursing, Columbus, OH, United States
y Department of Emergency Medicine, University of Alabama School of Medicine, Birmingham, Alabama, United States
z Division of Acute Care Surgery, Department of Surgery, University of Alabama School of Medicine, Birmingham, Alabama, United States
aa Center for Injury Science, University of Alabama at Birmingham, Birmingham, Alabama, United States
ab Department of Emergency Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, United States
ac Department of Emergency Medicine, Emory University School of Medicine, Georgia, Atlanta, Georgia
ad Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, United States
ae Department of Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania, United States
af Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States
ag Division of Traumatology, Department of Surgery, Surgical Critical Care and Emergency Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, United States
ah Einstein Medical Center, Philadelphia, Pennsylvania, United States
ai Department of Emergency Medicine, Wayne State University, Ascension St. John Hospital, Detroit, MI, United States
aj Department of Emergency Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, United States
ak Department of Emergency Medicine, Saint Joseph Mercy Hospital, Ypsilanti, MI, United States
al Department of Emergency Medicine, University of Massachusetts Medical School-Baystate, Springfield, Massachusetts, United States
am Department of Emergency Medicine, McGovern Medical School at UTHealth, Houston, Texas, United States
an Department of Emergency Medicine, Harvard Medical School, Boston, Massachusetts, United States
ao National Center for PTSD, Behavioral Science Division, VA Boston Healthcare System, Boston, Massachusetts, United States
ap Department of Psychiatry, Boston University School of Medicine, Boston, Massachusetts, United States
aq National Center for PTSD, Clinical Neurosciences Division, VA Connecticut Healthcare System, West Haven, CT, United States
ar Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut, United States
as Department of Psychology, Yale University, New Haven, Connecticut, United States
at Division of Biosciences, Ohio State University College of Dentistry, Columbus, OH, United States
au Institute for Behavioral Medicine Research, OSU Wexner Medical Center, Columbus, OH, United States
av Department of Psychiatry, Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts, United States
aw Stanley Center for Psychiatric Research, Broad Institute, Cambridge, Massachusetts, United States
ax Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, MI, United States
ay Department of Internal Medicine-Rheumatology, University of Michigan Medical School, Ann Arbor, MI, United States
az Kolling Institute, University of Sydney, St. Leonards, Sydney, NSW, Australia
ba Faculty of Medicine and Health, University of Sydney, Northern Sydney Local Health District, Sydney, NSW, Australia
bb Physical Therapy & Human Movement Sciences, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States
bc Department of Health Care Policy, Harvard Medical School, Boston, Massachusetts, United States
bd Department of Epidemiology, Harvard TH Chan School of Public Health, Harvard University, Boston, Massachusetts, United States
be Department of Emergency Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
bf Department of Psychiatry, Institute for Trauma Recovery, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
Abstract
Background: Prior sexual trauma (ST) is associated with greater risk for posttraumatic stress disorder after a subsequent traumatic event; however, the underlying neurobiological mechanisms remain opaque. We investigated longitudinal posttraumatic dysfunction and amygdala functional dynamics following admission to an emergency department for new primarily nonsexual trauma in participants with and without previous ST. Methods: Participants (N = 2178) were recruited following acute trauma exposure (primarily motor vehicle collision). A subset (n = 242) completed magnetic resonance imaging that included a fearful faces task and a resting-state scan 2 weeks after the trauma. We investigated associations between prior ST and several dimensions of posttraumatic symptoms over 6 months. We further assessed amygdala activation and connectivity differences between groups with or without prior ST. Results: Prior ST was associated with greater posttraumatic depression (F1,1120 = 28.35, p = 1.22 × 10−7, ηp2 = 0.06), anxiety (F1,1113 = 17.43, p = 3.21 × 10−5, ηp2 = 0.05), and posttraumatic stress disorder (F1,1027 = 11.34, p = 7.85 × 10−4, ηp2 = 0.04) severity and more maladaptive beliefs about pain (F1,1113 = 8.51, p = .004, ηp2 = 0.02) but was not related to amygdala reactivity to fearful versus neutral faces (all ps > .05). A secondary analysis revealed an interaction between ST and lifetime trauma load on the left amygdala to visual cortex connectivity (peak Z value: −4.41, corrected p < .02). Conclusions: Findings suggest that prior ST is associated with heightened posttraumatic dysfunction following a new trauma exposure but not increased amygdala activity. In addition, ST may interact with lifetime trauma load to alter neural circuitry in visual processing regions following acute trauma exposure. Further research should probe the relationship between trauma type and visual circuitry in the acute aftermath of trauma. © 2023 The Authors
Author Keywords
Longitudinal study; Neuroimaging; Posttraumatic stress disorder; Sexual trauma
Funding details
National Institute of Mental HealthNIMHK00MH119603, U01MH110925
MAYDAY Fund
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Plasma inflammation for predicting phenotypic conversion and clinical progression of autosomal dominant frontotemporal lobar degeneration
(2023) Journal of Neurology, Neurosurgery and Psychiatry, art. no. jnnp-2022-330866, .
Asken, B.M.a b , Ljubenkov, P.A.b , Staffaroni, A.M.b , Casaletto, K.B.b , Vandevrede, L.b , Cobigo, Y.b , Rojas-Rodriguez, J.C.b , Rankin, K.P.b , Kornak, J.c , Heuer, H.b , Shigenaga, J.d , Appleby, B.S.e , Bozoki, A.C.f , Domoto-Reilly, K.g , Ghoshal, N.h , Huey, E.i , Litvan, I.j , Masdeu, J.C.k , Mendez, M.F.l , Pascual, B.k , Pressman, P.m , Tartaglia, M.C.n o , Kremers, W.p , Forsberg, L.K.q , Boeve, B.F.q , Boxer, A.L.b , Rosen, H.J.b , Kramer, J.H.b
a Department of Clinical and Health Psychology, 1Florida Alzheimer’s Disease Research Center, Fixel Institute for Neurological Diseases, University of Florida, Gainesville, FL, United States
b Department of Neurology, Weill Institute for Neurosciences, Memory and Aging Center, University of California, San Francisco, CA, United States
c Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, United States
d Department of Medicine, Veterans Affairs Health Care System, San Francisco, CA, United States
e Departments of Neurology, Psychiatry, and Pathology, Case Western Reserve, Cleveland, OH, United States
f Department of Neurology, University of North Carolina, Chapel Hill, NC, United States
g Department of Neurology, University of Washington School of Medicine, Seattle, WA, United States
h Department of Neurology, Washington University, St. Louis, MO, United States
i Departments of Psychiatry and Neurology, Columbia University, New York, NY, United States
j Department of Neurology, University of California, San Diego, San Diego, CA, United States
k Department of Neurology, Nantz National Alzheimer Center, Houston Methodist, Houston, TX, United States
l Department of Neurology, University of California, Los Angeles, CA, United States
m Department of Neurology, University of Colorado Denver School of Medicine, Aurora, CO, United States
n Tanz Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, ON, Canada
o Canadian Sports Concussion Project, Toronto, ON, Canada
p Department of Quantitative Health Sciences, Division of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, MN, United States
q Department of Neurology, Mayo Clinic, Rochester, MN, United States
Abstract
Background: Measuring systemic inflammatory markers may improve clinical prognosis and help identify targetable pathways for treatment in patients with autosomal dominant forms of frontotemporal lobar degeneration (FTLD). Methods: We measured plasma concentrations of IL-6, TNFα and YKL-40 in pathogenic variant carriers (MAPT, C9orf72, GRN) and non-carrier family members enrolled in the ARTFL-LEFFTDS Longitudinal Frontotemporal Lobar Degeneration consortium. We evaluated associations between baseline plasma inflammation and rate of clinical and neuroimaging changes (linear mixed effects models with standardised (z) outcomes). We compared inflammation between asymptomatic carriers who remained clinically normal (‘asymptomatic non-converters’) and those who became symptomatic (‘asymptomatic converters’) using area under the curve analyses. Discrimination accuracy was compared with that of plasma neurofilament light chain (NfL). Results: We studied 394 participants (non-carriers=143, C9orf72=117, GRN=62, MAPT=72). In MAPT, higher TNFα was associated with faster functional decline (B=0.12 (0.02, 0.22), p=0.02) and temporal lobe atrophy. In C9orf72, higher TNFα was associated with faster functional decline (B=0.09 (0.03, 0.16), p=0.006) and cognitive decline (B=-0.16 (-0.22,-0.10), p<0.001), while higher IL-6 was associated with faster functional decline (B=0.12 (0.03, 0.21), p=0.01). TNFα was higher in asymptomatic converters than non-converters (β=0.29 (0.09, 0.48), p=0.004) and improved discriminability compared with plasma NfL alone ( “R2=0.16, p=0.007; NfL: OR=1.4 (1.03, 1.9), p=0.03; TNFα: OR=7.7 (1.7, 31.7), p=0.007). Conclusions: Systemic proinflammatory protein measurement, particularly TNFα, may improve clinical prognosis in autosomal dominant FTLD pathogenic variant carriers who are not yet exhibiting severe impairment. Integrating TNFα with markers of neuronal dysfunction like NfL could optimise detection of impending symptom conversion in asymptomatic pathogenic variant carriers and may help personalise therapeutic approaches. © Author(s) (or their employer(s)) 2023.
Author Keywords
CLINICAL NEUROLOGY; FRONTOTEMPORAL DEMENTIA
Funding details
National Institute on AgingNIA
National Institute of Neurological Disorders and StrokeNINDSU54 NS092089
National Center for Advancing Translational SciencesNCATSU01 AG045390
Rainwater Charitable FoundationRCF
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Protocol for the Ketamine for Postoperative Avoidance of Depressive Symptoms (K-PASS) feasibility study: A randomized clinical trial
(2022) F1000Research, 11, art. no. 510, .
Fritz, B.A.a , Tellor Pennington, B.R.a , Palanca, B.J.A.a b , Schweiger, J.A.b , Willie, J.T.c , Farber, N.B.b
a Department of Anesthesiology, Washington University in St. Louis, St. Louis, MO 63110, United States
b Department of Psychiatry, Washington University in St. Louis, St. Louis, MO 63110, United States
c Department of Neurosurgery, Washington University in St. Louis, St. Louis, MO 63110, United States
Abstract
Background: Postoperative depressive symptoms are associated with pain, readmissions, death, and other undesirable outcomes. Ketamine produces rapid but transient antidepressant effects in the perioperative setting. Longer infusions confer lasting antidepressant activity in patients with treatment-resistant depression, but it is unknown whether a similar approach may produce a lasting antidepressant effect after surgery. This protocol describes a pilot study that will assess the feasibility of conducting a larger scale randomized clinical trial addressing this knowledge gap. Methods: This single-center, double-blind, placebo-controlled pilot trial involves the enrollment of 32 patients aged 18 years or older with a history of depression scheduled for surgery with planned intensive care unit admission. On the first day following surgery and extubation, participants will be randomized to an intravenous eight-hour infusion of either ketamine (0.5 mg kg -1 over 10 minutes followed by a continuous rate of 0.3 mg kg -1 h -1) or an equal volume of normal saline. Depressive symptoms will be quantified using the Montgomery-Asberg Depression Rating Scale preoperatively and serially up to 14 days after the infusion. To detect ketamine-induced changes on overnight sleep architecture, a wireless headband will be used to record electroencephalograms preoperatively, during the study infusion, and after infusion. The primary feasibility endpoints will include the fraction of patients approached who enroll, the fraction of randomized patients who complete the study infusion, and the fraction of randomized patients who complete outcome data collection. Conclusions: This pilot study will evaluate the feasibility of a future large comparative effectiveness trial of ketamine to reduce depressive symptoms in postsurgical patients. Registration: K-PASS is registered on ClinicalTrials.gov: https://clinicaltrials.gov/ct2/show/NCT05233566 NCT05233566 ; registered February 10, 2022. Copyright: © 2022 Fritz BA et al.
Author Keywords
Depression; Feasibility; Ketamine; Protocol; Randomized Clinical Trial; Surgery
Funding details
P50 MH122351
National Institutes of HealthNIH
National Institute of Mental HealthNIMH
Foundation for Anesthesia Education and ResearchFAER1U01MH128483, MRTG08152020
Document Type: Article
Publication Stage: Final
Source: Scopus
Functional tic-like presentations differ strikingly from Provisional Tic Disorder
(2022) F1000Research, 11, art. no. 1566, .
Arbuckle, A.L.a , Bihun, E.C.a , Schlaggar, B.L.b c d , Black, K.J.a e f g
a Department of Psychiatry, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, United States
b Kennedy Krieger Institute, Baltimore, MD 21205, United States
c Department of Neurology, Johns Hopkins Medicine, Baltimore, MD 21287, United States
d Department of Pediatrics, Johns Hopkins Medicine, Baltimore, MD 21287, United States
e Department of Neurology, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, United States
f Department of Radiology, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, United States
g Department of Neuroscience, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, United States
Abstract
Background: Recent years have seen a dramatic increase in new “tic” cases in teens and young adults. These individuals often present with fulminant onset of symptoms not commonly seen in Tourette syndrome (TS) and are often diagnosed with Functional Neurological Symptom Disorder (FND-tic). However, some authors have questioned whether this illness truly differs from typical Provisional Tic Disorder (PTD) and TS. Previous studies have compared FND-tic, usually a few months after symptom onset, to patients with TS, usually years after symptom onset. We sought to test whether the presenting symptoms of FND-tic differ substantially from those in patients at a similar duration of symptoms who are later diagnosed with TS. Methods: This comparative study examines clinical features summarized from published reports of FND-tic with novel data from a longitudinal study of PTD. This study came from a referral center for TS and tic disorders and included 89 children with tics whose first tic occurred a median of 3.6 months earlier, nearly all of whom were diagnosed with a chronic tic disorder at follow-up. Specifically, we examine clinical features identified in a recent literature review as supporting a diagnosis of FND-tic, including symptom characteristics, course, severity and comorbidity. Results: Several clinical features dramatically distinguish the patients diagnosed with FND-tic from those diagnosed with typical PTD. For example, coprophenomena are reported at or shortly after symptom onset in over half of FND-tic patients, whereas even several months after onset, coprophenomena had occurred in only 1 of 89 children with PTD. Six clinical features each have a positive predictive value over 90% for FND-tic diagnosis if prior probability is 50%. Conclusions: These new data provide strong evidence supporting the diagnostic validity of FND-tic as distinct from TS. Copyright: © 2022 Arbuckle AL et al.
Author Keywords
Conversion Disorder; Diagnosis; Differential; Functional Neurological Symptom Disorder; Provisional Tic Disorder; Tic Disorders/classification; Tourette Syndrome
Funding details
National Institutes of HealthNIHK01MH104592, K24MH087913, R01MH104030, R21NS091635
University of WashingtonUW
Institute of Clinical and Translational SciencesICTSUL1RR024992, UL1TR000448
Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNICHDU54HD087011
Document Type: Article
Publication Stage: Final
Source: Scopus