“Hierarchical and nonhierarchical features of the mouse visual cortical network” (2022) Nature Communications
Hierarchical and nonhierarchical features of the mouse visual cortical network(2022) Nature Communications, 13 (1), art. no. 503, .
D’Souza, R.D.a , Wang, Q.a b , Ji, W.a , Meier, A.M.a , Kennedy, H.c d , Knoblauch, K.c e , Burkhalter, A.a
a Department of Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, United Statesb Allen Institute for Brain Science, Seattle, WA 98109, United Statesc Stem Cell and Brain Research Institute, Université Lyon, Université Claude Bernard Lyon 1, INSERM, Bron, Franced Institute of Neuroscience, State Key Laboratory of Neuroscience, Chinese Academy of Sciences Key Laboratory of Primate Neurobiology, Shanghai, 200031, Chinae National Centre for Optics, Vision and Eye Care, Faculty of Health and Social Sciences, University of South-Eastern Norway, Hasbergsvei 36, Kongsberg, 3616, Norway
AbstractNeocortical computations underlying vision are performed by a distributed network of functionally specialized areas. Mouse visual cortex, a dense interareal network that exhibits hierarchical properties, comprises subnetworks interconnecting distinct processing streams. To determine the layout of the mouse visual hierarchy, we have evaluated the laminar patterns formed by interareal axonal projections originating in each of ten areas. Reciprocally connected pairs of areas exhibit feedforward/feedback relationships consistent with a hierarchical organization. Beta regression analyses, which estimate a continuous hierarchical distance measure, indicate that the network comprises multiple nonhierarchical circuits embedded in a hierarchical organization of overlapping levels. Single-unit recordings in anaesthetized mice show that receptive field sizes are generally consistent with the hierarchy, with the ventral stream exhibiting a stricter hierarchy than the dorsal stream. Together, the results provide an anatomical metric for hierarchical distance, and reveal both hierarchical and nonhierarchical motifs in mouse visual cortex. © 2022, The Author(s).
Funding detailsNational Eye InstituteNEIANR-11-LABX-0042, R01 EY016184, R01 EY020523, R01 EY022090, R01 EY027383Agence Nationale de la RechercheANRA2P2MC, ANR-15-CE32-0016, ANR-17-HBPR-0003, ANR-17-NEUC-0004, ANR-19-CE37-0000Université de LyonUDLANR-11-IDEX-0007
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Grandi Byen—supporting child growth and development through integrated, responsive parenting, nutrition and hygiene: study protocol for a randomized controlled trial” (2022) BMC Pediatrics
Grandi Byen—supporting child growth and development through integrated, responsive parenting, nutrition and hygiene: study protocol for a randomized controlled trial(2022) BMC Pediatrics, 22 (1), art. no. 54, .
Kohl, P.L.a , Gyimah, E.A.a , Diaz, J.b , Kuhlmann, F.M.c , Dulience, S.J.-L.a , Embaye, F.a , Brown, D.S.a , Guo, S.a , Luby, J.L.d , Nicholas, J.L.e , Turner, J.f , Chapnick, M.a , Pierre, J.M.g , Boncy, J.h , St. Fleur, R.i , Black, M.M.j , Iannotti, L.L.a
a Brown School, Washington University in St. Louis, 1 Brookings Dr., Campus Box 1196, St. Louis, MO 63130, United Statesb Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Washington University School of Medicine in St. Louis, 660 S. Euclid Ave., St. Louis, MO 63110, United Statesc Division of Infectious Diseases, Washington University School of Medicine in St. Louis, 660 S. Euclid Ave., St. Louis, MO 63110, United Statesd Department of Psychiatry, Washington University School of Medicine in St. Louis, 660 S. Euclid Ave., St. Louis, MO 63110, United Statese Department of Radiology, School of Medicine, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106, United Statesf McKelvey School of Engineering, Washington University in St. Louis, 1 Brookings Dr., St. Louis, MO 63130, United Statesg Unité de Coordination du Programme National d’Alimentation et de Nutrition, Ministère de la Santé Publique et de la Population, 1, Angle Avenue Maïs Gaté et, Rue Jacques Roumain, Port-au-Prince, Haitih Laboratoire National de Santé Publique, Ministère de la Santé Publique et de la Population, 1, Angle Avenue Maïs Gaté et, Rue Jacques Roumain, Port-au-Prince, Haitii Hôpital Universitaire Justinien, Cap-Haitien, Haitij Department of Pediatrics, University of Maryland School of Medicine, 655 W. Baltimore Street, Baltimore, MD 21201, United States
AbstractBackground: Poor child growth and development outcomes stem from complex relationships encompassing biological, behavioral, social, and environmental conditions. However, there is a dearth of research on integrated approaches targeting these interwoven factors. The Grandi Byen study seeks to fill this research gap through a three-arm longitudinal randomized controlled trial which will evaluate the impact of an integrated nutrition, responsive parenting, and WASH (water, sanitation and hygiene) intervention on holistic child growth and development. Methods: We will recruit 600 mother-infant dyads living in Cap-Haitien, Haiti and randomize them equally into one of the following groups: 1) standard well-baby care; 2) nutritional intervention (one egg per day for 6 months); and 3) multicomponent Grandi Byen intervention (responsive parenting, nutrition, WASH + one egg per day for 6 months). Primary outcomes include child growth as well as cognitive, language, motor, and social-emotional development. The study also assesses other indicators of child health (bone maturation, brain growth, diarrheal morbidity and allergies, dietary intake, nutrient biomarkers) along with responsive parenting as mediating factors influencing the primary outcomes. An economic evaluation will assess the feasibility of large-scale implementation of the interventions. Discussion: This study builds on research highlighting the importance of responsive parenting interventions on overall child health, as well as evidence demonstrating that providing an egg daily to infants during the complementary feeding period can prevent stunted growth. The multicomponent Grandi Byen intervention may provide evidence of synergistic or mediating effects of an egg intervention with instruction on psychoeducational parenting and WASH on child growth and development. Grandi Byen presents key innovations with implications for the well-being of children living in poverty globally. Trial registration: NCT04785352. Registered March 5, 2021 at https://clinicaltrials.gov/. © 2022, The Author(s).
Author KeywordsChild development; Integrated parenting intervention; Nutrition; Responsive parenting; Stunting
Funding detailsPublic Health InstitutePHIWashington University in St. LouisWUSTLEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNICHD
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Ketamine as a therapeutic agent for depression and pain: mechanisms and evidence” (2022) Journal of the Neurological Sciences
Ketamine as a therapeutic agent for depression and pain: mechanisms and evidence(2022) Journal of the Neurological Sciences, 434, art. no. 120152, .
Subramanian, S.a , Haroutounian, S.b , Palanca, B.J.A.a b c , Lenze, E.J.a
a Department of Psychiatry, Washington University in St. Louis School of Medicine, St. Louis, MO, United Statesb Department of Anesthesiology, Washington University in St. Louis School of Medicine, St. Louis, MO, United Statesc Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, United States
AbstractKetamine is an anesthetic drug which is now used to treat chronic pain conditions and psychiatric disorders, especially depression. It is an N-methyl-D-aspartate (NMDA) receptor antagonist with additional effects on α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, opioid receptors, and monoaminergic receptors. This article focuses on ketamine’s role in treating depression and pain, two commonly comorbid challenging conditions with potentially shared neurobiologic circuitry. Many clinical trials have utilized intravenous or intranasal ketamine for treating depression and pain. Intravenous ketamine is more bioavailable than intranasal ketamine and both are effective for acute depressive episodes. Intravenous ketamine is advantageous for post-operative analgesia and is associated with a reduction in total opioid requirements. Few studies have treated chronic pain or concurrent depression and pain with ketamine. Larger, randomized control trials are needed to examine the safety and efficacy of intravenous vs. intranasal ketamine, ideal target populations, and optimal dosing to treat both depression and pain. © 2022 Elsevier B.V.
Author KeywordsEsketamine; Interventional psychiatry; Ketamine; Major depressive disorder; Pain
Funding detailsNational Institute of Mental HealthNIMHR25 MH112473U.S. Food and Drug AdministrationFDANational Institute on AgingNIAOffice of Behavioral and Social Sciences ResearchOBSSRJames S. McDonnell FoundationJSMFAmerican Foundation for Suicide PreventionAFSPSidney R. Baer, Jr. FoundationRochePatient-Centered Outcomes Research InstitutePCORIFoundation for Barnes-Jewish HospitalFBJHNational Center for Complementary and Integrative HealthNCCIHJanssen PharmaceuticalsMcDonnell Center for Systems NeuroscienceJazz PharmaceuticalsH. Lundbeck A/S
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Head tremor in cervical dystonia: Quantifying severity with computer vision” (2022) Journal of the Neurological Sciences
Head tremor in cervical dystonia: Quantifying severity with computer vision(2022) Journal of the Neurological Sciences, 434, art. no. 120154, .
Vu, J.P.a , Cisneros, E.a , Lee, H.Y.a , Le, L.a , Chen, Q.a , Guo, X.A.a , Rouzbehani, R.a , Jankovic, J.b , Factor, S.c , Goetz, C.G.d , Barbano, R.L.e , Perlmutter, J.S.f g , Jinnah, H.A.c h , Pirio Richardson, S.i j , Stebbins, G.T.d , Elble, R.k , Comella, C.L.d , Peterson, D.A.a l
a Institute for Neural Computation, University of California, San Diego, La Jolla, CA, United Statesb Parkinson’s Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, TX, United Statesc Department of Neurology, Emory University School of Medicine, Atlanta, GA, United Statesd Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, United Statese Department of Neurology, University of Rochester, Rochester, NY, United Statesf Department of Neurology, Washington University School of Medicine, St. Louis, MO, United Statesg Departments of Radiology, Neuroscience, Physical Therapy, and Occupational Therapy, Washington University School of Medicine, St. Louis, MO, United Statesh Departments of Human Genetics, Emory University School of Medicine, Atlanta, GA, United Statesi Department of Neurology, University of New Mexico Health Sciences Center, Albuquerque, NM, United Statesj Neurology Service, New Mexico Veterans Affairs Health Care System, Albuquerque, NM, United Statesk Department of Neurology, Southern Illinois University School of Medicine, Springfield, IL, United Statesl Computational Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, CA, United States
AbstractBackground: Head tremor (HT) is a common feature of cervical dystonia (CD), usually quantified by subjective observation. Technological developments offer alternatives for measuring HT severity that are objective and amenable to automation. Objectives: Our objectives were to develop CMOR (Computational Motor Objective Rater; a computer vision-based software system) to quantify oscillatory and directional aspects of HT from video recordings during a clinical examination and to test its convergent validity with clinical rating scales. Methods: For 93 participants with isolated CD and HT enrolled by the Dystonia Coalition, we analyzed video recordings from an examination segment in which participants were instructed to let their head drift to its most comfortable dystonic position. We evaluated peak power, frequency, and directional dominance, and used Spearman’s correlation to measure the agreement between CMOR and clinical ratings. Results: Power averaged 0.90 (SD 1.80) deg2/Hz, and peak frequency 1.95 (SD 0.94) Hz. The dominant HT axis was pitch (antero/retrocollis) for 50%, roll (laterocollis) for 6%, and yaw (torticollis) for 44% of participants. One-sided t-tests showed substantial contributions from the secondary (t = 18.17, p < 0.0001) and tertiary (t = 12.89, p < 0.0001) HT axes. CMOR’s HT severity measure positively correlated with the HT item on the Toronto Western Spasmodic Torticollis Rating Scale-2 (Spearman’s rho = 0.54, p < 0.001). Conclusions: We demonstrate a new objective method to measure HT severity that requires only conventional video recordings, quantifies the complexities of HT in CD, and exhibits convergent validity with clinical severity ratings. © 2022 Elsevier B.V.
Author KeywordsComputer vision; Head tremor; Severity rating; TWSTRS; Video
Funding detailsW81XWH-17-1-0393National Institutes of HealthNIHAG-64937, AG050263, ES029524, NS075321, NS075527, NS092865, NS097437, NS097799, NS103957, NS107281, NS109487, P20 GM109899, R61 AT010753, U10 NS077366, U10NS077384, U19 NS110456U.S. Department of DefenseDODW81XWH-19-CTRR-CTA, W81XWH-217-1-0393National Institute on AgingNIAR01AG065214, RO1NS118146National Institute of Neurological Disorders and StrokeNINDSNS065701, NS116025Michael J. Fox Foundation for Parkinson’s ResearchMJFFHuntington’s Disease Society of AmericaHDSAParkinson’s Disease FoundationPDFDystonia Medical Research FoundationDMRFCHDI FoundationCHDINational Center for Advancing Translational SciencesNCATSU54 TR001456Teva Pharmaceutical IndustriesAmerican Parkinson Disease AssociationAPDAAbbVieFoundation for Barnes-Jewish HospitalFBJHAllerganParkinsonfondenInternational Essential Tremor FoundationIETFBoston Scientific CorporationBSCBenign Essential Blepharospasm Research FoundationBEBRFNational Spasmodic Dysphonia AssociationNSDAACADIA PharmaceuticalsACADIADystonia CoalitionGovernment of South AustraliaRevanceRVNC
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Negative and depressive symptoms differentially relate to real-world anticipatory and consummatory pleasure in schizophrenia” (2022) Schizophrenia Research
Negative and depressive symptoms differentially relate to real-world anticipatory and consummatory pleasure in schizophrenia(2022) Schizophrenia Research, 241, pp. 72-77.
Merchant, J.T.a , Moran, E.K.a b , Barch, D.M.a b c
a Department of Psychological & Brain Sciences, Washington University in St. Louis, St. Louis, MO 63130, United Statesb Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, United Statesc Department of Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110, United States
AbstractIt has been suggested that schizophrenia is associated with deficits in anticipatory but not consummatory pleasure, though there is mixed support for this hypothesis. As individuals with schizophrenia can experience both negative and depressive symptoms, symptom heterogeneity in this population could contribute to these mixed hedonic findings. Specifically, while some research suggests that negative symptoms of schizophrenia are related to reduced anticipatory but not consummatory pleasure, research on major depressive disorder suggests that depressive symptoms are associated with both decreased anticipatory and consummatory pleasure. Still, it is unclear whether depressive symptoms are associated with experiences of pleasure in schizophrenia as they are in major depressive disorder. Thus, the present study used Ecological Momentary Assessment (four prompts per day over one week) to investigate the unique relationships of negative and depressive symptoms with daily reports of real-world anticipatory and consummatory pleasure in 63 individuals with schizophrenia. Higher negative symptoms related to reduced anticipatory but not consummatory pleasure. On the other hand, higher depressive symptoms related to reductions in both anticipatory and consummatory pleasure. Overall, these results indicate that negative and depressive symptoms are differentially associated with hedonic experience in schizophrenia, and suggest the need to account for the severity of both these symptom types when examining pleasure in this population. Elucidating the nature of these symptom contributions to hedonic impairments could increase causal understanding of these deficits and contribute to the development of more targeted treatments to enhance motivation and pleasure in schizophrenia. © 2022 Elsevier B.V.
Author KeywordsAnhedonia; Anticipatory pleasure; Consummatory pleasure; Depression; Ecological momentary assessment; Schizophrenia
Funding detailsNational Institute of Mental HealthNIMHR37-MH066031
Document Type: ArticlePublication Stage: FinalSource: Scopus
“The Sulfated Steroids Pregnenolone Sulfate and Dehydroepiandrosterone Sulfate Inhibit the α1β3γ2L GABAA Receptor by Stabilizing a Novel Nonconducting State” (2022) Molecular Pharmacology
The Sulfated Steroids Pregnenolone Sulfate and Dehydroepiandrosterone Sulfate Inhibit the α1β3γ2L GABAA Receptor by Stabilizing a Novel Nonconducting State(2022) Molecular Pharmacology, 101 (2), pp. 68-77.
Pierce, S.R., Germann, A.L., Steinbach, J.H., Akk, G.
Department of Anesthesiology (S.R.P., A.L.G., G.A.) and the Taylor Family Institute for Innovative Psychiatric Research (J.H.S., Washington University School of Medicine, St. Louis, MO, United States
AbstractThe GABAA receptor is inhibited by the endogenous sulfated steroids pregnenolone sulfate (PS) and dehydroepiandrosterone sulfate (DHEAS). It has been proposed in previous work that these steroids act by enhancing desensitization of the receptor. Here, we have investigated the modulatory effects of the steroids on the human α1β3γ2L GABAA receptor. Using electrophysiology and quantitative model-based data analysis, we show that exposure to the steroid promotes occupancy of a nonconducting state that retains high affinity to the transmitter but whose properties differ from those of the classic, transmitter-induced desensitized state. From the analysis of the inhibitory actions of two combined steroids, we infer that PS and DHEAS act through shared or overlapping binding sites. SIGNIFICANCE STATEMENT: Previous work has proposed that sulfated neurosteroids inhibit the GABAA receptor by enhancing the rate of entry into the desensitized state. This study shows that the inhibitory steroids pregnenolone sulfate and dehydroepiandrosterone sulfate act through a common interaction site by stabilizing a distinct nonconducting state. Copyright © 2022 by The American Society for Pharmacology and Experimental Therapeutics.
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Alterations of host-gut microbiome interactions in multiple sclerosis” (2022) eBioMedicine
Alterations of host-gut microbiome interactions in multiple sclerosis(2022) eBioMedicine, 76, art. no. 103798, .
Cantoni, C.a , Lin, Q.b , Dorsett, Y.c , Ghezzi, L.a d , Liu, Z.e , Pan, Y.e , Chen, K.e , Han, Y.f , Li, Z.f , Xiao, H.f , Gormley, M.g , Liu, Y.g , Bokoliya, S.c , Panier, H.c , Suther, C.f , Evans, E.a , Deng, L.a h , Locca, A.a , Mikesell, R.a , Obert, K.a , Newland, P.i , Wu, Y.b , Salter, A.j , Cross, A.H.a k , Tarr, P.I.l , Lovett-Racke, A.g , Piccio, L.a k m , Zhou, Y.c
a Department of Neurology, Washington University School of Medicine, St. Louis, MO, United Statesb Department of Computer Science and Engineering, University of Connecticut, Storrs, CT, United Statesc Department of Medicine, UConn Health, Farmington, CT, United Statesd Dino Ferrari Center, University of Milan, Milan, Italye Department of Statistics, University of Connecticut, Storrs, CT, United Statesf Department of Food Science, University of Massachusetts, Amherst, Massachusetts, United Statesg Department of Microbial Infection and Immunity, Ohio State University, Columbus, OH, United Statesh Department of Anesthesiology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, Chinai Barnes Jewish College, Goldfarb School of Nursing, St. Louis, MO, United Statesj Division of Biostatistics, School of Medicine, Washington University, St. Louis, MO, United Statesk Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, United Statesl Departments of Pediatrics and Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, United Statesm Brain and Mind Centre, School of Medical Sciences, University of Sydney, Sydney, NSW 2050, Australia
AbstractBackground: Multiple sclerosis (MS) has a complex genetic, immune and metabolic pathophysiology. Recent studies implicated the gut microbiome in MS pathogenesis. However, interactions between the microbiome and host immune system, metabolism and diet have not been studied over time in this disorder. Methods: We performed a six-month longitudinal multi-omics study of 49 participants (24 untreated relapse remitting MS patients and 25 age, sex, race matched healthy control individuals. Gut microbiome composition and function were characterized using 16S and metagenomic shotgun sequencing. Flow cytometry was used to characterize blood immune cell populations and cytokine profiles. Circulating metabolites were profiled by untargeted UPLC-MS. A four-day food diary was recorded to capture the habitual dietary pattern of study participants. Findings: Together with changes in blood immune cells, metagenomic analysis identified a number of gut microbiota decreased in MS patients compared to healthy controls, and microbiota positively or negatively correlated with degree of disability in MS patients. MS patients demonstrated perturbations of their blood metabolome, such as linoleate metabolic pathway, fatty acid biosynthesis, chalcone, dihydrochalcone, 4-nitrocatechol and methionine. Global correlations between multi-omics demonstrated a disrupted immune-microbiome relationship and a positive blood metabolome-microbiome correlation in MS. Specific feature association analysis identified a potential correlation network linking meat servings with decreased gut microbe B. thetaiotaomicron, increased Th17 cell and greater abundance of meat-associated blood metabolites. The microbiome and metabolome profiles remained stable over six months in MS and control individuals. Interpretation: Our study identified multi-system alterations in gut microbiota, immune and blood metabolome of MS patients at global and individual feature level. Multi-OMICS data integration deciphered a potential important biological network that links meat intakes with increased meat-associated blood metabolite, decreased polysaccharides digesting bacteria, and increased circulating proinflammatory marker. Funding: This work was supported by the Washington University in St. Louis Institute of Clinical and Translational Sciences, funded, in part, by Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH). Cantoni C. was supported by the National MS Society Career Transition Fellowship (TA-180531003) and by donations from Whitelaw Terry, Jr. / Valerie Terry Fund. Ghezzi L. was supported by the Italian Multiple Sclerosis Society research fellowship (FISM 2018/B/1) and the National Multiple Sclerosis Society Post-Doctoral Fellowship (FG-190734474). Anne Cross was supported by The Manny & Rosalyn Rosenthal-Dr. John L. Trotter MS Center Chair in Neuroimmunology of the Barnes-Jewish Hospital Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. © 2022 The Authors
Author KeywordsDiet; Microbiome; Multi-omics; Multiple sclerosis
Funding detailsNational Institutes of HealthNIHNational Multiple Sclerosis SocietyNMSSFG-1907–34474, TA-1805–31003BiogenNational Center for Advancing Translational SciencesNCATSR01 NS102633–04Foundation for Barnes-Jewish HospitalFBJHAssociazione Italiana Sclerosi MultiplaAISMFISM 2018/B/1University of MassachusettsUMASS31003, 34474, FG-1907, PRJNA634779, R01 NS102633, TA-1805Institute of Clinical and Translational SciencesICTSUL1 TR000448
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Importance of CSF-based Aβ clearance with age in humans increases with declining efficacy of blood-brain barrier/proteolytic pathways” (2022) Communications Biology
Importance of CSF-based Aβ clearance with age in humans increases with declining efficacy of blood-brain barrier/proteolytic pathways(2022) Communications Biology, 5 (1), p. 98.
Elbert, D.L.a , Patterson, B.W.b , Lucey, B.P.c d , Benzinger, T.L.S.d e , Bateman, R.J.c d
a Department of Neurology, Dell Medical School, University of Texas at Austin, TX, Austin, United Statesb Department of Medicine, Washington University in St. Louis, St. Louis, MO, USAc Department of Neurology, Washington University School of Medicine, St. Louis, MO, USAd Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis, MO, USAe Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA
AbstractThe kinetics of amyloid beta turnover within human brain is still poorly understood. We previously found a dramatic decline in the turnover of Aβ peptides in normal aging. It was not known if brain interstitial fluid/cerebrospinal fluid (ISF/CSF) fluid exchange, CSF turnover, blood-brain barrier function or proteolysis were affected by aging or the presence of β amyloid plaques. Here, we describe a non-steady state physiological model developed to decouple CSF fluid transport from other processes. Kinetic parameters were estimated using: (1) MRI-derived brain volumes, (2) stable isotope labeling kinetics (SILK) of amyloid-β peptide (Aβ), and (3) lumbar CSF Aβ concentration during SILK. Here we show that changes in blood-brain barrier transport and/or proteolysis were largely responsible for the age-related decline in Aβ turnover rates. CSF-based clearance declined modestly in normal aging but became increasingly important due to the slowing of other processes. The magnitude of CSF-based clearance was also lower than that due to blood-brain barrier function plus proteolysis. These results suggest important roles for blood-brain barrier transport and proteolytic degradation of Aβ in the development Alzheimer’s Disease in humans. © 2022. The Author(s).
Document Type: ArticlePublication Stage: FinalSource: Scopus
“2-(4-Hydroxyphenyl)benzothiazole dicarboxylate ester TACN chelators for 64Cu PET imaging in Alzheimer’s disease” (2022) Dalton Transactions
2-(4-Hydroxyphenyl)benzothiazole dicarboxylate ester TACN chelators for 64Cu PET imaging in Alzheimer’s disease(2022) Dalton Transactions, 51 (3), pp. 1216-1224.
Wang, Y.a , Huynh, T.T.b c , Bandara, N.b , Cho, H.-J.a , Rogers, B.E.b , Mirica, L.M.a d
a Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United Statesb Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO 63108, United Statesc Department of Chemistry, Washington University, St. Louis, MO 63130, United Statesd Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, United States
AbstractHerein we report a new series of bifunctional chelators (BFCs) with high affinity for amyloid β aggregates, strong binding affinity towards Cu(ii), and favorable lipophilicity for potential blood–brain barrier (BBB) penetration. The alkyl carboxylate ester pendant arms show high binding affinity towards Cu(ii). The BFCs form stable 64Cu-radiolabeled complexes and exhibit favorable partition coefficient (log D) values of 0.75–0.95. Among the five compounds tested, 64Cu-YW-1 and 64Cu-YW-13 complexes exhibit significant staining of amyloid plaques in ex vivo autoradiography studies. This journal is © The Royal Society of Chemistry
Funding detailsNational Institutes of HealthNIHR01GM114588University of WashingtonUW
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Increased Connectivity among Sensory and Motor Regions during Visual and Audiovisual Speech Perception” (2022) The Journal of Neuroscience: The Official Journal of the Society for Neuroscience
Increased Connectivity among Sensory and Motor Regions during Visual and Audiovisual Speech Perception(2022) The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 42 (3), pp. 435-442.
Peelle, J.E.a , Spehar, B.a , Jones, M.S.a , McConkey, S.a , Myerson, J.b , Hale, S.b , Sommers, M.S.b , Tye-Murray, N.a
a Department of Otolaryngology, Washington University in St. Louis, St. Louis, MO 63110, United Statesb Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, MO 63130, United States
AbstractIn everyday conversation, we usually process the talker’s face as well as the sound of the talker’s voice. Access to visual speech information is particularly useful when the auditory signal is degraded. Here, we used fMRI to monitor brain activity while adult humans (n = 60) were presented with visual-only, auditory-only, and audiovisual words. The audiovisual words were presented in quiet and in several signal-to-noise ratios. As expected, audiovisual speech perception recruited both auditory and visual cortex, with some evidence for increased recruitment of premotor cortex in some conditions (including in substantial background noise). We then investigated neural connectivity using psychophysiological interaction analysis with seed regions in both primary auditory cortex and primary visual cortex. Connectivity between auditory and visual cortices was stronger in audiovisual conditions than in unimodal conditions, including a wide network of regions in posterior temporal cortex and prefrontal cortex. In addition to whole-brain analyses, we also conducted a region-of-interest analysis on the left posterior superior temporal sulcus (pSTS), implicated in many previous studies of audiovisual speech perception. We found evidence for both activity and effective connectivity in pSTS for visual-only and audiovisual speech, although these were not significant in whole-brain analyses. Together, our results suggest a prominent role for cross-region synchronization in understanding both visual-only and audiovisual speech that complements activity in integrative brain regions like pSTS.SIGNIFICANCE STATEMENT In everyday conversation, we usually process the talker’s face as well as the sound of the talker’s voice. Access to visual speech information is particularly useful when the auditory signal is hard to understand (e.g., background noise). Prior work has suggested that specialized regions of the brain may play a critical role in integrating information from visual and auditory speech. Here, we show a complementary mechanism relying on synchronized brain activity among sensory and motor regions may also play a critical role. These findings encourage reconceptualizing audiovisual integration in the context of coordinated network activity. Copyright © 2022 the authors.
Author Keywordsaudiovisual integration; language; lipreading; speech; speechreading
Document Type: ArticlePublication Stage: FinalSource: Scopus
“A spatially embedded cortical connectome reveals complex transformations” (2022) Neuron
A spatially embedded cortical connectome reveals complex transformations(2022) Neuron, 110 (2), pp. 185-187.
Hayashi, T.a , Kennedy, H.b , Van Essen, D.C.c
a Laboratory for Brain Connectomics Imaging, RIKEN Center for Biosystems Dynamics Research, 6-7-3 MI R&D Center 3F, Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan; Department of Brain Connectomics, Kyoto University Graduate School of Medicine, Kyoto, Japanb Inserm, Stem Cell and Brain Research Institute U1208, Univ. Lyon, Université Claude Bernard Lyon 1, Bron, France; Institute of Neuroscience, Key Laboratory of Primate Neurobiology, Chinese Academy of Sciences, Shanghai 200031, Chinac Department of Neuroscience, Washington University School of Medicine, St. Louis, MO, USA. Electronic address: vanessen@wustl.edu
AbstractIn this issue of Neuron, Xu et al. (2022) use electrical microstimulation of macaque prefrontal cortex combined with functional MRI to map weighted orderly topographic relationships with other association cortex domains, revealing a spatially embedded large-scale organization likely to be functionally important. Copyright © 2021 Elsevier Inc. All rights reserved.
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Association Between Time Spent Outdoors and Risk of Multiple Sclerosis” (2022) Neurology
Association Between Time Spent Outdoors and Risk of Multiple Sclerosis(2022) Neurology, 98 (3), pp. e267-e278.
Sebastian, P., Cherbuin, N., Barcellos, L.F., Roalstad, S., Casper, C., Hart, J., Aaen, G.S., Krupp, L., Benson, L., Gorman, M., Candee, M., Chitnis, T., Goyal, M., Greenberg, B., Mar, S., Rodriguez, M., Rubin, J., Schreiner, T., Waldman, A., Weinstock-Guttman, B., Graves, J., Waubant, E., Lucas, R., US Network of Pediatric Multiple Sclerosis Centers
From the Australian National University Medical School (P.S.), Centre for Research on Ageing, Health and Wellbeing (N.C.), and National Centre for Epidemiology and Population Health (R.L.), Australian National University, Canberra; Division of Epidemiology (L.F.B.), University of California Berkeley; Department of Pediatrics (S.R., C.C.), University of Utah School of Medicine, Salt Lake City; Pediatric Multiple Sclerosis Center (J.H.) and Department of Neurology (E.W.), University of California San Francisco; Pediatric Multiple Sclerosis Center (G.S.A.), Loma Linda University Children’s Hospital, CA; MS Comprehensive Care Center (L.K.), New York University Langone, NY; Pediatric Multiple Sclerosis and Related Disorders Program (L.B., M. Gorman), Boston Children’s Hospital, MA; Division of Pediatric Neurology (M.C.), University of Utah Primary Children’s Hospital, Salt Lake City; Partners Pediatric Multiple Sclerosis Center (T.C.), Massachusetts General Hospital for Children, Boston; Department of Radiology (M. Goyal), Washington University St. Louis, MO; Department of Neurology (B.G.), University of Texas Southwestern, Dallas; Pediatric-Onset Demyelinating Diseases and Autoimmune Encephalitis Center (S.M.), St. Louis Children’s Hospital, Washington University School of Medicine, MO; Mayo Clinic Pediatric Multiple Sclerosis Center (M.R.), Mayo Clinic, Rochester, MN; Department of Pediatric Neurology (J.R.), Northwestern Feinberg School of Medicine, Chicago, IL; Children’s Hospital Colorado (T.S.), University of Colorado, Denver; Division of Neurology (A.W.), Children’s Hospital of Philadelphia, PA; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, State University of New York Buffalo; and Department of Neurosciences (J.G.), University of California San Diego
AbstractBACKGROUND AND OBJECTIVES: This study aims to determine the contributions of sun exposure and ultraviolet radiation (UVR) exposure to risk of pediatric-onset multiple sclerosis (MS). METHODS: Children with MS and controls recruited from multiple centers in the United States were matched on sex and age. Multivariable conditional logistic regression was used to investigate the association of time spent outdoors daily in summer, use of sun protection, and ambient summer UVR dose in the year before birth and the year before diagnosis with MS risk, with adjustment for sex, age, race, birth season, child’s skin color, mother’s education, tobacco smoke exposure, being overweight, and Epstein-Barr virus infection. RESULTS: Three hundred thirty-two children with MS (median disease duration 7.3 months) and 534 controls were included after matching on sex and age. In a fully adjusted model, compared to spending <30 minutes outdoors daily during the most recent summer, greater time spent outdoors was associated with a marked reduction in the odds of developing MS, with evidence of dose-response (30 minutes-1 hour: adjusted odds ratio [AOR] 0.48, 95% confidence interval [CI] 0.23-0.99, p = 0.05; 1-2 hours: AOR 0.19, 95% CI 0.09-0.40, p < 0.001). Higher summer ambient UVR dose was also protective for MS (AOR 0.76 per 1 kJ/m2, 95% CI 0.62-0.94, p = 0.01). DISCUSSION: If this is a causal association, spending more time in the sun during summer may be strongly protective against developing pediatric MS, as well as residing in a sunnier location. © 2021 American Academy of Neurology.
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Paeonol Ameliorates Chronic Itch and Spinal Astrocytic Activation via CXCR3 in an Experimental Dry Skin Model in Mice” (2022) Frontiers in Pharmacology
Paeonol Ameliorates Chronic Itch and Spinal Astrocytic Activation via CXCR3 in an Experimental Dry Skin Model in Mice(2022) Frontiers in Pharmacology, 12, art. no. 805222, .
Wang, W.a b , Li, Q.a b , Zhao, Z.c d , Liu, Y.e , Wang, Y.e , Xiong, H.a b , Mei, Z.a b
a School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan, Chinab Institute of Ethnomedicine, South-Central University for Nationalities, Wuhan, Chinac Washington University School of Medicine, St. LouisMO, United Statesd Barnes-Jewish Hospital, St. Louis, MO, United Statese College of Life Sciences, South-Central University for Nationalities, Wuhan, China
AbstractPaeonol is a bioactive phenol presents mainly in Paeonia suffruticosa Andr. (Paeoniaceae), Paeonia lactiflora Pall., and Dioscorea japonica Thunb. (Dioscoreaceae), harboring various pharmacological activities including anti-inflammatory, antioxidant, immune regulatory activity and reverse chemoresistance. Recent reports revealed paeonol exhibited good effects on chronic dermatitis, such as atopic dermatitis (AD) and psoriasis. However, whether paeonol is effective for dry skin disease and its mechanism of action still remain unclear. In this study, we analysed the effects of paeonol on a mouse model of dry skin treated with acetone-ether-water (AEW), which showed impressive activities in reducing scratching behavior and skin inflammation. To elucidate the underlying molecular targets for the anti-pruritic ability of paeonol, we screened the expression of possible chemokine pathways in the spinal cord. The expression of CXCR3 was significantly alleviated by paeonol, which increased greatly in the spinal neurons of AEW mice. In addition, treatment of paeonol significantly inhibited AEW-induced expression of astrocyte activity-dependent genes including Tlr4, Lcn2 and Hspb1 et al. The inhibitory effects of paeonol on scratching behavior and astrocytic activation in the spinal cord induced by AEW were abolished when CXCR3 was antagonized or genetically ablated. Taken together, our results indicated that paeonol can ameliorate AEW-induced inflammatory response and itching behavior, and reduce the expression of spinal astrocyte activity-dependent genes induced by AEW, which are driven by CXCR3. Copyright © 2022 Wang, Li, Zhao, Liu, Wang, Xiong and Mei.
Author KeywordsAEW; anti-pruritic; astrocyte; CXCR3; inflammation; paeonol
Funding detailsSouth-Central University of NationalitiesSCUNCZJ19001National Major Science and Technology Projects of China2017ZX09301060Major Scientific and Technological Special Project of Guizhou Province2020ACA019
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Association Between Anatomical Location of Surgically Induced Lesions and Postoperative Seizure Outcome in Temporal Lobe Epilepsy” (2022) Neurology
Association Between Anatomical Location of Surgically Induced Lesions and Postoperative Seizure Outcome in Temporal Lobe Epilepsy(2022) Neurology, 98 (2), pp. E141-E151.
Gleichgerrcht, E.a , Drane, D.L.c , Keller, S.S.d e , Davis, K.A.f , Gross, R.g , Willie, J.T.g h , Pedersen, N.c , de Bezenac, C.d , Jensen, J.b , Kuzniecky, R.i , Bonilha, L.a
a Department of Neurology, Medical University of South Carolina, Charleston, United Statesb Center for Biomedical Imaging, Medical University of South Carolina, Charleston, United Statesc Department of Neurology, Emory University, Atlanta, GA, United Statesd Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdome Walton Centre NHS Foundation Trust, Liverpool, United Kingdomf Department of Neurology University of Pennsylvania, Philadelphia, United Statesg Department of Neurosurgery, Emory University, Atlanta, GA, United Statesh Department of Neurological Surgery, Washington University, St. Louis, MO, United Statesi Department of Neurology, Hofstra University, NorthwellNY, United States
AbstractBackground and Objectives To determine the association between surgical lesions of distinct gray and white structures and connections with favorable postoperative seizure outcomes. Methods Patients with drug-resistant temporal lobe epilepsy (TLE) from 3 epilepsy centers were included. We employed a voxel-based and connectome-based mapping approach to determine the association between favorable outcomes and surgery-induced temporal lesions. Analyses were conducted controlling for multiple confounders, including total surgical resection/ablation volume, hippocampal volumes, side of surgery, and site where the patient was treated. Results The cohort included 113 patients with TLE (54 women; 86 right-handed; mean age at seizure onset 16.5 years [SD 11.9]; 54.9% left) who were 61.1% free of disabling seizures (Engel Class 1) at follow-up. Postoperative seizure freedom in TLE was associated with (1) surgical lesions that targeted the hippocampus as well as the amygdala–piriform cortex complex and entorhinal cortices; (2) disconnection of temporal, frontal, and limbic regions through loss of white matter tracts within the uncinate fasciculus, anterior commissure, and fornix; and (3) functional disconnection of the frontal (superior and middle frontal gyri, orbitofrontal region) and temporal (superior and middle pole) lobes. Discussion Better postoperative seizure freedom is associated with surgical lesions of specific structures and connections throughout the temporal lobes. These findings shed light on the key components of epileptogenic networks in TLE and constitute a promising source of new evidence for future improvements in surgical interventions. © 2022 Lippincott Williams and Wilkins. All rights reserved.
Funding detailsNational Institute of Neurological Disorders and StrokeNINDS1R01NS110347-01A
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Economic Choices under Simultaneous or Sequential Offers Rely on the Same Neural Circuit” (2022) The Journal of Neuroscience: The Official Journal of the Society for Neuroscience
Economic Choices under Simultaneous or Sequential Offers Rely on the Same Neural Circuit(2022) The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 42 (1), pp. 33-43.
Shi, W.a , Ballesta, S.a , Padoa-Schioppa, C.a b c
a Department of Neuroscienceb Department of Economicsc Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO 63110, United States
AbstractA series of studies in which monkeys chose between two juices offered in variable amounts identified in the orbitofrontal cortex (OFC) different groups of neurons encoding the value of individual options (offer value), the binary choice outcome (chosen juice), and the chosen value. These variables capture both the input and the output of the choice process, suggesting that the cell groups identified in OFC constitute the building blocks of a decision circuit. Several lines of evidence support this hypothesis. However, in previous experiments offers were presented simultaneously, raising the question of whether current notions generalize to when goods are presented or are examined in sequence. Recently, Ballesta and Padoa-Schioppa (2019) examined OFC activity under sequential offers. An analysis of neuronal responses across time windows revealed that a small number of cell groups encoded specific sequences of variables. These sequences appeared analogous to the variables identified under simultaneous offers, but the correspondence remained tentative. Thus, in the present study, we examined the relation between cell groups found under sequential versus simultaneous offers. We recorded from the OFC while monkeys chose between different juices. Trials with simultaneous and sequential offers were randomly interleaved in each session. We classified cells in each choice modality, and we examined the relation between the two classifications. We found a strong correspondence; in other words, the cell groups measured under simultaneous offers and under sequential offers were one and the same. This result indicates that economic choices under simultaneous or sequential offers rely on the same neural circuit.SIGNIFICANCE STATEMENT Research in the past 20 years has shed light on the neuronal underpinnings of economic choices. A large number of results indicates that decisions between goods are formed in a neural circuit within the orbitofrontal cortex. In most previous studies, subjects chose between two goods offered simultaneously. Yet, in daily situations, goods available for choice are often presented or examined in sequence. Here we recorded neuronal activity in the primate orbitofrontal cortex alternating trials under simultaneous and under sequential offers. Our analyses demonstrate that the same neural circuit supports choices in the two modalities. Hence, current notions on the neuronal mechanisms underlying economic decisions generalize to choices under sequential offers. Copyright © 2022 the authors.
Author Keywordsdecision making; monkey; neuroeconomics; orbitofrontal cortex; subjective value
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Perspective on the Relationship between GABAA Receptor Activity and the Apparent Potency of an Inhibitor” (2022) Current Neuropharmacology
Perspective on the Relationship between GABAA Receptor Activity and the Apparent Potency of an Inhibitor(2022) Current Neuropharmacology, 20 (1), pp. 90-93.
Germann, A.L.a , Pierce, S.R.a , Evers, A.S.a b , Steinbach, J.H.a b , Akk, G.a b
a Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, United Statesb The Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine, St. Louis, MO 63110, United States
AbstractBackground: In electrophysiological experiments, inhibition of a receptor-channel, such as the GABAA receptor, is measured by co-applying an agonist producing a predefined control response with an inhibitor to calculate the fraction of the control response remaining in the presence of the inhibitor. The properties of the inhibitor are determined by fitting the inhibition concentra-tion-response relationship to the Hill equation to estimate the midpoint (IC50) of the inhibition curve. Objective: We sought to estimate sensitivity of the fitted IC50 to the level of activity of the control response. Methods: The inhibition concentration-response relationships were calculated for models with distinct mechanisms of inhibition. In Model I, the inhibitor acts allosterically to stabilize the resting state of the receptor. In Model II, the inhibitor competes with the agonist for a shared binding site. In Model III, the inhibitor stabilizes the desensitized state. Results: The simulations indicate that the fitted IC50 of the inhibition curve is sensitive to the degree of activity of the control response. In Models I and II, the IC50 of inhibition was increased as the probability of being in the active state (PA) of the control response increased. In Model III, the IC50 of inhibition was reduced at higher PA. Conclusion: We infer that the apparent potency of an inhibitor depends on the PA of the control re-sponse. While the calculations were carried out using the activation and inhibition properties that are representative of the GABAA receptor, the principles and conclusions apply to a wide variety of re-ceptor-channels. © 2022 Bentham Science Publishers.
Author KeywordsActivation; GABAA receptor; IC50; Inhibition; Modeling
Funding detailsNational Institute of General Medical SciencesNIGMSR01GM108580, R01GM108799, R35GM140947Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine in St. Louis
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Intrinsic Mechanisms in the Gating of Resurgent Na+ Currents” (2022) eLife
Intrinsic Mechanisms in the Gating of Resurgent Na+ Currents(2022) eLife, 11, art. no. e70173, .
Ransdell, J.L.a , Moreno, J.D.c , Bhagavan, D.c , Silva, J.R.c , Nerbonne, J.M.a b
a Department of Medicine, Cardiovascular Division, Washington University in St. Louis, St. Louis, MO 63110, United Statesb Department of Developmental Biology, Washington University in St. Louis, St. Louis, MO 63110, United Statesc Biomedical Engineering, Washington University in St. Louis, St. Louis, MO 63110, United States
AbstractThe resurgent component of the voltage-gated sodium current (INaR) is a depolarizing conductance, revealed on membrane hyperpolarizations following brief depolarizing voltage steps, which has been shown to contribute to regulating the firing properties of numerous neuronal cell types throughout the central and peripheral nervous systems. Although mediated by the same voltage-gated sodium (Nav) channels that underlie the transient and persistent Nav current components, the gating mechanisms that contribute to the generation of INaR remain unclear. Here, we characterized Nav currents in mouse cerebellar Purkinje neurons, and used tailored voltage-clamp protocols to define how the voltage and the duration of the initial membrane depolarization affect the amplitudes and kinetics of INaR. Using the acquired voltage-clamp data, we developed a novel Markov kinetic state model with parallel (fast and slow) inactivation pathways and, we show that this model reproduces the properties of the resurgent, as well as the transient and persistent, Nav currents recorded in (mouse) cerebellar Purkinje neurons. Based on the acquired experimental data and the simulations, we propose that resurgent Na+ influx occurs as a result of fast inactivating Nav channels transitioning into an open/conducting state on membrane hyperpolarization, and that the decay of INaR reflects the slow accumulation of recovered/opened Nav channels into a second, alternative and more slowly populated, inactivated state. Additional simulations reveal that extrinsic factors that affect the kinetics of fast or slow Nav channel inactivation and/or impact the relative distribution of Nav channels in the fast-and slow-inactivated states, such as the accessory Navβ4 channel subunit, can modulate the amplitude of INaR. © 2022, eLife Sciences Publications Ltd. All rights reserved.
Author KeywordsINaR; Markov modelling; Mouse cerebellar Purkinje neurons; Nav channel gating
Funding detailsNational Institutes of HealthNIHF32 NS090765, R01 HL136553, R01 NS065761, T32 HL007081Foundation for Barnes-Jewish HospitalFBJH
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Risk Factors for Phenoconversion in Rapid Eye Movement Sleep Behavior Disorder” (2022) Annals of Neurology
Risk Factors for Phenoconversion in Rapid Eye Movement Sleep Behavior Disorder(2022) Annals of Neurology, .
Zhang, H.a b , Iranzo, A.c , Högl, B.d , Arnulf, I.e , Ferini-Strambi, L.f , Manni, R.g , Miyamoto, T.h , Oertel, W.H.i , Dauvilliers, Y.j , Ju, Y.-E.k , Puligheddu, M.l , Sonka, K.m , Pelletier, A.n , Montplaisir, J.Y.n o , Stefani, A.d , Ibrahim, A.d , Frauscher, B.d , Leu-Semenescu, S.e , Zucconi, M.f , Terzaghi, M.g , Miyamoto, M.p , Janzen, A.i , Figorilli, M.l , Fantini, M.L.l q , Postuma, R.B.b n
a Department of Neurology, Xuanwu Hospital Capital Medical University, Beijing, Chinab Department of Neurology, McGill University, Montreal General Hospital, Montreal, QC, Canadac Neurology Service, Hospital Clinic of Barcelona, August Pi i Sunyer Biomedical Research Institute, Center for Biomedical Research on Neurodegenerative Diseases, Barcelona, Spaind Department of Neurology, Innsbruck Medical University, Innsbruck, Austriae Paris Brain Institute and Sleep Disorder Unit, Pitié-Salpêtrière Hospital, Public Hospital Network of Paris, Sorbonne University, Paris, Francef Sleep Disorders Center, Vita-Salute San Raffaele University, Milan, Italyg C. Mondino National Neurological Institute, Pavia, Italyh Department of Neurology, Dokkyo Medical University Saitama Medical Center, Saitama, Japani Department of Neurology, Philipps University, Marburg, Germanyj Department of Neurology, Gui de Chauliac Hospital, Montpellier, National Institute of Health and Medical Research U1061, Montpellier, Francek Department of Neurology, Washington University School of Medicine, St Louis, MO, United Statesl Sleep Center, Department of Cardiovascular and Neurological Sciences, University of Cagliari, Cagliari, Italym Department of Neurology, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republicn Center for Advanced Studies in Sleep Medicine, Montreal Sacred Heart Hospital, Montreal, QC, Canadao Department of Psychiatry, University of Montreal, Montreal, QC, Canadap Department of Neurology, Dokkyo Medical University School of Medicine, Tochigi, Japanq Department of Neurology, University of Auvergne, Clermont-Ferrand, France
AbstractObjective: This study was undertaken to follow up predictive factors for α-synuclein–related neurodegenerative diseases in a multicenter cohort of idiopathic/isolated rapid eye movement sleep behavior disorder (iRBD). Methods: Patients with iRBD from 12 centers underwent a detailed assessment for potential environmental and lifestyle risk factors via a standardized questionnaire at baseline. Patients were then prospectively followed and received assessments for parkinsonism or dementia during follow-up. The cumulative incidence of parkinsonism or dementia was estimated with competing risk analysis. Cox regression analyses were used to evaluate the predictive value of environmental/lifestyle factors over a follow-up period of 11 years, adjusting for age, sex, and center. Results: Of 319 patients who were free of parkinsonism or dementia, 281 provided follow-up information. After a mean follow-up of 5.8 years, 130 (46.3%) patients developed neurodegenerative disease. The overall phenoconversion rate was 24.2% after 3 years, 44.8% after 6 years, and 67.5% after 10 years. Patients with older age (adjusted hazard ratio [aHR] = 1.05) and nitrate derivative use (aHR = 2.18) were more likely to phenoconvert, whereas prior pesticide exposure (aHR = 0.21–0.64), rural living (aHR = 0.53), lipid-lowering medication use (aHR = 0.59), and respiratory medication use (aHR = 0.36) were associated with lower phenoconversion risk. Risk factors for those converting to primary dementia and parkinsonism were generally similar, with dementia-first converters having lower coffee intake and beta-blocker intake, and higher occurrence of family history of dementia. Interpretation: Our findings elucidate the predictive values of environmental factors and comorbid conditions in identifying RBD patients at higher risk of phenoconversion. ANN NEUROL 2022. © 2022 American Neurological Association.
Funding detailsCanadian Institutes of Health ResearchIRSCFonds de Recherche du Québec – SantéFRQS
Document Type: ArticlePublication Stage: Article in PressSource: Scopus
“Metabolic sensing in AgRP neurons integrates homeostatic state with dopamine signalling in the striatum” (2022) eLife
Metabolic sensing in AgRP neurons integrates homeostatic state with dopamine signalling in the striatum(2022) eLife, 11, art. no. e72668, .
Reichenbach, A.a , Clarke, R.E.a , Stark, R.a , Lockie, S.H.a , Mequinion, M.a , Dempsey, H.a , Rawlinson, S.a , Reed, F.a , Sepehrizadeh, T.b , Deveer, M.b , Munder, A.C.a c , Nunez-Iglesias, J.d , Spanswick, D.C.a e , Mynatt, R.f , Kravitz, A.V.g , Dayas, C.V.h , Brown, R.c i , Andrews, Z.B.a
a Monash Biomedicine Discovery Institute and Department of Physiology, Monash University, Clayton, Australiab Monash Biomedical Imaging Facility, Monash University, Clayton, Australiac Florey Institute of Neuroscience & Mental Health, Parkville, Australiad Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University, Clayton, Australiae Warwick Medical School, University of Warwick, Coventry, United Kingdomf Gene Nutrient Interactions Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, United Statesg Departments of Psychiatry, Anesthesiology, and Neuroscience, Washington University in St Louis, St Louis, United Statesh School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, Australiai Department of Biochemistry and Pharmacology, University of Melbourne, Parkville, Australia
AbstractAgouti-related peptide (AgRP) neurons increase motivation for food, however, whether metabolic sensing of homeostatic state in AgRP neurons potentiates motivation by inter-acting with dopamine reward systems is unexplored. As a model of impaired metabolic-sensing, we used the AgRP-specific deletion of carnitine acetyltransferase (Crat) in mice. We hypothesised that metabolic sensing in AgRP neurons is required to increase motivation for food reward by modulating accumbal or striatal dopamine release. Studies confirmed that Crat deletion in AgRP neurons (KO) impaired ex vivo glucose-sensing, as well as in vivo responses to peripheral glucose injection or repeated palatable food presentation and consumption. Impaired metabolic-sensing in AgPP neurons reduced acute dopamine release (seconds) to palatable food consumption and during operant responding, as assessed by GRAB-DA photometry in the nucleus accumbens, but not the dorsal striatum. Impaired metabolic-sensing in AgRP neurons suppressed radiolabelled 18F-fDOPA accumulation after ~30 min in the dorsal striatum but not the nucleus accumbens. Impaired metabolic sensing in AgRP neurons suppressed motivated operant responding for sucrose rewards during fasting. Thus, metabolic-sensing in AgRP neurons is required for the appropriate temporal integration and transmission of homeostatic hunger-sensing to dopamine signalling in the striatum. © 2022, eLife Sciences Publications Ltd. All rights reserved.
Funding detailsNational Health and Medical Research CouncilNHMRCAPP1126724, APP1154974Monash UniversityMU
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Continuous real-time prediction of surgical case duration using a modular artificial neural network” (2022) British Journal of Anaesthesia
Continuous real-time prediction of surgical case duration using a modular artificial neural network(2022) British Journal of Anaesthesia, .
Jiao, Y.a , Xue, B.b , Lu, C.b , Avidan, M.S.a , Kannampallil, T.a c
a Department of Anesthesiology, Washington University School of Medicine in St Louis, St Louis, MO, United Statesb Department of Computer Science and Engineering, Washington University in St Louis, St Louis, MO, United Statesc Institute for Informatics, Washington University School of Medicine in St Louis, St Louis, MO, United States
AbstractBackground: Real-time prediction of surgical duration can inform perioperative decisions and reduce surgical costs. We developed a machine learning approach that continuously incorporates preoperative and intraoperative information for forecasting surgical duration. Methods: Preoperative (e.g. procedure name) and intraoperative (e.g. medications and vital signs) variables were retrieved from anaesthetic records of surgeries performed between March 1, 2019 and October 31, 2019. A modular artificial neural network was developed and compared with a Bayesian approach and the scheduled surgical duration. Continuous ranked probability score (CRPS) was used as a measure of time error to assess model accuracy. For evaluating clinical performance, accuracy for each approach was assessed in identifying cases that ran beyond 15:00 (commonly scheduled end of shift), thus identifying opportunities to avoid overtime labour costs. Results: The analysis included 70 826 cases performed at eight hospitals. The modular artificial neural network had the lowest time error (CRPS: mean=13.8; standard deviation=35.4 min), which was significantly better (mean difference=6.4 min [95% confidence interval: 6.3–6.5]; P<0.001) than the Bayesian approach. The modular artificial neural network also had the highest accuracy in identifying operating theatres that would overrun 15:00 (accuracy at 1 h prior=89%) compared with the Bayesian approach (80%) and a naïve approach using the scheduled duration (78%). Conclusions: A real-time neural network model using preoperative and intraoperative data had significantly better performance than a Bayesian approach or scheduled duration, offering opportunities to avoid overtime labour costs and reduce the cost of surgery by providing superior real-time information for perioperative decision support. © 2022 British Journal of Anaesthesia
Author Keywordsartificial neural network; economics; healthcare costs; machine learning; operating theatre efficiency; procedure duration; statistical model; surgery
Funding detailsWashington University School of Medicine in St. LouisWUSM
Document Type: ArticlePublication Stage: Article in PressSource: Scopus
“Personality Pathology Predicts Increased Informant-Reported, but Not Performance-Based, Cognitive Decline: Findings From Two Samples” (2022) Personality Disorders: Theory, Research, and Treatment
Personality Pathology Predicts Increased Informant-Reported, but Not Performance-Based, Cognitive Decline: Findings From Two Samples(2022) Personality Disorders: Theory, Research, and Treatment, 13 (1), pp. 30-40.
Cruitt, P.J., Hill, P.L., Oltmanns, T.F.
Department of Psychological and Brain Sciences, Washington University in St. Louis, United States
AbstractResearch on the relationship between normal-range personality and cognitive aging has demonstrated consistent, modest effects. The current investigation increases our understanding of unhealthy cognitiveaging by testing whether personality disorders (PDs), specifically borderline, avoidant, and obsessive–compulsive PDs, show prospective associations with the onset of cognitive problems. Interpersonalstressful life events and social support were expected to mediate these relationships. The currentinvestigation used data from 2 longitudinal studies of older adulthood: the Alzheimer’s disease ResearchCenter cohort (ADRC, N = 434, Mage = 69.95, 56% women) and the St. Louis Personality and AgingNetwork study (SPAN, N = 1,058, Mage = 65.92, 54% women). The ADRC study administered a batteryof neuropsychological tests to assess cognitive ability/memory. Borderline PD was measured with acomposite from the NEO Five-Factor Inventory. The SPAN study administered self-, informant, andinterview measures of the three PDs; a free-recall task; and an informant report measure of cognitiveproblems. Borderline PD features exhibited cross-sectional correlations with memory (ADRC: r=-.11;SPAN: all rs = -.08), general cognitive ability (ADRC: r = -.11), and informant-reported cognitiveproblems (rs ranged from.15 to.39). Most importantly, borderline PD features predicted an increase ininformant-reported cognitive problems in SPAN participants (standardized bs =.13 and.15) over a 2-year period, but they did not predict a deterioration in the performance-based cognitive measures ineither study. Avoidant and obsessive– compulsive PDs exhibited little association with cognitive aging.Neither interpersonal variable mediated any of these effects © 2021 American Psychological Association
Author KeywordsAging; Borderline personality disorder; Cognitive decline; Memory; Personality pathology
Funding details5 T32 AG000030-39, R01-AG045231, R01-AG056517National Institute on AgingNIAP01-AG026276, P01-AG03991
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Comparison of ETDRS 7-Field to 4-Widefield Digital Imaging in the Evaluation of Diabetic Retinopathy Severity” (2022) Translational Vision Science and Technology
Comparison of ETDRS 7-Field to 4-Widefield Digital Imaging in the Evaluation of Diabetic Retinopathy Severity(2022) Translational Vision Science and Technology, 11 (1), art. no. 13, .
Blodi, B.A.a , Domalpally, A.a b , Tjaden, A.H.b , Barrett, N.a , Chew, E.Y.c , Knowler, W.C.d , Lee, C.G.e , Pi-Sunyer, X.f , Wallia, A.g , White, N.H.h , Temprosa, M.b
a Wisconsin Reading Center, Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI, United Statesb Biostatistics Center and Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Rockville, MD, United Statesc Division of Epidemiology and Clinical Applications, Clinical Trials Branch, National Eye Institute, National Institutes of Health, Bethesda, MD, United Statesd Diabetes Epidemiology and Clinical Research Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ, United Statese Division of Diabetes, Endocrinology and Metabolic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, United Statesf Columbia University Irving Medical Center, New York, NY, United Statesg Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, United Statesh Division of Endocrinology and Diabetes, Department of Pediatrics, Washington University in St. Louis, St. Louis, MO, United States
AbstractPurpose: To compare Early Treatment Diabetic Retinopathy Study (ETDRS) severity levels between two digital fundus imaging protocols for research studies of diabetic retinopathy: the gold standard 7-field (7F) imaging and the more recent 4-widefield (4W) imaging. Methods: Two hundred twenty-two participants enrolled in the Diabetes Prevention Program Outcomes Study underwent concurrent 7F and 4W imaging. The ETDRS levels from 220 paired gradable images were determined by masked graders. Each image was graded by two independent graders with adjudication by a senior grader, if necessary. Percent agreement between graders and between imaging protocols was evaluated with kappa statistics and weighted kappa statistics. Results: Of 220 gradable eyes, diabetic retinopathy was seen in 11.8%; this was mild in 10.4% and more than mild in 1.4% using 7F imaging. The ETDRS levels showed exact agreement of 95% between 7F and 4W imaging (weighted kappa 0.86). Intergrader agreement for each modality had exact agreement of 89% (weighted kappa of 0.73) for 7F and 91% (weighted kappa 0.77) for 4W. Conclusions: There is substantial agreement in the ETDRS severity level between the 7F and 4W digital imaging protocols, demonstrating that the two imaging protocols are interchangeable. Both 4W and 7F digital imaging protocols can be used for assessing ETDRS levels, even in populations with minimal diabetic retinopathy. Translational Relevance: The 4W protocol requires fewer images than the 7F, is more comfortable for the patients, is easier for photographic capture, and provides diabetic retinopathy data that is equivalent to the 7F imaging protocol. © 2022 The Authors.
Author KeywordsDiabetic retinopathy; Digital imaging; ETDRS grading
Funding detailsNational Institutes of HealthNIHU01 DK048339, U01 DK048349, U01 DK048375, U01 DK048377, U01 DK048380, U01 DK048381, U01 DK048387, U01 DK048397, U01 DK048400, U01 DK048404, U01 DK048406, U01 DK048407, U01 DK048411, U01 DK048412, U01 DK048413, U01 DK048434, U01 DK048437, U01 DK048443, U01 DK048468, U01 DK048485, U01 DK048489, U01 DK048514Centers for Disease Control and PreventionCDCAmerican Diabetes AssociationADANational Institute on AgingNIANational Heart, Lung, and Blood InstituteNHLBINational Eye InstituteNEINational Cancer InstituteNCINational Institute of Diabetes and Digestive and Kidney DiseasesNIDDKNational Institute of Child Health and Human DevelopmentNICHDNational Center for Research ResourcesNCRROffice of Research on Women’s HealthORWHU.S. Department of Veterans AffairsVAResearch to Prevent BlindnessRPBHenry M. Jackson FoundationHJFMerckIndian Health ServiceIHSNational Institute on Minority Health and Health DisparitiesNIMHD
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Does ventricle size contribute to cognitive outcomes in posthemorrhagic hydrocephalus? Role of early definitive intervention” (2022) Journal of Neurosurgery. Pediatrics
Does ventricle size contribute to cognitive outcomes in posthemorrhagic hydrocephalus? Role of early definitive intervention(2022) Journal of Neurosurgery. Pediatrics, 29 (1), pp. 10-20.
Paturu, M.a , Triplett, R.L.b , Thukral, S.a , Alexopoulos, D.b , Smyser, C.D.b c , Limbrick, D.D.a , Strahle, J.M.a d
a Departments of Neurological Surgeryb 2Neurologyc 4Radiology, Washington University in St. LouisMOd 3Pediatrics
AbstractOBJECTIVE: Posthemorrhagic hydrocephalus (PHH) is associated with significant morbidity, smaller hippocampal volumes, and impaired neurodevelopment in preterm infants. The timing of temporary CSF (tCSF) diversion has been studied; however, the optimal time for permanent CSF (pCSF) diversion is unknown. The objective of this study was to determine whether cumulative ventricle size or timing of pCSF diversion is associated with neurodevelopmental outcome and hippocampal size in preterm infants with PHH. METHODS: Twenty-five very preterm neonates (born at ≤ 32 weeks’ gestational age) with high-grade intraventricular hemorrhage (IVH), subsequent PHH, and pCSF diversion with a ventriculoperitoneal shunt (n = 20) or endoscopic third ventriculostomy (n = 5) were followed until 2 years of age. Infants underwent serial cranial ultrasounds from birth until 1 year after pCSF diversion, brain MRI at term-equivalent age, and assessment based on the Bayley Scales of Infant and Toddler Development, Third Edition, at 2 years of age. Frontooccipital horn ratio (FOHR) measurements were derived from cranial ultrasounds and term-equivalent brain MRI. Hippocampal volumes were segmented and calculated from term-equivalent brain MRI. Cumulative ventricle size until the time of pCSF diversion was estimated using FOHR measurements from each cranial ultrasound performed prior to permanent intervention. RESULTS: The average gestational ages at tCSF and pCSF diversion were 28.9 and 39.0 weeks, respectively. An earlier chronological age at the time of pCSF diversion was associated with larger right hippocampal volumes on term-equivalent MRI (Pearson’s r = -0.403, p = 0.046) and improved cognitive (r = -0.554, p = 0.047), motor (r = -0.487, p = 0.048), and language (r = -0.414, p = 0.021) outcomes at 2 years of age. Additionally, a smaller cumulative ventricle size from birth to pCSF diversion was associated with larger right hippocampal volumes (r = -0.483, p = 0.014) and improved cognitive (r = -0.711, p = 0.001), motor (r = -0.675, p = 0.003), and language (r = -0.618, p = 0.011) outcomes. There was no relationship between time to tCSF diversion or cumulative ventricle size prior to tCSF diversion and neurodevelopmental outcome or hippocampal size. Finally, a smaller cumulative ventricular size prior to either tCSF diversion or pCSF diversion was associated with a smaller ventricular size 1 year after pCSF diversion (r = 0.422, p = 0.040, R2 = 0.178 and r = 0.519, p = 0.009, R2 = 0.269, respectively). CONCLUSIONS: In infants with PHH, a smaller cumulative ventricular size and shorter time to pCSF diversion were associated with larger right hippocampal volumes, improved neurocognitive outcomes, and reduced long-term ventriculomegaly. Future prospective randomized studies are needed to confirm these findings.
Author Keywordsendoscopic third ventriculostomy; ETV; intraventricular hemorrhage; posthemorrhagic hydrocephalus; ventriculoperitoneal shunt
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Modeling the Effects of HIV and Aging on Resting-State Networks Using Machine Learning” (2021) Journal of Acquired Immune Deficiency Syndromes (1999)
Modeling the Effects of HIV and Aging on Resting-State Networks Using Machine Learning(2021) Journal of Acquired Immune Deficiency Syndromes (1999), 88 (4), pp. 414-419.
Luckett, P.H.a , Paul, R.H.b , Hannon, K.a , Lee, J.J.c , Shimony, J.S.c , Meeker, K.L.a , Cooley, S.A.a , Boerwinkle, A.H.a , Ances, B.M.a
a Department of Neurology, Washington University School of Medicine, St. Louis, MO, United Statesb Department of Psychological Sciences, University of Missouri Saint Louis, St. Louis, Missouri; andc Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, United States
AbstractBACKGROUND: The relationship between HIV infection, the functional organization of the brain, cognitive impairment, and aging remains poorly understood. Understanding disease progression over the life span is vital for the care of people living with HIV (PLWH). SETTING: Virologically suppressed PLWH (n = 297) on combination antiretroviral therapy and 1509 HIV-uninfected healthy controls were evaluated. PLWH were further classified as cognitively normal (CN) or cognitively impaired (CI) based on neuropsychological testing. METHODS: Feature selection identified resting-state networks (RSNs) that predicted HIV status and cognitive status within specific age bins (younger than 35 years, 35-55 years, and older than 55 years). Deep learning models generated voxelwise maps of RSNs to identify regional differences. RESULTS: Salience (SAL) and parietal memory networks (PMNs) differentiated individuals by HIV status. When comparing controls with PLWH CN, the PMN and SAL had the strongest predictive strength across all ages. When comparing controls with PLWH CI, the SAL, PMN, and frontal parietal network (FPN) were the best predictors. When comparing PLWH CN with PLWH CI, the SAL, FPN, basal ganglia, and ventral attention were the strongest predictors. Only minor variability in predictive strength was observed with aging. Anatomically, differences in RSN topology occurred primarily in the dorsal and rostral lateral prefrontal cortex, cingulate, and caudate. CONCLUSION: Machine learning identified RSNs that classified individuals by HIV status and cognitive status. The PMN and SAL were sensitive for discriminating HIV status, with involvement of FPN occurring with cognitive impairment. Minor differences in RSN predictive strength were observed by age. These results suggest that specific RSNs are affected by HIV, aging, and HIV-associated cognitive impairment. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
Document Type: ArticlePublication Stage: FinalSource: Scopus
“A Survey of Cannabis Use in a Large US-Based Cohort of People with Multiple Sclerosis” (2021) International Journal of MS Care
A Survey of Cannabis Use in a Large US-Based Cohort of People with Multiple Sclerosis(2021) International Journal of MS Care, 23 (6), pp. 245-252.
Salter, A.a , Fox, R.J.b , Cutter, G.c , Marrie, R.A.d , Nichol, K.E.e , Steinerman, J.R.e , Smith, K.M.J.e
a Washington University in St Louis, St Louis, MO, United Statesb Mellen Center for Multiple Sclerosis, Cleveland Clinic, Cleveland, OH, United Statesc The University of Alabama at Birmingham, Birmingham, AL, United Statesd Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canadae Greenwich Biosciences, Inc, Carlsbad, CA, United States
AbstractBackground: As cannabis products become increasingly accessible across the United States, it is important to understand the contemporary use of cannabis for managing multiple sclerosis (MS) symptoms. Methods: We invited participants with MS from the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry (aged 18 years or older) to complete a supplemental survey on cannabis use between March and April 2020. Participants reported cannabis use, treated symptoms, patterns, preferences, methods of use, and the factors limiting use. Findings are reported using descriptive statistics. Results: Of the 6934 participants invited, 3249 responded. Of the respondents, 31% reported having ever used cannabis to treat MS symptoms, with 20% currently using cannabis. The remaining 69% had never used cannabis for MS symptoms, for reasons including not enough data about efficacy (40%) and safety (27%), and concerns about legality (25%) and cost (18%). The most common symptoms current users were attempting to treat were spasticity (80%), pain (69%), and sleep problems (61%). Ever users (vs never users) were more likely to be younger, be non-White, have lower education, reside in the Northeast and West, be unemployed, be younger at symptom onset, be currently smoking, and have higher levels of disability and MS-related symptoms (all P < .001). Conclusions: Despite concerns about insufficient safety and efficacy data, legality, and cost, almost one-third of NARCOMS Registry respondents report having tried nonprescription cannabis products in an attempt to alleviate their symptoms. Given the lack of efficacy and safety data on such products, future research in this area is warranted. Int J MS Care. 2021;23:245-252. © 2021 Consortium of Multiple Sclerosis Centers.
Funding detailsU.S. Department of DefenseDODNational Multiple Sclerosis SocietyNMSSNovartisSanofiBiogenMultiple Sclerosis Scientific Research FoundationMSSRFCanadian Institutes of Health ResearchIRSCCrohn’s and Colitis Canada
Document Type: ArticlePublication Stage: FinalSource: Scopus
“NARCOMS and Other Registries in Multiple Sclerosis: Issues and Insights” (2021) International Journal of MS Care
NARCOMS and Other Registries in Multiple Sclerosis: Issues and Insights(2021) International Journal of MS Care, 23 (6), pp. 276-285. Cited 1 time.
Marrie, R.A.a , Cutter, G.R.b , Fox, R.J.c , Vollmer, T.d , Tyry, T.e , Salter, A.f
a Department of Internal Medicine and Department of Community Health Sciences, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canadab Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, United Statesc Mellen Center for Multiple Sclerosis, Neurological Institute, Cleveland Clinic, Cleveland, OH, United Statesd Department of Neurology, Rocky Mountain Multiple Sclerosis Center at Anschutz Medical Campus, University of Colorado Denver, Denver, CO, United Statese Department of Neurology, Rocky Mountain Multiple Sclerosis Center at Anschutz Medical Campus, University of Colorado Denver, Phoenix, AZ, United Statesf Division of Biostatistics, Washington University in St Louis, St Louis, MO, United States
AbstractObservational studies and registries can play a critical role in elucidating the natural and treated history of multiple sclerosis (MS) and identifying factors associated with outcomes such as disability and health-related quality of life. The North American Research Committee on Multiple Sclerosis (NARCOMS) Registry is one of multiple registries worldwide that focuses on people with MS, but one of the very few patient-driven MS registries. On the 25th anniversary of the first data collection for the NARCOMS Registry, we discuss the importance of disease registries in the MS field, describe key concepts related to registry design and management, and highlight findings from MS registries relevant to clinical care or health policy. Int J MS Care. 2021;23:276-284. © 2021 Consortium of Multiple Sclerosis Centers.
Funding detailsNovartisBiogenTG Therapeutics
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Characterizing Long-term Disability Progression and Employment in NARCOMS Registry Participants with Multiple Sclerosis Taking Dimethyl Fumarate” (2021) International Journal of MS Care
Characterizing Long-term Disability Progression and Employment in NARCOMS Registry Participants with Multiple Sclerosis Taking Dimethyl Fumarate(2021) International Journal of MS Care, 23 (6), pp. 239-244.
Salter, A.a , Lancia, S.a , Cutter, G.b , Fox, R.J.c , Marrie, R.A.d , Mendoza, J.P.e , Lewin, J.B.e
a Division of Biostatistics, School of Medicine, Washington University in St Louis, St Louis, MO, United Statesb Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, United Statesc Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, Cleveland, OH, United Statesd Department of Medicine and Department of Community Health Sciences, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canadae Department of Medicine and Department of Community Health Sciences, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Biogen, Cambridge, MA, United States
AbstractBackground: Delayed-release dimethyl fumarate (DMF) is effective in relapsing-remitting multiple sclerosis (RRMS), but long-term effects of DMF on disability and disease progression in clinical settings are unknown. We evaluated disability and employment outcomes in persons with RRMS treated with DMF for up to 5 years. Methods: This longitudinal study included US North American Research Committee on Multiple Sclerosis (NARCOMS) Registry participants with RRMS reporting DMF initiation in fall 2013 through spring 2018 with 1 year or more of follow-up. Time to 6-month confirmed disability progression (≥1-point increase in Patient-Determined Disease Steps [PDDS] score) and change in employment status were evaluated using Kaplan-Meier analysis. Participants were censored at last follow-up or at DMF discontinuation, whichever came first. Results: During the study, 725 US participants with RRMS had at least 1 year of DMF follow-up data, of whom most were female and White. At year 5, 69.9% (95% CI, 65.4%-73.9%) of these participants were free from 6-month confirmed disability progression, and 84.7% (95% CI, 78.6%- 89.2%) were free from conversion to secondary progressive MS. Of 116 participants with data at baseline and year 5, most had stable or improved PDDS and Performance Scales scores over 5 years. Of 322 participants 62 years and younger and employed at the index survey, 66.0% (95% CI, 57.6%- 73.1%) were free from a negative change in employment type over 5 years. Conclusions: Most US NARCOMS Registry participants treated up to 5 years with DMF remained free from 6-month confirmed disability progression and conversion to secondary progressive MS and had stable disability and employment status. These results support the long-term stability of disability and work-related outcomes with disease-modifying therapy. Int J MS Care. 2021;23:239-244. © 2021 Consortium of Multiple Sclerosis Centers.
Funding detailsU.S. Department of DefenseDODNational Multiple Sclerosis SocietyNMSSNovartisBiogenTeva Pharmaceutical IndustriesArthritis SocietyMultiple Sclerosis Society of CanadaMSSOCCrohn’s and Colitis Canada
Document Type: ArticlePublication Stage: FinalSource: Scopus
“The prospective association between periodontal disease and brain imaging outcomes: The Atherosclerosis Risk in Communities study” (2021) Journal of Clinical Periodontology
The prospective association between periodontal disease and brain imaging outcomes: The Atherosclerosis Risk in Communities study(2021) Journal of Clinical Periodontology, .
Adam, H.S.a , Lakshminarayan, K.a , Wang, W.a , Norby, F.L.b , Mosley, T.c , Walker, K.A.d , Gottesman, R.F.e , Meyer, K.f , Hughes, T.M.g , Pankow, J.S.a , Wong, D.F.h , Jack, C.R., Jr.i , Sen, S.j , Lutsey, P.L.a , Beck, J.k , Demmer, R.T.a l
a Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, United Statesb Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Health System, Los Angeles, CA, United Statesc Department of Medicine, University of Mississippi Medical Center, Jackson, MS, United Statesd Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United Statese Stroke Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD, United Statesf Department of Nutrition, University of North Carolina, Chapel Hill, Chapel Hill, NC, United Statesg Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, United Statesh Mallinckrodt Institute of Radiology, Washington University in St. Louis Missouri, St. Louis, MO, United Statesi Department of Radiology, Mayo Clinic, Rochester, MN, United Statesj Department of Neurology, University of South Carolina, School of Medicine, Columbia, SC, United Statesk Division of Comprehensive Oral Health – Periodontology, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, United Statesl Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, United States
AbstractAim: We investigate if periodontal disease is prospectively associated with cerebrovascular and neurodegenerative markers of dementia and Alzheimer’s pathology. Materials and Methods: N = 1306 participants (Visit 5 mean age = 76.5 [standard deviation = 5.4] years) in the Atherosclerosis Risk in Communities study with completed dental exams at Visit 4 underwent brain magnetic resonance imaging scans at Visit 5 while N = 248 underwent positron emission tomography scans. Participants were classified as edentulous or, among the dentate, by the modified Periodontal Profile Class. Brain volumes were regressed on periodontal status in linear regressions. Cerebrovascular measures and β-amyloid positivity were regressed on periodontal status in logistic regressions. Results: Periodontal disease was not associated with brain volumes, microhaemorrhages, or elevated β-amyloid. Compared with periodontally healthy individuals, odds ratios [95% confidence interval] for all-type infarcts were 0.37 [0.20, 0.65] for severe tooth loss and 0.56 [0.31, 0.99] for edentulous participants. Conclusions: Within the limitations of this study, periodontal disease was not associated with altered brain volumes, microhaemorrhages, or β-amyloid positivity. Tooth loss was associated with lower odds of cerebral infarcts. © 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Funding detailsNational Institutes of HealthNIHU.S. Department of Health and Human ServicesHHS2U01HL096814, 2U01HL096899, 2U01HL096902, 2U01HL096917, HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700004I, HHSN268201700005I, U012U01HL096812National Institute on AgingNIAR01AG040282National Heart, Lung, and Blood InstituteNHLBINational Institute on Deafness and Other Communication DisordersNIDCDR01‐HL70825National Institute of Neurological Disorders and StrokeNINDSNational Institute of Dental and Craniofacial ResearchNIDCRR01‐DE021418, R01‐DE021986National Center for Research ResourcesNCRR5T32 HL 7779–27, NHLBI‐CON000000080742, UL1‐TR001111Mayo Clinic
Document Type: ArticlePublication Stage: Article in PressSource: Scopus
“Cut points and sensitivity to change of the Enfranchisement scale of the Community Participation Indicators in adults with traumatic brain injury” (2021) PM and R
Cut points and sensitivity to change of the Enfranchisement scale of the Community Participation Indicators in adults with traumatic brain injury(2021) PM and R, .
Kersey, J.a , Baum, C.M.b , Hammel, J.c , Terhorst, L.d , McCue, M.e , Skidmore, E.R.a
a OTR/L, Department of Occupational Therapy, University of Pittsburgh, School of Health and Rehabilitation Science, Pittsburgh, PA, United Statesb OTR/L, Program in Occupational Therapy, Washington University in St. Louis, St. Louis, MO, United Statesc OTR/L, Department of Occupational Therapy, University of Illinois at Chicago, Chicago, IL, United Statesd Department of Occupational Therapy, University of Pittsburgh, School of Health and Rehabilitation Science, Pittsburgh, PA, United Statese Department of Rehabilitation Science and Technology, School of Health and Rehabilitation Sciences, University of Pittsburgh, Pittsburgh, PA, United States
AbstractBackground: Community participation is an important outcome of rehabilitation following traumatic brain injury. Yet, few measures assess inclusion and belonging (enfranchisement) as a dimension of community participation. The Enfranchisement scale of the Community Participation Indicators addresses this need. However, research on its psychometric properties is lacking. Objective: To examine cut points and sensitivity to change of the Enfranchisement scale of the Community Participation Indicators in adults with traumatic brain injury. Design: This was a repeated measures study with assessments administered twice (3 months apart). Setting: Assessments were administered either over the phone, virtually (Zoom), or in person at the participant’s home. Participants: A total of 44 participants from community settings who had either experienced a traumatic brain injury within the previous year or were receiving rehabilitation interventions were recruited. Main Outcome Measure: The Enfranchisement scale has two subscales: the Control subscale (range: 13-65) and the Importance subscale (range: 14-70). On both subscales, lower scores indicate better enfranchisement. Methods: The software SAS PROC Logistic and the macro %ROCPlot were used to examine cut points at varying levels of sensitivity and specificity. The area under the receiver operating characteristics curve was calculated to determine overall classification accuracy. Minimum detectable change and minimal clinically important difference were also calculated. Results: For the Control subscale, a cut point of 44 (area under the curve =.75), a minimum detectable change of 8, and a minimal clinically important difference of 5 were found. For the Importance subscale, a cut point of 39 (area under the curve =.81), a minimum detectable change of 8, and a minimal clinically important difference of 5 were found. Conclusions: The cut points resulted in good classification accuracy, providing support for their reliability. The results provided evidence that both subscales are sensitive to change in adults with brain injury. © 2021 American Academy of Physical Medicine and Rehabilitation.
Document Type: ArticlePublication Stage: Article in PressSource: Scopus
“The Shaping of Cognitive Control Based on the Adaptive Weighting of Expectations and Experience” (2021) Journal of Experimental Psychology: Learning Memory and Cognition
The Shaping of Cognitive Control Based on the Adaptive Weighting of Expectations and Experience(2021) Journal of Experimental Psychology: Learning Memory and Cognition, 47 (10), pp. 1563-1584. Cited 1 time.
Suh, J., Bugg, J.M.
Department of Psychological and Brain Sciences, Washington University in St. Louis, United States
AbstractExisting approaches in the literature on cognitive control in conflict tasks almost exclusively target the outcome of control (by comparing mean congruency effects) and not the processes that shape control. These approaches are limited in addressing a current theoretical issue—what contribution does learning make to adjustments in cognitive control? In the present study, we evaluated an alternative approach by reanalyzing existing data sets using generalized linear mixed models that enabled us to examine triallevel changes in control within abbreviated lists that varied in theoretically significant ways (e.g., probability of conflict; presence vs. absence of a precue). For the first time, this allowed us to characterize (a) the trial-by-trial signature of experience-based processes that support control as a list unfolds under various conditions and (b) how explicit precues conveying the expected probability of conflict within a list influence control learning. This approach uncovered novel theoretical insights: First, slopes representing control learning varied depending on whether a cue was available or not suggesting that explicit expectations about conflict affected whether and the rate at which control learning occurred; and second, this pattern was modulated by task demands and incentives. Additionally, analyses revealed a cue-induced heightening of control in high conflict likelihood lists that mean level analyses had failed to capture. The present study showed how control is shaped by the adaptive weighting of experience and expectations on a trial-by-trial basis and demonstrated the utility of a novel method for revealing the contributions of learning to control, and modulation of learning via precues. © 2021 American Psychological Association
Author KeywordsAttention; Cognitive control; Conflict monitoring; Learning; Stroop
Funding detailsNational Institutes of HealthNIHNational Institute on AgingNIA
Document Type: ArticlePublication Stage: FinalSource: Scopus