WashU weekly Neuroscience publications: April 7, 2024

Environmental and sociocultural factors are associated with pain-related brain structure among diverse individuals with chronic musculoskeletal pain: intersectional considerations
(2024) Scientific Reports, 14 (1), art. no. 7796, . 

Domenico, L.H.^a , Tanner, J.J.^b , Mickle, A.M.^c d , Terry, E.L.^a c , Garvan, C.^e , Lai, S.^f , Deshpande, H.^g , Staud, R.^h , Redden, D.ⁱ , Price, C.C.^b , Goodin, B.R.^j k , Fillingim, R.B.^c l , Sibille, K.T.^d e

^a Department of Biobehavioral Nursing Science, College of Nursing, University of Florida, 1225 Center Drive, Gainesville, FL 32610, United States
^b Department of Clinical and Health Psychology, University of Florida, 1225 Center Drive, Gainesville, FL 32603, United States
^c Pain Research and Intervention Center of Excellence, University of Florida, 2004 Mowry Road, Gainesville, FL 32610, United States
^d Department of Physical Medicine and Rehabilitation, University of Florida, 3450 Hull Road, Gainesville, FL 32607, United States
^e Department of Anesthesiology, Division of Pain Medicine, University of Florida, 1600 SW Archer Road, Gainesville, FL 32610, United States
^f Department of Radiation Oncology, University of Florida, 2000 SW Archer Road, Gainesville, FL 32610, United States
^g Department of Radiology, University of Alabama at Birmingham, 619 19th Street South, Birmingham, AL 35294, United States
^h Department of Rheumatology, College of Medicine, University of Florida, 1600 SW Archer Rd, Gainesville, FL 32610, United States
ⁱ Department of Biostatistics, University of Alabama at Birmingham, 1665 University Blvd #327, Birmingham, AL 35294, United States
^j Department of Psychology, University of Alabama at Birmingham, Campbell Hall 415, 1300 University Blvd, Birmingham, AL 35223, United States
^k Department of Anesthesiology, Washington University, 660 S Euclid Ave, St. Louis, MO 63110, United States
^l Department of Community Dentistry and Behavioral Science, University of Florida College of Dentistry, 1329 SW 16th Street, Gainesville, FL 32610-3628, United States

Abstract
Chronic musculoskeletal pain including knee osteoarthritis (OA) is a leading cause of disability worldwide. Previous research indicates ethnic-race groups differ in the pain and functional limitations experienced with knee OA. However, when socioenvironmental factors are included in analyses, group differences in pain and function wane. Pain-related brain structures are another area where ethnic-race group differences have been observed. Environmental and sociocultural factors e.g., income, education, experiences of discrimination, and social support influence brain structures. We investigate if environmental and sociocultural factors reduce previously observed ethnic-race group differences in pain-related brain structures. Data were analyzed from 147 self-identified non-Hispanic black (NHB) and non-Hispanic white (NHW), middle and older aged adults with knee pain in the past month. Information collected included health and pain history, environmental and sociocultural resources, and brain imaging. The NHB adults were younger and reported lower income and education compared to their NHW peers. In hierarchical multiple regression models, sociocultural and environmental factors explained 6–37% of the variance in pain-related brain regions. Self-identified ethnicity-race provided an additional 4–13% of explanatory value in the amygdala, hippocampus, insula, bilateral primary somatosensory cortex, and thalamus. In the rostral/caudal anterior cingulate and dorsolateral prefrontal cortex, self-identified ethnicity-race was not a predictor after accounting for environmental, sociocultural, and demographic factors. Findings help to disentangle and identify some of the factors contributing to ethnic-race group disparities in pain-related brain structures. Numerous arrays of environmental and sociocultural factors remain to be investigated. Further, the differing sociodemographic representation of our NHB and NHW participants highlights the role for intersectional considerations in future research. © The Author(s) 2024.

Author Keywords
Environmental;  Ethnicity-race;  Musculoskeletal pain;  Neuroimaging;  Sociocultural

Document Type: Article
Publication Stage: Final
Source: Scopus

Multiomics analysis to explore blood metabolite biomarkers in an Alzheimer’s Disease Neuroimaging Initiative cohort
(2024) Scientific Reports, 14 (1), art. no. 6797, . 

Oka, T.^a , Matsuzawa, Y.^a , Tsuneyoshi, M.^b , Nakamura, Y.^b , Aoshima, K.^c d , Tsugawa, H.^a e f g , Weiner, M.^h , Aisen, P.ⁱ , Petersen, R.^j , Jack, C.R., Jr.^j , Jagust, W.^k , Trojanowki, J.Q.^l , Toga, A.W.^m , Beckett, L.ⁿ , Green, R.C.^o p , Saykin, A.J.^q , Morris, J.^r , Shaw, L.M.^s , Liu, E.^t , Montine, T.^u , Thomas, R.G.ⁱ , Donohue, M.ⁱ , Walter, S.ⁱ , Gessert, D.ⁱ , Sather, T.ⁱ , Jiminez, G.ⁱ , Harvey, D.ⁿ , Donohue, M.ⁱ , Bernstein, M.^j , Fox, N.^v , Thompson, P.^w , Schuff, N.^x , DeCArli, C.ⁿ , Borowski, B.^j , Gunter, J.^j , Senjem, M.^j , Vemuri, P.^j , Jones, D.^j , Kantarci, K.^j , Ward, C.^j , Koeppe, R.A.^y , Foster, N.^z , Reiman, E.M.^aa , Chen, K.^aa , Mathis, C.^ab , Landau, S.^k , Cairns, N.J.^r , Householder, E.^r , Reinwald, L.T.^r , Lee, V.^ac , Korecka, M.^ac , Figurski, M.^ac , Crawford, K.^m , Neu, S.^m , Foroud, T.M.^q , Potkin, S.^ad , Shen, L.^q , Kelley, F.^q , Kim, S.^q , Nho, K.^q , Kachaturian, Z.^ae , Frank, R.^af , Snyder, P.J.^ag , Molchan, S.^ah ai , Kaye, J.^aj , Quinn, J.^aj , Lind, B.^aj , Carter, R.^aj , Dolen, S.^aj , Schneider, L.S.^ak , Pawluczyk, S.^ak , Beccera, M.^ak , Teodoro, L.^ak , Spann, B.M.^ak , Brewer, J.^al , Vanderswag, H.^al , Fleisher, A.^al , Heidebrink, J.L.^y , Lord, J.L.^y , Petersen, R.^j , Mason, S.S.^j , Albers, C.S.^j , Knopman, D.^j , Johnson, K.^j , Doody, R.S.^am , Meyer, J.V.^am , Chowdhury, M.^am , Rountree, S.^am , Dang, M.^am , Stern, Y.^an , Honig, L.S.^an , Bell, K.L.^an , Ances, B.^ao , Morris, J.C.^ao , Carroll, M.^ao , Leon, S.^ao , Householder, E.^ao , Mintun, M.A.^ao , Schneider, S.^ao , Oliver, A.^ao , Marson, D.^ap , Griffith, R.^ap , Clark, D.^ap , Geldmacher, D.^ap , Brockington, J.^ap , Roberson, E.^ap , Grossman, H.^aq , Mitsis, E.^aq , de Toledo-Morrell, L.^ar , Shah, R.C.^ar , Duara, R.^as , Varon, D.^as , Greig, M.T.^as , Roberts, P.^as , Albert, M.^at , Onyike, C.^at , D’Agostino, D.^at , Kielb, S.^at , Galvin, J.E.^au , Pogorelec, D.M.^au , Cerbone, B.^au , Michel, C.A.^au , Rusinek, H.^au , de Leon, M.J.^au , Glodzik, L.^au , De Santi, S.^au , Doraiswamy, P.M.^av , Petrella, J.R.^av , Wong, T.Z.^av , Arnold, S.E.^s , Karlawish, J.H.^s , Wolk, D.^s , Smith, C.D.^aw , Jicha, G.^aw , Hardy, P.^aw , Sinha, P.^aw , Oates, E.^aw , Conrad, G.^aw , Lopez, O.L.^aw , Oakley, M.^ab , Simpson, D.M.^ab , Porsteinsson, A.P.^ax , Goldstein, B.S.^ax , Martin, K.^ax , Makino, K.M.^ax , Ismail, M.S.^ax , Brand, C.^ax , Mulnard, R.A.^ay , Thai, G.^ay , Mc Adams Ortiz, C.^ay , Womack, K.^az , Mathews, D.^az , Quiceno, M.^az , Arrastia, R.D.^az , King, R.^az , Weiner, M.^az , Cook, K.M.^az , DeVous, M.^az , Levey, A.I.^ba , Lah, J.J.^ba , Cellar, J.S.^ba , Burns, J.M.^bb , Anderson, H.S.^bb , Swerdlow, R.H.^bb , Apostolova, L.^bc , Tingus, K.^bc , Woo, E.^bc , Silverman, D.H.S.^bc , Lu, P.H.^bc , Bartzokis, G.^bc , Graff Radford, N.R.^bd , Parfitt, F.^bd , Kendall, T.^bd , Johnson, H.^bd , Farlow, M.R.^q , Hake, A.M.^q , Matthews, B.R.^q , Herring, S.^q , Hunt, C.^q , van Dyck, C.H.^be , Carson, R.E.^be , MacAvoy, M.G.^be , Chertkow, H.^bf , Bergman, H.^bf , Hosein, C.^bf , Black, S.^bg , Stefanovic, B.^bg , Caldwell, C.^bg , Hsiung, G.Y.R.^bh , Feldman, H.^bh , Mudge, B.^bh , Assaly, M.^bh , Kertesz, A.^bi , Rogers, J.^bi , Trost, D.^bi , Bernick, C.^bj , Munic, D.^bj , Kerwin, D.^bk , Mesulam, M.M.^bk , Lipowski, K.^bk , Wu, C.K.^bk , Johnson, N.^bk , Sadowsky, C.^bl , Martinez, W.^bl , Villena, T.^bl , Turner, R.S.^bm , Johnson, K.^bm , Reynolds, B.^bm , Sperling, R.A.^o , Johnson, K.A.^o , Marshall, G.^o , Frey, M.^o , Yesavage, J.^bn , Taylor, J.L.^bn , Lane, B.^bn , Rosen, A.^bn , Tinklenberg, J.^bn , Sabbagh, M.N.^bo , Belden, C.M.^bo , Jacobson, S.A.^bo , Sirrel, S.A.^bo , Kowall, N.^bp , Killiany, R.^bp , Budson, A.E.^bp , Norbash, A.^bp , Johnson, P.L.^bp , Obisesan, T.O.^bq , Wolday, S.^bq , Allard, J.^bq , Lerner, A.^br , Ogrocki, P.^br , Hudson, L.^br , Fletcher, E.^bs , Carmichael, O.^bs , Olichney, J.^bs , DeCarli, C.^bs , Kittur, S.^bt , Borrie, M.^bu , Lee, T.Y.^bu , Bartha, R.^bu , Johnson, S.^bv , Asthana, S.^bv , Carlsson, C.M.^bv , Potkin, S.G.^bw , Preda, A.^bw , Nguyen, D.^bw , Tariot, P.^aa , Fleisher, A.^aa , Reeder, S.^aa , Bates, V.^bx , Capote, H.^bx , Rainka, M.^bx , Scharre, D.W.^by , Kataki, M.^by , Adeli, A.^by , Zimmerman, E.A.^bz , Celmins, D.^bz , Brown, A.D.^bz , Pearlson, G.D.^ca , Blank, K.^ca , Anderson, K.^ca , Santulli, R.B.^cb , Kitzmiller, T.J.^cb , Schwartz, E.S.^cb , Sink, K.M.^cc , Williamson, J.D.^cc , Garg, P.^cc , Watkins, F.^cc , Ott, B.R.^cd , Querfurth, H.^cd , Tremont, G.^cd , Salloway, S.^ce , Malloy, P.^ce , Correia, S.^ce , Rosen, H.J.^h , Miller, B.L.^h , Mintzer, J.^cf , Spicer, K.^cf , Bachman, D.^cf , Finger, E.^cg , Pasternak, S.^cg , Rachinsky, I.^cg , Rogers, J.^cg , Kertesz, A.^cg , Drost, D.^cg , Pomara, N.^ch , Hernando, R.^ch , Sarrael, A.^ch , Schultz, S.K.^ci , Ponto, L.L.B.^ci , Shim, H.^ci , Smith, K.E.^ci , Relkin, N.^cj , Chaing, G.^cj , Raudin, L.^cj , Smith, A.^ck , Fargher, K.^ck , Raj, B.A.^ck

^a Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, Tokyo, Japan
^b Human Biology Integration Foundation, Eisai Co., Ltd., Ibaraki, Japan
^c Microbes & amp; Host Defense Domain, Eisai Co., Ltd., Ibaraki, Japan
^d School of Integrative and Global Majors, University of Tsukuba, Ibaraki, Japan
^e RIKEN Center for Sustainable Resource Science, Yokohama, Japan
^f RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
^g Graduate School of Medical Life Science, Yokohama City University, Yokohama, Japan
^h UC San Francisco, San Francisco, United States
ⁱ UC San Diego, San Diego, United States
^j Mayo Clinic, Rochester, United States
^k UC Berkeley, Berkeley, United States
^l U Pennsylvania, Philadelphia, United States
^m USC, Los Angeles, United States
ⁿ UC Davis, Davis, United States
^o Brigham and Women’s Hospital, Boston, United States
^p Harvard Medical School, Cambridge, United States
^q Indiana University, Bloomington, United States
^r Washington University St. Louis, St. Louis, United States
^s University of Pennsylvania, Philadelphia, United States
^t Janssen Alzheimer Immunotherapy, South San Francisco, United States
^u University of Washington, Seattle, United States
^v University of London, London, United Kingdom
^w USC School of Medicine, Greenville, United States
^x UCSF MRI, San Francisco, United States
^y University of Michigan, Ann Arbor, United States
^z University of Utah, Salt Lake City, United States
^aa Banner Alzheimer’s Institute, Phoenix, United States
^ab University of Pittsburgh, Pittsburgh, United States
^ac UPenn School of Medicine, Philadelphia, United States
^ad UC Irvine, Irvine, United States
^ae Khachaturian, Radebaugh & amp; Associates, Inc and Alzheimer’s Association’s Ronald and Nancy Reagan’s Research Institute, Chicago, United States
^af General Electric, Boston, United States
^ag Brown University, Providence, United States
^ah National Institute on Aging, Bethesda, United States
^ai National Institutes of Health, Bethesda, United States
^aj Oregon Health and Science University, Portland, United States
^ak University of Southern California, Los Angeles, United States
^al University of California San Diego, La Jolla, United States
^am Baylor College of Medicine, Houston, United States
^an Columbia University Medical Center, New York, United States
^ao Washington University, St. Louis, United States
^ap University of Alabama Birmingham, Birmingham, United States
^aq Mount Sinai School of Medicine, New York, United States
^ar Rush University Medical Center, Chicago, United States
^as Wien Center, Vienna, Austria
^at Johns Hopkins University, Baltimore, United States
^au New York University, New York, United States
^av Duke University Medical Center, Durham, United States
^aw University of Kentucky, Lexington, United States
^ax University of Rochester Medical Center, New York, United States
^ay University of California, Irvine, United States
^az University of Texas Southwestern Medical School, Dallas, United States
^ba Emory University, Atlanta, United States
^bb University of Kansas, Medical Center, Lawrence, United States
^bc University of California, Los Angeles, Los Angeles, United States
^bd Mayo Clinic, Jacksonville, United States
^be Yale University School of Medicine, New Haven, United States
^bf McGill Univ., Montreal Jewish General Hospital, Montreal, Canada
^bg Sunnybrook Health Sciences, Toronto, ON, Canada
^bh U.B.C. Clinic for AD & amp; Related Disorders, Vancouver, Canada
^bi Cognitive Neurology St. Joseph’s, London, ON, United States
^bj Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, United States
^bk Northwestern University, Evanston, United States
^bl Premiere Research Inst (Palm Beach Neurology), West Palm Beach, United States
^bm Georgetown University Medical Center, Washington, United States
^bn Stanford University, Stanford, United States
^bo Banner Sun Health Research Institute, Sun City, United States
^bp Boston University, Boston, United States
^bq Howard University, Washington, United States
^br Case Western Reserve University, Cleveland, United States
^bs University of California, Davis Sacramento, Davis, United States
^bt Neurological Care of CNY, Syracuse, United States
^bu Parkwood Hospital, London, Canada
^bv University of Wisconsin, Madison, United States
^bw University of California, Irvine BIC, Irvine, United States
^bx Dent Neurologic Institute, Amherst, United States
^by Ohio State University, Columbus, United States
^bz Albany Medical College, Albany, United States
^ca Hartford Hosp, Olin Neuropsychiatry Research Center, Hartford, United States
^cb Dartmouth Hitchcock Medical Center, Lebanon, United States
^cc Wake Forest University Health Sciences, Winston-Salem, United States
^cd Rhode Island Hospital, Providence, United States
^ce Butler Hospital, Providence, United States
^cf Medical University South Carolina, Charleston, United States
^cg St. Joseph’s Health Care, London, Canada
^ch Nathan Kline Institute, Orangeburg, United States
^ci University of Iowa College of Medicine, Iowa City, United States
^cj Cornell University, Ithaca, United States
^ck University of South Florida: USF Health Byrd Alzheimer’s Institute, Tampa, United States

Abstract
Alzheimer’s disease (AD) is a neurodegenerative disease that commonly causes dementia. Identifying biomarkers for the early detection of AD is an emerging need, as brain dysfunction begins two decades before the onset of clinical symptoms. To this end, we reanalyzed untargeted metabolomic mass spectrometry data from 905 patients enrolled in the AD Neuroimaging Initiative (ADNI) cohort using MS-DIAL, with 1,304,633 spectra of 39,108 unique biomolecules. Metabolic profiles of 93 hydrophilic metabolites were determined. Additionally, we integrated targeted lipidomic data (4873 samples from 1524 patients) to explore candidate biomarkers for predicting progressive mild cognitive impairment (pMCI) in patients diagnosed with AD within two years using the baseline metabolome. Patients with lower ergothioneine levels had a 12% higher rate of AD progression with the significance of P = 0.012 (Wald test). Furthermore, an increase in ganglioside (GM3) and decrease in plasmalogen lipids, many of which are associated with apolipoprotein E polymorphism, were confirmed in AD patients, and the higher levels of lysophosphatidylcholine (18:1) and GM3 d18:1/20:0 showed 19% and 17% higher rates of AD progression, respectively (Wald test: P = 3.9 × 10–8 and 4.3 × 10–7). Palmitoleamide, oleamide, diacylglycerols, and ether lipids were also identified as significantly altered metabolites at baseline in patients with pMCI. The integrated analysis of metabolites and genomics data showed that combining information on metabolites and genotypes enhances the predictive performance of AD progression, suggesting that metabolomics is essential to complement genomic data. In conclusion, the reanalysis of multiomics data provides new insights to detect early development of AD pathology and to partially understand metabolic changes in age-related onset of AD. © The Author(s) 2024.

Document Type: Article
Publication Stage: Final
Source: Scopus

De novo variants in FRYL are associated with developmental delay, intellectual disability, and dysmorphic features
(2024) American Journal of Human Genetics, 111 (4), pp. 742-760. 

Pan, X.^a b , Tao, A.M.^c , Lu, S.^a b , Ma, M.^a b , Hannan, S.B.^a b , Slaugh, R.^d , Drewes Williams, S.^e , O’Grady, L.^f g , Kanca, O.^a b , Person, R.^h , Carter, M.T.ⁱ , Platzer, K.^j , Schnabel, F.^j , Abou Jamra, R.^j , Roberts, A.E.^k l , Newburger, J.W.^k m , Revah-Politi, A.ⁿ , Granadillo, J.L.^d , Stegmann, A.P.A.^o , Sinnema, M.^o , Accogli, A.^p q , Salpietro, V.^r , Capra, V.^s , Ghaloul-Gonzalez, L.^e t , Brueckner, M.^u v , Simon, M.E.H.^w , Sweetser, D.A.^f x , Glinton, K.E.^a y , Kirk, S.E.^z aa , Burrage, L.C.^ad , Heaney, J.D.^ad , Kim, S.-Y.^ad , Lanza, D.G.^ad , Liu, Z.^ad , Mao, D.^ad , Milosavljevic, A.^ad , Nagamani, S.C.S.^ad , Posey, J.E.^ad , Ramamurthy, U.^ad , Ramanathan, V.^ad , Rogers, J.^ad , Rosenfeld, J.A.^ad , Roth, M.^ad , Zahedi Darshoori, R.^ad , Wangler, M.F.^a b , Yamamoto, S.^a b ab , Chung, W.K.^ac , Bellen, H.J.^a ab , Baylor College of Medicine Center for Precision Medicine Models^ae

^a Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, United States
^b Jan & Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX, United States
^c Vagelos School of Physicians and Surgeons, Columbia University, New York, NY, United States
^d Division of Genetics and Genomic Medicine, Department of Pediatrics, Washington University in St. Louis School of Medicine, St. Louis, MO, United States
^e Division of Genetic and Genomic Medicine, Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA, United States
^f Division of Medical Genetics & Metabolism, Massachusetts General for Children, Boston, MA, United States
^g MGH Institute of Health Professions, Charlestown, MA, United States
^h GeneDx, LLC, Gaithersburg, MD, United States
ⁱ Department of Genetics, Children’s Hospital of Eastern Ontario, Ottawa, ON, Canada
^j Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany
^k Department of Cardiology, Boston Children’s Hospital, Boston, MA, United States
^l Department of Medicine, Division of Genetics, Boston Children’s Hospital, Boston, MA, United States
^m Department of Pediatrics, Harvard Medical School, Boston, MA, United States
ⁿ Institute for Genomic Medicine and Precision Genomics Laboratory, Columbia University Irving Medical Center, New York, NY, United States
^o Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, Netherlands
^p Division of Medical Genetics, Department of Medicine, McGill University Health Center, Montreal, QC, Canada
^q Department of Human Genetics, McGill University, Montreal, QC, Canada
^r Department of Neuromuscular Disorders, University College London Institute of Neurology, Queen Square, London, United Kingdom
^s Unit of Medical Genetics and Genomics, IRCCS Istituto Giannina Gaslini, Genoa, Italy
^t Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, United States
^u Department of Pediatrics, Yale University School of Medicine, New Haven, CT, United States
^v Department of Genetics, Yale University School of Medicine, New Haven, CT, United States
^w Department of Medical Genetics, University Medical Center Utrecht, Utrecht, Netherlands
^x Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, United States
^y Department of Genetics, Texas Children’s Hospital, Houston, TX, United States
^z Section of Hematology/Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX, United States
^aa Texas Children’s Cancer and Hematology Center, Houston, TX, United States
^ab Department of Neuroscience, Baylor College of Medicine, Houston, TX, United States
^ac Departments of Pediatrics, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States

Abstract
FRY-like transcription coactivator (FRYL) belongs to a Furry protein family that is evolutionarily conserved from yeast to humans. The functions of FRYL in mammals are largely unknown, and variants in FRYL have not previously been associated with a Mendelian disease. Here, we report fourteen individuals with heterozygous variants in FRYL who present with developmental delay, intellectual disability, dysmorphic features, and other congenital anomalies in multiple systems. The variants are confirmed de novo in all individuals except one. Human genetic data suggest that FRYL is intolerant to loss of function (LoF). We find that the fly FRYL ortholog, furry (fry), is expressed in multiple tissues, including the central nervous system where it is present in neurons but not in glia. Homozygous fry LoF mutation is lethal at various developmental stages, and loss of fry in mutant clones causes defects in wings and compound eyes. We next modeled four out of the five missense variants found in affected individuals using fry knockin alleles. One variant behaves as a severe LoF variant, whereas two others behave as partial LoF variants. One variant does not cause any observable defect in flies, and the corresponding human variant is not confirmed to be de novo, suggesting that this is a variant of uncertain significance. In summary, our findings support that fry is required for proper development in flies and that the LoF variants in FRYL cause a dominant disorder with developmental and neurological symptoms due to haploinsufficiency. © 2024 American Society of Human Genetics

Author Keywords
developmental delay;  Drosophila;  FRYL;  furry;  intellectual disability;  rare disease

Funding details
Huffington Foundation
Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNICHD
Office of Research Infrastructure ProgramsORIP, NIH
National Heart, Lung, and Blood InstituteNHLBIU01HL131003
3HP-HP-FPA ERN-01-2016/739516
Baylor College of MedicineP50HD103555
National Institutes of HealthNIHU54OD030165, R24OD031447
National Center for Advancing Translational SciencesNCATSUL1TR001873

Document Type: Article
Publication Stage: Final
Source: Scopus

Association of healthy sleep patterns with risk of mortality and life expectancy at age of 30 years: a population-based cohort study
(2024) QJM: An International Journal of Medicine, 117 (3), pp. 177-186. 

Li, H.^a b , Qian, F.^c d , Han, L.^e , Feng, W.^f , Zheng, D.^g , Guo, X.^b g , Zhang, H.^h i

^a Department of Cardiac Surgery, Heart Center, Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
^b Beijing Municipal Key Laboratory of Clinical Epidemiology, Beijing, China
^c Section of Cardiovascular Medicine, Boston Medical Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, United States
^d Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
^e Medical Research Center, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
^f Neuroscience Department, Washington University in Saint Louis, St. Louis, MO, United States
^g Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing, China
^h Department of Cardiovascular Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
ⁱ Beijing Lab for Cardiovascular Precision Medicine, Beijing, China

Abstract
Background: The importance of sleep on cardiovascular health has been increasingly acknowledged. However, the effect of combined sleep behaviors on life expectancy remains understudied. Aim: To investigate the association between sleep patterns with total and cause-specific mortality and life expectancy, using a nationally representative sample of US adults. Design: Population-based cohort study. Methods: This cohort study included 172 321 adults aged 18 years or older in the National Health Interview Survey (2013–18) with linkage to the National Death Index records up to 31 December 2019. The life expectancy at the age of 30 years by the number of low-risk sleep scores was estimated using a flexible parametric survival model. Results: During a median follow-up of 4.3 years, of the 172 321 adults (50.9% women; mean [SE] age, 46.98 [0.10] years), 8681 individuals died. The adjusted hazard ratios (95% confidence intervals [CI]) of participants with five vs. 0–1 low-risk sleep factors for all-cause, cardiovascular, and cancer mortality were 0.70 (0.63–0.77), 0.79 (0.67–0.93) and 0.81 (0.66–0.98), respectively. Nearly 8% (population attributable fraction 7.9%, 95% CI: 5.5–10.4) of mortality in this cohort could be attributed to suboptimal sleep patterns. When compared to those with 0–1 low-risk sleep factors, life expectancy at the age of 30 years for individuals with all five low-risk sleep factors was 4.7 (95% CI: 2.7–6.7) years greater for men and 2.4 (95% CI: 0.4–4.4) years greater for women. Conclusions: Our findings suggest that greater adherence to a low-risk sleep pattern may lead to significant gains in life expectancy among US adults. © 2024 Oxford University Press. All rights reserved.

Document Type: Article
Publication Stage: Final
Source: Scopus

VCP Inhibition Augments NLRP3 Inflammasome Activation
(2024) Inflammation, . 

Sharma, A., Dhavale, D.D., Kotzbauer, P.T., Weihl, C.C.

Department of Neurology, Hope Center for Neurological Diseases, Washington University School of Medicine, St. Louis, MO 63110, United States

Abstract
Lysosomal membrane permeabilization caused either via phagocytosis of particulates or the uptake of protein aggregates can trigger the activation of NLRP3 inflammasome- an intense inflammatory response that drives the release of the pro-inflammatory cytokine IL-1β by regulating the activity of CASPASE 1. The maintenance of lysosomal homeostasis and lysosomal membrane integrity is facilitated by the AAA+ ATPase, VCP/p97 (VCP). However, the relationship between VCP and NLRP3 inflammasome activity remains unexplored. Here, we demonstrate that the VCP inhibitors, DBeQ and ML240 elicit the activation of NLRP3 inflammasome in bone marrow-derived macrophages (BMDMs) when used as activation stimuli. Moreover, genetic inhibition of VCP or VCP chemical inhibition enhances lysosomal membrane damage and augments LLoME-associated NLRP3 inflammasome activation in BMDMs. Similarly, VCP inactivation also augments NLRP3 inflammasome activation mediated by aggregated alpha-synuclein fibrils and lysosomal damage. These data suggest that VCP is a participant in the complex regulation of NLRP3 inflammasome activation. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024.

Author Keywords
Alpha-synuclein fibrils;  ASC speck;  Bone marrow-derived macrophages;  LLoMe;  NLRP3 inflammasome;  TAT-Cre recombinase;  VCP/p97

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

Healthy adults favor stable left/right hand choices over performance at an unconstrained reach-to-grasp task
(2024) Experimental Brain Research, . 

Kim, T.^a c d , Zhou, R.^b , Gassass, S.^a , Soberano, T.^a , Liu, L.^b , Philip, B.A.^a

^a Program in Occupational Therapy, Washington University School of Medicine, St. Louis, MO, United States
^b Department of Biostatistics, Washington University School of Medicine, St. Louis, MO, United States
^c Department of Kinesiology, The Pennsylvania State University, University Park, PA, United States
^d Department of Physical Medicine and Rehabilitation, Penn State College of Medicine, Hershey, PA, United States

Abstract
Reach-to-grasp actions are fundamental to the daily activities of human life, but few methods exist to assess individuals’ reaching and grasping actions in unconstrained environments. The Block Building Task (BBT) provides an opportunity to directly observe and quantify these actions, including left/right hand choices. Here we sought to investigate the motor and non-motor causes of left/right hand choices, and optimize the design of the BBT, by manipulating motor and non-motor difficulty in the BBT’s unconstrained reach-to-grasp task. We hypothesized that greater motor and non-motor (e.g. cognitive/perceptual) difficulty would drive increased usage of the dominant hand. To test this hypothesis, we modulated block size (large vs. small) to influence motor difficulty, and model complexity (10 vs. 5 blocks per model) to influence non-motor difficulty, in healthy adults (n = 57). Our data revealed that increased motor and non-motor difficulty led to lower task performance (slower task speed), but participants only increased use of their dominant hand only under the most difficult combination of conditions: in other words, participants allowed their performance to degrade before changing hand choices, even though participants were instructed only to optimize performance. These results demonstrate that hand choices during reach-to grasp actions are more stable than motor performance in healthy right-handed adults, but tasks with multifaceted difficulties can drive individuals to rely more on their dominant hand. © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2024.

Author Keywords
(4 to6): hand choice;  Block-building task;  Reaching and grasping;  Task difficulty

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

Modeling Momentary Reciprocal Associations Between Negative Affect and Craving for Alcohol and Cannabis Using Dynamic Structural Equation Modeling
(2024) Psychology of Addictive Behaviors, . 

Waddell, J.T.^a , Carpenter, R.W.^b , Frumkin, M.R.^c , McNamara, I.A.^b , Ellingson, J.M.^d

^a Department of Psychology, Arizona State University, United States
^b Department of Psychology, University of Missouri-St. Louis, United States
^c Department of Psychological and Brain Sciences, Washington University in St. Louis, United States
^d Department of Psychiatry, School of Medicine, University of Colorado Anschutz Medical Campus, United States

Abstract
Objective: Negative reinforcement models suggest that negative affect should predict event-level substance use, however, supporting daily-life evidence is lacking. One reason may be an emphasis in ecological momentary assessment (EMA) research on use behavior, which is subject to contextual and societal constraints that other substance outcomes, such as craving, may not be subject to. Therefore, the present study tested momentary, within-person reciprocal relations among negative affect and craving for alcohol and cannabis in daily life. Method: Adults (N = 48) completed 60 days of EMA, consisting of four daily reports spanning 7 a.m.–11 p.m. assessing current negative affect and alcohol/cannabis craving. Preregistered analyses used dynamic structural equation modeling to test whether (a) within-person increases in negative affect co-occurred with within-person increases in alcohol and cannabis craving, and (b) within-person increases in negative affect predicted later within-person increases in craving (and vice versa), and (c) relations differed by substance use frequency. Results: Within-person increases in negative affect were contemporaneously associated with within-person increases in alcohol and cannabis craving. However, increases in negative affect did not prospectively predict increases in craving, and within-person increases in craving did not prospectively predict within-person increases in negative affect. Within-person relations were not moderated by substance use frequency. Conclusions: Negative affect and craving were associated in community adults. However, results advance a growing body of EMA work suggesting that the association of daily-life negative affect and substance use is, at best, not straightforward. Careful attention is needed to better translate existing negative reinforcement theory to the realities of daily life. © 2024 American Psychological Association

Author Keywords
alcohol craving;  cannabis craving;  ecological momentary assessment;  negative affect;  negative reinforcement

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

Maternal Prenatal Social Disadvantage and Neonatal Functional Connectivity: Associations With Psychopathology Symptoms at Age 12 Months
(2024) Developmental Psychology, . 

Herzberg, M.P.^a , Nielsen, A.N.^b , Brady, R.^b , Kaplan, S.^b , Alexopoulos, D.^b , Meyer, D.^b , Arora, J.^c , Miller, J.P.^c , Smyser, T.A.^a , Barch, D.M.^a d e , Rogers, C.E.^a f , Warner, B.B.^f , Smyser, C.D.^b e f , Luby, J.L.^a

^a Department of Psychiatry, Washington University in St. Louis, United States
^b Department of Neurology, Washington University in St. Louis, United States
^c Department of Biostatistics, Washington University in St. Louis, United States
^d Department of Psychological and Brain Sciences, Washington University in St. Louis, United States
^e Department of Radiology, Washington University in St. Louis, United States
^f Department of Pediatrics, Washington University in St. Louis, United States

Abstract
Recent research has reported effects of socioeconomic status on neurobehavioral development as early as infancy, including positive associations between income and brain structure, functional connectivity, and behavior later in childhood (Ramphal, Whalen, et al., 2020; Triplett et al., 2022). This study extends this literature by investigating the relation of maternal prenatal social disadvantage (PSD) to neonatal amygdala and hippocampus functional connectivity and whether socioeconomic-related alterations in functional connectivity subsequently predict behavior at age 12 months in a large, socioeconomically diverse sample (N = 261 mother–infant dyads). PSD was assessed across gestation; neonatal magnetic resonance imaging was completed within the first weeks of life; and infant internalizing and externalizing symptoms were evaluated using the Infant–Toddler Social and Emotional Assessment at age 12 months. The results showed that PSD was significantly related to neonatal right amygdala and left hippocampus functional connectivity with prefrontal and motor-related regions. Social disadvantagerelated right amygdala and left hippocampus functional connectivity with these regions was subsequently related to infant externalizing and internalizing symptoms at age 12 months. Building off an emerging literature exploring prenatal impacts on neonatal functional connectivity, this study further emphasizes the important role of the maternal environment during gestation on infant brain function and its relationship with externalizing and internalizing behavior in the first years of life. The results suggest that the prenatal socioeconomic environment may be a promising target for interventions aimed at improving infant neurobehavioral outcomes. © 2024 American Psychological Association

Author Keywords
externalizing;  functional connectivity;  neonatal imaging;  socioeconomic status

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

Racial disparities among mild stroke survivors: predictors of home discharge from a retrospective analysis
(2024) Topics in Stroke Rehabilitation, . 

Bright, L.^a , Baum, C.M.^a b c , Roberts, P.^d e f

^a Program in Occupational Therapy, Washington University School of Medicine, St. Louis, MO, United States
^b Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
^c Brown School of Social Work, Washington University in St. Louis, St. Louis, MO, United States
^d Department of Physical Medicine and Rehabilitation, Cedars-Sinai, Los Angeles, CA, United States
^e Department of Enterprise Information Services, Cedars-Sinai, Los Angeles, CA, United States
^f Department of Medical Affairs, Cedars-Sinai, Los Angeles, CA, United States

Abstract
Background: Half of all strokes are classified as mild, and most mild stroke survivors are discharged home after their initial hospitalization without any post-acute rehabilitation despite experiencing cognitive, psychosocial, motor, and mobility impairments. Objectives: To investigate the demographic and clinical characteristics of mild stroke survivors and their association with discharge location. Methods: This is a retrospective analysis of mild stroke survivors from 2015–2023 in an academic medical center. Demographic characteristics, clinical measures, and discharge locations were obtained from the electronic health record. The Social Vulnerability Index was used to measure the community vulnerability. Associations between variables and discharge location were examined using bivariate logistic regression analysis. Results: There were 2,953 mild stroke survivors included in this study. The majority of participants were White (65.46%), followed by Black (19.40%). Black stroke survivors and individuals with higher social vulnerability had a higher proportion of discharges to skilled nursing facilities (p = 0.001). Black patients and patients with high vulnerability in housing type and transportation were less likely to be discharged home. Conclusions: Mild stroke survivors have a high rate of home discharge, potentially because less severe stroke symptoms have a reduced need for intensive care. Racial disparities in discharge location were evident, with Black stroke survivors experiencing higher rates of institutionalized care and lower likelihood of being discharged home compared to White counterparts, emphasizing the importance of addressing these disparities for equitable healthcare delivery and optimal outcomes. © 2024 Taylor & Francis Group, LLC.

Author Keywords
mild stroke;  patient discharge;  race factors;  social vulnerability;  Stroke

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

APOE2 gene therapy reduces amyloid deposition and improves markers of neuroinflammation and neurodegeneration in a mouse model of Alzheimer disease
(2024) Molecular Therapy, . 

Jackson, R.J.^a b , Keiser, M.S.^c , Meltzer, J.C.^a b , Fykstra, D.P.^a b , Dierksmeier, S.E.^a b e , Hajizadeh, S.^f h i , Kreuzer, J.^f g , Morris, R.^f , Melloni, A.^a , Nakajima, T.^a b , Tecedor, L.^c , Ranum, P.T.^c , Carrell, E.^c , Chen, Y.^c , Nishtar, M.A.^a b , Holtzman, D.M.^j , Haas, W.^f g , Davidson, B.L.^c d , Hyman, B.T.^a b

^a Alzheimer Research Unit, Massachusetts General Hospital Institute for Neurodegenerative Disease, Charlestown, MA 02129, United States
^b Department of Neurology, Massachusetts General Hospital and NeuroDiscovery Center, Harvard Medical School, Boston, MA 02114, United States
^c Raymond G. Perelman Center for Cellular and Molecular Therapeutics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, United States
^d Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States
^e Medical Sciences Division, University of Oxford, Oxford, OX3 9DU, United Kingdom
^f Krantz Family Center for Cancer Research, Massachusetts General Hospital, MA, Boston, 02114, United Kingdom
^g Department of Medicine, Harvard Medical School, Boston, MA 02115, United States
^h Broad Institute of MIT and Harvard, Cambridge, MA 02142, United States
ⁱ Institute of Molecular Biosciences, University of Graz, Graz, 8010, Austria
^j Department of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer’s Disease Research Center, Washington University in St. Louis, St. Louis, MO 63108, United States

Abstract
Epidemiological studies show that individuals who carry the relatively uncommon APOE ε2 allele rarely develop Alzheimer disease, and if they do, they have a later age of onset, milder clinical course, and less severe neuropathological findings than people without this allele. The contrast is especially stark when compared with the major genetic risk factor for Alzheimer disease, APOE ε4, which has an age of onset several decades earlier, a more aggressive clinical course and more severe neuropathological findings, especially in terms of the amount of amyloid deposition. Here, we demonstrate that brain exposure to APOE ε2 via a gene therapy approach, which bathes the entire cortical mantle in the gene product after transduction of the ependyma, reduces Aβ plaque deposition, neurodegenerative synaptic loss, and, remarkably, reduces microglial activation in an APP/PS1 mouse model despite continued expression of human APOE ε4. This result suggests a promising protective effect of exogenous APOE ε2 and reveals a cell nonautonomous effect of the protein on microglial activation, which we show is similar to plaque-associated microglia in the brain of Alzheimer disease patients who inherit APOE ε2. These data increase the potential that an APOE ε2 therapeutic could be effective in Alzheimer disease, even in individuals born with the risky ε4 allele. © 2024 The Authors

Author Keywords
AAV;  Alzheimer disease;  APOE;  APOE2;  gene therapy;  microglia;  neuroinflammation

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

Variation in diurnal cortisol patterns among the Indigenous Shuar of Amazonian Ecuador
(2024) American Journal of Human Biology, . 

Liebert, M.A.^a , Urlacher, S.S.^b c , Madimenos, F.C.^d e , Gildner, T.E.^f , Cepon-Robins, T.J.^g , Harrington, C.J.^h , Bribiescas, R.G.ⁱ , Sugiyama, L.S.^h , Snodgrass, J.J.^h j k

^a Department of Anthropology, Northern Arizona University, Flagstaff, AZ, United States
^b Department of Anthropology, Baylor University, Waco, TX, United States
^c Child and Brain Development Program, CIFAR, Toronto, ON, Canada
^d Department of Anthropology, Queens College (CUNY), Flushing, NY, United States
^e New York Consortium of Evolutionary Primatology (NYCEP), CUNY Graduate Center, New York, NY, United States
^f Department of Anthropology, Washington University in St. Louis, St. Louis, MO, United States
^g Department of Anthropology, University of Colorado, Colorado Springs, Colorado, Springs, CO, United States
^h Department of Anthropology, University of Oregon, Eugene, OR, United States
ⁱ Department of Anthropology, Yale University, New Haven, CT, United States
^j Center for Global Health, University of Oregon, Eugene, OR, United States
^k Global Station for Indigenous Studies and Cultural Diversity, Hokkaido University, Sapporo, Japan

Abstract
Objectives: The hypothalamic–pituitary–adrenal (HPA) axis and its primary end product, the glucocorticoid cortisol, are major components of the evolved human stress response. However, most studies have examined these systems among populations in high-income settings, which differ from the high pathogen and limited resource contexts in which the HPA axis functioned for most of human evolution. Methods: We investigated variability in diurnal salivary cortisol patterns among 298 Indigenous Shuar from Amazonian Ecuador (147 males, 151 females; age 2–86 years), focusing on the effects of age, biological sex, and body mass index (BMI) in shaping differences in diurnal cortisol production. Saliva samples were collected three times daily (waking, 30 minutes post-waking, evening) for three consecutive days to measure key cortisol parameters: levels at waking, the cortisol awakening response, the diurnal slope, and total daily output. Results: Age was positively associated with waking levels and total daily output, with Shuar juveniles and adolescents displaying significantly lower levels than adults (p <.05). Sex was not a significant predictor of cortisol levels (p >.05), as Shuar males and females displayed similar patterns of diurnal cortisol production across the life course. Moreover, age, sex, and BMI significantly interacted to moderate the rate of diurnal cortisol decline (p =.027). Overall, Shuar demonstrated relatively lower cortisol concentrations than high-income populations. Conclusions: This study expands the documented range of global variation in HPA axis activity and diurnal cortisol production and provides important insights into the plasticity of human stress physiology across diverse developmental and socioecological settings. © 2024 Wiley Periodicals LLC.

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

Social Priming of Speech Perception: The Role of Individual Differences in Implicit Racial and Ethnic Associations
(2024) Journal of Experimental Psychology: Human Perception and Performance, 50 (4), pp. 329-357. 

McLaughlin, D.J.^a b , Van Engen, K.J.^a

^a Department of Psychological and Brain Sciences, Washington University in St. Louis, United States
^b Basque Center on Cognition, Brain and Language, Spain

Abstract
Prior research has shown that visual information, such as a speaker’s perceived race or ethnicity, prompts listeners to expect a specific sociophonetic pattern (“social priming”). Indeed, a picture of an East Asian face may facilitate perception of second language (L2) Mandarin Chinese-accented English but interfere with perception of first language- (L1-) accented English. The present study builds on this line of inquiry, addressing the relationship between social priming effects and implicit racial/ethnic associations for L1- and L2-accented speech. For L1-accented speech, we found no priming effects when comparing White versus East Asian or Latina primes. For L2- (Mandarin Chinese-) accented speech, however, transcription accuracy was slightly better following an East Asian prime than a White prime. Across all experiments, a relationship between performance and individual differences in implicit associations emerged, but in no cases did this relationship interact with the priming manipulation. Ultimately, exploring social priming effects with additional methodological approaches, and in different populations of listeners, will help to determine whether these effects operate differently in the context of L1- and L2-accented speech. © 2024 American Psychological Association

Author Keywords
implicit bias;  language attitudes;  social priming;  speech perception

Document Type: Article
Publication Stage: Final
Source: Scopus

Use of a Blood Biomarker Test Improves Economic Utility in the Evaluation of Older Patients Presenting with Cognitive Impairment
(2024) Population Health Management, . 

Canestaro, W.J.^a , Bateman, R.J.^b , Holtzman, D.M.^b , Monane, M.^c , Braunstein, J.B.^c

^a Department of Management and Organization, Foster School of Business, University of Washington, Seattle, WA, United States
^b Department of Neurology, Washington University School of Medicine in St. Louis, St. Louis, MO, United States
^c C2N Diagnostics, LLC, St. Louis, MO, United States

Abstract
More than 16 million Americans living with cognitive impairment warrant a diagnostic evaluation to determine the cause of this disorder. The recent availability of disease-modifying therapies for Alzheimer’s disease (AD) is expected to significantly drive demand for such diagnostic testing. Accurate, accessible, and affordable methods are needed. Blood biomarkers (BBMs) offer advantages over usual care amyloid positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers in these regards. This study used a budget impact model to assess the economic utility of the PrecivityAD® blood test, a clinically validated BBM test for the evaluation of brain amyloid, a pathological hallmark of AD. The model compared 2 scenarios: (1) baseline testing involving usual care practice, and (2) early use of a BBM test before usual care CSF and PET biomarker use. At a modest 40% adoption rate, the BBM test scenario had comparable sensitivity and specificity to the usual care scenario and showed net savings in the diagnostic work-up of $3.57 million or $0.30 per member per month in a 1 million member population, translating to over $1B when extrapolated to the US population as a whole and representing a 11.4% cost reduction. Savings were driven by reductions in the frequency and need for CSF and PET testing. Additionally, BBM testing was associated with a cost savings of $643 per AD case identified. Use of the PrecivityAD blood test in the clinical care pathway may prevent unnecessary testing, provide cost savings, and reduce the burden on both patients and health plans. © Joel B. Braunstein et al., 2024; Published by Mary Ann Liebert, Inc.

Author Keywords
Alzheimer’s disease;  blood biomarker;  budget impact model;  cost analysis;  diagnosis;  economic utility

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

A precision functional atlas of personalized network topography and probabilities
(2024) Nature Neuroscience, . 

Hermosillo, R.J.M.^a b , Moore, L.A.^a , Feczko, E.^b , Miranda-Domínguez, Ó.^a b , Pines, A.^c d , Dworetsky, A.^e f g , Conan, G.^a h , Mooney, M.A.^h i j k , Randolph, A.^a b , Graham, A.^h , Adeyemo, B.^l , Earl, E.^m , Perrone, A.^a , Carrasco, C.M.^a b , Uriarte-Lopez, J.^h , Snider, K.^h , Doyle, O.^h , Cordova, M.^n o , Koirala, S.^a p , Grimsrud, G.J.^a , Byington, N.^a , Nelson, S.M.^a b , Gratton, C.^f g q , Petersen, S.^{e l q r s} , Feldstein Ewing, S.W.^t , Nagel, B.J.^h , Dosenbach, N.U.F.^l , Satterthwaite, T.D.^d u , Fair, D.A.^a b p

^a Masonic Institute for the Developing Brain, University of Minnesota, Minneapolis, MN, United States
^b Department of Pediatrics, University of Minnesota, Minneapolis, MN, United States
^c Department of Neuroscience, University of Pennsylvania, Philadelphia, PA, United States
^d Penn Lifespan Informatics and Neuroimaging Center, University of Pennsylvania, Philadelphia, PA, United States
^e Department of Radiology, Washington University School of Medicine, St. Louis, MO, United States
^f Department of Psychology, Northwestern University, Evanston, IL, United States
^g Department of Psychology, Florida State University, Tallahassee, FL, United States
^h Department of Psychiatry, Oregon Health & amp; Science University, Portland, OR, United States
ⁱ Department of Medical Informatics and Clinical Epidemiology, Oregon Health and Science University, Portland, OR, United States
^j Knight Cancer Institute, Oregon Health & amp; Science University, Portland, OR, United States
^k Center for Mental Health Innovation, Oregon Health and Science University, Portland, OR, United States
^l Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
^m Data Science and Sharing Team, National Institute of Mental Health, Bethesda, MD, United States
ⁿ Joint Doctoral Program in Clinical Psychology, San Diego State University, San Diego, CA, United States
^o Joint Doctoral Program in Clinical Psychology, University of California San Diego, San Diego, CA, United States
^p Institute of Child Development, University of Minnesota, Minneapolis, MN, United States
^q Department of Psychological and Brain Sciences, Washington University School of Medicine, St. Louis, MO, United States
^r Department of Neuroscience, Washington University School of Medicine, St. Louis, MO, United States
^s Department of Biomedical Engineering, Washington University School of Medicine, St. Louis, MO, United States
^t Department of Psychology, University of Rhode Island, Kingston, RI, United States
^u Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, United States

Abstract
Although the general location of functional neural networks is similar across individuals, there is vast person-to-person topographic variability. To capture this, we implemented precision brain mapping functional magnetic resonance imaging methods to establish an open-source, method-flexible set of precision functional network atlases—the Masonic Institute for the Developing Brain (MIDB) Precision Brain Atlas. This atlas is an evolving resource comprising 53,273 individual-specific network maps, from more than 9,900 individuals, across ages and cohorts, including the Adolescent Brain Cognitive Development study, the Developmental Human Connectome Project and others. We also generated probabilistic network maps across multiple ages and integration zones (using a new overlapping mapping technique, Overlapping MultiNetwork Imaging). Using regions of high network invariance improved the reproducibility of executive function statistical maps in brain-wide associations compared to group average-based parcellations. Finally, we provide a potential use case for probabilistic maps for targeted neuromodulation. The atlas is expandable to alternative datasets with an online interface encouraging the scientific community to explore and contribute to understanding the human brain function more precisely. © The Author(s) 2024.

Funding details
National Institute of Mental HealthNIMHU01DA041148, R37MH125829, U24DA055330, R01MH120482, R01MH096773, R01 MH115357, R01EB022573
National Institutes of HealthNIHU01DA041093, U01DA041048, U01DA041022, U01DA041117, U01DA041089, U01DA041028, U24DA041123, U01DA050989, U01DA050987, U01DA051016, U01DA051018, U24DA041147, U01DA051039, U01DA041120, U01DA041025, U01DA050988, U01DA041174, U01DA041134, U01DA051037, U01DA041106, U01DA041156, U01DA051038

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