Hope Center Member Publications: April 7, 2024

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

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

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

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