Intrinsic adaptive plasticity in mouse and human sensory neurons
(2025) The Journal of General Physiology, 157 (1), .
McIlvried, L.A.a , Del Rosario, J.S.a , Pullen, M.Y.a , Wangzhou, A.b , Sheahan, T.D.a , Shepherd, A.J.a , Slivicki, R.A.a , Lemen, J.A.c , Price, T.J.b , Copits, B.A.a , Gereau, R.W., 4tha d
a Washington University Pain Center and Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, United States
b Department of Neuroscience and Center for Advanced Pain Studies, University of Texas at Dallas, Dallas, TX, United States
c Mid-America Transplant, St. Louis, MO, United States
d Department of Neuroscience and Department of Biomedical Engineering, Washington University School of Medicine, St. Louis, MO, United States
Abstract
In response to changes in activity induced by environmental cues, neurons in the central nervous system undergo homeostatic plasticity to sustain overall network function during abrupt changes in synaptic strengths. Homeostatic plasticity involves changes in synaptic scaling and regulation of intrinsic excitability. Increases in spontaneous firing and excitability of sensory neurons are evident in some forms of chronic pain in animal models and human patients. However, whether mechanisms of homeostatic plasticity are engaged in sensory neurons of the peripheral nervous system (PNS) is unknown. Here, we show that sustained depolarization (induced by 24-h incubation in 30 mM KCl) induces compensatory changes that decrease the excitability of mouse and human sensory neurons without directly opposing membrane depolarization. Voltage-clamp recordings show that sustained depolarization produces no significant alteration in voltage-gated potassium currents, but a robust reduction in voltage-gated sodium currents, likely contributing to the overall decrease in neuronal excitability. The compensatory decrease in neuronal excitability and reduction in voltage-gated sodium currents reversed completely following a 24-h recovery period in a normal medium. Similar adaptive changes were not observed in response to 24 h of sustained action potential firing induced by optogenetic stimulation at 1 Hz, indicating the need for prolonged depolarization to drive engagement of this adaptive mechanism in sensory neurons. Our findings show that mouse and human sensory neurons are capable of engaging adaptive mechanisms to regulate intrinsic excitability in response to sustained depolarization in a manner similar to that described in neurons in the central nervous system. © 2024 McIlvried et al.
Document Type: Article
Publication Stage: Final
Source: Scopus
Associations between prenatal caffeine exposure and child development: Longitudinal results from the Adolescent Brain Cognitive Development (ABCD) Study
(2025) Neurotoxicology and Teratology, 107, art. no. 107404, .
Modi, H.a b , Baranger, D.A.A.a , Paul, S.E.a , Gorelik, A.J.a , Hornstein, A.a , Balbona, J.V.b , Agrawal, A.b , Bijsterbosch, J.D.c , Bogdan, R.a
a Department of Psychological and Brain Sciences, Washington University in Saint Louis, St. Louis, MO, United States
b Department of Psychiatry, Washington University in Saint Louis, United States
c Department of Radiology, Washington University in Saint Louis, United States
Abstract
Objective: Though caffeine use during pregnancy is common, its longitudinal associations with child behavioral and physical health outcomes remain poorly understood. Here, we estimated associations between prenatal caffeine exposure, body mass index (BMI), and behavior as children enter adolescence. Method: Longitudinal data and caregiver-reported prenatal caffeine exposure were obtained from the ongoing Adolescent Brain and Cognitive Development (ABCD)SM Study, which recruited 11,875 children aged 9–11 years at baseline from 21 sites across the United States starting June 1, 2016. Prenatal caffeine exposure was analyzed as a 4-level categorical variable, and further group contrasts were used to characterize “any exposure” and “daily exposure” groups. Outcomes included psychopathology characteristics in children, sleep problems, and BMI. Potentially confounding covariates included familial (e.g., income, familial psychopathology), pregnancy (e.g., prenatal substance exposure), and child (e.g., caffeine use) variables. Results: Among 10,873 children (5686 boys [52.3 %]; mean [SD] age, 9.9 [0.6] years) with nonmissing prenatal caffeine exposure data, 6560 (60 %) were exposed to caffeine prenatally. Relative to no exposure, daily caffeine exposure was associated with higher child BMI (β = 0.08; FDR-corrected p = 0.02), but was not associated with child behavior following correction for multiple testing. Those exposed to two or more cups of caffeine daily (n = 1028) had greater sleep problems than those with lower/no exposure (β > 0.92; FDR-corrected p < 0.04). Conclusion: Daily prenatal caffeine exposure is associated with heightened childhood BMI, and when used multiple times a day greater sleep problems even after accounting for potential confounds. Whether this relationship is a consequence of prenatal caffeine exposure or its correlated factors remains unknown. © 2024 The Authors
Author Keywords
Child development; Longitudinal; Mental health; Prenatal caffeine exposure; Psychopathology
Funding details
National Institute of Mental HealthNIMH
National Institutes of HealthNIH
Secretaría de Educación PúblicaSEPF31AA029934
Secretaría de Educación PúblicaSEP
R01MH132962, U01DA055367S, R01MH128286, R01HD113188, R01AG061162, U01DA055367, R21AA027827, K99AA030808
National Science FoundationNSFDGE-213989
National Science FoundationNSF
Document Type: Article
Publication Stage: Final
Source: Scopus
Maternal obesogenic diet operates at the tumor cell of origin to increase incidence and decrease latency of neurofibromatosis type 1 optic pathway glioma
(2024) Neuro-oncology, 26 (12), pp. 2339-2351.
Chan, A.a , Zhang, K.a , Martin, G.a , Bano, S.a , Chatterjee, J.b , Mahto, S.a , Wang, A.a , Gutmann, D.H.b , Brossier, N.M.a
a Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, United States
b Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
Abstract
BACKGROUND: Pediatric low-grade glioma incidence has been rising in the United States, mirroring the rising rates of pediatric and maternal obesity. Recently, children of obese mothers were demonstrated to develop brain tumors at higher rates. Importantly, obesity in the United States is largely driven by diet, given the prevalence of high-fat and high-sugar (HFHS) food choices. Since high-fat diet exposure can increase embryonic neuroglial progenitor cell (NPC) proliferation, the potential cells of origin for a low-grade glioma, we hypothesized that in utero exposure to an obesogenic diet would modify pediatric brain penetrance and latency by affecting the tumor cell of origin. METHODS: We employed several murine models of the neurofibromatosis type 1 (NF1) pediatric brain tumor predisposition syndrome, in which optic pathway gliomas (Nf1-OPGs) arise from neuroglial progenitor cells in the embryonic third ventricular zone (TVZ). We exposed dams and offspring to an obesogenic HFHS diet or control chow and analyzed fetal neurodevelopment at E19.5 and tumor formation at 6 weeks-3 months. RESULTS: Progeny from HFHS diet-exposed dams demonstrated increased TVZ NPC proliferation and glial differentiation. Dietary switch cohorts confirmed that these effects were dependent upon maternal diet, rather than maternal weight. Obesogenic diet (Ob) similarly accelerated glioma formation in a high-penetrance Nf1-OPG strain and increased glioma penetrance in 2 low-penetrance Nf1-OPG strains. In contrast, Ob exposure in the postnatal period alone did not recapitulate these effects. CONCLUSIONS: These findings establish maternal obesogenic diet as a risk factor for murine Nf1-OPG formation, acting in part through in utero effects on the tumor cell of origin. © The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact jou
Author Keywords
maternal high-fat diet; neurofibromatosis; obesity; optic pathway glioma; pediatric brain tumor
Document Type: Article
Publication Stage: Final
Source: Scopus
Cannabis Use and Trajectories of Depression and Stress Across the Prenatal Period
(2024) JAMA Network Open, 7 (12), p. e2451597.
Constantino-Pettit, A.a , Tillman, R.a , Wilson, J.a , Lashley-Simms, N.a , Vatan, N.b , Atkinson, A.c , Leverett, S.D.a d , Lenze, S.a , Smyser, C.D.e , Bogdan, R.f , Rogers, C.a , Agrawal, A.a
a Department of Psychiatry, Washington University in St Louis, School of Medicine, St Louis, MO, United States
b Washington University in St Louis School of Medicine, St Louis, MO, United States
c Meharry Medical College School of Medicine, Nashville, TN, United States
d Division of Biology & Biomedical Sciences, Neurosciences Program, Washington University in St Louis, St Louis, MO, United States
e Department of Neurology, Washington University in St Louis, St Louis, MO, United States
f Department of Psychological and Brain Sciences, Washington University in St Louis, St Louis, MO, United States
Abstract
Importance: Cannabis use among pregnant individuals has increased. Depression and stress are frequently reported motives for cannabis use that may prolong using cannabis during pregnancy. Objective: To examine associations between changes in depression, stress, and self-reported prenatal cannabis use (PCU), to examine motives for PCU, and to examine whether trajectories of depression and stress vary across individuals who report using cannabis to cope with mental health symptoms and/or stress, those who use cannabis for other reasons, and those who do not report PCU. Design, Setting, and Participants: This cohort study recruited pregnant individuals at an obstetric clinic at an academic hospital between July 2019 and January 2024 and followed them during pregnancy. Pregnant individuals with a history of lifetime cannabis use were included. Individuals reporting heavy episodic alcohol use or with other illicit drug use were excluded. Exposure: Self-reported PCU. Main Outcomes and Measures: The primary outcomes were self-reported depression (Edinburgh Postnatal Depression Scale), stress (Cohen Perceived Stress Scale), and cannabis use at each trimester during pregnancy, as well as motives for cannabis use during the first trimester (T1). Stability and changes in depression and stress scores and categorical self-reported prenatal cannabis use from T1 to the third trimester (T3) were estimated using individual linear growth curve models. Results: In this sample of 504 patients (all identified as women; median [IQR] age, 26 [18-40] years), 236 individuals (46.8%) reported PCU after pregnancy knowledge. Depression, stress, and PCU decreased from T1 to T3 (all slope estimates less than -0.29; SEs, 0.23-0.7; all P < .001). There were positive associations between depression and PCU at T1 (r = 0.17; P = .004) and in their rate of change (r = 0.18; P = .01). Only T1 stress and PCU were correlated (r = 0.14; P = .004). Participants reporting PCU for mental health reasons (137 participants [58.1%]) had the highest depression scores at each trimester; however, their rate of change in depression was statistically equivalent to those who did not use cannabis. Conclusions and Relevance: In this cohort study of PCU, participants who used cannabis did not experience a more significant decline in stress or depression symptoms compared with those who did not use cannabis. Individuals who used cannabis for mental health reasons did not hasten a decrease in their symptoms. Health care professionals are encouraged to enhance prenatal individuals’ access to empirically supported treatments for depression and stress.
Document Type: Article
Publication Stage: Final
Source: Scopus
Microglial CD2AP deficiency exerts protection in an Alzheimer’s disease model of amyloidosis
(2024) Molecular Neurodegeneration, 19 (1), art. no. 95, .
Zhang, L.a , Huang, L.a , Zhou, Y.a , Meng, J.a , Zhang, L.a , Zhou, Y.a , Zheng, N.a , Guo, T.a , Zhao, S.a , Wang, Z.a , Huo, Y.a , Zhao, Y.a , Chen, X.-F.a , Zheng, H.a , Holtzman, D.M.b , Zhang, Y.-W.a
a Xiamen Key Laboratory of Brain Center, The First Affiliated Hospital of Xiamen University, and Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, School of Medicine, Xiamen University, Fujian, Xiamen, 361102, China
b Department of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer’s Disease Research Center, Washington University School of Medicine, St. Louis, MO, United States
Abstract
Background: The CD2-associated protein (CD2AP) was initially identified in peripheral immune cells and regulates cytoskeleton and protein trafficking. Single nucleotide polymorphisms (SNPs) in the CD2AP gene have been associated with Alzheimer’s disease (AD). However, the functional role of CD2AP, especially its role in microglia during AD onset, remains elusive. Methods: CD2AP protein levels in cultured primary cells and in 5xFAD mice was studied. Microglial CD2AP-deficient mice were crossed with 5xFAD mice and the offspring were subjected to neuropathological assessment, behavioral tests, electrophysiology, RNA-seq, Golgi staining, and biochemistry analysis. Primary microglia were also isolated for assessing their uptake and morphology changes. Results: We find that CD2AP is abundantly expressed in microglia and its levels are elevated in the brain of AD patients and the 5xFAD model mice at pathological stages. We demonstrate that CD2AP haploinsufficiency in microglia significantly attenuates cognitive and synaptic deficits, weakens the response of microglia to Aβ and the formation of disease-associated microglia (DAM), and alleviates synapse loss in 5xFAD mice. We show that CD2AP-deficient microglia exhibit compromised uptake ability. In addition, we find that CD2AP expression is positively correlated with the expression of the complement C1q that is important for synapse phagocytosis and the formation of DAM in response to Aβ deposition. Moreover, we reveal that CD2AP interacts with colony stimulating factor 1 receptor (CSF1R) and regulates CSF1R cell surface levels, which may further affect C1q expression. Conclusions: Our results demonstrate that CD2AP regulates microgliosis and identify a protective function of microglial CD2AP deficiency against Aβ deposition, suggesting the importance of detailed investigation of AD-associated genes in different brain cells for thoroughly understanding their exact contribution to AD. © The Author(s) 2024.
Author Keywords
Alzheimer’s disease; C1q; CD2AP; CSF1R; Disease-associated microglia; Microglia; β-amyloid
Funding details
National Natural Science Foundation of ChinaNSFCU21A20361, 82130039
National Natural Science Foundation of ChinaNSFC
Fundamental Research Funds for the Central Universities20720220133
Fundamental Research Funds for the Central Universities
Document Type: Article
Publication Stage: Final
Source: Scopus
Increased White Matter Aerobic Glycolysis in Multiple Sclerosis
(2024) Annals of Neurology, .
Brier, M.R.a b , Judge, B.a , Ying, C.b , Salter, A.c , An, H.b , Patel, A.d , Wang, Q.b , Wang, Y.b e , Cross, A.H.a , Naismith, R.T.a , Benzinger, T.L.S.b , Goyal, M.S.a b
a Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
b Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, United States
c Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX, United States
d Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
e Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO, United States
Abstract
Objective: Despite treatments which reduce relapses in multiple sclerosis (MS), many patients continue to experience progressive disability accumulation. MS is associated with metabolic disruptions and cerebral metabolic stress predisposes to tissue injury and possibly impaired remyelination. Additionally, myelin homeostasis is metabolically expensive and reliant on glycolysis. We investigated cerebral metabolic changes in MS and when in the disease course they occurred, and assessed their relationship with microstructural changes. Methods: This study used combined fluorodeoxyglucose (FDG) positron emission tomography (PET) and magnetic resonance imaging (MRI) to measure cerebral metabolic rate of glucose and oxygen, thereby quantifying glycolysis. Twelve healthy controls, 20 patients with relapsing MS, and 13 patients with non-relapsing MS were studied. Relapsing patients with MS were treatment naïve and scanned pre- and post-initiation of high efficacy disease modifying therapy. Results: In normal appearing white matter, we observed increased glucose utilization and reduced oxygen utilization in newly diagnosed MS, consistent with increased glycolysis. Increased glycolysis was greater in patients with a longer disease duration course and higher disability. Among newly diagnosed patients, different treatments had differential impacts on glucose utilization. Last, whereas hypermetabolism within lesions was clearly associated with inflammation, no such relationship was found within normal appearing white matter. Interpretation: Increased white matter glycolysis is a prominent feature of cerebral metabolism in MS. It begins early in the disease course, increases with disease duration and is independent of microstructural evidence of inflammation in normal appearing white matter. Optimization of the metabolic environment may be an important component of therapies designed to reduce progressive disability. ANN NEUROL 2024. © 2024 American Neurological Association.
Funding details
School of Medicine, Washington University in St. LouisWUSM
National Multiple Sclerosis SocietyNMSS
Mallinckrodt Institute of Radiology, School of Medicine, Washington University in St. LouisMIR
National Center for Advancing Translational SciencesNCATS
National Institutes of HealthNIHBI‐2105‐37656, R21MH131962
National Institutes of HealthNIH
Institute of Clinical and Translational SciencesICTSUL1TR002345
Institute of Clinical and Translational SciencesICTS
Foundation for Barnes-Jewish HospitalFBJHRF1AG073210
Foundation for Barnes-Jewish HospitalFBJH
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Differences in baseline cognitive performance between participants with early-onset and late-onset Alzheimer’s disease: Comparison of LEADS and ADNI
(2024) Alzheimer’s and Dementia, . Cited 1 time.
Hammers, D.B.a , Eloyan, A.b , Thangarajah, M.b , Taurone, A.b , Beckett, L.c , Gao, S.d , Polsinelli, A.J.a , Kirby, K.a , Dage, J.L.a , Nudelman, K.e , Aisen, P.f , Reman, R.f , La Joie, R.g , Lagarde, J.g , Atri, A.h , Clark, D.a , Day, G.S.i , Duara, R.j , Graff-Radford, N.R.i , Honig, L.S.k , Jones, D.T.l , Masdeu, J.C.m , Mendez, M.F.n , Womack, K.o , Musiek, E.o , Onyike, C.U.p , Riddle, M.q , Grant, I.r , Rogalski, E.s , Johnson, E.C.B.t , Salloway, S.q , Sha, S.J.u , Turner, R.S.v , Wingo, T.S.w , Wolk, D.A.x , Carrillo, M.C.y , Dickerson, B.C.z , Rabinovici, G.D.g aa , Apostolova, L.G.a e ab , the LEADS Consortium 1 for the Alzheimer’s Disease Neuroimaging Initiativeac
a Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, United States
b Department of Biostatistics, Center for Statistical Sciences, Brown University, Providence, RI, United States
c Department of Public Health Sciences, University of California—Davis, Davis, CA, United States
d Department of Biostatistics, Indiana University School of Medicine, Indianapolis, IN, United States
e Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, United States
f Alzheimer’s Therapeutic Research Institute, University of Southern California, San Diego, CA, United States
g Department of Neurology, University of California—San Francisco, San Francisco, CA, United States
h Banner Sun Health Research Institute, Sun City, AZ, United States
i Department of Neurology, Mayo Clinic, Jacksonville, FL, United States
j Wien Center for Alzheimer’s Disease and Memory Disorders, Mount Sinai Medical Center, Miami, FL, United States
k Taub Institute and Department of Neurology, Columbia University Irving Medical Center, New York, NY, United States
l Department of Neurology, Mayo Clinic, Rochester, MN, United States
m Nantz National Alzheimer Center, Houston Methodist and Weill Cornell Medicine, Houston, TX, United States
n Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States
o Department of Neurology, Washington University in St. Louis, St. Louis, MO, United States
p Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States
q Department of Neurology, Alpert Medical School, Brown University, Providence, RI, United States
r Department of Psychiatry and Behavioral Sciences, Mesulam Center for Cognitive Neurology and Alzheimer’s Disease, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
s Healthy Aging & Alzheimer’s Research Care Center, Department of Neurology, University of Chicago, Chicago, IL, United States
t Department of Neurology, Emory University School of Medicine, Atlanta, GA, United States
u Department of Neurology & Neurological Sciences, Stanford University, Palo Alto, CA, United States
v Department of Neurology, Georgetown University, Washington, DC, United States
w Department of Neurology, UC Davis Alzheimer’s Disease Research Center, University of California—Davis, Davis, CA, United States
x Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
y Medical & Scientific Relations Division, Alzheimer’s Association, Chicago, IL, United States
z Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
aa Department of Radiology & Biomedical Imaging, University of California—San Francisco, San Francisco, CA, United States
ab Department of Radiology and Imaging Sciences, Center for Neuroimaging, Indiana University School of Medicine Indianapolis, Indianapolis, IN, United States
Abstract
INTRODUCTION: Early-onset Alzheimer’s disease (EOAD) and late-onset Alzheimer’s disease (LOAD) share similar amyloid etiology, but evidence from smaller-scale studies suggests that they manifest differently clinically. Current analyses sought to contrast the cognitive profiles of EOAD and LOAD. METHODS: Z-score cognitive-domain composites for 311 amyloid-positive sporadic EOAD and 314 amyloid-positive LOAD participants were calculated from baseline data from age-appropriate control cohorts. Z-score composites were compared between AD groups for each domain. RESULTS: After controlling for cognitive status, EOAD displayed worse visuospatial, executive functioning, and processing speed/attention skills relative to LOAD, and LOAD displayed worse language, episodic immediate memory, and episodic delayed memory. DISCUSSION: Sporadic EOAD possesses distinct cognitive profiles relative to LOAD. Clinicians should be alert for non-amnestic impairments in younger patients to ensure proper identification and intervention using disease-modifying treatments. Highlights: Both early-onset Alzheimer’s disease (EOAD) and late-onset Alzheimer’s disease (LOAD) participants displayed widespread cognitive impairments relative to their same-aged peers. Cognitive impairments were more severe for EOAD than for LOAD participants in visuospatial and executive domains. Memory and language impairments were more severe for LOAD than for EOAD participants Results were comparable after removing clinical phenotypes of posterior cortical atrophy (PCA), primary progressive aphasia (lv-PPA), and frontal-variant AD. © 2024 The Author(s). Alzheimer’s & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer’s Association.
Author Keywords
Alzheimer’s disease; amnestic; early-onset; late-onset; non-amnestic
Funding details
BioClinica
National Institute of Biomedical Imaging and BioengineeringNIBIB
AbbVie
Biogen
Alzheimer’s Disease Neuroimaging InitiativeADNI
National Institute on AgingNIA
Alzheimer’s Drug Discovery FoundationADDF
Alzheimer’s AssociationAAP30AG066506, P30 AG010124, U01 AG016976, P50AG047366, P30 AG013854, P30 AG062422, P30 AG010133, LEADS GENETICS‐19‐639372, P30 AG062421, P50 AG005681, P50 AG008702, P50 AG005146, P50 AG025688, P50 AG023501
Alzheimer’s AssociationAA
Fondation pour la Recherche sur AlzheimerU24AG021886, R56 AG057195, U01AG6057195
Fondation pour la Recherche sur Alzheimer
U.S. Department of DefenseDODW81XWH‐12‐2‐0012
U.S. Department of DefenseDOD
National Institutes of HealthNIHU01 AG024904
National Institutes of HealthNIH
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Full-field, frequency-domain comparison of simulated and measured human brain deformation
(2024) Biomechanics and Modeling in Mechanobiology, art. no. 081006, .
Arani, A.H.G.a , Okamoto, R.J.a , Escarcega, J.D.a , Jerusalem, A.b , Alshareef, A.A.c , Bayly, P.V.a
a Mechanical Engineering and Materials Science, Washington University, St. Louis, MO, United States
b Department of Engineering Science, University of Oxford, Oxford, OX1 3PJ, United Kingdom
c Department of Mechanical Engineering, University of South Carolina, Columbia, SC, United States
Abstract
We propose a robust framework for quantitatively comparing model-predicted and experimentally measured strain fields in the human brain during harmonic skull motion. Traumatic brain injuries (TBIs) are typically caused by skull impact or acceleration, but how skull motion leads to brain deformation and consequent neural injury remains unclear and comparison of model predictions to experimental data remains limited. Magnetic resonance elastography (MRE) provides high-resolution, full-field measurements of dynamic brain deformation induced by harmonic skull motion. In the proposed framework, full-field strain measurements from human brain MRE in vivo are compared to simulated strain fields from models with similar harmonic loading. To enable comparison, the model geometry and subject anatomy, and subsequently, the predicted and measured strain fields are nonlinearly registered to the same standard brain atlas. Strain field correlations (Cv), both global (over the brain volume) and local (over smaller sub-volumes), are then computed from the inner product of the complex-valued strain tensors from model and experiment at each voxel. To demonstrate our approach, we compare strain fields from MRE in six human subjects to predictions from two previously developed models. Notably, global Cv values are higher when comparing strain fields from different subjects (Cv~0.6–0.7) than when comparing strain fields from either of the two models to strain fields in any subject. The proposed framework provides a quantitative method to assess similarity (and to identify discrepancies) between model predictions and experimental measurements of brain deformation and thus can aid in the development and evaluation of improved models of brain biomechanics. © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2024.
Author Keywords
Brain simulation; Frequency-domain comparison; Magnetic resonance elastography; Nonlinear registration; Strain fields; Traumatic brain injury
Funding details
National Institutes of HealthNIHU01 NS112120
National Institutes of HealthNIH
Document Type: Article
Publication Stage: Article in Press
Source: Scopus