Multimodal macroscopic brain abnormalities in schizophrenia converge on insular, mediofrontal, and sensorimotor cortices and link with glial cell expression but not with recent evolutionary change
- 1Technical University of Munich
Abstract
BackgroundSchizophrenia is characterized by widespread structural and functional brain abnormalities, yet it remains unclear whether these alterations converge across imaging modalities and whether such convergence is associated with underlying cellular distribution and evolution of the human cortex.
MethodsWe performed coordinate-based meta-analyses of seven whole-brain neuroimaging modalities, including cortical thickness, gyrification, voxel-based morphometry, amplitude of low-frequency fluctuations, regional homogeneity, regional cerebral blood flow (all based on magnetic resonance imaging), and glucose metabolism based on [18F]-Fluorodeoxyglucose positron emission tomography. The analyses included 200 studies (209 datasets) comprising 11,794 patients with schizophrenia and 10,342 healthy controls. After single-modality meta-analyses using seed-based d-mapping, the meta-analytic result maps were integrated using orthonormal projective non-negative matrix factorization. Finally, the resulting component maps were related to maps of cortical cell type-specific gene expression and human-specific cortical evolution.
ResultsMultimodal integration identified a robust convergence pattern centered in bilateral insular, mediofrontal, and lateral sensorimotor cortices, with the strongest contributions from regional homogeneity, cerebral blood flow, and amplitude of low-frequency fluctuations. The convergence pattern showed significant spatial correspondence with cortical gene expression profiles of astrocytes, microglia, and oligodendrocyte progenitor cells. In contrast, we found no evidence for a preferential localization to regions of human-specific cortical expansion or connectivity.
ConclusionsStructural and functional brain abnormalities in schizophrenia converge on an insular-mediofrontal-sensorimotor pattern that aligns with glial gene expression profiles. These results support glia-related regional vulnerability as an organizing principle of multimodal brain abnormalities in schizophrenia.
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BibTeX
@misc{thalhammer2026multimodal,
title = {{Multimodal macroscopic brain abnormalities in schizophrenia converge on insular, mediofrontal, and sensorimotor cortices and link with glial cell expression but not with recent evolutionary change}},
author = {M. Thalhammer and P. Rossmueller and C. Meng and J. Priller and C. Sorg and F. Brandl},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.30.26364383},
url = {https://www.medrxiv.org/content/10.64898/2026.09.30.26364383v1},
note = {CC BY-ND},
}
RIS
TY - UNPB
TI - Multimodal macroscopic brain abnormalities in schizophrenia converge on insular, mediofrontal, and sensorimotor cortices and link with glial cell expression but not with recent evolutionary change
AU - M. Thalhammer
AU - P. Rossmueller
AU - C. Meng
AU - J. Priller
AU - C. Sorg
AU - F. Brandl
PY - 2026
DA - 2026/09/30
PB - medRxiv
DO - 10.64898/2026.09.30.26364383
UR - https://www.medrxiv.org/content/10.64898/2026.09.30.26364383v1
AB - BackgroundSchizophrenia is characterized by widespread structural and functional brain abnormalities, yet it remains unclear whether these alterations converge across imaging modalities and whether such convergence is associated with underlying cellular distribution and evolution of the human cortex. MethodsWe performed coordinate-based meta-analyses of seven whole-brain neuroimaging modalities, including cortical thickness, gyrification, voxel-based morphometry, amplitude of low-frequency fluctuations, regional homogeneity, regional cerebral blood flow (all based on magnetic resonance imaging), and glucose metabolism based on [18F]-Fluorodeoxyglucose positron emission tomography. The analyses included 200 studies (209 datasets) comprising 11,794 patients with schizophrenia and 10,342 healthy controls. After single-modality meta-analyses using seed-based d-mapping, the meta-analytic result maps were integrated using orthonormal projective non-negative matrix factorization. Finally, the resulting component maps were related to maps of cortical cell type-specific gene expression and human-specific cortical evolution. ResultsMultimodal integration identified a robust convergence pattern centered in bilateral insular, mediofrontal, and lateral sensorimotor cortices, with the strongest contributions from regional homogeneity, cerebral blood flow, and amplitude of low-frequency fluctuations. The convergence pattern showed significant spatial correspondence with cortical gene expression profiles of astrocytes, microglia, and oligodendrocyte progenitor cells. In contrast, we found no evidence for a preferential localization to regions of human-specific cortical expansion or connectivity. ConclusionsStructural and functional brain abnormalities in schizophrenia converge on an insular-mediofrontal-sensorimotor pattern that aligns with glial gene expression profiles. These results support glia-related regional vulnerability as an organizing principle of multimodal brain abnormalities in schizophrenia.
ER -