Spatial correspondence between spontaneous brain activity alterations and normative molecular and neurochemical architecture in pediatric epilepsy.
4 affiliations
- 1Department of Imaging Center, Jiangxi Provincial Children's Hospital, Nanchang, China.
- 2Queen Mary School, Jiangxi Medical College, Nanchang University, Nanchang, China.
- 3School of Biological and Behavioural Sciences, Queen Mary University of London, London, UK.
- 4Department of Neurology, Jiangxi Provincial Children's Hospital, Nanchang, China.
Abstract
Pediatric epilepsy is increasingly recognized as a disorder of distributed brain networks, but the molecular context of spontaneous brain activity alterations remains incompletely understood. This study investigated regional spontaneous brain activity alterations in pediatric epilepsy and their spatial correspondence with normative molecular reference maps. In this observational case-control neuroimaging study, resting-state functional magnetic resonance imaging (rs-fMRI) data from 44 children with epilepsy and 44 healthy controls selected using group-level frequency matching for age and sex were analyzed. Amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF) were compared between groups. The unthresholded signed ALFF case-control t-map was subsequently parcellated using the Schaefer 2018 400-parcel atlas. The 200 left-hemisphere cortical parcels were spatially related to normative adult Allen Human Brain Atlas gene-expression data using partial least squares (PLS) regression, and the whole-cortex ALFF map was compared with 39 normative adult neurotransmitter maps. First partial least squares component (PLS1) explained 36.42% of the variance in the left-hemisphere cortical ALFF map and was significant under 10,000 spherical spin permutations (P_spin=0.0004); regional PLS1 scores were positively associated with ALFF t-values (ρ=0.5650, P_spin=0.0004). PLS1-associated genes were enriched for synaptic, ion-transport, membrane-regulation, and neuronal-projection annotations, and inhibitory-neuron gene sets showed significant enrichment (P=0.0014). The signed ALFF map showed inverse spatial associations with the MU_CARFENTANIL_c11 μ-opioid receptor map (median Spearman ρ=-0.3317, mean Fisher z=-0.3448, P_spin=0.0003, q_FDR =0.0044) and the mGluR5_abp_hc73_smart map (median Spearman ρ=-0.2610, mean Fisher z=-0.2672, P_spin=0.0001, q_FDR =0.0022). These findings provide indirect atlas-based spatial molecular context for the pediatric imaging phenotype. Because the molecular maps were derived from independent adult reference datasets, the associations should not be interpreted as patient-specific gene-expression or receptor measurements, causal mechanisms, or developmentally matched molecular abnormalities.
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BibTeX
@article{yu2026spatial,
title = {{Spatial correspondence between spontaneous brain activity alterations and normative molecular and neurochemical architecture in pediatric epilepsy.}},
author = {Yang-Hong Yu and Xi-Long Zhang and Zhan-Xiang Hu and Zi-Dong Huang and Ji-Hua Xie and Jun Tao and Yu-Mei Huang and Xiao-Gen Xu and Zhu-Qiang Wu},
journal = {Quantitative imaging in medicine and surgery},
year = {2026},
month = sep,
doi = {10.21037/qims-2026-1111},
url = {https://europepmc.org/article/MED/42997930},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Spatial correspondence between spontaneous brain activity alterations and normative molecular and neurochemical architecture in pediatric epilepsy.
AU - Yang-Hong Yu
AU - Xi-Long Zhang
AU - Zhan-Xiang Hu
AU - Zi-Dong Huang
AU - Ji-Hua Xie
AU - Jun Tao
AU - Yu-Mei Huang
AU - Xiao-Gen Xu
AU - Zhu-Qiang Wu
PY - 2026
DA - 2026/09/30
JO - Quantitative imaging in medicine and surgery
DO - 10.21037/qims-2026-1111
UR - https://europepmc.org/article/MED/42997930
AB - Pediatric epilepsy is increasingly recognized as a disorder of distributed brain networks, but the molecular context of spontaneous brain activity alterations remains incompletely understood. This study investigated regional spontaneous brain activity alterations in pediatric epilepsy and their spatial correspondence with normative molecular reference maps. In this observational case-control neuroimaging study, resting-state functional magnetic resonance imaging (rs-fMRI) data from 44 children with epilepsy and 44 healthy controls selected using group-level frequency matching for age and sex were analyzed. Amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF) were compared between groups. The unthresholded signed ALFF case-control t-map was subsequently parcellated using the Schaefer 2018 400-parcel atlas. The 200 left-hemisphere cortical parcels were spatially related to normative adult Allen Human Brain Atlas gene-expression data using partial least squares (PLS) regression, and the whole-cortex ALFF map was compared with 39 normative adult neurotransmitter maps. First partial least squares component (PLS1) explained 36.42% of the variance in the left-hemisphere cortical ALFF map and was significant under 10,000 spherical spin permutations (P_spin=0.0004); regional PLS1 scores were positively associated with ALFF t-values (ρ=0.5650, P_spin=0.0004). PLS1-associated genes were enriched for synaptic, ion-transport, membrane-regulation, and neuronal-projection annotations, and inhibitory-neuron gene sets showed significant enrichment (P=0.0014). The signed ALFF map showed inverse spatial associations with the MU_CARFENTANIL_c11 μ-opioid receptor map (median Spearman ρ=-0.3317, mean Fisher z=-0.3448, P_spin=0.0003, q_FDR =0.0044) and the mGluR5_abp_hc73_smart map (median Spearman ρ=-0.2610, mean Fisher z=-0.2672, P_spin=0.0001, q_FDR =0.0022). These findings provide indirect atlas-based spatial molecular context for the pediatric imaging phenotype. Because the molecular maps were derived from independent adult reference datasets, the associations should not be interpreted as patient-specific gene-expression or receptor measurements, causal mechanisms, or developmentally matched molecular abnormalities.
SN - 2223-4292
SN - 2223-4306
ER -