Although the substantia nigra (SN) has been implicated in temporal lobe epilepsy (TLE) pathophysiology, clinical studies remain scarce. This study aimed to characterize alterations in SN susceptibility, white matter (WM) microstructure, and functional connectivity (FC), as well as their associations with cognitive functions in TLE patients.
This study included 20 right-TLE (RTLE), 21 left-TLE (LTLE), and 23 healthy controls (HCs). Multimodal neuroimaging was used to assess the susceptibility, diffusion tensor imaging metrics, and FC of SN subregions. Group differences were examined by analysis of covariance. Exploratory correlation analyses were performed to evaluate associations between imaging metrics and cognitive performance.
RTLE patients showed higher susceptibility (post-hoc
P
= 0.015 vs. HCs;
P
= 0.002 vs. LTLE) and radial diffusivity (RD) (post-hoc
P
= 0.014 vs. HCs;
P
= 0.001 vs. LTLE) in the contralateral substantia nigra pars reticulata (SNr), alongside lower fractional anisotropy (FA) (post-hoc
P
= 0.009 vs. HCs;
P
= 0.006 vs. LTLE) in the contralateral substantia nigra pars compacta (SNc). LTLE patients exhibited decreased FA in the ipsilateral SNr (post-hoc
P
< 0.001 vs. HCs;
P
= 0.001 vs. RTLE) and reduced connectivity between the left SNc and the right superior parietal lobule (
P
= 0.026, cluster-level FDR corrected). Susceptibility and RD positively correlated in the contralateral SNr of RTLE cohorts (
r
= 0.564, uncorrected
P
= 0.010). Exploratory analyses suggested associations between SNr susceptibility, FA, and cognitive performance in TLE patients (all uncorrected
P
< 0.05).
Our multimodal findings suggest subregion- and laterality-specific alterations in the SN of patients with TLE, with patterns differing between RTLE and LTLE.
Xu Zhao, Huiting Wu, Si Jian et al.· BMC Medical Imaging· 0 citations
Background Temporal lobe epilepsy (TLE) is increasingly recognized as a network disorder, yet reported regional intrinsic neural activity alterations from resting-state fMRI studies remain spatially heterogeneous. This study aimed to determine whether these heterogeneous alterations converge onto a shared functional network and to characterize its normative transcriptomic and neurochemical correlates. Methods Using a coordinate-based network mapping approach (functional connectivity network mapping, FCNM), we delineated a common brain network functionally connected to regional intrinsic neural activity alterations reported across 20 published neuroimaging studies. The robustness of the resulting network was assessed in an independent cross-scanner validation connectome and across different seed sizes. We further characterized this TLE-related network by correlating its spatial topography with microscale gene expression data from the Allen Human Brain Atlas (AHBA) and with normative neurotransmitter receptor and transporter distributions derived from the JuSpace toolbox. Results Twenty studies comprising 345 foci of regional intrinsic neural activity alteration in TLE were included. The FCNM analysis revealed that heterogeneous regional alterations in TLE converged onto a common functional brain network. This network exhibited the greatest spatial overlap with the default mode network (DMN), while also showing substantial overlap with the limbic network (LN). Transcriptomic analysis revealed that the network’s topography was spatially correlated with gene expression profiles significantly enriched in adaptive immune response pathways, particularly antigen processing and presentation. Neurochemically, the TLE-related network exhibited a significant positive spatial correlation with the distribution of the 5-hydroxytryptamine receptor 1A (5-HT1A). Conclusion Our findings reconcile previously inconsistent reports of regional intrinsic neural activity alterations in TLE by demonstrating their convergence onto a shared brain network, primarily the DMN and LN. By linking this TLE-related network to specific normative transcriptomic and neurochemical signatures, we propose a multi-scale neurobiological framework for the disorder. These findings should be interpreted as spatial associations based on normative datasets rather than direct evidence of disease-specific molecular alterations. This framework reframes TLE from a collection of disparate regional changes toward a core network dysfunction with distinct molecular correlates, thereby opening new avenues for targeted, network-based interventions.
Liang-Liang Ma, Lingling Yang, Bao-Zhen Zhou et al.· Frontiers in Molecular Neuro...· 0 citations
