Aug 2026· Frontiers in Molecular Neuroscience· Vol 19· 0 citations· 105 references
Medicine
TL;DR
These 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, and propose a multi-scale neurobiological framework for the disorder.
Abstract
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.
Background Migraine is a prevalent and disabling neurological disorder. Resting-state functional magnetic resonance imaging (rs-fMRI) studies have investigated regional intrinsic neural activity alterations in migraine but have often yielded inconsistent findings. Emerging network perspectives suggest that brain disorders may be better understood through disruptions in large-scale networks. Methods This systematic review included 31 rs-fMRI studies (1,238 migraine patients; 1,005 controls; 302 altered ALFF/ReHo coordinates) to clarify these discrepancies. Using functional connectivity network mapping (FCNM) with Human Connectome Project data (n = 1,093), we identified that heterogeneous regional intrinsic neural activity alterations in migraine converge onto common brain functional networks. Spatial relationships between the identified brain networks and the distribution of major neurotransmitter receptors/transporters were subsequently characterized using the Juspace toolbox. Results FCNM analysis revealed that heterogeneous regional intrinsic neural activity alterations reported in migraine studies mapped to common brain functional networks, particularly within visual, somatomotor, and attention systems. The FCNM-identified migraine network exhibited significant spatial correlations with normative distributions of metabotropic glutamate receptor 5 (mGluR5), 5-hydroxytryptamine receptor 2A (5-HT2A), and noradrenaline transporter (NAT). Conclusion These findings suggest that intrinsic neural dysfunctions in migraine map to large-scale networks with multi-neurochemical susceptibility. This framework suggests that heterogeneous regional intrinsic activity alterations in migraine are preferentially connected to visual, somatomotor, and attentional systems and are spatially aligned with normative neurochemical maps. These findings are hypothesis-generating and should not be interpreted as evidence of causality or patient-specific receptor alterations.
Hu-Cheng Yang, Si-Jia Bian, Xi-Lei Gao et al.· Frontiers in Neurology· 0 citations
BACKGROUND
Although structural and functional alterations in borderline personality disorder (BPD) have been widely reported in neuroimaging studies, the findings remain heterogeneous. Emerging consensus suggests that these distributed alterations may converge on a common pathological network associated with BPD, providing a network-level framework for elucidating the neural basis of the disorder.
METHODS
We integrated findings from 96 publications covering 2325 patients with BPD and 2356 healthy controls across gray matter volume, task-induced activation, and resting-state activity modalities. Using the functional connectivity network mapping (FCNM) approach, we projected the reported alterations onto a large-scale functional connectome (n = 872) to localize brain alteration networks associated with BPD. We then evaluated the spatial relationship between these networks and 19 neurotransmitter distribution maps.
RESULTS
We identified three distinct networks. The gray matter volume alteration network involved the precentral/postcentral gyrus and temporal gyrus, predominantly within the somatomotor (12.24%) and subcortical networks (8.65%). The task-induced activation network was mainly located in the insula/putamen, primarily associated with the ventral attention network (18.83%). The resting-state network encompassed the superior frontal gyrus, precuneus, and angular gyrus, dominated by the default mode network (53.86%). The structural network exhibited spatial correlations with the serotonin transporter, while the task-induced network was associated with noradrenergic and cholinergic systems.
CONCLUSIONS
These findings suggest BPD might be characterized by structural deficits in somatic-emotional integration and functional dysregulation in salience detection and self-referential processing. This network-level framework helps address previously existing inconsistencies and suggests that these brain alterations may be related to specific neurotransmitters.
Leyi Zhang, Yiding Han, Y. Ou et al.· Journal of Affective Disorde...· 0 citations
Background Functional magnetic resonance imaging (fMRI) has revealed abnormal brain activity patterns in stroke patients, yet the genetic correlates underlying functional homotopy – defined as synchronized spontaneous activity between bilateral homologous brain regions – remain poorly characterized. This study investigates the genetic basis of voxel-mirrored homotopic connectivity (VMHC) abnormalities in stroke patients. Methods We analyzed resting-state fMRI data from 50 stroke patients and 50 healthy controls (HC) to quantify VMHC. Spatial transcriptome-neuroimaging correlations were established using the Allen Human Brain Atlas (AHBA) to identify VMHC-associated genes. Transcriptomic analyses combined pathway-centric functional annotation (DAVID) with protein-protein interaction (PPI) network modeling (STRING v12.0). Results Stroke patients exhibited significantly reduced VMHC in the rectus gyrus, superior temporal gyrus, middle occipital gyrus, cuneus, and right calcarine/left posterior cingulate gyrus (p < 0.05, GRF-corrected). VMHC alterations correlated positively and negatively with 1,198 genes each. Transcriptomic profiling revealed significant enrichment in synaptic vesicle trafficking, mitochondrial energy metabolism, and neuroinflammation-related pathways. PPI mapping uncovered multi-tiered networks with hub genes including BRCA1, CDK9, ACTB, and ATP6V1A/F involved in transcriptional regulation, cytoskeletal dynamics, and vesicular acidification. Conclusion This multimodal integration study elucidates polygenic correlates of post-stroke VMHC abnormalities, demonstrating that interhemispheric coordination may depend on synergistic interactions among functionally diverse gene clusters. Our findings provide a molecular framework for understanding post-stroke neural network reorganization and offer a link between functional neuroimaging phenotypes and gene expression, though all associations remain correlational and require mechanistic validation.
Ri-Bo Chen, Yu-Xuan He, Xin Huang et al.· Frontiers in Cellular Neuros...· 0 citations
The human brain operates through large-scale networks whose subcortical components are critical for consciousness, emotion, and cognition. While cortical network connectivity has been mapped with increasing precision, subcortical network mapping has lagged far behind due to two fundamental barriers: the overlapping and correlated nature of brain networks, which conventional analytic methods cannot disentangle, and the inherently low signal-to-noise ratio of functional imaging data within the subcortex. As a result, no consensus or normative atlas for subcortical functional brain connectivity exists-a critical gap that has impeded both basic neuroscience and the development of targeted neuromodulatory therapies. In this work, we address these barriers using NASCAR, a tensor decomposition method explicitly designed to separate overlapping and correlated networks, applied to resting-state functional MRI data from 1,000 healthy individuals in the Human Connectome Project. This approach enabled us to fractionate four large-scale brain networks into 15 highly reproducible subnetworks spanning both cortical and subcortical structures, revealing their sites of neuroanatomic overlap and defining a normative whole-brain functional atlas grounded in subcortical connectivity. As proof of principle for the translational potential of this framework, we show that individual patterns of subnetworks predict levels of consciousness in patients with severe traumatic brain injury. By establishing a gold-standard, openly accessible reference for subcortical functional brain organization, this work expands the landscape of human brain network mapping and opens avenues for precision targeting in the treatment of a broad spectrum of neurological and psychiatric disorders.
Jian Li, A. Atalay, Mark D. Olchanyi et al.· Proceedings of the National...· 0 citations
Objective. Temporal lobe epilepsy (TLE) is associated with disrupted functional integrity in the amygdala-hippocampus complex. Cortico-cortical evoked potentials (CCEPs) can characterize this disruption and have been proposed as biomarkers of the epileptogenic zone (EZ), but their study is typically limited by the spatial sampling bias inherent to whole-brain intracranial EEG. We investigated how epileptogenicity shapes effective connectivity in the amygdala-hippocampus complex, whether structural connectivity underlies it, and ultimately derived a multimodal EZ biomarker. Methods. We retrospectively included 71 patients (50 adults, 21 children) who underwent single-pulse electrical stimulation protocols with intracranial contacts in the amygdala or hippocampus; 15 also underwent diffusion MRI. CCEPs were visually detected, and the latency and amplitude of the first response peak (D1) were extracted. Structural connectivity metrics (tract length, quantitative and fractional anisotropy, mean diffusivity) were derived between the same contacts. A Bayesian linear mixed model (BLMM) related D1 latency to clinical, neurophysiological, and structural predictors, handling missing DTI values jointly within the model. A corrected latency score was then built to discriminate epileptogenic from non-epileptogenic contacts. Results. Among 6257 possible stimulation-recording pairs, 1027 CCEPs were detected with a significantly higher rate in the hippocampus compared to the amygdala. The BLMM identified robust associations between D1 latency and epileptogenicity, epilepsy type, ipsilateral stimulation, stimulation site (hippocampus/amygdala), and quantitative and fractional anisotropy. The resulting EZ score, obtained by extracting the EZ term's contribution from the BLMM equation, demonstrated an ability to discriminate epileptogenic contacts, showing a balanced accuracy of 78% (sensitivity 86%, specificity 71%), and the resulting EZ probability, based on an elastic net logistic regression, showed a balanced accuracy of 84% (sensitivity 86%, specificity 82%). Discussion. These findings suggest that effective connectivity results from the interplay of opposing physiological (here amygdala vs. hippocampus) and pathological (epilepsy-related) influences rather than a simple facilitation within the EZ, and that white matter microstructure independently contributes to this timing. Connectivity is slower within the EZ itself, with an even greater delay observed in its vicinity compared to other brain areas. The resulting EZ score offers a practical, closed-form tool to strengthen EZ localization, and paves the way toward a structurally informed, CCEP-based framework extendable to other brain regions.
O. Feys, M. Josyula, N. Sinha et al.· medRxiv· 0 citations
The multimodal findings suggest that increased hippocampal connectivity in the epileptogenic hemisphere may reflect pathological hypersynchronization that disrupts efficient memory network coordination in TLE and highlight hippocampal connectivity as a promising candidate biomarker for characterizing individual memory outcomes.
Ruxue Gong, Xiaolong Peng, Rebecca W. Roth et al.· Epilepsia· 0 citations
We use cookies to run the site and, with your consent, for analytics and to show ads.
See our Cookie Policy.
