Aug 2026· Epilepsy Currents· 0 citations· 11 references
Medicine
TL;DR
Thalamo-cortical synchrony is identified as a network-level feature associated with CS expression in DR-TLE, suggesting that clinical expression reflects network dynamics beyond seizure origin.
Abstract
Thalamo-cortical synchrony shapes seizure expression in human temporal lobe epilepsy Aung T, Li J, Tumnark T, Belly C, Thomas J, Jaber K, Parikh P, Zafar M, Southwell D, Chauvel P, Frauscher B, Gonzalez-Martinez J. Nat Commun. Published online May 25, 2026. doi:10.1038/s41467-026-73053-9 In drug-resistant temporal lobe epilepsy (DR-TLE), some seizures are clinically symptomatic while others remain electrographic despite arising from the same seizure-onset zone (SOZ), suggesting that clinical expression reflects network dynamics beyond seizure origin. We examined whether thalamo-cortical network engagement differs between clinical seizure (CS) and non-CS (NCS). We analyzed 286 seizures from 62 DR-TLE patients recorded using stereoelectroencephalography with pulvinar and/or anterior thalamic group coverage. Thalamo-cortical synchrony during the first 20 s of seizure onset was quantified as correlation between stereoelectroencephalography-derived time-frequency patterns in thalamic nuclei and the cortical SOZ. Synchrony was significantly stronger during CS than NCS (P < .0001, δ > 0.6), including within-subject analyses, and was independent of other clinical variables, including postsurgical outcome. Linear mixed-effects modeling identified seizure type as the sole independent predictor of synchrony (P = .0069). These findings identify thalamo-cortical synchrony as a network-level feature associated with CS expression in DR-TLE.
Thalamic organization differentially contributes to clinical conditions in epilepsy. Communications Medicine in press Zhang Q, Javidi SS, Ankeeta A, Sperling MR, Zhang Z, Tracy JI. Communications Medicine in press. Background: The thalamus plays an important role in key clinical conditions of focal temporal lobe epilepsy (TLE), but no investigation has examined whether the same thalamic local and connectome properties shape a patient's status across these different conditions. Methods: This retrospective longitudinal MRI study used resting-state fMRI and structural imaging to identify whole-brain focal/regional and connectome-level features associated with 6 binary clinical conditions of TLE (pre-/postsurgery, seizure and neurocognitive outcomes, pathology, seizure subtype, and SOZ lateralization) in 91 patients across 2 centers (age range: 15-65 years) and 85 matched healthy participants (age range: 18-60 years). Results: Across conditions, relative to all other brain regions, thalamic features exert the strongest influence. Specifically, thalamic focal and connectome intrinsic activity and gray matter volume are robustly associated with postsurgical reorganization. Presurgical thalamic hyperconnectivity predicts poorer seizure control, whereas postsurgical reorganization is not associated with either seizure outcome. Neuropsychological outcomes are subsequently examined and show associations with local ipsilateral thalamic properties. Namely, presurgical organization of the ipsilateral thalamus is associated with better preservation of cognitive performance, whereas postsurgical organization is associated with greater cognitive decline. Conclusions: Our results expand and refine our understanding of the thalamus as a region showing robust and recurrent associations across multiple clinical conditions of TLE. Importantly, we distinguish its role in pre- versus postsurgical brain organization with respect to seizure and neuropsychological outcomes, highlighting its importance for planning and prognosis in epilepsy surgery.
Initial evidence is provided that intra-thalamic functional connectivity, particularly within the bilateral VA complex, is associated with FBTCS history in TLE and varies with lateralization of seizureonset, and may represent a biomarker for FBTCS.
Stacy N. Hudgins, Michael R. Sperling, H. Ayaz et al.· Epilepsia· 1 citation
Focal impaired consciousness seizures (FICS) are among the most common seizure types in epilepsy and are a major cause of reduced QOL, occurring predominantly in temporal lobe epilepsy. Although seizure activity often remains confined to a focal temporal lobe network, patients develop widespread impairment of consciousness, indicating dysfunction of distributed brain systems rather than local seizure activity alone. Over the past two decades, converging evidence from human electrophysiological recordings, neuroimaging, and experimental animal models has substantially advanced our understanding of the neural mechanisms underlying this phenomenon. This review summarizes current knowledge of the clinical features and pathophysiology of FICS in temporal lobe epilepsy. We discuss evidence supporting the network inhibition hypothesis, in which seizure activity propagates from the hippocampus to subcortical relay structures that suppress the ascending arousal system, leading to impaired consciousness. We further examine emerging evidence implicating thalamocortical oscillations as a potential mechanism of cortical disconnection and review findings on the bilateral network engagement observed during FICS. By reviewing the substantial progress in defining the circuitry underlying impaired consciousness, we highlight the key questions that remain to be addressed in future research.
Zhi-Wen Zhou, Atsushi Kasai· Biological and Pharmaceutica...· 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
Overall, the available evidence supports a transition from a predominantly hippocampocentric framework toward a distributed thalamocortical network model of TLE, and emerging longitudinal evidence further suggests that thalamocortical networks may undergo postoperative reorganization following successful epilepsy surgery.
Giuseppina Bevacqua, Marco Ciavarro, L. Gaetani et al.· Brain Structure and Function· 0 citations
Successful TLE surgery is associated with partial restoration of cholinergic arousal network connectivity, supporting the idea that seizure cessation enables recovery of brain networks disrupted by recurrent seizures.
Addison C Cavender, D. Doss, Ghassan S Makhoul et al.· Epilepsia· 0 citations
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