Jul 2026· Journal of Neurosurgery· pp.
1-10
· 0 citations· 43 references
Medicine
TL;DR
Abnormalities of cortical wiring costs were observed in mTLE-HS, particularly in patients with postoperative seizure recurrence, offering novel insights into the underlying pathophysiology of this illness and providing potential for outcome prediction.
Abstract
Objective
Postoperative seizure recurrence in mesial temporal lobe epilepsy (mTLE) with hippocampal sclerosis (HS) has been linked to alterations in structural network organization. However, existing studies have primarily focused on white matter pathways, while gray matter wiring attributes remain largely unknown. This study aimed to investigate whether alterations in gray matter wiring costs are associated with postoperative seizure recurrence in mTLE with HS.
Methods
Forty-seven patients with unilateral mTLE who underwent surgery and 48 matched healthy controls were enrolled in the study. All patients had pathologically confirmed HS and were classified as seizure-free (SF; n = 27) or non-seizure-free (NSF; n = 20) with ≥ 2 years of follow-up. Based on preoperative 3D T1-weighted MRI, surface-based geodesic metrics were computed as proxies of cortical wiring costs. Global and local wiring costs were compared across groups, and a support vector machine (SVM) classifier was used to determine their individual-level classification value for postoperative seizure outcomes.
Results
Global wiring costs decreased in the ipsilateral temporal cortex in patients with mTLE-HS, with a more significant and widespread reduction in the NSF group. Local wiring costs showed diffuse intra- and interregional abnormalities within the sensorimotor and default mode networks in patient groups, with more pronounced disturbances in the NSF group. These wiring abnormalities were not affected by hippocampal subfield atrophy, epilepsy duration, or antiseizure medications, and could train SVM models to distinguish NSF patients from SF patients (area under the receiver operating characteristic curve = 0.86).
Conclusions
Abnormalities of cortical wiring costs were observed in mTLE-HS, particularly in patients with postoperative seizure recurrence. These abnormalities may reflect increased long-range connectivity and short-range reorganization within gray matter, offering novel insights into the underlying pathophysiology of this illness and providing potential for outcome prediction.
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, Derek J. Doss, Ghassan S Makhoul et al.· Epilepsia· 0 citations
The model achieved high specificity in predicting long-term seizure recurrence, which supports its potential clinical utility for postoperative risk stratification and counseling rather than surgical exclusion and underscores the translational potential of network-level biomarkers to complement conventional predictors.
V.Yu. Karpychev, Rebecca W. Roth, William Yun et al.· Neurology· 0 citations
Four of the six frontotemporal regions showing the largest morphometric alterations in MDD also exhibit reduced cortical thickness in mTLE patients with past or future depression, which supports depression in mTLE as an expression of network pathology common to MDD, while residual regional differences may help explain the distinct phenotypic presentations of depression in these neuropsychiatric disorders.
Philip Fink-Jensen, B. Ozenne, Ane G. Kloster et al.· Epileptic disorders· 0 citations
Abstract Anterior temporal lobectomy (ATL) remains the standard surgical treatment for pharmacoresistant temporal lobe epilepsy (TLE), yet long-term seizure freedom remains suboptimal. Neuroimaging studies show neocortical metabolic abnormalities beyond the mesiotemporal epicentre, but how such patterns inform resection extent remains unclear. We hypothesized that neocortical hypometabolism in TLE follows a quantifiable spatial gradient that can be translated into personalized surgical strategies. Our multicentre study included 358 participants across discovery, validation, and sensitivity analyses. Multimodal MRI and FDG-PET data were processed to derive vertex-wise structural, intensity, and metabolic features. Individual metabolic abnormalities were quantified using a normative asymmetry modelling approach. In the discovery cohort (227 patients undergoing ATL and 37 healthy controls), we characterized the topography of neocortical hypometabolism, and evaluated its correspondence to cytoarchitectural profiles, multimodal MRI features, and hippocampal measures. Three gradient-informed surgical metrics were evaluated in relation to seizure outcomes, with replication in an independent prospective validation cohort of 38 patients undergoing ATL. An additional sensitivity cohort comprising 56 surgical candidates, whose procedure spared the temporal neocortex was included to assess the robustness. Neocortical hypometabolism in TLE followed a spatially organized gradient, with the most severe hypometabolism at the hippocampal-neocortical interface that diminished with increasing geodesic distance (r = 0.955, Pperm < 0.001). Regions closer to the interface exhibited lower cytoarchitectonic differentiation and stronger FLAIR-related alterations. Hippocampal abnormalities also showed distance-dependent coupling with neocortical metabolism (r = 0.871, Pperm < 0.001). Among surgical metrics, greater resection of severe hypometabolism was associated with seizure freedom (OR = 1.448, P = 0.022). The association was replicated in the validation cohort. The present study identified a hypometabolic gradient in TLE, which covaries with cytoarchitectonic organization, microstructural changes, and hippocampal-neocortical interactions. The gradient provides a biologically grounded framework for precise surgical planning, emphasizing that targeting severe hypometabolism may optimize prognosis.
J. Mo, F. Fadaie, J. Lam et al.· medRxiv· 0 citations
INTRODUCTION
Temporal lobe epilepsy (TLE), particularly mesial temporal lobe epilepsy (MTLE), often presents with visual working memory (VWM) impairments, with potential heterogeneity between hippocampal sclerosis (HS) and MRI-negative subtypes. However, task-related electrophysiological (EEG) evidence regarding brain network alterations during VWM processing in MTLE remains limited. This study aims to identify shared brain network alterations and their behavioral correlates in patients with MTLE and to further characterize subtype-specific differences between HS-MTLE and MRI negative-MTLE.
METHODS
We recruited 60 right-handed participants, including 30 patients with MTLE (12 HS-MTLE, 18 MRI negative-MTLE) and 30 healthy controls (HCs). All participants completed the Chinese version of the Wechsler Memory Scale-Revised (WMS-RC) and performed a VWM task during simultaneous EEG recording. Graph theory analysis was used to assess the in-degree and out-degree of directed functional networks in the theta and gamma frequency bands; the results were correlated with clinical and cognitive behavioral indicators.
RESULTS
Behaviorally, patients with MTLE showed significant VWM impairments compared with HCs, with no significant difference between HS and MRI-negative subtypes. Common network alterations in patients with MTLE included decreased theta-band connectivity from occipital to temporal regions, with this theta-band connectivity significantly associated with slower task responses and reduced accuracy. In subgroup analysis, the HS-MTLE group showed reduced theta outflow and abnormally enhanced gamma activity in posterior occipital regions. Conversely, the MRI negative-MTLE group showed more widespread increases in gamma-band in-degree and out-degree across anterior regions, including prefrontal, frontocentral, and temporal areas.
CONCLUSION
Patients with MTLE share a common alteration in occipital-to-temporal information transfer during VWM. Exploratory analyses suggest distinct network alterations between HS-MTLE and MRI negative-MTLE, presenting with abnormalities in posterior and anterior networks, respectively. These hypothesis-generating findings provide electrophysiological evidence to support precise subtyping of MTLE and targeted cognitive intervention development.
Sha Huang, Ziwei Tian, Quan Wang et al.· Neurobiology of Disease· 0 citations
OBJECTIVE
Focal-to-bilateral tonic-clonic seizures (FBTCS) in temporal lobe epilepsy (TLE) involve thalamocortical networks, yet the functional integrity and role of specific thalamic subregions in seizure generalization remain unclear. In this cross-sectional study, we investigated whether thalamic subregion functional connectivity patterns distinguish TLE patients with and without FBTCS and tested for laterality-specific differences between right TLE (RTLE) and left TLE (LTLE.
METHODS
We analyzed resting-state functional magnetic resonance imaging (fMRI) data from 166 patients with TLE (71 RTLE, 95 LTLE; 120 FBTCS+, and 46 FBTCS-) and 119 healthy participants. Thalamic parcellation identified eight bilateral regions of interest. We computed graph theory measures of regional segregation, connection density, and integration, as well as intrinsic connectivity contrast to characterize thalamic subregion network topology. Sensitivity analyses controlled for pathology subgroup and anti-seizure medication burden.
RESULTS
TLE patients exhibited reduced cross-hemispheric functional connectivity between bilateral ventral anterior (VA) thalamic regions compared with controls. Compared with patients with LTLE, patients with RTLE showed more pronounced ipsilateral VA hypoconnectivity and more disrupted nodal topology (clustering coefficient, degree centrality, local efficiency) in the ipsilateral VAia. Within RTLE, FBTCS+ patients (vs FBTCS-) showed ipsilateral connectivity reductions and cross-hemispheric VA reductions that increased with illness duration. Within LTLE, FBTCS+ patients (vs FBTCS-) showed bilateral connectivity increases in the ventral posterior medial subregion. Sensitivity analyses confirmed that these findings were robust across pathology subtypes and independent of anti-seizure medication burden.
SIGNIFICANCE
These findings provide initial evidence that intra-thalamic functional connectivity, particularly within the bilateral VA complex, is associated with FBTCS history in TLE and varies with lateralization of seizureonset. The observations may represent a biomarker for FBTCS, but whether this is causal or an epiphenomenon of this seizure type remains to be determined.
Stacy N. Hudgins, Michael R Sperling, Hasan Ayaz et al.· Epilepsia· 0 citations