Operating directly on routine preoperative evaluations without requiring additional testing, this computational framework disentangles pathological burden from network reserve, providing scalable, biologically interpretable biomarkers to guide personalized risk counselling and network-informed surgical planning.
Abstract
Cognitive outcomes following temporal lobe epilepsy surgery are highly heterogeneous and remain difficult to predict using traditional threshold-based neuropsychological classifications. Here, we implemented Subtype and Stage Inference (SuStaIn) on preoperative neuropsychology to model cognitive function as a continuous network-level process reflecting both pathological burden and compensatory reserve. We identified three distinct latent trajectories: Verbal, Naming, and Visual. The Verbal subtype reflected classic mesial temporal pathology, where postoperative decline aligned with functional adequacy of residual hippocampal tissue. Conversely, the Naming subtype represented a neocortical-predominant 'Temporal Plus' phenotype; despite lower rates of hippocampal sclerosis, these individuals showed severe postoperative verbal memory vulnerability due to un-reorganized frontotemporal language networks. The Visual trajectory demonstrated progressive visuospatial decline with distinct sex-specific reserve profiles and poorer visual recall outcomes. Crucially, these progression-based trajectories outperformed conventional static classifications in predicting 12-month postoperative outcomes on unseen test data. Operating directly on routine preoperative evaluations without requiring additional testing, this computational framework disentangles pathological burden from network reserve, providing scalable, biologically interpretable biomarkers to guide personalized risk counselling and network-informed surgical planning.
A hypometabolic gradient is identified in TLE, which covaries with cytoarchitectonic organization, microstructural changes, and hippocampal-neocortical interactions and 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
Cognitive impairment affects up to 80% of patients with drug resistant epilepsy (DRE), yet the basis for this impairment in patients with otherwise comparable disease characteristics remains poorly understood. Prior work has largely focused on identifying focal nodes responsible for cognitive decline, leaving the broader network reorganization associated with cognitive preservation poorly characterized. In this study, we hypothesized that the brain's capacity to reorganize its functional network hubs, rather than the degree of underlying pathology, distinguishes cognitively resilient from cognitively impaired patients. We studied a retrospective cohort of 105 DRE patients and 60 healthy controls who underwent resting-state functional neuroimaging. DRE patients were stratified into epilepsy cognitively neutral (ECN) and epilepsy cognitively impaired (ECI) subgroups based on comprehensive neuropsychological profiling spanning both domain-general and domain-specific levels. The subgroups did not differ in key disease characteristics including epilepsy duration, age of onset, seizure lateralization, and lesion status (p>0.05). We characterized hub organization across the whole brain, canonical functional networks and subcortical levels and summarized each subject's functional reorganization using the hub disruption index. We found that whole brain topology is preserved in both groups whereas disruption concentrates in the salience network and dissociates within subcortical structures with reduced hippocampal node strength in both groups and increased thalamic node strength, with the latter more pronounced with cognitive burden. Inter-network connectivity shifted from focal, selective up-regulation in ECN to diffuse hyperconnectivity in ECI. Critically, the hub disruption index (HDI) for centrality separated the groups where the ECN group showed the greatest redistribution of centrality from canonical hubs towards alternative relay regions whereas ECI demonstrated comparatively little reorganization (ECN vs ECI: d=0.52, p=0.029; Bonferroni corrected). The same pattern held within individual domains, with greater hub reorganization in patients whose language and memory function was preserved. These cross-sectional findings link cognitive impairment in epilepsy to a reduced capacity for adaptive hub reorganization rather than to pathology alone. Because the HDI for centrality is computable at the individual level, it may offer an objective imaging biomarker to complement neuropsychological testing, aid identification of patients at risk for cognitive decline, and inform prognostic counseling and surgical planning in DRE.
T. Imtiaz, A. Lucas, E. Zhang et al.· medRxiv· 0 citations
Epilepsy surgery preserved intellectual functioning, particularly in FL and PC procedures, however, persistent VCI decline in H and TL groups suggests effects on verbal abilities associated with temporal lobe involvement, and group-level trajectories rather than individual outcomes.
Geisa de Angelis, L. E. Lopes-Santos, D. Aragon et al.· Epilepsia· 0 citations
OBJECTIVE
Left anterior temporal lobe resection (TLR) in people with epilepsy is associated with a high risk of postoperative verbal memory decline. Whereas substantial evidence supports the role of preoperative verbal memory in predicting postoperative verbal memory change, the potential contribution of preoperative visual memory has been rarely investigated.
METHODS
We retrospectively analyzed data from 105 people with left TLR due to mesial temporal sclerosis and typical language dominance. Multiple linear and logistic regression analyses were conducted to predict the extent and risk of significant postoperative verbal memory decline based on preoperative verbal and visual memory performance, as well as clinical variables (age at surgery, age at onset, and preoperative focal to bilateral tonic-clonic seizures). In exploratory analyses, we examined the influence of dichotomized preoperative verbal and visual memory performance (impaired vs. unimpaired) on the extent and frequency of postoperative verbal memory decline, as well as the potential influence of general intellectual ability.
RESULTS
Regression analyses showed that higher preoperative verbal memory performance was associated with more pronounced and more frequent postoperative verbal memory decline, whereas higher preoperative visual memory performance was associated with less severe and less frequent verbal memory decline. Clinical variables did not improve model prediction. Analyses with dichotomized preoperative verbal and visual memory performance confirmed the results of the regression analyses. General intellectual ability had an additional influence on postoperative verbal memory change, without changing the predictive value of preoperative verbal or visual memory performance.
SIGNIFICANCE
These findings demonstrate a cross-material relationship between preoperative visual memory and postoperative verbal memory change following left TLR. Whereas preoperative verbal memory performance likely represents functional adequacy, preoperative visual memory appears to represent functional reserve. Therefore, our findings reconcile these two concepts of postoperative verbal memory change. Additionally, the influence of general intellectual ability suggests relevance of more general cognitive reserve.
L. Reisch, A. Hagemann, J. L. Hopf et al.· Epilepsia· 0 citations