Preoperative limbic cortical thinning in mesial temporal lobe epilepsy surgical candidates is associated with pre-existing and de novo postoperative depression.
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.
Abstract
Objective
Depression is common in mesial temporal lobe epilepsy (mTLE), but its neuroanatomical basis-and overlap with major depressive disorder (MDD)-remains poorly defined. We investigated whether the cortical and subcortical alterations reported in MDD are also present in mTLE and leveraged the frequent occurrence of depression after epilepsy surgery to test whether such changes predate the onset of post-surgical depression.
Methods
Eighty-nine mTLE patients scheduled for anterior temporal lobectomy were classified as never depressed (NoD, n = 42), depressed before surgical evaluation (PreD, n = 23), or developing de-novo depression after surgery (PostD, n = 22). Pre-operative 3 T MRI (1 mm T1, T2, FLAIR) was processed with FreeSurfer v6.3. Six frontotemporal-limbic regions showing the largest MDD effects in ENIGMA studies-orbitofrontal cortex, rostral anterior cingulate, insula, fusiform gyrus, hippocampus, posterior cingulate-were analyzed using a latent variable model.
Results
Depression status significantly influenced combined morphology in both hemispheres (p < 0.05). Relative to NoD, both PreD and PostD groups showed reduced cortical thickness in the orbitofrontal cortex, fusiform gyrus, insula, and rostral anterior cingulate (Cohen's d = -0.04 to -0.14). Hippocampal volume and posterior cingulate thickness did not differ between groups.
Significance
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. This shared frontotemporal thinning pattern 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. In PostD patients, these abnormalities were already present pre-operatively, consistent with a pre-existing vulnerability rather than a purely psychosocial reaction to surgery or epilepsy per se.
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
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.
Fei Zhu, Bo Tao, Yue Li et al.· Journal of Neurosurgery· 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
BACKGROUND
Temporal lobe epilepsy (TLE), frequently associated with mesial temporal sclerosis (MTS), is the most common form of focal epilepsy in adults and is often accompanied by depressive symptoms that impair quality of life. While anterior hippocampectomy is an established surgical approach for drug-resistant TLE, its postoperative psychiatric and psychosocial impact remains insufficiently studied, particularly in non-Western populations. This study assessed changes in depressive symptoms and quality of life following anterior hippocampectomy in a Middle Eastern cohort.
METHODS
Depression was assessed preoperatively and at 1- and 3-month follow-up using the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) and Beck Depression Inventory (BDI). Quality of life was measured using the World Health Organization Quality-of-Life (WHOQOL) scale.
RESULTS
Forty patients were included, of whom 18/40 (45.0%) screened positive for depression at baseline. BDI scores decreased significantly over time (p = 0.011) and WHOQOL scores improved significantly across follow-up (p = 0.016). PNDDI-E scores showed a non-significant reduction over time (p = 0.055). 9/18 (50.0%) of patients who screened positive for depression preoperatively converted to screen-negative status at 3 months, while 4/22 (18.2%) of preoperatively screen-negative patients developed new screen-positive status. Improvements in BDI and WHOQOL scores were not significantly influenced by age, sex, education, or surgical laterality.
CONCLUSIONS
Anterior hippocampectomy in patients with drug-resistant TLE was associated with significant early improvements in BDI-II and WHOQOL scores. These findings should be regarded as preliminary given the small sample size, short follow-up, and absence of postoperative seizure outcome data. Given that a subset of patients may develop new or worsened depressive symptoms postoperatively, routine psychiatric screening and postoperative psychological support remain essential.
Shiva Karimiziarani, Iman Kiani, N. Shahmansouri et al.· Epilepsy Research· 0 citations
Background. Temporal lobe epilepsy (TLE) is the most common drug-resistant focal epilepsy, and a substantial subgroup develops focal-to-bilateral tonic-clonic seizures (FBTCS) carrying heightened risk for SUDEP, cognitive decline, and poor surgical outcomes. The subcortical network mechanisms that index seizure generalization, their dependence on onset laterality, and their utility as biomarkers are poorly defined. Methods. Resting-state fMRI was acquired from 166 TLE patients (120 FBTCS+, 46 FBTCS-; 71 right TLE, 95 left TLE) and 119 healthy controls. Functional network connectivity and graph-theoretic analyses quantified clustering coefficient, degree centrality, local efficiency, and intrinsic connectivity contrast across 16 bilateral thalamic regions (Aim 1) and 54 ROIs spanning thalamus, hippocampus, amygdala, caudate, putamen, globus pallidus, and nucleus accumbens (Aim 2). A prespecified rmMANCOVA cascade tested covariate robustness of FBTCS effects. Aim 3 used nested 10x5 cross-validated linear SVMs with bootstrap and DeLong inference, prespecified sensitivity analyses, and permutation testing to compare connectivity versus standard clinical features for FBTCS classification. Results. Aim 1 showed reduced cross-hemispheric ventral anterior thalamic connectivity in TLE, with more pronounced ipsilateral dysfunction in right TLE; only right-TLE FBTCS+ patients showed ipsilateral VA disruption that worsened with illness duration. Aim 2 identified six bilateral subcortical subnetworks with reduced clustering coefficient in left ventroposterior lateral thalamus, left ventral anterior caudate, and right ventroposterior putamen in FBTCS+ patients. Right TLE FBTCS+ patients showed elevated bilateral nucleus accumbens cross-hemispheric connectivity that tracked with recent seizure burden, dissociating a state-dependent accumbens marker from trait-like thalamo-striatal desegregation. In Aim 3, connectivity outperformed clinical features in pooled TLE (AUC 0.618 vs 0.418, delta-AUC = +0.200, DeLong p = .005) and most strongly in right TLE (AUC 0.657 vs 0.311, delta-AUC = +0.346, DeLong p = .002). Left TLE was null across all panels, serving as a within-study negative control. Ventroposterior thalamus and nucleus accumbens emerged as top discriminators. Conclusions. Subcortical connectivity abnormalities in TLE organize into limbic-thalamo-striatal subnetworks with state- versus trait-like dissociation. Connectivity features discriminate FBTCS status beyond clinical features in pooled and right TLE, while left TLE remains null. These signatures motivate prospective external validation as candidate FBTCS risk-stratification biomarkers and targets for personalized treatment.
SUMMARY
In mesial temporal lobe epilepsy, resection or ablation-typically of anterior temporal structures-is highly successful in achieving seizure freedom. However, in a substantial proportion of patients, seizures recur for unclear reasons. Invasive hippocampal recordings suggest that, in some patients, hippocampal seizures are highly focal, often restricted to the anterior or posterior hippocampus. This led us to hypothesize that resection or ablation limited to the hippocampal subregion(s) involved at seizure onset is more likely to control seizures than surgery that does not address the specific onset locations. We present a case in which seizures were successfully controlled after posterior hippocampal ablation, as well as a retrospective case series of 18 patients in which 10 cases demonstrated focal onsets within the anterior or posterior hippocampus. Better outcomes occurred when surgery was concordant with the onset region(s) versus discordant (n = 7 concordant vs. 11 discordant patients, P = 0.046, Barnard Exact test). These data suggest that mesial temporal lobe epilepsy can be subdivided according to whether the hippocampal onset pattern is focal or nonfocal, and that targeting localized seizure onset zones within the hippocampus can be effective for seizure control, while limiting surgical morbidity and potentially the risk of adverse cognitive outcomes.
Robert Rifkin, Hart Fogel, Andrew J. Michalak et al.· Journal of clinical neurophy...· 0 citations