Resting-state functional brain changes in temporal lobe epilepsy with comorbid depression: A meta-analysis

To compare the differences in functional brain activity between patients with temporal lobe epilepsy comorbid with depressive disorder (TLE-D) and those with temporal lobe epilepsy without depressive disorder (TLE-ND) via a meta‑analysis of resting‑state functional magnetic resonance imaging (rs-fMRI) studies, and to explore the functional brain activity features associated with depressive symptoms.

Systematic searches were conducted in PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang Data from database inception to September 2026 to identify cross-sectional studies comparing rs-fMRI-derived differences in functional brain activity between patients with temporal lobe epilepsy comorbid with depressive disorder (TLE-D) and those without depressive disorder (TLE-ND). Eligible rs-fMRI metrics included regional brain activity indices and functional connectivity indices. A meta-analysis of studies reporting regional brain activity indices was performed using anisotropic effect-size signed differential mapping (AES-SDM). Due to their limited number, studies reporting functional connectivity indices were only described narratively. Study selection and data extraction were then completed, and a voxel-based meta-analysis of the included studies was performed with AES-SDM.

A total of six studies yielding nine datasets met the inclusion criteria, involving 100 patients with TLE-D and 108 patients with TLE-ND. Meta-analysis showed that, compared with the TLE-ND group, the TLE-D group had significantly increased spontaneous brain activity in the right precuneus, right angular gyrus, right superior frontal gyrus, left middle frontal gyrus, and left cerebellum (analyzed via AES-SDM with an initial exploratory threshold of uncorrected voxel-level P < 0.005 and cluster size ≥10 voxels, and validated by leave-one-out sensitivity analysis). No brain regions with significantly decreased spontaneous brain activity were detected.

These exploratory findings suggest that, compared with patients with TLE-ND, patients with TLE-D show distinct patterns of functional brain activity in multiple key nodes of the default mode network, including the precuneus and angular gyrus, as well as in prefrontal-related regions. These differences may provide preliminary neuroimaging evidence for understanding the neural mechanisms underlying depressive symptoms associated with temporal lobe epilepsy.