Objective:

Background:

The insula, located deep within the lateral sulcus, is increasingly recognized as a hub for multimodal processing, contributing to somatosensory, viscerosensory, cognitive, behavioral, autonomic, language, and motor functions. While hippocampal pathology is classically linked to memory decline in epilepsy, emerging evidence suggests the insula may independently modulate memory processes.

Design/Methods:

We conducted a retrospective analysis of patients evaluated for epilepsy surgery at our tertiary center between 2020 and 2024. Clinical, neuroimaging, and neurophysiological data were systematically reviewed, with particular attention to insular involvement on scalp EEG and stereo-EEG.

Results:

Twelve patients (7 females, 5 males; age 27-55 years) were included. All had MRI-negative findings; six demonstrated bitemporal hypometabolism on PET. Auras were reported in 10/12 patients; all had focal impaired-awareness seizures, and 10/12 also experienced generalized tonic-clonic seizures. All were on polytherapy. Seizure onset localized to the hippocampus in 11 patients (ipsilateral in 6, bilateral in 5), and to the right insula in 1 patient. Insular involvement was bilateral in 9 patients and unilateral in 3. Neuropsychological testing revealed moderate to severe memory impairment in 8 patients, mild in 2, and intact memory in 2. Patients with insular seizure onset or bilateral hippocampal onset with insular involvement exhibited greater memory impairment compared to those with isolated hippocampal onset with or without ipsilateral insular spread.

Conclusions:

Insular involvement in temporal epilepsy is associated with greater memory decline, suggesting that impairment is not solely attributable to hippocampal dysfunction or seizure propagation. These findings support a potential intrinsic role of the insula in memory processing. Further large-scale studies are needed to validate these observations and clarify the insula’s role in epilepsy-related cognitive decline.