Cognitive outcomes after deep brain stimulation in drug-resistant epilepsy: A comparison of anterior thalamic and hippocampal stimulation

Objective: Deep brain stimulation (DBS) of the anterior thalamic nucleus (ATN) and hippocampus is an emerging therapy for drug-resistant epilepsy (DRE) when resective surgery is not feasible. We aimed to evaluate the long-term cognitive outcomes of these two DBS targets, hypothesizing that both interventions preserve cognitive function. Methods: We conducted a retrospective analysis of DRE patients who underwent ATN-DBS (n = 12) or hippocampal DBS (n = 10) and completed comprehensive neuropsychological testing before surgery and after ≥18 months of stimulation. Testing assessed general cognition, intellectual function, memory, language, and executive function. Changes in performance (post- minus pre-DBS) were analyzed within each group and between groups, with appropriate correction for multiple comparisons. Results: At median follow-ups of 44.33 months (ATN-DBS) and 28.60 months (Hip-DBS), both groups achieved comparable seizure reductions, particularly for disabling seizures (ATN-DBS: 73.05%; Hip-DBS: 76.76%). No significant cognitive decline was observed in either group across any domain. After FDR correction, no cognitive measure showed significant change (p > 0.05 for all). Unadjusted comparisons revealed modest improvement trends in visuospatial reasoning with ATN-DBS (Perceptual Reasoning Index, p = 0.047 uncorrected) and semantic verbal fluency with hippocampal DBS (p = 0.041 uncorrected), but these did not remain significant after correction. Between-group comparisons identified no significant cognitive differences. Significance: ATN and hippocampal stimulation demonstrated comparable efficacy for seizure control while maintaining cognitive stability over long-term follow-up. Despite targeting key structures in memory and cognitive networks, neither approach produced measurable cognitive deterioration. These findings provide critical reassurance regarding the cognitive safety of DBS in epilepsy and suggest that target selection can prioritize optimizing seizure control without compromising cognitive function. Plain Language Summary: This study compared cognitive outcomes in patients with difficult-to-treat epilepsy who received deep brain stimulation (DBS) in one of two brain regions: the anterior thalamic nucleus or the hippocampus. Both treatments effectively reduced seizures by over 70%. Importantly, after 2–4 years of continuous stimulation, neither treatment caused any decline in thinking abilities such as memory, language, nor problem-solving – despite targeting brain regions critical for these functions. This provides reassurance that DBS represents a cognitively safe option for epilepsy patients who cannot undergo traditional surgery.