Authors :
Presenting Author: Adeel Ilyas, MD – University of Alabama at Birmingham
Jay Gavvala, MD – UTHealth Houston
Sandipan Pati, MD – University of Minnesota
Nitin Tandon, MD – McGovern Medical School, University of Texas Health Science Center at Houston
Yosefa Modiano, PhD – McGovern Medical School at University of Texas Health Science Center, Houston
Rationale:
Intracranial neuromodulation – encompassing both open-loop Deep Brain Stimulation (DBS) and closed-loop Responsive Neurostimulation (RNS) – has emerged as a transformative therapy for medically refractory epilepsy. While early randomized trials demonstrated no significant cognitive decline with either approach, the impact of stimulation modality – duty cycle versus responsive detection – on neuropsychological outcomes remains unclear. This study directly compares cognitive, domain-specific outcomes between open-loop DBS and closed-loop RNS to assess whether one paradigm offers superior cognitive preservation or benefit.
Methods:
In this single-center retrospective analysis, we evaluated patients who underwent either open-loop DBS or closed-loop RNS therapy with pre- and post-operative neuropsychological assessments at 8 months (IQR: 6-15 months). Cognitive outcomes were categorized into five domains: attention/processing speed (D1), executive function (D2), language (D3), visuospatial abilities (D4), and verbal learning (D5). Change scores were calculated as post- minus pre-operative z-scores (compared to population level norms). Group-level comparisons of domain-specific change were conducted using independent t-tests.
Results:
A total of 42 patients were included (open-loop: n=24; closed-loop: n=18). Demographic characteristics including FSIQ (open-loop: −1 ± 12 vs. closed-loop: 2 ± 7; p = 0.388) were comparable between groups. No statistically significant differences were observed between stimulation paradigms across any cognitive domains: (D1, z: -0.39±0.69 versus -0.27±0.53, p=0.624; D2, z: -0.10±1.31 versus -0.38±1.07 p=0.577; D3: -0.19±0.90 versus -0.48±0.66 p=0.357; D4, z-score: -0.02±0.58 versus -0.21±0.69, p=0.477; D5: 0.11±1.15 versus -0.28±0.62, p=0.459).
Conclusions:
Neuropsychological outcomes following neuromodulation in epilepsy are comparable between open- and closed-loop paradigms. These findings suggest that stimulation mode alone does not primarily drive cognitive outcome. The wide variability observed may reflect differences in stimulation targets (e.g., thalamic versus cortical), programming parameters, and heterogeneity of cognitive functioning at baseline. Future studies should stratify outcomes by target anatomy and stimulation characteristics to identify cognitive predictors and optimize individualized therapy. Cognitive testing should be conducted serially to monitor for changes related to stimulation parameters.
Funding: NA