Skuteczność kliniczna i mechanizmy elektrofizjologiczne neurmodulacji zamkniętopętlowej w leczeniu epilepsji opornej na leki

Abstract Objective To evaluate the clinical efficacy of closed-loop neuromodulation for drug-resistant epilepsy and to characterize its electrophysiological mechanisms by combining intracranial and scalp EEG, thereby providing experimental evidence for optimizing treatment protocols and identifying multidimensional efficacy biomarkers. Methods Eight patients with drug-resistant epilepsy who underwent closed-loop neuromodulation implantation were enrolled and followed for 12–24 months. Clinical efficacy was evaluated using the seizure reduction rate and the responder rate. Linear mixed-effects models and within-subject Spearman rank correlation analyses were used to systematically characterize the population-level associations and inter-individual heterogeneity between stimulation parameters and clinical efficacy. Interictal intracranial EEG (recorded before stimulation onset and at 12 months postoperatively) and scalp EEG (international 10–20 system) were collected, and power spectral density and the phase lag index were used to quantify frequency-band-specific EEG activity and brain functional connectivity, with correction for multiple comparisons. Results At 12 months postoperatively, the overall seizure reduction rate was 56.3% (P 0.8, large effect sizes), with no significant changes in the low-frequency bands. The high-gamma band exhibited a heterogeneous network reorganization pattern characterized by significantly enhanced functional connectivity within the epileptogenic zone and suppressed long-range propagation pathways. Scalp EEG showed diffuse changes, with significantly increased whole-brain delta power and significantly decreased beta power, whereas inter-electrode phase synchrony showed no statistically significant differences across frequency bands. Gamma-band power changed in opposite directions between intracranial and scalp EEG. Conclusion Closed-loop neuromodulation is a safe and effective treatment for drug-resistant epilepsy. Its efficacy accumulates over time and is patient-specific, with no universally optimal programming parameters. The electrophysiological mechanism is closely related to the plastic reorganization of epileptic networks induced by chronic targeted stimulation: the increased intracranial gamma/high-gamma power suggests functional restoration of local parvalbumin (PV)-positive inhibitory interneuron microcircuits in the epileptogenic zone, with the excitation–inhibition balance re-established toward a physiological steady state; the heterogeneous changes in high-gamma connectivity may limit the transregional propagation of epileptiform discharges. The scalp EEG pattern of enhanced slow-wave and attenuated fast-wave activity reflects an overall downregulation of whole-brain cortical excitability. The opposite changes in intracranial and scalp gamma-band power may provide key experimental evidence for a deeper understanding of the mechanisms of closed-loop neuromodulation and for establishing a multidimensional electrophysiological biomarker system for efficacy evaluation.