Circadian changes in aperiodic activity are correlated with seizure reduction in patients with mesial temporal lobe epilepsy treated with responsive neurostimulation

Abstract

Objectives: Responsive neurostimulation (RNS) is an established therapy for drug-resistant epilepsy that delivers direct electrical brain stimulation in response to detected epileptiform activity. However, despite an overall reduction in seizure frequency, clinical outcomes are variable, and few patients become seizure-free. The aim of this retrospective study was to evaluate aperiodic electrophysiological activity, associated with excitation/inhibition balance, as a novel electrographic biomarker of seizure reduction to aid early prognostication of the clinical response to RNS.

Methods: We identified patients with intractable mesial temporal lobe epilepsy who were implanted with the RNS System between 2015 and 2021 at the University of Utah. We parameterized the neural power spectra from intracranial RNS System recordings during the first 3 months following implantation into aperiodic and periodic components. We then correlated circadian changes in aperiodic and periodic parameters of baseline neural recordings with seizure reduction at the most recent follow-up.

Results: Seizure reduction was correlated significantly with a patient's average change in the day/night aperiodic exponent (r = .50, p = .016, n = 23 patients) and oscillatory alpha power (r = .45, p = .042, n = 23 patients) across patients for baseline neural recordings. The aperiodic exponent reached its maximum during nighttime hours (12 a.m. to 6 a.m.) for most responders (i.e., patients with at least a 50% reduction in seizures).

Significance: These findings suggest that circadian modulation of baseline broadband activity is a biomarker of response to RNS early during therapy. This marker has the potential to identify patients who are likely to respond to mesial temporal RNS. Furthermore, we propose that less day/night modulation of the aperiodic exponent may be related to dysfunction in excitation/inhibition balance and its interconnected role in epilepsy, sleep, and memory.

Keywords: RNS; aperiodic exponent; biomarker; circadian rhythms; neurostimulation.