Modulation of the thalamus by microburst vagus nerve stimulation: a feasibility study protocol

Vagus nerve stimulation (VNS) was the first device-based therapy for epilepsy, having launched in 1994 in Europe and 1997 in the United States. Since then, significant advances in the understanding of the mechanism of action of VNS and the central neurocircuitry that VNS modulates have impacted how the therapy is practically implemented. However, there has been little change to VNS stimulation parameters since the late 1990s. Short bursts of high frequency stimulation have been of increasing interest to other neuromodulation targets e.g., the spine, and these high frequency bursts elicit unique effects in the central nervous system, especially when applied to the vagus nerve. In the current study, we describe a protocol design that is aimed to assess the impact of high frequency bursts of stimulation, called “Microburst VNS”, in subjects with refractory focal and generalized epilepsies treated with this novel stimulation pattern in addition to standard anti-seizure medications. This protocol also employed an investigational, fMRI-guided titration protocol that permits personalized dosing of Microburst VNS among the treated population depending on the thalamic blood-oxygen-level-dependent signal. The study was registered on clinicaltrials.gov (NCT03446664). The first subject was enrolled in 2018 and the final results are expected in 2023

Auras localized to the temporal lobe disrupt verbal memory and learning — Causal evidence from direct electrical stimulation of the hippocampus

Auras (focal aware seizure; FAS) are subjective ictal events with retained consciousness. Epileptiform activities can disrupt cognitive tasks, but studies are limited to seizures with impaired awareness. As a proof of concept, we examined the cognitive effects of direct electrical stimulation to the left hippocampus which induced a habitual FAS in a patient with left mesial temporal lobe epilepsy. During the induced habitual FAS, verbal memory performance declined significantly as compared to pre-stimulation testing. Tasks measuring auditory working memory and psychomotor processing speed were not affected by the stimulation. The study confirms that FAS can impair episodic verbal memory and learning. Keywords: Verbal memory, Aura, Focal aware seizure, Learning, Hippocampus, Epileps