Abstracts

Rationale: Direct intracranial electrical EBS stimulation (iEBS) is a rapidly developing technology, which already has clinical applications in epilepsy, as well as select movement and neuropsychiatric disorders. Current stimulation paradigms mostly use high frequency, high amplitude stimulation, independent of ongoing network dynamics. However, both pathological and physiological patterns are often highly rhythmic. Novel iEBS paradigms to specifically modulate rhythmic neuronal activity patterns may provide a promising approach to either more efficiently disrupt pathological patterns such as seizures, or strengthen physiological oscillations which are thought to be involved in cognitive processes such as memory formation and attention. Methods: Since little is known about the degree to which ongoing rhythmic patterns can be modulated by iEBS in humans, in the current study, we applied electrical stimulation protocols covering several frequency bands (delta, theta, alpha, beta) to selected cortical regions (pre-central, superior temporal, parietal). Our goal was to test if we could achieve stimulation frequency-specific effects in the stimulated and connected brain areas in epilepsy patients being evaluated with intracranial electrodes for seizure onset localization. We repeatedly applied brief bursts (<2 sec) of low amplitude (0.5 – 3 mA) electrical pulses (<0.4 msec width) through electrodes implanted in the frontal, temporal, and parietal regions. We stimulated in a closed-loop approach at different frequencies centered around the prominent spectral peaks of the activity in the targeted brain areas, as well as open-loop at a wider range of frequencies. Results: We found that this rhythmic, low amplitude stimulation can indeed entrain neuronal oscillations. Stimulating within a 2 Hz window of a spectral peak induced adaptation of the oscillation towards the frequency of stimulated frequency. Notably, the effects outlasted the electrical stimulation in a frequency-specific manner. Conclusions: These findings may help to develop novel iEBS paradigms to prevent and interrupt seizures, as well as elucidate the mechanistic roles of neuronal oscillations in cognitive processes. While the current project was a proof of concept study, these paradigms will have to be applied during pathological rhythms and during behavior to test their functional consequences. Funding: NIH grant U01 NS098976-01. NYS DOH ECRIP award