Abstracts

Rationale: Recent animal work has suggested that the mammalian diving reflex (MDR) may be involved in sudden unexpected death in epilepsy (SUDEP). Clinical data suggests that the MDR is mediated by the carotid body and its afferents. Our recent work has demonstrated that electrical stimulation of the carotid body can prevent ictal MDR deaths in rats (unpublished). Stimulation of the carotid body is difficult because the structure is small and located near the carotid sinus. Conventional electrodes are large and place pressure on the carotid sinus, negatively impacting blood pressure regulation and causing nonseizing sudden deaths in animals (unpublished). If carotid body stimulation can prevent death, then we must improve stimulation techniques to place less pressure on the baroreceptor.

Methods: We fabricated microelectrodes by sputtering 1 µm gold and coating with 20 µm parylene to create a loose, flexible electrode which does not fully encircle the target. We applied interferential waveforms similar to those described in Grossman et al. 2017 which utilize multiple high frequency waveforms to create a low frequency envelope. These techniques can deeply penetrate tissue, causing effect at lower thresholds with less tissue damage. We compared the results to traditional electrodes. In these experiments we anesthetized Long Evans rats with urethane (1.4g / kg). In some experiments we placed electrodes at the carotid body and measured blood pressure, heart rate, and respiratory rate, to evaluate mechanical effects and stimulation parameters. In some experiments we placed electrodes at the sciatic nerve and measured EMG to verify interferential waveform techniques can properly activate neuronal firing. Ictal stimulation has not yet been attempted with these electrodes.

Results: Traditional cuff electrodes cause significant dysregulation of blood pressure when placed on or near the carotid body. Nonseizing MDR trials are fatal in animals with a cuff electrode placed, but never in controls. Conversely, microelectrodes cause no noticeable change in heart rate, blood pressure, or respiratory rate and can yield similar recruitment. Neural recruitment data from the sciatic show that interferential techniques achieve neural stimulation at significantly lower thresholds than traditional cuff electrodes, particularly with a looser fitting electrode.

Conclusions: Utilizing microelectrode fabrication and interferential stimulation techniques we can effectively stimulate the carotid body without causing negative baroreceptor side effects. Intervention at the carotid body or its afferents may be a clinically relevant pathway to prevent SUDEP in humans. Microelectrode techniques may allow better access to targets previously unreachable in a chronic setting. These techniques may allow more efficient, deeply targeted stimulation than was previously possible, which may also improve other epilepsy stimulation treatment techniques, like vagal nerve stimulation or responsive neurostimulation.

Funding: Please list any funding that was received in support of this abstract.: NIH OD023847.