Abstracts

Breathing and the amygdala: potential implications for SUDEP

Abstract number : 1.056
Submission category : 1. Translational Research: 1C. Human Studies
Year : 2017
Submission ID : 349356
Source : www.aesnet.org
Presentation date : 12/2/2017 5:02:24 PM
Published date : Nov 20, 2017, 11:02 AM

Authors :
William Nobis, Feinberg School of Medicine, Northwestern University; Jessica Templer, Northwestern Neurolgoy; Stephan Schuele, Northwestern University; Guangyu Zhou, Northwestern University; and Christina Zelano, Northwestern University

Rationale: Sudden unexplained death in epilepsy (SUDEP) is the most frequent cause of death in epilepsy patients. It has proven difficult to link the myriad proposed and known pathologic features of SUDEP including ictal arrhythmias, ictal or postictal central apnea and autonomic dysregulation. The extended amygdala is a part of the central autonomic network that is interconnected between higher order cortical areas, brainstem, and hypothalamic networks raising the possibility that it could be the missing link in the mediation of SUDEP. This region is activated by seizures, and its activation can have powerful effects on heart rate, blood pressure and respiratory function through its projections to brainstem areas that control cardiorespiratory function.  Recent intracranial EEG data from other groups have shown that electrical stimulation of the human amygdala induces apnea, suggesting a role for the amygdala in controlling respiration. In this study we confirm previous findings in a larger group of patients with temporal lobe epilepsy (TLE). Second, we test the hypothesis that stimulation induced apnea could be prevented through both conscious and unconscious behavioral interventions. Methods: Six surgical TLE patients who were undergoing functional mapping involving electrical stimulation of implanted depth electrodes are included. As part of the clinically determined surgical plan, each patient had depth electrodes implanted in the amygdala. The electrodes were used both to record local field potential data with the intent of recording seizures, and to deliver electrical stimulation with the intent of functional mapping prior to resection.  Amygdala stimulation was conducted with standard clinical mapping parameters. Apnea was confirmed by real time monitoring of respiratory signals on the acquisition computer. To begin the experimental session, the patient was instructed to sit quietly and relax. After the patient was breathing regularly for at least 30 seconds, a bipolar electrical stimulation train was administered to the two mesial-most amygdala depth contacts (Pulse duration 0.3 s, 50 Hz, 1-10mA; Nihon Kohden). Stimulation was administered with no visual or auditory warnings or cues so the patient was unaware when it was delivered. Patients who participated in the mouth breathing experiment were asked to breathe through their mouth but otherwise relax and sit quietly. Results: Our data confirm the prior observations that amygdala stimulation can induce apnea.  Electrical stimulation of the amygdala reliably induced hypopnea or apnea in 6 out of 6 patients tested. Our results further suggest this apnea can be overcome with preserved consciousness - in 2 out of 2 patients apnea does not occur during mouth breathing and in 3 of 3 patients it can be interrupted with a prompt to take a breath. Finally, in patients where there were multiple amygdalar depths, stimulation induced apnea occurred only when stimulating the mesial most contacts, suggesting that extended amygdala nuclei may be critical in mediating this effect. Conclusions: Our study contributes to the emerging literature on respiratory control and the amygdala, including methods of interruption of apnea. It is our hope that understanding how we can prevent amygdala-stimulation-induced apnea will pave the way for research into potential avenues to explore for the prevention of SUDEP as well as provide avenues for more detailed pre-clinical evaluation of the mechanisms and pathways involved. Funding: CURE Taking Flight Award
Translational Research