A human amygdala site that inhibits respiration and elicits apnea in pediatric epilepsy
Ariane E. Rhone, … , John A. Wemmie, Brian J. Dlouhy
Ariane E. Rhone, … , John A. Wemmie, Brian J. Dlouhy
Published March 12, 2020
Citation Information: JCI Insight. 2020;5(6):e134852. https://doi.org/10.1172/jci.insight.134852.
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Clinical Medicine Neuroscience

A human amygdala site that inhibits respiration and elicits apnea in pediatric epilepsy

Abstract

BACKGROUND Seizure-induced inhibition of respiration plays a critical role in sudden unexpected death in epilepsy (SUDEP). However, the mechanisms underlying seizure-induced central apnea in pediatric epilepsy are unknown.METHODS We studied 8 pediatric patients with intractable epilepsy undergoing intracranial electroencephalography. We recorded respiration during seizures and during electrical stimulation mapping of 174 forebrain sites. A machine-learning algorithm was used to delineate brain regions that inhibit respiration.RESULTS In 2 patients, apnea coincided with seizure spread to the amygdala. Supporting a role for the amygdala in breathing inhibition in children, electrically stimulating the amygdala produced apnea in all 8 subjects (3–17 years old). These effects did not depend on epilepsy type and were relatively specific to the amygdala, as no other site affected breathing. Remarkably, patients were unaware that they had stopped breathing, and none reported dyspnea or arousal, findings critical for SUDEP. Finally, a machine-learning algorithm based on 45 stimulation sites and 210 stimulation trials identified a focal subregion in the human amygdala that consistently produced apnea. This site, which we refer to as the amygdala inhibition of respiration (AIR) site includes the medial subregion of the basal nuclei, cortical and medial nuclei, amygdala transition areas, and intercalated neurons.CONCLUSIONS A focal site in the amygdala inhibits respiration and induces apnea (AIR site) when electrically stimulated and during seizures in children with epilepsy. This site may prove valuable for determining those at greatest risk for SUDEP and as a therapeutic target.FUNDING National Institute of Neurological Disorders and Stroke — Congress of Neurological Surgeons, National Institute of General Medical Sciences, Roy J. Carver Charitable Trust.

Authors

Ariane E. Rhone, Christopher K. Kovach, Gail I.S. Harmata, Alyssa W. Sullivan, Daniel Tranel, Michael A. Ciliberto, Matthew A. Howard, George B. Richerson, Mitchell Steinschneider, John A. Wemmie, Brian J. Dlouhy

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Figure 2

Apnea coincided with seizure spread to the amygdala.

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Apnea coincided with seizure spread to the amygdala. (A) 3D surface-rend...
(A) 3D surface-rendered MR image of P407’s right convexity with locations of cortical electrode contacts (black circles) in the frontal, temporal, and parietal lobes. (B) T1-weighted structural MR images showing the hippocampal and amygdala-depth electrodes and artifact produced by each electrode contact. (C) Schematic illustrating seizure spread from the lateral temporal cortex (purple circle, seizure onset) to the amygdala (red circle). (D) iEEG of seizure originating in lateral temporal cortex (purple circle in A) and spreading quickly to the amygdala (red circle in B). Breathing is normal until seizure activity spreads to the amygdala, which coincides with apnea and loss of normal breathing (inspiration is plotted up). The seizure spreads 10 seconds later to multiple other recording contacts in the hippocampus, temporal cortex, and parietal cortex, as colored in A and B, and then generalizes, at which point motion artifact obscures the respiratory signal. Normal breathing is observed after seizure end.