TY - JOUR
T1 - A human amygdala site that inhibits respiration and elicits apnea in pediatric epilepsy
AU - Rhone, Ariane E.
AU - Kovach, Christopher K.
AU - Harmata, Gail I.S.
AU - Sullivan, Alyssa W.
AU - Tranel, Daniel
AU - Ciliberto, Michael A.
AU - Howard, Matthew A.
AU - Richerson, George B.
AU - Steinschneider, Mitchell
AU - Wemmie, John A.
AU - Dlouhy, Brian J.
N1 - Funding Information:
Support for this work was provided by the Roy J. Carver Charitable Trust (to BJD), the National Institute of Neurological Disorders and Stroke - Congress of Neurological Surgeons K12 Getch Scholar Award (to BJD), the National Institute of General Medical Sciences training grant T32 GM067795 (to GISH), and the National Institute of General Medical Sciences training grant T32 GM108540 (to AWS). The graphical abstract was created with BioRender.
Funding Information:
Support for this work was provided by the Roy J. Carver Charitable Trust (to BJD), the National Institute of Neurological Disorders and Stroke — Congress of Neurological Surgeons K12 Getch Scholar Award (to BJD), the National Institute of General Medical Sciences training grant T32 GM067795 (to GISH), and the National Institute of General Medical Sciences training grant T32 GM108540 (to AWS). The graphical abstract was created with BioRender.
Publisher Copyright:
Copyright: © 2020, American Society for Clinical Investigation.
PY - 2020/3/26
Y1 - 2020/3/26
N2 - 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.
AB - 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.
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U2 - 10.1172/jci.insight.134852
DO - 10.1172/jci.insight.134852
M3 - Article
C2 - 32163374
AN - SCOPUS:85082825494
SN - 2379-3708
VL - 5
JO - JCI Insight
JF - JCI Insight
IS - 6
M1 - e134852
ER -