Journal article
Failure to breathe persists without air hunger or alarm following amygdala seizures
JCI insight, Vol.8(22), e172423
11/22/2023
DOI: 10.1172/jci.insight.172423
PMCID: PMC10721319
PMID: 37788112
Abstract
Postictal apnea is thought to be a major cause of sudden unexpected death in epilepsy (SUDEP). However, the mechanisms underlying postictal apnea are unknown. To understand causes of postictal apnea, we used a multimodal approach to study brain mechanisms of breathing control in 20 patients (ranging from pediatric to adult) undergoing intracranial electroencephalography (iEEG) for intractable epilepsy. Our results indicate that amygdala seizures can cause postictal apnea. Moreover, we identified a distinct region within the amygdala where electrical stimulation was sufficient to reproduce prolonged breathing loss persisting well beyond the end of stimulation. The persistent apnea was resistant to rising CO2 levels, and air hunger failed to occur, suggesting impaired CO2 chemosensitivity. Using es-fMRI, a novel approach combining electrical stimulation with functional MRI, we found amygdala stimulation altered BOLD activity in the pons/medulla and ventral insula. Together, these findings suggest that seizure activity in a focal subregion of the amygdala is sufficient to suppress breathing and air hunger for prolonged periods of time in the postictal period, likely via brainstem and insula sites involved in chemosensation and interoception. They further provide new insights into SUDEP, may help identify those at greatest risk, and may lead to treatments to prevent SUDEP.
Details
- Title: Subtitle
- Failure to breathe persists without air hunger or alarm following amygdala seizures
- Creators
- Gail I.S. HarmataAriane E. RhoneChristopher K. KovachSukhbinder KumarMd Rakibul MowlaRup K. SainjuYasunori NagahamaHiroyuki OyaBrian K. GehlbachMichael A. CilibertoRashmi N. MuellerHiroto KawasakiKyle T.S. PattinsonKristina SimonyanPaul W. DavenportMatthew A Howard IIIMitchell SteinschneiderAubrey C. ChanGeorge B. RichersonJohn A. WemmieBrian J. Dlouhy
- Resource Type
- Journal article
- Publication Details
- JCI insight, Vol.8(22), e172423
- DOI
- 10.1172/jci.insight.172423
- PMID
- 37788112
- PMCID
- PMC10721319
- NLM abbreviation
- JCI Insight
- ISSN
- 2379-3708
- eISSN
- 2379-3708
- Grant note
- DOI: 10.13039/100000065, name: National Institute of Neurological Disorders and Stroke, award: K08NS112573, K12NS080223, R01NS113764; DOI: 10.13039/100005653, name: Congress of Neurological Surgeons, award: Getch scholar award; DOI: 10.13039/100000057, name: National Institute of General Medical Sciences, award: T32GM067795; name: National Institute of Health Research Biomedical Research Centre based at Oxford University Hospitals NHS Trust and the University of Oxford, award: na; DOI: 10.13039/100000025, name: National Institute of Mental Health, award: T32MH019113, R01MH113325; DOI: 10.13039/100000026, name: National Institute on Drug Abuse, award: R01DA052953; name: Roy J Carver Trust, award: n/a; DOI: 10.13039/100000738, name: U.S. Department of Veterans Affairs, award: Merit Review Award; name: Philanthropic support, award: n/a
- Language
- English
- Electronic publication date
- 10/03/2023
- Date published
- 11/22/2023
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Psychiatry; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Anesthesia; Neurology (Pediatrics); Neurosurgery; Otolaryngology; Health, Sport, and Human Physiology ; Internal Medicine
- Record Identifier
- 9984473410702771
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