RT Journal Article
SR Electronic
T1 Breathing Inhibited When Seizures Spread to the Amygdala and upon Amygdala Stimulation
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 10281
OP 10289
DO 10.1523/JNEUROSCI.0888-15.2015
VO 35
IS 28
A1 Brian J. Dlouhy
A1 Brian K. Gehlbach
A1 Collin J. Kreple
A1 Hiroto Kawasaki
A1 Hiroyuki Oya
A1 Colin Buzza
A1 Mark A. Granner
A1 Michael J. Welsh
A1 Matthew A. Howard
A1 John A. Wemmie
A1 George B. Richerson
YR 2015
UL http://www.jneurosci.org/content/35/28/10281.abstract
AB Sudden unexpected death in epilepsy (SUDEP) is increasingly recognized as a common and devastating problem. Because impaired breathing is thought to play a critical role in these deaths, we sought to identify forebrain sites underlying seizure-evoked hypoventilation in humans. We took advantage of an extraordinary clinical opportunity to study a research participant with medically intractable epilepsy who had extensive bilateral frontotemporal electrode coverage while breathing was monitored during seizures recorded by intracranial electrodes and mapped by high-resolution brain imaging. We found that central apnea and O2 desaturation occurred when seizures spread to the amygdala. In the same patient, localized electrical stimulation of the amygdala reproduced the apnea and O2 desaturation. Similar effects of amygdala stimulation were observed in two additional subjects, including one without a seizure disorder. The participants were completely unaware of the apnea evoked by stimulation and expressed no dyspnea, despite being awake and vigilant. In contrast, voluntary breath holding of similar duration caused severe dyspnea. These findings suggest a functional connection between the amygdala and medullary respiratory network in humans. Moreover, they suggest that seizure spread to the amygdala may cause loss of spontaneous breathing of which patients are unaware, and thus has potential to contribute to SUDEP.SIGNIFICANCE STATEMENT Sudden unexpected death in epilepsy (SUDEP) is the most common cause of death in patients with chronic refractory epilepsy. Impaired breathing during and after seizures is common and suspected to play a role in SUDEP. Understanding the cause of this peri-ictal hypoventilation may lead to preventative strategies. In epilepsy patients, we found that seizure invasion of the amygdala co-occurred with apnea and oxygen desaturation, and electrical stimulation of the amygdala reproduced these respiratory findings. Strikingly, the subjects were unaware of the apnea. These findings indicate a functional connection between the amygdala and brainstem respiratory network in humans and suggest that amygdala seizures may cause loss of spontaneous breathing of which patients are unaware—a combination that could be deadly.