Sukhbinder Kumar, Ariane E. Rhone, Christopher K. Kovach, Md Rakibul Mowla, Aubrey C. Chan, Christopher M. Garcia, Hiroto Kawasaki, Rashmi N. Mueller, Justin D. Kuhn, Ryan T. Frede, Michael A. Ciliberto, Theresa M. Czech, Sreenath Thati Ganganna, James W. M. Owens, Ania K. Dabrowski, Brittany N. Sprigg, Matthew A. Howard, 3rd, Kai Hwang, José L. Herrero, Kyle T. S. Pattinson, George B. Richerson, John A. Wemmie, and Brian J. Dlouhy
Journal of Neurophysiology, Ahead of Print.
Abstract
Breathing is generated by brainstem respiratory networks but can be controlled and modulated by forebrain activity. The recent clinical adoption of thalamic electrode implantation during intracranial electroencephalography (iEEG) provides a rare opportunity to examine the role of the human thalamus in respiratory control. Here, we tested whether thalamic stimulation alters breathing in 11 patients undergoing iEEG for epilepsy monitoring. Across 412 stimulation trials at 108 thalamic sites, thalamic stimulation induced central apnea in every participant. Apnea occurred in isolation without sensory or motor effects and without awareness of breathing cessation. Apnea occurred with stimulation of either the right or left thalamus and was observed across all ages, including participants as young as 22 mo. Volitional breathing and speech were preserved, indicating that respiratory motor pathways remained functional. In contrast, except for the amygdala, stimulation of other forebrain regions, including the hippocampus, insula, cingulate, and frontal, temporal, and parietal cortices, did not affect breathing. Respiratory inhibition depended on thalamic location, occurring most consistently with stimulation of the ventral lateral anterior (VLa) and ventral anterior (VA) nuclei. A machine learning algorithm localized the focal apneic region within the anterior motor thalamus, centered in VLa and extending into VA. Identification of a focal apneic site in the VLa/VA motor thalamus expands thalamic function, revealing a forebrain node capable of overriding brainstem respiratory control. This circuit may coordinate breathing with volitional behaviors such as speech, and dysfunction of this circuit may play a role in central apnea disorders, including sleep apnea, SUDEP, and SIDS.
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