Abstract
Humans exhibit changes in heart rate during cognitive and emotional events, and dysregulation of this brain–heart coupling is a hallmark of many psychiatric disorders. Yet, whether and how circuits that regulate decision making exert direct control over heart physiology remains poorly understood, particularly in primates. In this thesis, we identify a prefrontal–hypothalamic circuit that exerts powerful, bidirectional control over heart rate in monkeys. We show that focal activation of a small ventral subregion within the ventrolateral prefrontal cortex (area 47/12; a12) evokes rapid and robust decreases in heart rate, whereas neighboring prefrontal regions produce weaker or no effects. Anatomical tracing reveals prominent projections from a12 to a circumscribed region of lateral hypothalamus (LHA), and stimulation of this LHA target recapitulates the cardiac effects of prefrontal activation. Conversely, chemogenetic inactivation of a12 or its projections to LHA increases heart rate, demonstrating that this pathway can provide tonic inhibitory control over cardiac function. To establish cell-type-specific and minimally invasive causal control of this circuit, we developed a primate sonogenetic approach based on ultrasound activation of TRPV1-expressing CaMKII+ neurons. Sonogenetic stimulation of a12 produces significant heart rate variability changes, resembling key features of electrical stimulation effects, and these responses are attenuated by inactivation of LHA, confirming that prefrontal control of heart rate relies in large part on this pathway. Consistent with the hierarchical organization of this circuit, stimulation of LHA produces faster, stronger, state-independent effects, whereas stimulation of a12 produces effects that vary with internal states. Together, these results identify a prefrontal–hypothalamic circuit that links cognitive control systems to autonomic physiology in primates, revealing a mechanistic substrate for brain–body interactions and a potential therapeutic target for disorders of cognitive–autonomic dysregulation.
Committee Chair
Hong Chen
Committee Members
Ilya Monosov, Jianmin Cui; Marco Pignatelli; ShiNung Ching
Degree
Doctor of Philosophy (PhD)
Author's Department
Biomedical Engineering
Document Type
Dissertation
Date of Award
4-29-2026
Language
English (en)
DOI
https://doi.org/10.7936/3pef-ma73
Recommended Citation
Xu, Kevin, "A prefrontal cortex-hypothalamus circuit for heart rate control in non-human primates" (2026). McKelvey School of Engineering Graduate Student Theses & Dissertations. 1378.
The definitive version is available at https://doi.org/10.7936/3pef-ma73