Distributed Neural Substrates for Autonomic Control During Human Thermoregulation: Brain Network Configurations of Sympathetic and Parasympathetic Innervation.

Autonomic control during sympathetic and parasympathetic innervation is essential to human thermoregulation. Sympathetic and parasympathetic nervous systems (NS) are subserved by distinct peripheral pathways, where this distinction was believed to carry forward to the central nervous system (CNS). Generally, however, brain function is implemented across distributed network architecture, and while distributed processing may be plausibly true of autonomic control during human thermoregulation, this has never been demonstrated from in vivo signals. Here we show that sympathetic- or parasympathetic innervation during thermoregulatory challenge evoke a milieu of conjoint (Sympathetic ∩ Parasympathetic) and disjoint [(Sympathetic [Formula: see text][Formula: see text]Parasympathetic) and (Parasympathetic [Formula: see text][Formula: see text]Sympathetic)] cross-connectomic network configurations. fMRI data were collected while participants were subjected to a whole-body thermoregulatory paradigm with alternating epochs for sympathetic (whole-body cooling) and parasympathetic (whole-body rewarming) innervation. From the fMRI timeseries signals, condition-evoked changes in functional connectivity were estimated across a 262-region connectome (34,191 region pairs across the cerebrum and midbrain). Results affirmed the existence of (a) an extensive conjoint functional substrate for autonomic control, complemented by (b) disjoint substrates of the insula and the brainstem (respectively associated with interoceptive and homeostatic processing). Sympathetic innervation evoked predominantly cooperative network interactions, whereas parasympathetic innervation evoked a balance of cooperative and antagonistic interactions. These results are the first to demonstrate that autonomic control during human thermoregulation relies on distributed brain network interactions, where these interactions are partially sensitive to the demands of the externally oriented sympathetic NS, against those of the internally oriented parasympathetic NS.