Abstract The periaqueductal gray (PAG) is a small midbrain structure that surrounds the cerebral aqueduct, regulates brain–body communication, and is often studied for its role in “fight-or-flight” and “freezing” responses to threat. We used ultra-high field 7-Tesla fMRI to resolve the PAG in humans and distinguish it from the cerebral aqueduct, examining its in vivo function in humans during a working memory task (N = 87). Relative to baseline fixation, both mild and moderate task-elicited cognitive demands elicited bilateral BOLD increases in ventrolateral PAG (vlPAG), a region previously observed to show increased activity during anticipated painful threat in both non-human and human animals. The present task posed only the most minimal (if any) “threat”. The mild-demand condition involved a task easier than remembering a phone number, elicited a heart rate decrease relative to baseline, yet nonetheless elicited a bilateral vlPAG response. Across PAG voxels, BOLD signal intensity correlated with changes in physiological reactivity (relative to baseline) and showed some evidence of spatial organization along the rostral–caudal axis. These findings suggest that the PAG may have a broader role in coordinating brain—body communication during a minimally to moderately demanding task, even in the absence of threat.

7-Tesla evidence for columnar and rostral–caudal organization of the human periaqueductal gray response in the absence of threat: a working memory study