Distinct networks of periaqueductal gray columns in pain and threat processing

Sean Wang, Jennika Veinot, Amita Goyal, Ali Khatibi, Sara Lazar, Javeria Ali Hashmi

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Noxious events that can cause physical damage to the body are perceived as threats. In the brainstem, the periaqueductal gray (PAG) ensures survival by generating an appropriate response to these threats. Hence, the experience of pain is coupled with threat signaling and interfaces in the dl/l and vlPAG columns. In this study, we triangulate the functional circuits of the dl/l and vlPAG by using static and time-varying functional connectivity (FC) in multiple fMRI scans in healthy participants (n = 37, 21 female). The dl/l and vlPAG were activated during cue, heat, and rating periods when the cue signaled a high threat of experiencing heat pain and when the incoming intensity of heat pain was unknown. Responses were significantly lower after low threat cues. The two regions responded similarly to the cued conditions but showed prominent distinctions in the extent of FC with other brain regions. Thus, both static and time-varying FC showed significant differences in the functional circuits of dl/l and vlPAG in rest and task scans. The dl/lPAG consistently synchronized with the salience network and the thalamus, suggesting a role in threat detection, while the vlPAG exhibited more widespread synchronization and frequently connected with memory/language and sensory regions. Hence, these two PAG regions process heat pain when stronger pain is expected or when it is uncertain, and preferentially synchronize with distinct brain circuits in a reproducible manner. The dl/lPAG seems more directly involved in salience detection, while the vlPAG seems engaged in contextualizing threats.
Original languageEnglish
Article number118936
Early online date29 Jan 2022
Publication statusPublished - 15 Apr 2022


  • PAG
  • brainstem
  • descending inhibition
  • expectation
  • fMRI
  • functional MRI
  • functional connectivity
  • networks
  • nociception
  • pain
  • parasympathetic
  • prediction
  • resting state
  • salience
  • sympathetic
  • task based connectivity
  • threat
  • time varying
  • top-down

ASJC Scopus subject areas

  • Neurology
  • Cognitive Neuroscience


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