Human medullary responses to cooling and rewarming the skin: A functional MRI study

Robin M. McAllen, Michael Farrell, John M. Johnson, David Trevaks, Leonie Cole, Michael J. McKinley, Graeme Jackson, Derek A. Denton, Gary F. Egan

Research output: Contribution to journalArticlepeer-review

69 Scopus citations


A fall in skin temperature precipitates a repertoire of thermoregulatory responses that reduce the likelihood of a decrease in core temperature. Studies in animals suggest that medullary raphé neurons are essential for cold-defense, mediating both the cutaneous vasoconstrictor and thermogenic responses to ambient cooling; however, the involvement of raphé neurons in human thermoregulation has not been investigated. This study used functional MRI with an anatomically guided region of interest (ROI) approach to characterize changes in the blood oxygen level-dependent (BOLD) signal within the human medulla of nine normal subjects during non-noxious cooling and rewarming of the skin by a water-perfused body suit. An ROI covering 4.9 ± 0.3 mm2 in the ventral midline of the medulla immediately caudal to the pons (the rostral medullary raphé) showed an increase in BOLD signal of 3.9% (P < 0.01) during periods of skin cooling, compared with other times. Overall, that signal showed a strong inverse correlation (R = 0.48, P < 0.001) with skin temperature. A larger ROI covering the internal medullary cross section at the same level (area, 126 ± 15 mm2) showed no significant change in mean BOLD signal with cooling (+0.2%, P > 0.05). These findings demonstrate that human rostral medullary raphé neurons are selectively activated in response to a thermoregulatory challenge and point to the location of thermoregulatory neurons homologous to those of the raphé pallidus nucleus in rodents.

Original languageEnglish (US)
Pages (from-to)809-813
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number3
StatePublished - Jan 17 2006
Externally publishedYes


  • Functional neuroimaging
  • Raphé
  • Rostral medulla
  • Thermoregulation

ASJC Scopus subject areas

  • General


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