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

doi:10.1073/pnas.0509862103

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

^*Howard Florey Institute of Experimental Physiology and Medicine, ^§Centre for Neuroscience, and Departments of ^††Physiology and ^†Anatomy and Cell Biology, University of Melbourne, Melbourne, Victoria 3010, Australia; ^¶Department of Physiology, University of Texas Health Sciences Center, San Antonio, TX 78229; ^∥Brain Research Institute, Austin Health, West Heidelberg, Victoria 3084, Australia; and ^**Baker Heart Research Institute, Alfred Hospital, Prahran, Victoria 3181, Australia

Contributed by Derek A. Denton, November 12, 2005

Abstract

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.

Footnotes

↵ ‡ To whom correspondence may be sent at the * address. E-mail: rmca{at}hfi.unimelb.edu.au. ^‡‡To whom correspondence may be sent at the †† address. E-mail: d.denton{at}hfi.unimelb.edu.au.
Conflict of interest statement: No conflicts declared.
Abbreviations: BOLD, blood oxygen level-dependent; ROI, region of interest.