TY - JOUR
T1 - Detailed organisation of the human midbrain periaqueductal grey revealed using ultra-high field magnetic resonance imaging
AU - Tinoco Mendoza, Fernando A.
AU - Hughes, Timothy E.S.
AU - Robertson, Rebecca V.
AU - Crawford, Lewis S.
AU - Meylakh, Noemi
AU - Macey, Paul M.
AU - Macefield, Vaughan G.
AU - Keay, Kevin A.
AU - Henderson, Luke A.
N1 - Funding Information:
We wish to thank the many volunteers in this study. The authors acknowledge the facilities and scientific and technical assistance of the Australian National Imaging Facility, a National Collaborative Research Infrastructure Strategy (NCRIS) capability, at Melbourne Brain Centre Imaging Unit, University of Melbourne. This work was funded by the National Health and Medical Research Council of Australia Grant 1130280.
Funding Information:
We wish to thank the many volunteers in this study. The authors acknowledge the facilities and scientific and technical assistance of the Australian National Imaging Facility, a National Collaborative Research Infrastructure Strategy (NCRIS) capability, at Melbourne Brain Centre Imaging Unit, University of Melbourne. This work was funded by the National Health and Medical Research Council of Australia Grant 1130280 .
Publisher Copyright:
© 2022 The Authors
PY - 2023/2/1
Y1 - 2023/2/1
N2 - The midbrain periaqueductal grey (PAG) is a critical region for the mediation of pain-related behavioural responses. Neuronal tract tracing techniques in experimental animal studies have demonstrated that the lateral column of the PAG (lPAG) displays a crude somatotopy, which is thought to be critical for the selection of contextually appropriate behavioural responses, without the need for higher brain input. In addition to the different behavioural responses to cutaneous and muscle pain – active withdrawal versus passive coping – there is evidence that cutaneous pain is processed in the region of the lPAG and muscle pain in the adjacent ventrolateral PAG (vlPAG). Given the fundamental nature of these behavioural responses to cutaneous and muscle pain, these PAG circuits are assumed to have been preserved, though yet to be definitively documented in humans. Using ultra-high field (7-Tesla) functional magnetic resonance imaging we determined the locations of signal intensity changes in the PAG during noxious cutaneous heat stimuli and muscle pain in healthy control participants. Images were processed and blood oxygen level dependant (BOLD) signal changes within the PAG determined. It was observed that noxious cutaneous stimulation of the lip, cheek, and ear evoked maximal increases in BOLD activation in the rostral contralateral PAG, whereas noxious cutaneous stimulation of the thumb and toe evoked increases in the caudal contralateral PAG. Analysis of individual participants demonstrated that these activations were located in the lPAG. Furthermore, we found that deep muscular pain evoked the greatest increases in signal intensity in the vlPAG. These data suggest that the crude somatotopic organization of the PAG may be phyletically preserved between experimental animals and humans, with a body-face delineation capable of producing an appropriate behavioural response based on the location and tissue origin of a noxious stimulus.
AB - The midbrain periaqueductal grey (PAG) is a critical region for the mediation of pain-related behavioural responses. Neuronal tract tracing techniques in experimental animal studies have demonstrated that the lateral column of the PAG (lPAG) displays a crude somatotopy, which is thought to be critical for the selection of contextually appropriate behavioural responses, without the need for higher brain input. In addition to the different behavioural responses to cutaneous and muscle pain – active withdrawal versus passive coping – there is evidence that cutaneous pain is processed in the region of the lPAG and muscle pain in the adjacent ventrolateral PAG (vlPAG). Given the fundamental nature of these behavioural responses to cutaneous and muscle pain, these PAG circuits are assumed to have been preserved, though yet to be definitively documented in humans. Using ultra-high field (7-Tesla) functional magnetic resonance imaging we determined the locations of signal intensity changes in the PAG during noxious cutaneous heat stimuli and muscle pain in healthy control participants. Images were processed and blood oxygen level dependant (BOLD) signal changes within the PAG determined. It was observed that noxious cutaneous stimulation of the lip, cheek, and ear evoked maximal increases in BOLD activation in the rostral contralateral PAG, whereas noxious cutaneous stimulation of the thumb and toe evoked increases in the caudal contralateral PAG. Analysis of individual participants demonstrated that these activations were located in the lPAG. Furthermore, we found that deep muscular pain evoked the greatest increases in signal intensity in the vlPAG. These data suggest that the crude somatotopic organization of the PAG may be phyletically preserved between experimental animals and humans, with a body-face delineation capable of producing an appropriate behavioural response based on the location and tissue origin of a noxious stimulus.
KW - Brainstem
KW - Functional MRI
KW - Pain
KW - Periaqueductal grey
KW - Somatotopy
UR - http://www.scopus.com/inward/record.url?scp=85144886036&partnerID=8YFLogxK
U2 - 10.1016/j.neuroimage.2022.119828
DO - 10.1016/j.neuroimage.2022.119828
M3 - Article
C2 - 36549431
AN - SCOPUS:85144886036
SN - 1053-8119
VL - 266
JO - NeuroImage
JF - NeuroImage
M1 - 119828
ER -