Detailed organisation of the human midbrain periaqueductal grey revealed using ultra-high field magnetic resonance imaging

The midbrain periaqueductal grey (PAG) is a critical region for the mediation of pain-related behavioural re-sponses. 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 con-textually 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 evi-dence 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. Im-ages 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 phyleti-cally 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.

Automated summary

The PAG is a critical region for pain-related responses and shows a crude somatotopy for contextually appropriate behavioral responses. Different regions in the PAG are activated by cutaneous and muscle pain. Using ultra-high field functional magnetic resonance imaging, it was found that the PAG exhibits different signal intensity changes in response to noxious stimuli. This suggests a preserved somatotopic organization in the PAG between animals and humans.