Functional neuroimaging studies in humans have shown that nociceptive stimuli elicit activity in a wide network of cortical areas commonly labeled as the "pain matrix" and thought to be preferentially involved in the perception of pain. Despite the fact that this "pain matrix" has been used extensively to build models of where and how nociception is processed in the human brain, convincing experimental evidence demonstrating that this network is specifically related to nociception is lacking. The aim of the present study was to determine whether there is at least a subset of the "pain matrix" that responds uniquely to nociceptive somatosensory stimulation. In a first experiment, we compared the fMRI brain responses elicited by a random sequence of brief nociceptive somatosensory, non-nociceptive somatosensory, auditory and visual stimuli, all presented within a similar attentional context. We found that the fMRI responses triggered by nociceptive stimuli can be largely explained by a combination of (1) multimodal neural activities (i.e., activities elicited by all stimuli regardless of sensory modality) and (2) somatosensory-specific but not nociceptive-specific neural activities (i.e., activities elicited by both nociceptive and non-nociceptive somatosensory stimuli). The magnitude of multimodal activities correlated significantly with the perceived saliency of the stimulus. In a second experiment, we compared these multimodal activities to the fMRI responses elicited by auditory stimuli presented using an oddball paradigm. We found that the spatial distribution of the responses elicited by novel non-target and novel target auditory stimuli resembled closely that of the multimodal responses identified in the first experiment. Taken together, these findings suggest that the largest part of the fMRI responses elicited by phasic nociceptive stimuli reflects non nociceptive-specific cognitive processes.
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