Abstract
Pain stimuli evoke widespread responses in the brain. However, our understanding of the physiological significance underlying heterogeneous response within different pain-activated and -deactivated regions is still limited. Using functional magnetic resonance imaging, we evaluated brain responses to a wide range of stimulus intensity levels (1 innocuous, 7 painful) in order to estimate region-specific stimulus-response functions, which we hypothesized could illuminate that region’s functional relationship to pain. Linear and nonlinear brain responses to pain were estimated through independent Legendre polynomial transformations of pain ratings within a general linear model. This approach identified at least 5 different, regionally specific activity profiles in the brain. Linearly increasing (eg, primary somatosensory/motor cortex, insulae) and intensity-independent (eg, secondary somatosensory cortex) activation was noted in traditional pain-processing areas, potentially reflecting sensory encoding and all-or-none salience responses, respectively. Multiple activity profiles were seen in areas of the default mode network (DMN): intensity-independent deactivation (eg, posterior cingulate cortex), linearly decreasing (eg, contralateral inferior parietal lobule), and quadratic (U-shaped; eg, medial prefrontal cortex). The latter observation suggests that: (1) different DMN subregions exhibit functional heterogeneity and (2) some DMN subregions respond in a percept-related manner to pain, suggesting closer linkage between the DMN and pain processing than previously thought. Future studies should apply a similar approach using innocuous stimuli of multiple intensities to evaluate whether the response profiles reported here can also be generalized to nonpainful somatosensory processing.
Highlights
Over the past two decades, neuroimaging studies have identified a widespread network of brain structures activated or deactivated by evoked pain stimuli
This approach is informative as it can potentially distinguish brain regions exhibiting activation/deactivation correlated with perceived pain from those regions in which response magnitude is independent of the perceptual response, and less likely to be involved in the encoding of sensory/affective components of pain
Our study demonstrated that brain areas exhibit at least five different pain-related S-R patterns: intensity-independent activation (‘Constant+’); intensity-independent deactivation (‘Constant−’); linearly increasing (‘Linear+’); linearly decreasing (‘Linear−’), and ‘Quadratic’
Summary
Over the past two decades, neuroimaging studies have identified a widespread network of brain structures activated or deactivated by evoked pain stimuli. Our understanding of the physiological significance associated with the response within each brain area is still limited This is true for the pain-related deactivations, which until recently have been relatively neglected [45]. One way to begin disentangling the role of different brain regions in pain processing is to examine their stimulus-response (S-R) function, in the context of stimulations at multiple levels of intensity. This approach is informative as it can potentially distinguish brain regions exhibiting activation/deactivation correlated with perceived pain from those regions in which response magnitude is independent of the perceptual response, and less likely to be involved in the encoding of sensory/affective components of pain. The shape of the S-R function for brain regions demonstrating pain intensity-dependent activity can provide meaningful information regarding the specific role that each region plays in pain processing
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