Connectivity of cingulo-frontal cortex and midbrain in pain modulation by attention

Neuroimaging studies with positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) have delineated a human pain matrix in vivo, including cortical and subcortical structures. Despite the recognition of cerebral structures engaged in pain transmission, the cerebral mechanisms involved in pain modulation, in particular antinociception, are still not well understood. Here, we investigated healthy volunteers using fMRI during experimental heat pain and attentional distraction induced by a visual incongruent color-word Stroop task. A factorial design permitted categorical and covariation analysis of four conditions, namely innocuous and noxious heat with and without distraction. Pain without distraction evoked an activation pattern similar to that known from previous neuroimaging pain studies. Distraction was associated with a significant reduction of the visual analogue scale (VAS) ratings for pain intensity and unpleasantness and a reduction of pain-related activation in multiple brain areas, particularly in the so-called medial pain system. Distraction significantly increased the activation of the cingulo-frontal cortex including the orbitofrontal and perigenual anterior cingulate cortex (ACC), the periaquaeductal gray (PAG) and posterior thalamus. Covariation analysis of the blood oxygen level dependent (BOLD) pattern in the cingulo-frontal cortex revealed a pain matrix consisting of midbrain (PAG) and posterior thalamic areas that appear to mediate antinociception during distraction, presumably via activation of descending inhibitory projections.