Attention to painful cutaneous laser stimuli evokes directed functional interactions between human sensory and modulatory pain-related cortical areas.

The human 'pain network' includes cortical areas that are activated during the response to painful stimuli (termed category 1) or during psychological processes that modulate pain, for example, distraction (termed category 2). These categories include parts of the parasylvian (PS), medial frontal (MF), and paracentral cortex (S1&M1). Here we test the hypothesis that causal interactions both within and between category 1 and category 2 modules occur during attention to a painful stimulus. Event-related causality (ERC) was calculated from local field potentials recorded directly from these cortical areas during the response to a painful cutaneous laser stimulus in patients being monitored for epilepsy. The number of electrodes involved in pairs with significant ERC in category 1 was greater for pre-stimulus vs post-stimulus and for attention vs distraction. This is consistent with our prior evidence that the category 1 'pain network' changes rapidly with time intervals and tasks. In contrast, the interaction between categories was often unchanged or stable across intervals and tasks, particularly in MF. The proportion of contacts involved in interactions with PS was greater during distraction vs attention while activation was less, which suggests that distraction involves an inhibitory process in PS. Functional interactions between categories were overwhelmingly in the direction from category 2>1, particularly for contacts in MF which often had a driver role. These results demonstrate that MF is densely interconnected throughout the 'pain network' so that stimulation of MF might be used to disrupt the 'pain network' as a therapy for pain.