The dorsomedial prefrontal cortex as a flexible hub mediating behavioral as well as local and distributed neural effects of social support context on pain: A Theta Burst Stimulation and TMS-EEG study

Increasing evidence points to an analgesic influence of social support context, in which the dorsomedial prefrontal cortex (dmPFC) may play a key role. Transcranial Magnetic Stimulation (TMS) has the capacity to causally modulate brain activity. This study was designed to investigate the potential role of dmPFC in orchestrating the behavioral and neural effects of social context during pain. Twenty-three healthy participants underwent a three-session cross-over, single-blinded, sham-controlled protocol in which they received Theta Burst Stimulation (TBS) (facilitatory intermittent TBS, suppressive continuous TBS, or Sham) delivered to the dmPFC. In each session, participants underwent cold pain while viewing an image of a romantic partner or a stranger. Effects of TBS to the dmPFC were assessed using a measure of pain perception, neural activity and network connectivity using electroencephalography (EEG) and TMS-EEG. In the stranger condition, pain experience increased following iTBS. This was associated with increased connectivity between central regions and fronto-parietal regions. In contrast, in the romantic partner condition, iTBS increased connectivity only between frontal and occipital regions and did not modulate pain experience. In line with recent studies, neither cTBS nor Sham stimulation elicited neural or behavioral changes. Together these findings suggest that the dmPFC has the capacity to causally modulate pain-related information integration and network configuration in a context-dependent manner.