Attention to painful cutaneous laser stimuli evokes directed functional connectivity between activity recorded directly from human pain-related cortical structures

Our previous studies show that attention to painful cutaneous laser stimuli is associated with functional connectivity between human primary somatosensory cortex (SI), parasylvian cortex (PS), and medial frontal cortex (MF), which may constitute a pain network. However, the direction of functional connections within this network is unknown. We now test the hypothesis that activity recorded from the SI has a driver role, and a causal influence, with respect to activity recorded from PS and MF during attention to a laser. Local field potentials (LFP) were recorded from subdural grid electrodes implanted for the treatment of epilepsy. We estimated causal influences by using the Granger causality (GRC), which was computed while subjects performed either an attention task (counting laser stimuli) or a distraction task (reading for comprehension). Before the laser stimuli, directed attention to the painful stimulus (counting) consistently increased the number of GRC pairs both within the SI cortex and from SI upon PS (SI > PS). After the laser stimulus, attention to a painful stimulus increased the number of GRC pairs from SI > PS, and SI > MF, and within the SI area. LFP at some electrode sites (critical sites) exerted GRC influences upon signals at multiple widespread electrodes, both in other cortical areas and within the area where the critical site was located. Critical sites may bind these areas together into a pain network, and disruption of that network by stimulation at critical sites might be used to treat pain.