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

Abstract

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.

EEG analysis reveals widespread directed functional interactions related to a painful cutaneous laser stimulus

“…Our prior studies of subdural recordings demonstrated the presence of critical sites that were associated with multiple significant ERC interactions in a laser attentiondistraction protocol (Liu et al 2011c). At critical sites, the numbers of ERC interactions during laser distraction and attention tasks were both larger than their median to a greater degree than expected at random.…”

“…In turn, the dDTF is a version of an earlier measure, the directed transfer function (DTF). The essential part of the ERC method is the statistical testing procedure that will reveal the significant changes in interchannel relationships after versus before the stimulus (i.e., event-related; Liu et al 2011c).…”

“…The computer programs for the above statistical tests were written in R language and have been previously tested and used in similar studies of multichannel human recordings (Liu et al 2011c). All the programs for the ERC analysis were written in C language in-house, developed in the Linux environment, and run on a computer cluster, which was implemented as one distributed system.…”

“…The results showed that the critical sites for this data set were Cz, C3, Pz, and O2 channels (Table 3). The activity at these channels may reflect activity at critical sites in the brain as identified by subdural recordings (Liu et al 2011c).…”

“…At critical sites, the number of interactions for sites overall was elevated both during attention to the painful laser stimulus and during distraction from the stimulus (Liu et al 2011c). This result suggests that functional interactions at critical sites may exert powerful, task-independent causal influences throughout the "pain network."…”