Dynamic functional connectivity underlying temporal summation of pain in fibromyalgia

Compared to healthy controls (HC), fibromyalgia (FM) patients exhibit enhanced temporal summation of pain (TSP) – i.e. perception of increasingly greater pain in response to repetitive or sustained noxious stimuli. Previous neuroimaging studies have linked static functional connectivity (sFC) and stimulus-evoked brain fMRI response to enhanced TSP in FM patients. However, dynamics of brain organization in FM underlying ongoing changes in pain perception, such as that during TSP, is not known. The purpose of this study was to investigate the dynamic changes in functional brain connectivity (dFC) occurring during TSP in FM. We collected high temporal resolution (TR=1.25s) 6-minute resting-state (REST) and tonic leg cuff pressure pain (PAIN) accelerated fMRI brain scan from 84 FM patients and 38 HCs. Pain ratings were collected retrospectively for each 2-minute block of the PAIN scan, and TSP was calculated as last minus first pain rating. We used an instantaneous phase synchrony analysis approach to estimate dFC, followed by the application of a multi-slice community detection algorithm to reveal the dynamic community organization of the brain over time. We found that FM patients exhibit greater TSP than HCs (meanFM = 17.93, meanHC = 9.47, p = 7.58 × 10-4). In FM (and not HC), during PAIN versus REST, fMRI signal from the contralateral leg area of primary somatosensory cortex (S1leg) spent more time in the same community as salience network regions. However, both FM and HC groups showed decreased S1leg community enmeshment with other somatotopic areas of S1 during PAIN compared to during REST. Furthermore, longer and more consistent enmeshment of the sensorimotor and salience communities throughout the PAIN scan was associated with greater TSP in FM patients. Overall, this study corroborates our prior tonic cuff pain static connectivity results and reveals that dynamics in brain organization track changes in pain perception reflecting TSP in FM. NCCIH, NIH R61/R33-AT009306 (VN) and NIAMS, NIH R01-AR064367 (VN, RRE).