Abnormal Resting-State Functional Connectivity in Patients with Chronic Fatigue Syndrome: Results of Seed and Data-Driven Analyses

Abstract

Although altered resting-state functional connectivity (FC) is a characteristic of many chronic pain conditions, it has not yet been evaluated in patients with chronic fatigue. Our objective was to investigate the association between fatigue and altered resting-state FC in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Thirty-six female subjects, 19 ME/CFS and 17 healthy controls, completed a fatigue inventory before undergoing functional magnetic resonance imaging. Two methods, (1) data driven and (2) model based, were used to estimate and compare the intraregional FC between both groups during the resting state (RS). The first approach using independent component analysis was applied to investigate five RS networks: the default mode network, salience network (SN), left frontoparietal networks (LFPN) and right frontoparietal networks, and the sensory motor network (SMN). The second approach used a priori selected seed regions demonstrating abnormal regional cerebral blood flow (rCBF) in ME/CFS patients at rest. In ME/CFS patients, Method-1 identified decreased intrinsic connectivity among regions within the LFPN. Furthermore, the FC of the left anterior midcingulate with the SMN and the connectivity of the left posterior cingulate cortex with the SN were significantly decreased. For Method-2, five distinct clusters within the right parahippocampus and occipital lobes, demonstrating significant rCBF reductions in ME/CFS patients, were used as seeds. The parahippocampal seed and three occipital lobe seeds showed altered FC with other brain regions. The degree of abnormal connectivity correlated with the level of self-reported fatigue. Our results confirm altered RS FC in patients with ME/CFS, which was significantly correlated with the severity of their chronic fatigue.

Keywords: ICA; chronic fatigue; connectivity; fMRI.

FIG. 1.

Spatial maps of resting-state networks and regional group differences in functional connectivity threshold t > 4.0; k > 15. R = Right, L = Left, x, y, and z coordinates are in Montreal Neurologic Institute space. (A–E) Representative group-level independent component for each of the five resting-state networks. (F–G) Regions of the cingulate cortex where myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients showed less connectivity with the salience and sensory motor networks. (H) Region of the left frontal gyrus where ME/CFS patients showed decreased intrinsic connectivity in the left frontoparietal network. Color images available online at www.liebertpub.com/brain