Abnormal Resting-State Functional Connectivity in Patients with Chronic Fatigue Syndrome: Results of Seed and Data-Driven Analyses. Gay C, et al. Brain Connect. 2015. Authors Gay C1, Robinson ME2, Lai S3, O'Shea A4, Craggs J5, Price DD6, Staud R7. Author information 1University of Florida, Gainesville, Florida, United States ; email@example.com. 2University of Florida, Gainesville, Florida, United States ; firstname.lastname@example.org. 3University of Florida, Gainesville, Florida, United States ; email@example.com. 4University of Florida, Gainesville, Florida, United States ; firstname.lastname@example.org. 5University of Missouri, Columbia, Missouri, United States ; email@example.com. 6University of Florida, Gainesville, Florida, United States ; firstname.lastname@example.org. 7University of Florida, Medicine , PO Box 100221 , Gainesville, Florida, United States , 32610-0221 ; email@example.com. Citation Brain Connect. 2015 Oct 9. [Epub ahead of print] Abstract Although altered resting-state functional connectivity 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 functional connectivity 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 intra-regional functional connectivity 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 (DMN), salience network (SN), left and right fronto-parietal networks (LFPN, RFPN), and 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 functional connectivity of the left anterior mid-cingulate 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 functional connectivity with other brain regions. The degree of abnormal connectivity correlated with the level of self-reported fatigue. Our results confirm altered RS functional connectivity in patients with ME/CFS which was significantly correlated with the severity of their chronic fatigue.