Background/Purpose: Myalgic encephalitis/chronic fatigue syndrome (CFS) is a debilitating disorder characterized by disabling fatigue and cognitive dysfunction. However, little is known regarding the neural mechanisms underlying fatigue in CFS. Recent work from our laboratory utilizing arterial spin labeling functional magnetic resonance imaging (ASL fMRI) indicates CFS patients have lower resting state regional cerebral blood flow (rCBF) in several areas associated with memory and attentional functioning, including parahippocampal gyrus, superior frontal gyrus, and anterior cingulate gyrus. This regional hypoperfusion may underlie CFS pathogenesis. The current report uses functional connectivity analysis to determine relationships between fatigue related brain regions in CFS patients compared healthy controls.

Methods: Participants were 16 CFS patients (M_age=52.33 years, SD=10.6) and 19 age/sex matched healthy controls (HC; M_age=48.74 years, SD=11.74). CFS was diagnosed in all patients using 1994 CDC criteria. All participants underwent T1-weighted structural MRI as well as a 6-minute pseudo-continuous arterial spin labeling (pCASL) sequence. pCASL allows the non-invasive quantification of CBF by magnetically labeling blood as it enters the brain. Imaging data were preprocessed in MATLAB 2011b using SPM version 12 and ASL tbx. 4D ASL images were realigned and coregistered to structural MRI prior to pairwise subtraction of control and label images to obtain the perfusion time series. Perfusion signal time series were then masked and normalized, and CBF was computed using the single-compartment ASL perfusion model (Wang et al., 2005). Functional connectivity analysis was conducted using the CONN toolbox. All effects noted below are significant at p<0.01.

Results:  ROI-to-ROI functional connectivity analysis utilizing the regions previously identified as being hypoperfused in CFS patients and regions associated with affective, cognitive, and motor function indicated differential patterns of functional connectivity between CFS patients and HC for several areas. Right parahippocampal gyrus connectivity with left medial temporal gyrus was higher in CFS patients than HC, whereas left parahippocampal gyrus connectivity to parietal operculum was lower in CFS patients than controls. Left superior frontal gyrus connectivity to right lingual gyrus was higher in CFS patients than HC, but connectivity to right frontal operculum was lower. Finally, anterior cingulate connectivity to the superior parietal lobule was higher in CFS patients than controls.

Conclusion: Results of our ASL based analyses demonstrated hypoperfusion in several brain regions of CFS patients associated with higher cognitive functions. Additionally, these regions also demonstrate altered functional connectivity in CFS patients compared to their healthy counterparts. Although preliminary, additional results also suggest abnormal relationships between functional connectivity as reflected by ASL fMRI and CFS symptoms (e.g., self-reported fatigue ratings).

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/abnormal-resting-state-functional-connectivity-in-chronic-fatigue-syndrome-patients-an-arterial-spin-labeling-fmri-study/