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. 2016 May;34(4):603-8.
doi: 10.1016/j.mri.2015.12.008. Epub 2015 Dec 18.

Abnormal resting state functional connectivity in patients with chronic fatigue syndrome: an arterial spin-labeling fMRI study

Jeff Boissoneault  1 , Janelle Letzen  1 , Song Lai  2 , Andrew O'Shea  1 , Jason Craggs  1 , Michael E Robinson  1 , Roland Staud  3
Affiliations

Abnormal resting state functional connectivity in patients with chronic fatigue syndrome: an arterial spin-labeling fMRI study

Jeff Boissoneault et al. Magn Reson Imaging. 2016 May.

Abstract

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disorder characterized by severe fatigue and neurocognitive dysfunction. Recent work from our laboratory and others utilizing arterial spin labeling functional magnetic resonance imaging (ASL) indicated that ME/CFS patients have lower resting state regional cerebral blood flow (rCBF) in several brain areas associated with memory, cognitive, affective, and motor function. This hypoperfusion may underlie ME/CFS pathogenesis and may result in alterations of functional relationships between brain regions. The current report used ASL to compare functional connectivity of regions implicated in ME/CFS between patients and healthy controls (HC).

Methods: Participants were 17 ME/CFS patients (Mage=48.88years, SD=12) fulfilling the 1994 CDC criteria and 17 age/sex matched HC (Mage=49.82years, SD=11.32). All participants underwent T1-weighted structural MRI as well as a 6-min pseudo-continuous arterial spin labeling (pCASL) sequence, which quantifies CBF by magnetically labeling blood as it enters the brain. Imaging data were preprocessed using SPM 12 and ASL tbx, and seed-to-voxel functional connectivity analysis was conducted using the CONN toolbox. All effects noted below are significant at p<0.05 with cluster-wise FDR correction for multiple comparisons.

Results: ME/CFS patients demonstrated greater functional connectivity relative to HC in bilateral superior frontal gyrus, ACC, precuneus, and right angular gyrus to regions including precuneus, right postcentral gyrus, supplementary motor area, posterior cingulate gyrus, and thalamus. In contrast, HC patients had greater functional connectivity than ME/CFS in ACC, left parahippocampal gyrus, and bilateral pallidum to regions including right insula, right precentral gyrus, and hippocampus. Connectivity of the left parahippocampal gyrus correlated strongly with overall clinical fatigue of ME/CFS patients.

Conclusion: This is the first ASL based connectivity analysis of patients with ME/CFS. Our results demonstrate altered functional connectivity of several regions associated with cognitive, affective, memory, and higher cognitive function in ME/CFS patients. Connectivity to memory related brain areas (parahippocampal gyrus) was correlated with clinical fatigue ratings, providing supporting evidence that brain network abnormalities may contribute to ME/CFS pathogenesis.

Keywords: Arterial spin labeling; Chronic fatigue syndrome; Functional connectivity; MRI.

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Figures

Figure 1
Figure 1
Right medial view illustrating the ACC (black circle) and the location of Cluster 1 (38, −8, −4), for which connectivity was higher in HC than ME/CFS. Regions included in the cluster include right insula, right planum polare, right temporal pole, right putamen, and right Heschl’s gyrus.
Figure 2
Figure 2
Posterior view showing location of the left PaHCG (black circle) and clusters 1 (56, 6, 44) and 2 (−54, −30, 52), for which HC had higher connectivity than ME/CFS. Cluster 1 regions include right precentral gyrus, right middle frontal gyrus, and right inferior frontal gyrus (pars opercularis and pars triangularis). Cluster 2 regions include left postcentral gyrus and left supramarginal gyrus
Figure 3
Figure 3
Right view showing location of the right SFG (black circle) and a significant cluster (0, −72, 52) where ME/CFS showed greater connectivity than HC to a 328 voxel cluster including precuneus and right postcentral gyrus (i.e., primary somatosensory cortex).
See this image and copyright information in PMC

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