Static and dynamic functional connectivity in patients with chronic fatigue syndrome: use of arterial spin labelling fMRI

Abstract

Studies using arterial spin labelling (ASL) have shown that individuals with chronic fatigue syndrome (CFS) have decreased regional cerebral blood flow, which may be associated with changes in functional neural networks. Indeed, recent studies indicate disruptions in functional connectivity (FC) at rest in chronically fatigued patients including perturbations in static FC (sFC), that is average FC at rest between several brain regions subserving neurocognitive, motor and affect-related networks. Whereas sFC often provides information of functional network reorganization in chronic illnesses, investigations of temporal changes in functional connectivity between multiple brain areas may shed light on the dynamic characteristics of brain network activation associated with such maladies. We used ASL fMRI in 19 patients with CFS and 15 healthy controls (HC) to examine both static and dynamic changes in FC among several a priori selected brain regions during a fatiguing cognitive task. HC showed greater increases than CFS in static FC (sFC) between insula and temporo-occipital structures and between precuneus and thalamus/striatum. Furthermore, inferior frontal gyrus connectivity to cerebellum, occipital and temporal structures declined in HC but increased in CFS. Patients also showed lower dynamic FC (dFC) between hippocampus and right superior parietal lobule. Both sFC and dFC correlated with task-related fatigue increases. These data provide the first evidence that perturbations in static and dynamic FC may underlie chronically fatigued patients' report of task-induced fatigue. Further research will determine whether such changes in sFC and dFC are also characteristic for other fatigued individuals, including patients with chronic pain, cancer and multiple sclerosis.

Keywords: MRI; arterial spin labelling; chronic fatigue; dynamic functional connectivity.

Figure 1

Axial, sagittal, and coronal views (centered at 47, −59, 14) indicating the location of a 211-voxel cluster where the slope of static FC with bilateral insula differed significantly between HC and CFS participants from the beginning to the end of the PASAT. This cluster included right middle temporal gyrus, right superior lateral occipital cortex, and right angular gyrus.

Figure 2

Axial, sagittal, and coronal views (centered at −12, 2, 0) illustrating a 157-voxel cluster including left pallidum, left thalamus, left putamen, left caudate, and left nucleus accumbens where the slope of static FC with precuneus differed significantly between HC and CFS participants from the beginning to the end of the PASAT.

Figure 3

Axial, sagittal, and coronal views (centered at 13, −49, −5) illustrating a 779-voxel cluster where the slope of static FC with inferior frontal gyrus differed significantly between HC and CFS participants from the beginning to the end of the PASAT. Regions included in the cluster were bilateral lingual gyrus, bilateral cerebellum and vermis, bilateral parahippocampal gyrus, and brainstem.

Figure 4

Scatterplot demonstrating the significant correlation between inferior frontal gyrus connectivity with the significant cluster shown in Figure 3 and change in fatigue following PASAT completion (r = 0.53, p = 0.001).

Figure 5

Scatterplot demonstrating the significant correlation between dynamic FC of hippocampus with right superior parietal lobule and change in fatigue following PASAT completion (r = −.49, p = 0.004).