Decreased Connectivity and Increased Blood Oxygenation Level Dependent Complexity in the Default Mode Network in Individuals with Chronic Fatigue Syndrome

Abstract

The chronic fatigue syndrome / myalgic encephalomyelitis (CFS) is a debilitating disease with unknown pathophysiology and no diagnostic test. This study investigated the default mode network (DMN) in order to understand the pathophysiology of CFS and to identify potential biomarkers. Using functional MRI (fMRI) collected from 72 subjects (45 CFS and 27 controls) with a temporal resolution of 0.798s, we evaluated the default mode network using static functional connectivity (FC), dynamic functional connectivity (DFC) and DFC complexity, blood oxygenation level dependent (BOLD) activation maps and complexity of activity. General linear model (GLM) univariate analysis was used for inter group comparison to account for age and gender differences. Hierarchical regression analysis was used to test whether fMRI measures could be used to explain variances of health scores. BOLD signals in the posterior cingulate cortex (PCC), the driving hub in the DMN, were more complex in CFS in both resting state and task (P < 0.05). The FCs between medial prefrontal cortex (mPFC) and both inferior parietal lobules (IPLs) were weaker (P < 0.05) during resting state, while during task mPFC-left IPL and mPFC-PCC were weaker (P < 0.05). The DFCs between the DMN hubs were more complex in CFS (P < 0.05) during task. Each of these differences accounted for 7-11% variability of health scores. This study showed that DMN activity is more complex and less coordinated in CFS, suggesting brain network analysis could be potential used as a diagnostic biomarker for CFS.

Using structural and functional MRI as a neuroimaging technique to investigate chronic fatigue syndrome/myalgic encephalopathy: a systematic review

“…29 In a recent study, Shan et al investigated CFS/ME using the Stroop task and could not find any differences between the groups. 40 However, when they examined the default mode network they found lower functional connectivity between medial prefrontal cortex, left inferior parietal lobule, medial prefrontal cortex and posterior cingulate cortex in CFS/ME. 40 ► Reward and motivation During a reward processing task/gambling task, the CFS/ME group showed significantly reduced activation in the right caudate and right globus pallidus compared with controls.…”

“…23 Shan et al 40 found decreased functional connectivity between the medial prefrontal cortex and both inferior parietal lobules. 40 On the other hand, Kim et al 24 reported an increase in functional connectivity between the posterior parietal cortex and the dorsal anterior cingulate cortex, rostral anterior cingulate cortex, middle temporal cortex and precuneus in participants with CFS/ ME compared with healthy controls. 24 Collectively the findings from rs-fMRI studies suggest dysfunctional connectivity across a number of neural networks in CFS/ME.…”

Neuroimaging characteristics of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a systematic review

“…A SPECT study reported that patients with ME/CFS presented more diffuse and less focal activation patterns than controls when performing the paced auditory serial addition test [19]. We identified 12 task functional MRI studies of ME/CFS [14,16,[20][21][22][23][24][25][26][27][28][29]. Different patterns of blood oxygenation level-dependent (BOLD) signal changes associated with tasks were reported in each article (detailed in SI).…”

“…Different patterns of blood oxygenation level-dependent (BOLD) signal changes associated with tasks were reported in each article (detailed in SI). Of these 12 studies, 10 articles reported that patients with ME/CFS either recruited additional brain regions or had a greater BOLD response than controls for cognitive tasks but with the same performance [16,[20][21][22][23][24][25][27][28][29], although decreased BOLD activity was also reported in specific regions. Two remaining studies tested basal ganglia function [14] and reward sensitivity [26] and observed lower BOLD changes in basal ganglia in gambling tasks [14] and lower BOLD changes in the putamen in low-reward condition gambling task [26].…”

Shared Microglial Mechanisms Underpinning Depression and Fatigue and Their Comorbidities

“…Just a single study tested TSPO binding through PET imaging study in CFS patients and found an increased widespread brain signal for this marker, an promising indicative of microglial activation [132]. Other imaging studies showed disturbed connectivity in prefrontal cortex and frontal networks in these patients (19,20), as well as impaired glutamate levels in this brain area [133,134]. On the other hand, regarding cytokines, several investigators have measured these markers levels in the blood of CFS patients, and interesting associations between IL-1 and other cytokine levels and fatigue symptoms have been reported [24].…”