Task-related cerebral blood flow changes in ME/CFS

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Cerebral blood flow in associated with memory, goal-oriented attention, and visual function was differentially associated with recovery from fatigue in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterised by often disabling fatigue lasting for more than six months, accompanied by numerous somatic symptoms, affecting nearly 0.5% of the general population write researchers led by Roland Straud at the department of medicine, University of Florida College of Medicine, Gainesville.

They write: “Although multiple biological and psychological mechanisms for ME/CFS have been investigated, little is known about the underlying neural underpinnings that initiate and sustain chronic fatigue. ME/CFS has been linked to aberrant autonomic nervous system activity involving the hypothalamic-pituitary-adrenal axis; pain-related pathways; and abnormal brain activity in parietal, cingulate, inferior frontal and superior temporal cortices, and the cerebellum.

“Similar abnormalities have been reported in individuals with fatigue related to multiple sclerosis, Parkinson’s disease and cancer. These brain regions are known to contribute to cognitive functioning, including working memory.

“Previous functional imaging studies of resting state cerebral blood flow (CBF) have reported inconsistent findings in ME/CFS patients. Using single-photon emission computed tomography (SPECT), Xenon-Computed Tomography, and arterial spin labelling (ASL) MRI, several studies demonstrated global cerebral hypoperfusion in ME/CFS patients, whereas other investigations found no CBF abnormalities. Additionally, neuroimaging studies have been used to inform the neurobiological underpinnings of task related fatigue, (compared to healthy controls (HC) ME/CFS patients have shown significantly increased brain activity in several cortical and subcortical regions during motor, auditory, and working memory tasks).

“Similar to several other investigations of ME/CFS patientsmthese studies revealed positive relationships of fatigue with the activation of fronto-parietal, cingulate, temporal, and cerebellar brain areas.

“We used ASL to study the dynamics of regional CBF (rCBF) changes related to mental fatigue in ME/CFS patients. We hypothesised that rCBF changes during a fatiguing cognitive task would differ between ME/CFS and HC participants in areas related to attention and memory. Because previous work from our group suggested that ME/CFS was associated with alterations in functional connectivity (FC) in a number of brain areas, we postulated that the same brain regions would be associated with fatigue related blood flow abnormalities during the performance of a cognitive task. If confirmed, such findings would improve our understanding of the neurobiological basis of task related worsening of fatigue in ME/CFS and could serve as biomarkers for patients diagnosed with this condition.”

Abstract
Purpose: One hallmark of chronic fatigue syndrome (ME/CFS) is task related worsening of fatigue. Global brain hypoperfusion, abnormal regional activation, and altered functional connectivity of brain areas associated with cognition and memory have been reported but remain controversial.
Methods: We enrolled 17 female participants fulfilling the CDC Criteria for ME/CFS and 16 matched healthy controls (HC). Using a 3T-Phillips Achieva MRI-scanner, pseudo-continuous arterial spin-labeling (pCASL), was used to study the dynamics of regional cerebral blood flow (rCBF) and their relationship to mental fatigue in ME/CFS patients and HC during a demanding cognitive task, i.e. modified Paced-Auditory-Serial-Addition-Testing (PASAT).
Results: ME/CFS subjects reported more fatigue than HC at baseline (p < .01). Global brain perfusion of ME/CFS and HC subjects was similar at rest. The PASAT resulted in significantly increased fatigue in ME/CFS participants and HC. Although not different between groups, overall CBF significantly increased over the first 3 min of the PASAT and then decreased thereafter. Regional CBF (rCBF) changes were significantly different between groups during the post-task recovery period. Whereas improvement of fatigue of ME/CFS subjects was associated with decreased rCBF in both superior temporal gyri (STG), precuneus, and fusiform gyrus, it was associated with increased rCBF in the same areas in HC.
Conclusions: Our results suggest that ME/CFS is associated with normal global CBF at rest and during a strenuous task (PASAT); however rCBF of several brain regions associated with memory, goal-oriented attention, and visual function was differentially associated with recovery from fatigue in ME/CFS patients and HC.

Authors
Roland Staud, Jeff Boissoneault, Jason G Craggs, Song Lai, Michael E Robinson

Fatigue abstract

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