Neural consequences of post-exertion malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract

Post exertion malaise is one of the most debilitating aspects of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, yet the neurobiological consequences are largely unexplored. The objective of the study was to determine the neural consequences of acute exercise using functional brain imaging. Fifteen female Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients and 15 healthy female controls completed 30min of submaximal exercise (70% of peak heart rate) on a cycle ergometer. Symptom assessments (e.g. fatigue, pain, mood) and brain imaging data were collected one week prior to and 24h following exercise. Functional brain images were obtained during performance of: 1) a fatiguing cognitive task - the Paced Auditory Serial Addition Task, 2) a non-fatiguing cognitive task - simple number recognition, and 3) a non-fatiguing motor task - finger tapping. Symptom and exercise data were analyzed using independent samples t-tests. Cognitive performance data were analyzed using mixed-model analysis of variance with repeated measures. Brain responses to fatiguing and non-fatiguing tasks were analyzed using linear mixed effects with cluster-wise (101-voxels) alpha of 0.05. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients reported large symptom changes compared to controls (effect size ≥0.8, p<0.05). Patients and controls had similar physiological responses to exercise (p>0.05). However, patients exercised at significantly lower Watts and reported greater exertion and leg muscle pain (p<0.05). For cognitive performance, a significant Group by Time interaction (p<0.05), demonstrated pre- to post-exercise improvements for controls and worsening for patients. Brain responses to finger tapping did not differ between groups at either time point. During number recognition, controls exhibited greater brain activity (p<0.05) in the posterior cingulate cortex, but only for the pre-exercise scan. For the Paced Serial Auditory Addition Task, there was a significant Group by Time interaction (p<0.05) with patients exhibiting increased brain activity from pre- to post-exercise compared to controls bilaterally for inferior and superior parietal and cingulate cortices. Changes in brain activity were significantly related to symptoms for patients (p<0.05). Acute exercise exacerbated symptoms, impaired cognitive performance and affected brain function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients. These converging results, linking symptom exacerbation with brain function, provide objective evidence of the detrimental neurophysiological effects of post-exertion malaise.

Task related cerebral blood flow changes of patients with chronic fatigue syndrome: an arterial spin labeling study

“…Additionally, the PASAT has good psychometric properties including high levels of internal consistency and test-retest reliability [34]. Moreover, it has been previously used as a cognitive challenge during functional brain imaging of fatigue [27,28]. …”

“…The sample size for this study was determined based on previous studies of functional brain abnormalities in ME/CFS [22,23,27,28]. These studies have indicated statistically large differences between HC and ME/CFS patients (e.g., Cohen’s d of ~1 in CBF between affected and unaffected individuals).…”

“…Additionally, neuroimaging studies have been used to inform the neurobiological underpinnings of task related fatigue, i.e. 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 [27,28]. Similar to several other investigations of ME/CFS patients [5,29] these studies revealed positive relationships of fatigue with the activation of fronto-parietal, cingulate, temporal, and cerebellar brain areas.…”

Dutch Health Council Advisory Report on Myalgic Encephalomyelitis and Chronic Fatigue Syndrome: Taking the Wrong Turn

“…Cognitive deficits, e.g., impairments in information processing speed, (working) memory, reaction time, and sustained attention, “can be identified if appropriate measures are used” [44]. Post-exertional “malaise” can be assessed objectively by comparing performance indicators (maximum workload, maximum oxygen uptake, anaerobic threshold and corresponding oxygen uptake) of two cardiopulmonary exercise tests with 24 h in-between [45] and comparing cognitive performance before and after a cardiopulmonary exercise test [46]. Orthostatic intolerance can be reflected by postural orthostatic tachycardia and instantaneous/delayed orthostatic hypotension during tilt table or active standing tests [47,48], and/or disequilibrium established by neurological tests, e.g., tandem gait test, standing on one leg test, and the Romberg test [49].…”

An Accurate Diagnosis of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome requires strict Clinical Case definitions and Objective Test Methods

“…between post-exertional malaise and the effect of exercise on the exercise capacity [41] and cognitive test scores [54], between orthostatic intolerance and tilt table test results [55], and between cognitive deficits and cognitive test performance during orthostatic stress [56].…”