A MENTALLY demanding task can unravel brain connectivity differences in people with chronic fatigue syndrome and long COVID, according to a new study. Researchers found distinct disruptions in how key brain regions coordinate during cognitive fatigue.
Mapping Brain Changes in Chronic Fatigue Syndrome and Long COVID
Chronic fatigue syndrome, also known as myalgic encephalomyelitis (CFS/ME), is marked by persistent fatigue, post exertional malaise, and cognitive difficulties that are poorly understood biologically. Similar symptoms have emerged in people with long COVID, prompting interest in shared neurological mechanisms. Functional connectivity imaging offers a way to examine how brain regions communicate during rest or mental effort. In this study, researchers used 7 Tesla functional MRI to explore whether patterns of brain connectivity during a demanding task differed between people with chronic fatigue syndrome, people with long COVID and healthy controls.
Stroop Task Imaging Reveals Disrupted Connectivity
The study analysed data from 78 participants, including 32 with chronic fatigue syndrome, 19 with long COVID and 27 healthy controls. All participants completed two rounds of a Stroop colour word task during scanning, one before fatigue developed and one after fatigue had set in. A total of 450 sagittal volumes were acquired and analysed using the CONN toolbox. In healthy controls, functional connectivity increased between subcortical regions from pre to post task, suggesting greater task engagement. In contrast, people with long COVID showed reduced connectivity between the nucleus accumbens and cerebellar vermis during the pre-phase p = 0.02, and increased connectivity between the prefrontal cortex and hippocampus during the post phase p = 0.02. People with chronic fatigue syndrome showed increased connectivity between the left cuneiform nucleus and right medulla p = 0.03. Reduced connectivity between the medulla and hippocampus p = 0.04 and between the nucleus accumbens and vermis p = 0.001 was also observed. Core network connectivity correlated with cognitive symptom severity in both patient groups.
Implications for Clinical Understanding and Care
The findings suggest that chronic fatigue syndrome involves dysregulated brain coordination during cognitive effort, rather than simple underperformance. Reduced dopaminergic hippocampal nucleus accumbens connectivity may help explain impaired motivation and cognition, while altered cerebellar and core network involvement points to potential biomarkers. Clinically, this supports patient reports that mental exertion has neurological consequences and reinforces the importance of pacing and rest. Future research may use these connectivity patterns to guide diagnosis, stratify patients, or evaluate targeted interventions for chronic fatigue syndrome and long COVID.
Reference
Inderyas M et al. Distinct functional connectivity patterns in myalgic encephalomyelitis and long COVID patients during cognitive fatigue: a 7 Tesla task-fMRI study. J Transl Med. 2026;DOI:10.1186/s12967-026-07708-y.
