Patients with fibromyalgia (FMS) and long COVID demonstrate "distinct but convergent" disruptions in large-scale brain network dynamics following mild physical exertion, according to findings presented at the recent ISMRM 2026 meeting.
Using 3-tesla functional MRI (fMRI), a team led by Aneurin Kennerly, PhD, of Manchester Metropolitan University in the U.K., identified neural "inefficiency signatures" in both conditions that may help explain the debilitating post-exertional symptoms common to both.
"[Our findings could offer] a potential biomarker for central dysregulation across chronic conditions," the group noted.
FMS and long COVID are both chronic conditions that can manifest as debilitating fatigue, pain, and cognitive dysfunction, all of which may be made worse by even mild physical exertion, Kennerly and colleagues wrote. They explained that "a hallmark of both conditions is an abnormal perception of effort and pain during exercise, which may reflect altered central processing rather than peripheral limitations alone."
fMRI using blood oxygen level-dependent (BOLD) imaging allows clinicians to track brain activity during exercise, particularly in regions involved in interoception, pain modulation, and motor control. Kennerly and colleagues conducted a study that included 18 participants divided into three groups of six (FMS, long COVID, and healthy controls) who underwent 3-tesla fMRI while performing a knee extension exercise; the exams were performed using a whole-brain 2D Gradient Recalled Echo-Echo Planar Imaging (GRE-EPI) sequence. T1-weighted structural images were also acquired.
On the day of imaging, participants completed a questionnaire regarding disease symptoms. The exercise consisted of isometric knee extension with a four-pound sandbag attached to the ankle for 120 to 180 seconds. Patients had a recovery period of 120 seconds.
Study design: During lab visits, participants filled in symptoms-related questionnaires, followed by Maximal Voluntary Contraction estimation. The MRI protocol comprised a T1 structural scan followed by a functional session (whole-brain blood oxygen level dependent, BOLD, measures) divided into 120 seconds of rest, 120 seconds of knee extension, and 120 seconds of recovery.Aneurin Kennerly, PhD, et al, ISMRM
The group found that, during the exercise phase, FMS participants showed "hyperconnectivity between sensorimotor and salience nodes, suggesting central sensitization and over-recruitment of pain-related pathways even under mild load." In contrast, long-COVID patients showed a diffuse connectivity increase across the brain's salience and default mode networks and in its frontoparietal regions -- which the investigators characterized as "compensatory but [metabolically] inefficient recruitment."
The recovery period revealed that healthy controls reestablished baseline modular brain organization within the post-exercise window while both the FMS and long COVID groups did not. Long-COVID participants showed the most persistent disruption, with broadly distributed connectivity remaining elevated throughout recovery -- a pattern consistent with "impaired task–rest switching rather than transient exertion-related activation," the group wrote.
The results suggest that while both conditions demonstrate reduced brain network flexibility and an inability to recover baseline brain states after mild exertion, the underlying mechanisms differ.
The authors plan further research that will track correlations between imaging metrics, perceived exertion scores, and symptom severity to better characterize the brain's reconfiguration efforts in chronic pain and fatigue syndromes.
