Predicting Potential Treatment Targets for Fatigue in Chronic Fatigue Syndrome Using Thalamic Seeding

Chronic fatigue syndrome (CFS) is a neurological disorder. Functional connectivity (FC) abnormalities have been implicated in fatigue symptoms, but candidate cortical targets for non-invasive brain stimulation (NIBS) remain unclear.

We recruited 100 CFS patients and 100 healthy controls (HC) and performed bilateral thalamic seeding to generate FC maps. Two approaches were used to identify candidate stimulation targets: normative analysis based on a public dataset of 1000 healthy individuals and individual analysis based on subject-specific FC patterns. FC peaks were evaluated at both vertex and sphere levels and examined in relation to fatigue severity measured by the 14-item Fatigue Scale (FS14). Finite element analysis (FEA) was used to estimate cortical regions potentially influenced by NIBS. In an additional longitudinal dataset of 35 CFS patients undergoing one month of Tai Chi exercise, we examined associations between exercise-induced FC changes within these regions and changes in fatigue severity.

Normative analysis identified a negative FC peak in the left lateral occipital cortex (MNI: -51.0, -77.5, 7.0), near the PO7 electrode, whose FC values were associated with both fatigue severity and exercise-related changes in fatigue. In contrast, individual analysis revealed substantial spatial variability in peak locations with low overlap across participants and inconsistent associations with fatigue severity.

These findings suggest that thalamic-surface FC alterations are associated with fatigue symptoms in CFS and the normative analysis may provide a practical reference framework for identifying candidate cortical targets for future NIBS studies.