Brain dynamics of attentional, default-mode and limbic networks are disrupted at rest in post-COVID-19 syndrome

Post-COVID-19 Syndrome (PCS) is characterised by persistent fatigue, cognitive impairments, and affective symptoms, yet its underlying neural mechanisms remain poorly understood. While static neuroimaging studies have identified resting-state connectivity abnormalities in PCS, such approaches fail to capture the brain's dynamic functional organisation. This represents a missed opportunity to understand how alterations in large-scale network interactions may contribute to the fluctuating symptom profile of PCS. Cognitive and emotional processes rely on the brain's capacity to flexibly reconfigure large-scale networks over time; disruptions in this dynamic repertoire may therefore play a role in PCS pathophysiology.

Resting-state fMRI data were acquired from 20 individuals with PCS (mean age = 41.8 years, SD = 9.4) and 20 age- and sex-matched healthy controls (mean age = 40.6 years, SD = 8.1) using a multi-echo sequence. Following denoising with multi-echo independent component analysis, we applied Leading Eigenvector Dynamics Analysis (LEiDA) to identify recurrent patterns of whole-brain phase synchrony. The optimal number of dynamic brain states was determined using the Dunn index. For each state, we quantified probability of occurrence, lifetime, and transition probabilities, and mapped spatial topographies onto canonical functional networks. Group differences were assessed using ANCOVAs controlling for age, sex, and handedness. Exploratory associations with clinical symptoms, cognitive performance, and inflammatory markers were examined using both frequentist and Bayesian approaches.

Five recurrent dynamic brain states were identified. Compared with controls, PCS participants showed reduced probability of occurrence and shorter lifetime of a visual/dorsal attention state, alongside increased probability of a limbic/default mode network (DMN) state. PCS was also characterised by tentative reduced transitions between visual/dorsal attention and frontoparietal-DMN states, and increased transitions from somatomotor/visual states toward the limbic-DMN configuration. Exploratory analyses (uncorrected for multiple comparisons) suggested that greater expression of the limbic-DMN state was associated with lower global cognitive performance (MoCA) and higher serum IL-1β levels, although these associations did not survive correction for multiple comparisons.

PCS is associated with a reorganisation of intrinsic brain dynamics, marked by a shift from externally oriented attentional states toward limbic-DMN configurations and reduced transition flexibility. These findings suggest that PCS may involve alterations in the dynamic balance of large-scale brain systems supporting attention and internally oriented processing. While exploratory, the observed patterns are consistent with a potential link between brain-state dynamics, cognitive function, and inflammatory signalling, and provide a systems-level framework for future studies of post-viral brain dysfunction.