Altered brain connectivity during cognitive exertion in long COVID


Leighton Barnden, Kiran Thapaliya, Natalie Eaton-Fitch, Markus Barth and Sonya Marshall-Gradisnik


Griffith University and University of Queensland, Australia


Frontiers in Neuroscience, 2023 June 22; 17:1182607


ME Research UK with the financial support of the Fred and Joan Davies Bequest

Key points

  • This study was part of a larger research project using magnetic resonance imaging (MRI) to investigate brainstem volume and functional connectivity in people with ME/CFS.
  • Detailed MRI scans were used to investigate communication between different areas of the brain – or functional connectivity – in people with long COVID while undergoing tests of concentration and attention.
  • Connectivity was higher in people with long COVID than in healthy controls for two connections: one linking the brainstem with the midbrain, and the other linking the brainstem with the default mode network.
  • In contrast, a previous study found that connectivity between these regions was weaker in people with ME/CFS.
  • The brainstem is responsible for many vital functions of life (breathing, consciousness, blood pressure, heart rate and sleep). The midbrain is an important connection point between other regions of the brain. The default mode network is active when you are daydreaming or letting your mind wander while you are at rest.
  • Most of the other connections assessed were weaker in people with long COVID than in healthy controls.


Introduction: Debilitating Long-Covid symptoms occur frequently after SARS-COVID-19 infection.

Methods: Functional MRI was acquired in 10 Long Covid (LCov) and 13 healthy controls (HC) with a 7 Tesla scanner during a cognitive (Stroop color-word) task. BOLD time series were computed for 7 salience and 4 default-mode network hubs, 2 hippocampus and 7 brainstem regions (ROIs). Connectivity was characterized by the correlation coefficient between each pair of ROI BOLD time series. We tested for HC versus LCov differences in connectivity between each pair of the 20 regions (ROI-to-ROI) and between each ROI and the rest of the brain (ROI-to-voxel). For LCov, we also performed regressions of ROI-to-ROI connectivity with clinical scores.

Results: Two ROI-to-ROI connectivities differed between HC and LCov. Both involved the brainstem rostral medulla, one connection to the midbrain, another to a DM network hub. Both were stronger in LCov than HC. ROI-to-voxel analysis detected multiple other regions where LCov connectivity differed from HC located in all major lobes. Most, but not all connections, were weaker in LCov than HC. LCov, but not HC connectivity, was correlated with clinical scores for disability and autonomic function and involved brainstem ROI.

Discussion: Multiple connectivity differences and clinical correlations involved brainstem ROIs. Stronger connectivity in LCov between the medulla and midbrain may reflect a compensatory response. This brainstem circuit regulates cortical arousal, autonomic function and the sleep–wake cycle. In contrast, this circuit exhibited weaker connectivity in ME/CFS. LCov connectivity regressions with disability and autonomic scores were consistent with altered brainstem connectivity in LCov.

Verified by MonsterInsights