Tag: neuropathology

Microstructural alterations in brain tissue of ME/CFS and long COVID using diffusion tensor imaging and diffusion kurtosis imaging

Abstract:

Introduction: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and long COVID have overlapping symptoms, such as profound fatigue, cognitive impairment, post-exertional malaise, pain and sleep disturbances that are debilitating and reduce quality of life. While Magnetic Resonance Imaging (MRI) techniques, specifically Diffusion Tensor Imaging (DTI) and Diffusion Kurtosis Imaging (DKI), have been used to investigate brain tissue microstructure in ME/CFS or long COVID, no study has yet combined these modalities to directly compare tissue microstructural differences between people living with ME/CFS and long COVID.

Methods: We recruited 37 ME/CFS participants (Age: 43.56 ± 12.5), 19 long COVID participants (Age: 47.92 ± 13.3), and 27 healthy controls (Age: 37.9 ± 10.4). Data were acquired using a 3 Tesla (3T) Prisma MRI scanner. DTI and DKI metrics were determined using MRtrix v3.0.7 and Designer V2.0 software, respectively. Voxel-based statistical analysis of cohort differences was performed using the Statistical Parametric Mapping (SPM12) toolbox in MATLAB. Correlation analysis was performed between DTI, DKI metrics and clinical measures such as duration of illness, fatigue severity, SF36 domains and WHODAS domains.

Results: Compared with healthy controls, individuals with ME/CFS showed microstructural alterations in the cingulum, supplementary motor areas, and parts of the corpus callosum (all p < 0.05). Long COVID participants demonstrated microstructural alterations in regions including the fusiform and precentral gyrus and in major white matter tracks (all p < 0.05). Direct comparisons between ME/CFS and long COVID revealed difference in the left corona radiata (p = 0.001).

Conclusion: This study identifies distinct tissue microstructural alterations in ME/CFS and long COVID and offers a vital insight into the neuropathological basis of shared symptoms in both conditions.

Source: Singh TB, Marshall-Gradisnik S, Barnden L, Eaton-Fitch N, Huynh TH, Inderyas M, Thapaliya K. Microstructural alterations in brain tissue of ME/CFS and long COVID using diffusion tensor imaging and diffusion kurtosis imaging. Front Med (Lausanne). 2026 Jul 17;13:1824498. doi: 10.3389/fmed.2026.1824498. PMID: 42539798; PMCID: PMC13424405. https://pmc.ncbi.nlm.nih.gov/articles/PMC13424405/ (Full text)

Connectivity between Salience and Default Mode Networks and subcortical nodes distinguishes between two classes of ME/CFS

Abstract:

Myalgic Encephalomyelitis or Chronic Fatigue Syndrome (ME/CFS) is a debilitating disease with unknown pathophysiology. Functional MRI (fMRI) studies in ME/CFS have reported disparate connectivities for the brain salience (SA) and default mode (DMN) networks.

In this study, we acquired resting state and task fMRI with an advanced scanner for improved subject numbers: 24 healthy controls (HC) and 42 ME/CFS patients, 18 meeting International Consensus Criteria (ICC) and 24 meeting Fukuda criteria. We evaluated mean FC between SA and DMN network hub, and subcortical regions known to be involved in ME/CFS. We tested the hypothesis that ME/CFS connectivity differed from HC and the ICC and Fukuda classes are distinguished by different connectivities with HC for different pairs of SA, DMN or subcortical hubs.

During resting state fMRI only two connections differed from HC, both for Fukuda ME/CFS and both with an SA hub. During task fMRI 10 ME/CFS connections differed from HC, 5 for ICC and 5 for Fukuda. None were common to both classes. Eight of the 10 different connections involved an SA hub, six of 10 were weaker in ME/CFS, 4 stronger.

SA connections to the hippocampus and brainstem reticular activation system (RAS) differed from and were stronger than HC. The SA mediates the relative activity of the DMN and executive networks and imbalance will have functional consequences. The RAS and hippocampus modulate cortical activation. Different regulatory connections are consistent with the impaired cognitive performance and sleep-wake cycle of ME/CFS. Different neuropathology is involved in ICC and Fukuda classes.

Source: Su J, Thapaliya K, Eaton-Fitch N, Marshall-Gradisnik SM, Barnden LR. Connectivity between Salience and Default Mode Networks and subcortical nodes distinguishes between two classes of ME/CFS. Brain Connect. 2022 Nov 9. doi: 10.1089/brain.2022.0049. Epub ahead of print. PMID: 36352819. https://pubmed.ncbi.nlm.nih.gov/36352819/