Tag: neurochemicals

Altered brain tissue microstructure and neurochemical profiles in long COVID and recovered COVID-19 individuals: A multimodal MRI study

Abstract:

Background: Diverse neurological symptoms are experienced by long COVID and COVID-19 recovered individuals. However, the long-term effects of SARS-CoV-2 in the brain of both groups are underexplored. This study aimed to investigate changes in tissue microstructural and brain neurochemical levels in long COVID and recovered COVID-19 patients compared to healthy controls.

Methods: We recruited 47 participants (long COVID = 19, COVID-recovered healthy controls = 12, and healthy controls without COVID-19 infection = 16) who underwent 3T MRI scans. We acquired T1 and T2 weighted images to assess myelin signal, diffusion weighted images to assess tissue microstructure, and magnetic resonance spectroscopy data to estimate brain neurochemical levels.

Findings: Our multimodal MRI study showed altered T1w/T2w signal between long COVID vs COVID-recovered-healthy controls, long COVID vs healthy controls, and COVID-recovered-healthy controls vs healthy controls. Furthermore, T1w/T2w signal intensity was significantly correlated with physical and cognitive function. Diffusion weighted imaging also showed altered tissue microstructure in these three group comparisons. However, brain neurochemicals were only significantly different between long COVID vs COVID-recovered-healthy controls.

Interpretation: This is one of the first studies to report different myelin signal and brain neurochemical changes between long COVID, COVID-recovered-healthy controls, and healthy controls without SARS-CoV-2 infection. These brain changes provide compelling evidence for the long-term effects of SARS-CoV-2 on brain function.

Source: Thapaliya K, Marshall-Gradisnik S, Inderyas M, Barnden L. Altered brain tissue microstructure and neurochemical profiles in long COVID and recovered COVID-19 individuals: A multimodal MRI study. Brain Behav Immun Health. 2025 Nov 25;50:101142. doi: 10.1016/j.bbih.2025.101142. PMID: 41404601; PMCID: PMC12704066. https://pmc.ncbi.nlm.nih.gov/articles/PMC12704066/ (Full text)

Imbalanced Brain Neurochemicals in long COVID and ME/CFS: A Preliminary Study using MRI

Abstract:

Purpose: Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) patients experience multiple complex symptoms, potentially linked to imbalances in brain neurochemicals. This study aims to measure brain neurochemical levels in long COVID and ME/CFS patients as well as healthy controls to investigate associations with severity measures.

Methods: Magnetic resonance spectroscopy (MRS) data was acquired with a 3T Prisma MRI scanner. We measured absolute levels of brain neurochemicals in the posterior cingulate cortex in long COVID (n=17), ME/CFS (n=17), and healthy controls (n=10) using Osprey software. The statistical analyses were performed using SPSS version 29. Age and sex were included as nuisance covariates.

Results: Glutamate levels were significantly higher in long COVID (p=0.02) and ME/CFS (p=0.017) than in healthy controls. No significant difference was found between the two patient cohorts. Additionally, N-acetyl-aspartate levels were significantly higher in long COVID patients (p=0.012). Importantly, brain neurochemical levels were associated with self-reported severity measures in long COVID and ME/CFS.

Conclusion: Our study identified significantly elevated Glutamate and N-acetyl-aspartate levels in long COVID and ME/CFS patients compared with healthy controls. No significant differences in brain neurochemicals were observed between the two patient cohorts, suggesting a potential overlap in their underlying pathology. These findings suggest that imbalanced neurochemicals contribute to the complex symptoms experienced by long COVID and ME/CFS patients.

Source: Thapaliya K, Marshall-Gradisnik S, Eaton-Fitch N, Eftekhari Z, Inderyas M, Barnden L. Imbalanced Brain Neurochemicals in long COVID and ME/CFS: A Preliminary Study using MRI. Am J Med. 2024 Apr 6:S0002-9343(24)00216-X. doi: 10.1016/j.amjmed.2024.04.007. Epub ahead of print. PMID: 38588934. https://www.sciencedirect.com/science/article/pii/S000293432400216X (Full text)

Neurochemical abnormalities in chronic fatigue syndrome: a pilot magnetic resonance spectroscopy study at 7 Tesla

Abstract:

Rationale: Chronic fatigue syndrome (CFS) is a common and burdensome illness with a poorly understood pathophysiology, though many of the characteristic symptoms are likely to be of brain origin. The use of high-field proton magnetic resonance spectroscopy (MRS) enables the detection of a range of brain neurochemicals relevant to aetiological processes that have been linked to CFS, for example, oxidative stress and mitochondrial dysfunction.

Methods: We studied 22 CFS patients and 13 healthy controls who underwent MRS scanning at 7 T with a voxel placed in the anterior cingulate cortex. Neurometabolite concentrations were calculated using the unsuppressed water signal as a reference.

Results: Compared to controls, CFS patients had lowered levels of glutathione, total creatine and myo-inositol in anterior cingulate cortex. However, when using N-acetylaspartate as a reference metabolite, only myo-inositol levels continued to be significantly lower in CFS participants.

Conclusions: The changes in glutathione and creatine are consistent with the presence of oxidative and energetic stress in CFS patients and are potentially remediable by nutritional intervention. A reduction in myo-inositol would be consistent with glial dysfunction. However, the relationship of the neurochemical abnormalities to the causation of CFS remains to be established, and the current findings require prospective replication in a larger sample.

Source: Godlewska BR, Williams S, Emir UE, Chen C, Sharpley AL, Goncalves AJ, Andersson MI, Clarke W, Angus B, Cowen PJ. Neurochemical abnormalities in chronic fatigue syndrome: a pilot magnetic resonance spectroscopy study at 7 Tesla. Psychopharmacology (Berl). 2021 Oct 5. doi: 10.1007/s00213-021-05986-6. Epub ahead of print. PMID: 34609538. https://pubmed.ncbi.nlm.nih.gov/34609538/