Tag: gray matter volume

SARS-CoV2 evokes structural brain changes resulting in declined executive function

Abstract:

Background: Several research has underlined the multi-system character of COVID-19. Though effects on the Central Nervous System are mainly discussed as disease-specific affections due to the virus’ neurotropism, no comprehensive disease model of COVID-19 exists on a neurofunctional base by now. We aimed to investigate neuroplastic grey- and white matter changes related to COVID-19 and to link these changes to neurocognitive testings leading towards a multi-dimensional disease model.

Methods: Groups of acutely ill COVID-19 patients (n = 16), recovered COVID-19 patients (n = 21) and healthy controls (n = 13) were prospectively included into this study. MR-imaging included T1-weighted sequences for analysis of grey matter using voxel-based morphometry and diffusion-weighted sequences to investigate white matter tracts using probabilistic tractography. Comprehensive neurocognitive testing for verbal and non-verbal domains was performed.

Results: Alterations strongly focused on grey matter of the frontal-basal ganglia-thalamus network and temporal areas, as well as fiber tracts connecting these areas. In acute COVID-19 patients, a decline of grey matter volume was found with an accompanying diminution of white matter tracts. A decline in executive function and especially verbal fluency was found in acute patients, partially persisting in recovered.

Conclusion: Changes in gray matter volume and white matter tracts included mainly areas involved in networks of executive control and language. Deeper understanding of these alterations is necessary especially with respect to long-term impairments, often referred to as ‘Post-COVID’.

Source: Deuter D, Hense K, Kunkel K, Vollmayr J, Schachinger S, Wendl C, Schicho A, Fellner C, Salzberger B, Hitzenbichler F, Zeller J, Vielsmeier V, Dodoo-Schittko F, Schmidt NO, Rosengarth K. SARS-CoV2 evokes structural brain changes resulting in declined executive function. PLoS One. 2024 Mar 12;19(3):e0298837. doi: 10.1371/journal.pone.0298837. PMID: 38470899; PMCID: PMC10931481. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10931481/ (Full text)

Cortical Grey matter volume depletion links to neurological sequelae in post COVID-19 “long haulers”

Abstract:

Objective: COVID-19 (SARS-CoV-2) has been associated with neurological sequelae even in those patients with mild respiratory symptoms. Patients experiencing cognitive symptoms such as “brain fog” and other neurologic sequelae for 8 or more weeks define “long haulers”. There is limited information regarding damage to grey matter (GM) structures occurring in COVID-19 “long haulers”. Advanced imaging techniques can quantify brain volume depletions related to COVID-19 infection which is important as conventional Brain MRI often fails to identify disease correlates. 3-dimensional voxel-based morphometry (3D VBM) analyzes, segments and quantifies key brain volumes allowing comparisons between COVID-19 “long haulers” and normative data drawn from healthy controls, with values based on percentages of intracranial volume.

Methods: This is a retrospective single center study which analyzed 24 consecutive COVID-19 infected patients with long term neurologic symptoms. Each patient underwent Brain MRI with 3D VBM at median time of 85 days following laboratory confirmation. All patients had relatively mild respiratory symptoms not requiring oxygen supplementation, hospitalization, or assisted ventilation. 3D VBM was obtained for whole brain and forebrain parenchyma, cortical grey matter (CGM), hippocampus, and thalamus.

Results: The results demonstrate a statistically significant depletion of CGM volume in 24 COVID-19 infected patients. Reduced CGM volume likely influences their long term neurological sequelae and may impair post COVID-19 patient’s quality of life and productivity.

Conclusion: This study contributes to understanding effects of COVID-19 infection on patient’s neurocognitive and neurological function, with potential for producing serious long term personal and economic consequences, and ongoing challenges to public health systems.

Source: Rothstein TL. Cortical Grey matter volume depletion links to neurological sequelae in post COVID-19 “long haulers”. BMC Neurol. 2023 Jan 17;23(1):22. doi: 10.1186/s12883-023-03049-1. PMID: 36647063; PMCID: PMC9843113. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9843113/ (Full text)

Larger gray matter volumes in neuropsychiatric long-COVID syndrome

Abstract:

Neuropsychiatric symptoms are the most common sequelae of long-COVID. As accumulating evidence suggests an impact of survived SARS-CoV-2-infection on brain physiology, it is necessary to further investigate brain structural changes in relation to course and neuropsychiatric symptom burden in long-COVID. To this end, the present study investigated 3T-MRI scans from long-COVID patients suffering from neuropsychiatric symptoms (n = 30), and healthy controls (n = 20). Whole-brain comparison of gray matter volume (GMV) was conducted by voxel-based morphometry.

To determine whether changes in GMV are predicted by neuropsychiatric symptom burden and/or initial severity of symptoms of COVID-19 and time since onset of COVID-19 stepwise linear regression analysis was performed. Significantly enlarged GMV in long-COVID patients was present in several clusters (spanning fronto-temporal areas, insula, hippocampus, amygdala, basal ganglia, and thalamus in both hemispheres) when compared to controls. Time since onset of COVID-19 was a significant regressor in four of these clusters with an inverse relationship. No associations with clinical symptom burden were found.

GMV alterations in limbic and secondary olfactory areas are present in long-COVID patients and might be dynamic over time. Larger samples and longitudinal data in long-COVID patients are required to further clarify the mediating mechanisms between COVID-19, GMV and neuropsychiatric symptoms.

Source: Besteher B, Machnik M, Troll M, Toepffer A, Zerekidze A, Rocktäschel T, Heller C, Kikinis Z, Brodoehl S, Finke K, Reuken PA, Opel N, Stallmach A, Gaser C, Walter M. Larger gray matter volumes in neuropsychiatric long-COVID syndrome. Psychiatry Res. 2022 Sep 6;317:114836. doi: 10.1016/j.psychres.2022.114836. Epub ahead of print. PMID: 36087363; PMCID: PMC9444315. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9444315/ (Full text)

Volumetric differences in hippocampal subfields and associations with clinical measures in myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients suffer from a cognitive and memory dysfunction. Because the hippocampus plays a key role in both cognition and memory, we tested for volumetric differences in the subfields of the hippocampus in ME/CFS.

We estimated hippocampal subfield volumes for 25 ME/CFS patients who met Fukuda criteria only (ME/CFSFukuda ), 18 ME/CFS patients who met the stricter ICC criteria (ME/CFSICC ), and 25 healthy controls (HC). Group comparisons with HC detected extensive differences in subfield volumes in ME/CFSICC but not in ME/CFSFukuda . ME/CFSICC patients had significantly larger volume in the left subiculum head (p < 0.001), left presubiculum head (p = 0.0020), and left fimbria (p = 0.004).

Correlations of hippocampus subfield volumes with clinical measures were stronger in ME/CFSICC than in ME/CFSFukuda patients. In ME/CFSFukuda patients, we detected positive correlations between fatigue and hippocampus subfield volumes and a negative correlation between sleep disturbance score and the right CA1 body volume.

In ME/CFSICC patients, we detected a strong negative relationship between fatigue and left hippocampus tail volume. Strong negative relationships were also detected between pain and SF36 physical scores and two hippocampal subfield volumes (left: GC-ML-DG head and CA4 head).

Our study demonstrated that volumetric differences in hippocampal subfields have strong statistical inference for patients meeting the ME/CFSICC case definition and confirms hippocampal involvement in the cognitive and memory problems of ME/CFSICC patients.

Source: Thapaliya K, Staines D, Marshall-Gradisnik S, Su J, Barnden L. Volumetric differences in hippocampal subfields and associations with clinical measures in myalgic encephalomyelitis/chronic fatigue syndrome. J Neurosci Res. 2022 Mar 31. doi: 10.1002/jnr.25048. Epub ahead of print. PMID: 35355311. https://onlinelibrary.wiley.com/doi/10.1002/jnr.25048  (Full study)

MEA Review: Grey and white matter differences in chronic fatigue syndrome

The ME Association of Great Britain has provided an excellent review of a recent study on brain matter abnormalities in ME/CFS patients. The study, Grey and white matter differences in Chronic Fatigue Syndrome – A voxel-based morphometry study, was conducted by Julia Newton’s group at Newcastle University. Below is an excerpt from Dr. Shepherd’s summary of the study. To read a full discussion, along with an excellent overview of brain pathology and the implications of these brain abnormalities, go HERE. You can download the full review as a PDF file.

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Comment from Dr Charles Shepherd, Hon Medical Adviser, ME Association:

This study was carried out in Newcastle by Professor Julia Newton and colleagues – a team who have not only achieved a long and distinguished record in ME/CFS research but also have access to patients who have been very carefully assessed from a clinical point of view. So, the results should be taken seriously.

As has been pointed out in this review, three of the main criticisms of previous neuroimaging studies involving people with ME/CFS is that the numbers involved have often been far too small; there has been a lack of information from other control groups that would be relevant in addition to the use of healthy controls; and that different imaging techniques have been used.  So, not surprisingly, the results are not always consistent.

Despite these caveats, these results clearly add weight to the findings from previous neuroimaging studies describing white matter abnormalities in ME/CFS but also raise the possibility of grey matter involvement in ME/CFS.

There are several possible explanations for these findings but no clear answer has emerged in the paper.  Are they a primary feature of ME/CFS?  Or are they secondary to other factors – e.g. duration of illness, decrease in activity, severity of fatigue – that are related to having ME/CFS?  The only way to find out is through further research into what is clearly an interesting aspect of neuropathology in ME/CFS.

A fully referenced summary of all the key findings from both functional and structural neuroimaging studies in ME/CFS can be found in the Research section of the ME Association ‘An Exploration of the Key Clinical Issues’ available from our online shop.

You can read the rest of this brief summary HERE.

Grey and white matter differences in Chronic Fatigue Syndrome – A voxel-based morphometry study

Abstract:

OBJECTIVE: Investigate global and regional grey and white matter volumes in patients with Chronic Fatigue Syndrome (CFS) using magnetic resonance imaging (MRI) and recent voxel-based morphometry (VBM) methods.

METHODS: Forty-two patients with CFS and thirty healthy volunteers were scanned on a 3-Tesla MRI scanner. Anatomical MRI scans were segmented, normalized and submitted to a VBM analysis using randomisation methods. Group differences were identified in overall segment volumes and voxel-wise in spatially normalized grey matter (GM) and white matter (WM) segments.

RESULTS: Accounting for total intracranial volume, patients had larger GM volume and lower WM volume. The voxel-wise analysis showed increased GM volume in several structures including the amygdala and insula in the patient group. Reductions in WM volume in the patient group were seen primarily in the midbrain, pons and right temporal lobe.

CONCLUSION: Elevated GM volume in CFS is seen in areas related to processing of interoceptive signals and stress. Reduced WM volume in the patient group partially supports earlier findings of WM abnormalities in regions of the midbrain and brainstem.

Source: Finkelmeyer A, He J, Maclachlan L, Watson S, Gallagher P, Newton JL, Blamire AM. Grey and white matter differences in Chronic Fatigue Syndrome – A voxel-based morphometry study. Neuroimage Clin. 2017 Sep 28;17:24-30. doi: 10.1016/j.nicl.2017.09.024. ECollection 2018. https://www.ncbi.nlm.nih.gov/pubmed/29021956