Investigation of BOLD signal intensities in long COVID patients using 7T functional MRI, 2026, Inderyas et al

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Investigation of BOLD signal intensities in long COVID patients using 7T functional MRI

Spoiler: Authors

Inderyas, Maira; Thapaliya, Kiran; Marshall-Gradisnik, Sonya; Barnden, Leighton

Abstract
Long COVID is increasingly associated with disruption in brain homeostasis, manifesting as severe neurological dysfunction, brain fog and cognitive impairment. This present study investigated localised cognitive deficits in long COVID patients by examining brain blood oxygenation-level-dependent (BOLD) signal activity using ultra-high-field 7Tesla (7T) task-based functional magnetic resonance imaging (fMRI).

Whole-brain BOLD signal differences were assessed across 19 long COVID patients, and 27 healthy controls (HC) including 12 COVID-recovered (Cov-RHC) and 15 COVID-19-naïve HC (nHC). 225 fMRI volumes were acquired during the Stroop colour-word task. Functional and anatomical images were processed using SPM12 for extracting BOLD signal intensity time course from whole-brain voxels for inferences between cohorts during task-fMRI.

Significantly low BOLD activation in long COVID patients was observed compared to Cov-RHC in the anterior cingulate cortex (p=0.002, cluster size= 650, Z-value=4.67), and the precuneus (p=<0.001, cluster size=1893, Z-value=4.67).

Furthermore, BOLD intensities in precuneus showed a negative association with self-reported pain scores (p=0.040) and the duration of illness (p=0.03) in long COVID patients, suggesting significant correlation between BOLD signal and increasing in duration of illness and pain levels.

No statistically significant BOLD differences were observed for inter-group comparisons between nHC vs. long COVID, and nHC vs. Cov-RHC. Response times to incongruent (p=0.002) and congruent task stimuli (p=0.001) significantly varied between nHC and long COVID cohorts demonstrating overall faster information processing by nHC.

Reduced BOLD signals to ‘core’ brain regions in long COVID imply reduced cognitive control by intrinsic networks that mediate information processing, cognitive and executive functions due to perturbations linked to cerebral blood flow, oxygenation status, and ongoing neuroinflammation.

Web | DOI | PDF | Brain, Behavior, & Immunity - Health | Open Access

 

[DHagen]

Significantly low BOLD activation in long COVID patients was observed compared to Cov-RHC in the anterior cingulate cortex (p=0.002, cluster size= 650, Z-value=4.67), and the precuneus (p=<0.001, cluster size=1893, Z-value=4.67).

No statistically significant BOLD differences were observed for inter-group comparisons between nHC vs. long COVID, and nHC vs. Cov-RHC.

From the paper:

While we expected to see significant BOLD signal differences between COVID-naïve normal HC and long COVID patients (19 long COVID vs 15 nHC), no significant clusters survived the activation cluster threshold. This is an interesting observation that needs to be tested for statistical rigour in larger cohort size. Nonetheless, current results emphasise the complex nature of post-viral fatigue syndromes, including CFS, accounting for brain differences that are so obscure, subtle and heterogeneous in nature to suggest distinct brain compensatory reorganisation in following recovery.

Alternatively, minimal task-relevant circuit recruitment evident from sluggish RTs in long COVID could reflect similar biological dynamics between long COVID and recovered individuals unlike those with no history of COVID-19 infection. A more plausible interpretation of the BOLD differences observed in long COVID and Cov-RHC can be deduced from observations that persistent immune activation leads to potential endothelial dysfunction and vascular leakage, with recovered individuals still reporting cognitive deficits in the absence of active COVID-19 symptoms (Hampshire et al., 2021; Petersen et al., 2023). Widespread fMRI ALFF in COVID-19 survivors suggests COVID-recovered healthy individuals do not achieve 100% recovery (Du et al., 2022). Such subtle differences observed as subtle connectivity differences Cov-RHC demonstrating longer RT (1.825±0.6) than normal HC(1.68±0.5) RT in the present study reinforce earlier evidence from literature.