Altered brain connectivity in Long Covid during cognitive exertion: a pilot study

Abstract

IntroductionDebilitating Long-Covid symptoms occur frequently after SARS-COVID-19 infection.MethodsFunctional 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.ResultsTwo 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.DiscussionMultiple 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.

Subcortical and default mode network connectivity is impaired in myalgic encephalomyelitis/chronic fatigue syndrome

“…Functional MRI was acquired as in Barnden et al (2023) on a 7 T whole-body MRI scanner (Siemens Healthcare, Erlangen, Germany) with a 32-channel coil (Nova MRI Wilmington, NC, United States). The data were acquired sagittally using a multiband echo-planar imaging (EPI) pulse sequence developed at the University of Minnesota (Auerbach et al, 2013) at a multiband factor of 3, repetition time (TR) of 2,000 ms, echo time (TE) of 22.4 ms, a flip angle of 70 o , an interleaved multi-slice mode, an acquisition matrix of 192×192, and a voxel size of 1.25 mm 3 .…”

“…The Stroop task was used in fMRI to investigate concentration and attention difficulties (Barnden et al, 2023). For each task, two colored words were displayed.…”

“…Mean reaction time and accuracy were estimated as in the study by Barnden et al (2023) for each trial for each subject group.…”

“…Finally, the duration of symptoms was assessed according to self-reported data as months and years. Autonomic "respiratory rate" (Resp) was extracted from the power spectra of a pulse oximeter and respiration strap time series recorded during the 7.5 min fMRI (peak frequency and full width of peak at half maximum) as in the study by Barnden et al (2023) (see Table 1). All the demographic and clinical measures of individuals are provided as Supplementary material.…”

“…Abnormal FC in the default mode network (DMN), salience network (SA), and affective networks was reported (Tanaka et al, 2006;Kim et al, 2015;Gay et al, 2016;Shan et al, 2018b;Su et al, 2023) for both the resting state and during cognitive tasks in ME/CFS patients. Lower FC in the intrinsic networks in ME/CFS patients (Boissoneault et al, 2016;Zinn et al, 2016;Manca et al, 2021;Rayhan and Baraniuk, 2021;Barnden et al, 2023;Su et al, 2023) could lead to deficits in executive function, such as memory, information processing speed, learning ability, and overall neurocognition (Menon, 2011). Hence, individual differences in connectivity patterns are important for cognitive and behavioral functions, with the brainstem and the cerebellum being particularly involved in cognitive impairment, motor dysfunction, and the sleep-wake cycle (Song and Zhu, 2021).…”