Analyzing Thalamocortical Functional Connectivity Differences in COVID Survivors.
Poster No:
1799
Submission Type:
Abstract Submission
Authors:
Sapna Mishra1, Tapan Gandhi1, Bharat Biswal2
Institutions:
1Indian Institute of Technology Delhi, New Delhi, Delhi, 2New Jersey Institute of Technology, Newark, NJ
First Author:
Co-Author(s):
Introduction:
The long-term neurological impact of COVID-19 has been the subject of intense investigation in the past years. Cognitive symptoms reported by COVID survivors including brain fog, inattention, memory issues, and fatigue may reflect in the functional connectivity patterns of the brain (Li et al. 2023, Hafiz et al. 2022). We hypothesize that the varied range of symptoms in COVID survivor may be linked to abnormalities in the thalamocortical network. Therefore, we conducted this cross-sectional study to investigate the resting state functional connectivity in the thalamocortical networks of COVID-recovered patients (CRPs).
Methods:
We acquired T1-weighted MRI and resting state fMRI scans (TR = 2s, 3.75 x 3.75 x 3 mm3) for 72 (17F, mean age=32.12 years) CRPs and 48 Healthy Controls (11F, mean age=31.87 years). The scans were conducted within six months of recovery from COVID-19 infection. The fMRI scans were pre-processed using SPM12 (www.fil.ion.ucl.ac.uk/spm/) including motion correction, slice time correction, coregistration, segmentation and normalization to MNI space. Further, temporal regression was performed with average white matter and CSF signals to minimize physiological contribution to BOLD. After bandpass filtering (0.01-0.1 Hz), an 8 mm FWHM Gaussian filter was used to smooth the fMRI scans.
To extract the functional connectivity in the thalamocortical network, six thalamic nuclei were selected as seeds, specified using a spherical region of interest (ROI) of radius 8 mm centered at the respective MNI coordinates. The nuclei studied here are the right and left Mediodorsal nuclei (MD), pulvinar nuclei (PUL), and the Ventral lateral nuclei (VL). The BOLD timeseries for each seed were obtained by averaging the voxels within the ROI. The thalamocortical functional connectivity (FC) of a nucleus with all other voxels in the brain was quantified using the Pearson correlation coefficient to generate a whole-brain FC map for each seed. The correlation values were Fisher-z transformed and then compared across the cohorts. For statistical comparison of thalamocortical connectivity between the cohorts, permutation testing was performed using FSL's randomise (fsl.fmrib.ox.ac.uk/fsl) algorithm and multiple comparison errors were corrected using the voxel-based thresholding (pcorr < 0.05).
To extract the functional connectivity in the thalamocortical network, six thalamic nuclei were selected as seeds, specified using a spherical region of interest (ROI) of radius 8 mm centered at the respective MNI coordinates. The nuclei studied here are the right and left Mediodorsal nuclei (MD), pulvinar nuclei (PUL), and the Ventral lateral nuclei (VL). The BOLD timeseries for each seed were obtained by averaging the voxels within the ROI. The thalamocortical functional connectivity (FC) of a nucleus with all other voxels in the brain was quantified using the Pearson correlation coefficient to generate a whole-brain FC map for each seed. The correlation values were Fisher-z transformed and then compared across the cohorts. For statistical comparison of thalamocortical connectivity between the cohorts, permutation testing was performed using FSL's randomise (fsl.fmrib.ox.ac.uk/fsl) algorithm and multiple comparison errors were corrected using the voxel-based thresholding (pcorr < 0.05).
Results:
Upon comparison of the cohorts, it was observed that the CRPs exhibited significant alterations in thalamocortical FC (CRP > HC) at several regions in the brain. With the seeds in the right and left MD nuclei, significant clusters were observed in the left white matter callosal body, left putamen, and left frontal pole (Figure 1). Further, the right lateral occipital cortex, anterior cingulate gyrus, left sub-callosal orbitofrontal cortex, and the right Heschl's gyrus showed enhanced FC with the PUL nuclei in CRPs (Figure 2). We did not observe any significant changes in thalamocortical FC with the right or left VL nuclei.
Conclusions:
The MD nucleus relays the input from the basal ganglia and the limbic system to the prefrontal cortex and prefrontal association areas and is primarily involved in higher cognitive processes including memory and attention (Mitchell et al. 2013). The PUL nuclei connect the visual cortex with higher association areas in the posterior parietal cortex and temporal lobe. The medial PUL nucleus also connects with the cingulate and is implicated in multisensory integration and visual attention regulation (Cappe et al. 2009). Display of abnormal FC in the MD and PUL thalamocortical circuits in COVID survivors may be linked to symptoms like brain fog, memory loss, fatigue, and inattention.
Overall, in this investigation, we observed that vital thalamocortical circuits involved in memory, planning, and attention show abnormal FC in COVID survivors, hinting at possible damage in this network. This can assist in directing future research into the neurological underpinnings of post COVID symptoms.
Overall, in this investigation, we observed that vital thalamocortical circuits involved in memory, planning, and attention show abnormal FC in COVID survivors, hinting at possible damage in this network. This can assist in directing future research into the neurological underpinnings of post COVID symptoms.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s)
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 2
Modeling and Analysis Methods:
fMRI Connectivity and Network Modeling 1
Novel Imaging Acquisition Methods:
BOLD fMRI
Keywords:
Anxiety
Data analysis
FUNCTIONAL MRI
Statistical Methods
Other - Thalamocortical functional connectivity, resting-state fMRI
1|2Indicates the priority used for review
Provide references using author date format
Hafiz, Rakibul. (2022), ‘Assessing functional connectivity differences and work-related fatigue in surviving COVID-negative patients.’ bioRxiv.
Li, Ruili. (2023), ‘Altered intrinsic brain activity and functional connectivity in COVID-19 hospitalized patients at 6-month follow-up,’ BMC Infectious Diseases, 23.1, 521.
Mitchell, Anna S. (2013). ‘What does the mediodorsal thalamus do?’ Frontiers in systems neuroscience vol. 7 no. 37.
Voruz, Philippe. (2022), ‘Functional connectivity underlying cognitive and psychiatric symptoms in post-COVID-19 syndrome: is anosognosia a key determinant?’ Brain Communications, 4.2.