Nien-Chu Shih1 and Jeiran Choupan1,2
1Laboratory of Neuro Imaging, USC Mark and Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States, 2NeuroScope Inc., New York, NY, United States
Synopsis
Keywords: Neurofluids, Neurofluids
Motivation: Perivascular space (PVS) is a pial-lined, fluid-filled structure that accompany penetrating arteries or draining veins from the cerebral cortex. PVS occupies a large portion of the cerebral tissue. The effect of PVS on the brain's functional connectivity has not yet been fully investigated.
Goal(s): In particular, our goal was to determine the link between PVS, sleep and brain functional connectivity.
Approach: We utilized the structural MRI and rs-fMRI data from the HCP-Aging dataset.
Results: Results demonstrated that BG-PVS volume fraction was positively associated with FC of the right anterior medial temporal gyrus and a cluster in temporal regions.
Impact: These findings suggest that PVS morphology may reflect changes in neural connectivity involved in memory-related processing and open a new PVS research field (structure to function) for investigation.
Introduction
It has been reported that functional disturbance of default mode network (DMN) appeared in patients with Alzheimer’s disease (AD) and early amyloid beta deposition is associated with abnormal DMN connections in cognitively healthy individuals1,2. In our prior research, we observed a notable reduction in PVS volume fraction in the anterior superior medial temporal lobe of individuals with mild cognitive impairment when compared to cognitively normal aging controls3. In addition, we found that healthy older adults who had better sleep quality had larger PVS volume fraction4. Despite the crucial role played by the brain clearance system in clearing amyloid beta and metabolic waste during sleep5,6 the relationship between PVS, sleep and functional connectivity (FC) in healthy individuals remains unknown. Therefore, we conducted an examination on resting state FC from the Human Connectome Project Aging (HCP-Aging)7 dataset to gain deeper insights into the link between PVS and FC in healthy individuals.Methods
Data of 512 healthy participants were utilized from HCP-Aging dataset. We quantified PVS volume fraction in centrum semiovale (CSO) and basal ganglia (BG) from the Enhanced PVS Contrast (EPC) image8. Sleep parameters were evaluated using the self-reported Pittsburgh Sleep Quality Index (PSQI) questionnaire. To investigate the link between sleep, PVS, and FC, we further categorized the participants by sleep quality scores into the following two groups: good sleep (PSQI score<=5, N=273), and poor sleep (PSQI score>5, N=239). Seed-to-voxel analysis using CONN toolbox9 examined the association between PVS volume fraction and the whole-brain FC of brain regions involved in DMN and bilateral anterior medial temporal gyrus (aMTG). Region of interest FC maps were regressed on PVS volume fraction in the general linear model, controlling for age and sex. Voxel threshold p < 0.001 and cluster-level p-FDR <0.05 were used, which were adjusted by FDR for multiple comparisons correction.Results
In all participants, we found that BG-PVS volume fraction was positively associated with FC of the MPFC and a cluster in frontal regions [maximum voxel at MNI coordinates: +6, +12, +66; t(510)= 4.68], including the right superior frontal gyrus and the right supplementary motor cortex and a cluster in temporal regions [maximum voxel at MNI coordinates: +48, +12, -8; t(510)= 4.22], including the right insular cortex and the right temporal pole. After controlling for age and sex, BG-PVS volume fraction was no longer associated with FC of the MPFC. However, BG-PVS volume fraction was still positively associated with FC of the right aMTG and a cluster in temporal regions [maximum voxel at MNI coordinates: +48, +14, -10; t(508)= 4.98], including the right temporal pole and the right insular cortex. However, we didn’t find a significant difference of FC between the poor sleep quality and good sleep quality subgroups. In addition, no association between CSO-PVS and FC was observed.Discussion
The MTG is involved in language and semantic memory processing, visual perception, and multimodal sensory integration. Recent advancements in tractography-based parcellation have pointed out that the aMTG is primarily responsible for sound recognition and semantic retrieval10. A meta-analysis has also highlighted the MTG's involvement in the DMN11. In addition, there is a strong anatomical connectivity between aMTG and the medial temporal lobe, encompassing structures like the hippocampus, lingual gyrus, and fusiform gyrus10. In this study, we found that individuals with larger PVS showed higher aMTG-temporal connectivity. Changes in aMTG-temporal connectivity may represent an alteration in language and memory processing. On the other hand, a previous study showed that the large waves of CSF inflow strongly correlated with changes in the blood-oxygen-level-dependent (BOLD) signals12. However, whether anatomically larger PVS represents higher cerebral blood flow remains unclear. Therefore, in the further study, we will include diffusion and Arterial Spin Labeling to investigate cerebral blood flow in PVS area.Conclusion
This is the first study of the PVS and FC. In this study, we found that BG-PVS volume fraction was positively associated with FC of the right aMTG and a cluster in temporal regions, which is involved in language and memory-related processing. Future studies may learn more from exploring PVS-related FC changes.Acknowledgements
This research was supported by the National Institute of Mental Health, and the National Institute on Aging of the NIH under Award Numbers RF1MH123223, and R01AG070825.References
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