Correlates of asymmetric venous drainage in resting state functional magnetic resonance imaging data

Abstract Functional magnetic resonance imaging (fMRI) is an indirect technique for measuring cerebral neural activity. It depends on the local cerebral vasculature and perfusion. It has thus been suggested that pathologies and normal variants of the cerebral vasculature can bias conclusions drawn from fMRI. The purpose of this study was to assess whether frequently observed asymmetries of the transverse sinuses are associated with apparent asymmetries of fMRI data timecourses. We re-analysed a publicly available resting state fMRI dataset (n = 135 healthy human subjects included in the main analysis). Voxel-mirrored homotopic connectivity (VMHC) was calculated as a measure of fMRI timecourse symmetry, reflecting the correlation of signal fluctuations in mirroring voxels in both cerebral hemispheres. Transverse sinus (TS) cross-sectional areas were measured in structural MRI data. In the main analysis, we assessed whether VMHC and TS asymmetry exhibited a negative linear association in brain areas near the transverse sinus. This was supplemented by exploratory whole brain analyses, including mapping of subthreshold effects. In the main hypothesis test, VMHC was not significantly associated with TS asymmetry in brain regions close to the transverse sinuses. In the whole brain analyses, VMHC was significantly negatively associated with TS asymmetry in more distant brain areas, and subthreshold effects resembled venous drainage patterns. The results suggest that part of the variance in resting state fMRI signal fluctuations might be explained by asymmetrical venous drainage. Thus, fMRI results might be confounded by the normal variability of the human intracranial venous system. Competing Interest Statement Christian Mathys: consulting and lecturing for Siemens on behalf of the employer (Evangelisches Krankenhaus Oldenburg). The other authors declare that they have no competing interests. Funding Statement This study did not receive any funding. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study is based on data from the Leipzig Study for Mind-Body-Emotion Interactions (LEMON) (Babayan et al., 2019, Sci Data 6, 180308, DOI: 10.1038/sdata.2018.308), publicly available in anonymized form at https://doi.org/10.18112/openneuro.ds000221.v1.0.0. Only the dataset version published under a public domain (CC0) license was used in this analysis. The LEMON study was carried out in accordance with the Declaration of Helsinki, and its study protocol was approved by the ethics committee at the medical faculty of the University of Leipzig (reference number 154/13-ff). As confirmed by the local ethics committee at the medical faculty of the University of Oldenburg, formal approval was not necessary for this secondary data analysis (waiver reference number: 2021-165). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability This study is based on data from the Leipzig Study for Mind-Body-Emotion Interactions (LEMON) (Babayan et al., 2019, Sci Data 6, 180308, DOI: 10.1038/sdata.2018.308), publicly available in anonymized form at https://doi.org/10.18112/openneuro.ds000221.v1.0.0.