Ophthalmic changes in a spaceflight analog are associated with brain functional reorganization

Following long‐duration spaceflight, some astronauts exhibit ophthalmic structural changes referred to as Spaceflight Associated Neuro‐ocular Syndrome (SANS). Optic disc edema is a common sign of SANS. The origin and effects of SANS are not understood as signs of SANS have not manifested in previous spaceflight analog studies. In the current spaceflight analog study, 11 subjects underwent 30 days of strict head down‐tilt bed rest in elevated ambient carbon dioxide (HDBR+CO2). Using functional magnetic resonance imaging (fMRI), we acquired resting‐state fMRI data at 6 time points: before (2), during (2), and after (2) the HDBR+CO2 intervention. Five participants developed optic disc edema during the intervention (SANS subgroup) and 6 did not (NoSANS group). This occurrence allowed us to explore whether development of signs of SANS during the spaceflight analog impacted resting‐state functional connectivity during HDBR+CO2. In light of previous work identifying genetic and biochemical predictors of SANS, we further assessed whether the SANS and NoSANS subgroups exhibited differential patterns of resting‐state functional connectivity prior to the HDBR+CO2 intervention. We found that the SANS and NoSANS subgroups exhibited distinct patterns of resting‐state functional connectivity changes during HDBR+CO2 within visual and vestibular‐related brain networks. The SANS and NoSANS subgroups also exhibited different resting‐state functional connectivity prior to HDBR+CO2 within a visual cortical network and within a large‐scale network of brain areas involved in multisensory integration. We further present associations between functional connectivity within the identified networks and previously identified genetic and biochemical predictors of SANS. Subgroup differences in resting‐state functional connectivity changes may reflect differential patterns of visual and vestibular reweighting as optic disc edema develops during the spaceflight analog. This finding suggests that SANS impacts not only neuro‐ocular structures, but also functional brain organization. Future prospective investigations incorporating sensory assessments are required to determine the functional significance of the observed connectivity differences. We investigated resting‐state functional connectivity (FC) during a spaceflight analog with elevated carbon dioxide. A subset of participants developed optic disc edema, a sign of spaceflight‐associated neuro‐ocular syndrome (SANS) during the spacefli