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

Abstract

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.

Impact of different ground-based microgravity models on human sensorimotor system

“…At the same time, a decrease in connectivity at rest after SF in the right insula which is part of the vestibular cortex indicates changes in the integration of neurosensory information: vestibular, visual, and proprioceptive ( Demertzi et al, 2016 ). In a study by McGregor et al (2021a) during 30 days of HDBR + CO 2 , five out of 11 subjects showed a sign of spaceflight-associated neuro-ocular syndrome (SANS)—optic disc edema, that was accompanied by a slowdown in reaction and movement time after exposure when performing a visuomotor adaptation task using a joystick ( Banker et al, 2021 ) and greater visual contributions to balance ( Hupfeld et al, 2020 ). Interestingly, in six subjects without signs of SANS (NoSANS), there was a greater decoupling between the insula and the other regions within the network during the baseline phase, as well as a decrease in connectivity between the right posterior parietal cortex and clusters in bilateral insular cortices during HDBR + CO 2 ( McGregor et al, 2021a ).…”

“…In a study by McGregor et al (2021a) during 30 days of HDBR + CO 2 , five out of 11 subjects showed a sign of spaceflight-associated neuro-ocular syndrome (SANS)—optic disc edema, that was accompanied by a slowdown in reaction and movement time after exposure when performing a visuomotor adaptation task using a joystick ( Banker et al, 2021 ) and greater visual contributions to balance ( Hupfeld et al, 2020 ). Interestingly, in six subjects without signs of SANS (NoSANS), there was a greater decoupling between the insula and the other regions within the network during the baseline phase, as well as a decrease in connectivity between the right posterior parietal cortex and clusters in bilateral insular cortices during HDBR + CO 2 ( McGregor et al, 2021a ). These observations are consistent with the results of Pechenkova et al (2019) , namely, indicating that such a decrease in connectivity may be associated with the theory of central adaptation, which downregulates vestibular input during space flight lessening sensory dissonance.…”

Effects of short-term −30° HDT on contrast sensitivity

“…Headward fluid shift, which is induced by HDT, is assumed to be one of the key factors of SANS (Gibson et al, 2012). In a spaceflight analog study, HDT posture and elevated ambient carbon dioxide induced optic disc edema in 5 of 11 subjects (McGregor et al, 2021). Although carbon dioxide was not elevated in our study, −30° HDT resulted in several symptoms, including piercing pain, blur acid, strain, eye burning, and dizziness.…”

Space Medicine: Inspiring a new generation of physicians

“…It is believed that microgravity mediated cephalad fluid shift is the primary causative factor leading to increased intracranial pressure, however its exact pathophysiology remains unclear 29 30. The effect of spaceflight on brain structure is being investigated, but a connection between SANS and brain structure or function (cognition) is yet to be definitively established 28 31…”

“…SANS is currently the focus of intensive study; it remains unclear whether it could pose a serious risk to participants in future spaceflights of long duration exploration class missions or whether any pre-existing morphological, genetic or physiological factors might alter or help predict and mitigate this risk. The high-priority placed by space agencies in developing countermeasures and diagnosing SANS may lead to many terrestrial benefits including novel non-invasive methods of measuring intracranial pressure thereby allowing us to better diagnose and manage pathologies such as hydrocephalus and idiopathic intracranial hypertension 28 30–34…”