Brains in Space - Knowledge Gaps, Assessment, and Potential Countermeasures

Prolonged spaceflight induces both structural and functional changes in the human brain, which may compromise astronaut health, cognition, and performance. MRI studies have consistently reported an upward brain shift, ventricular enlargement, and cerebrospinal fluid (CSF) redistribution following long-duration missions (Koppelmans et al., 2016). These findings suggest an altered pressure
environment in the cranial cavity (Roberts & Petersen, 2019; Van Ombergen et al., 2019). In addition to these structural changes, functional MRI has revealed spaceflight-induced changes in brain connectivity, with some modulations persisting for up to eight months after return to Earth (Jillings et al., 2023). Key regions such as the posterior cingulate cortex and thalamus show lasting reductions
in global connectivity, while the angular gyrus exhibits sustained increases, possibly reflecting sensorimotor recalibration and altered spatial orientation. Other areas, such as the insular cortex, demonstrate reversible changes, suggesting flexible adaptation in salience and interoceptive processing networks (Wuyts et al., 2025). Functional MRI has revealed decreased connectivity of visual cortical areas when participants perform a working memory task (Salazar et al., 2023), as well as evidence for compensatory recruitment of visual and somatosensory cortices when participants receive vestibular stimulation (Hupfeld et al., 2022).

These cerebral adaptations should be interpreted within the context of substantially elevated radiation, altered gravity, and the associated changes in afferent sensory inputs, prolonged isolation and confinement, limited recreational activity, and the constant awareness of the hostile environment (real and perceived risk). The headward fluid redistribution in weightlessness is suspected to mildly and persistently increase intracranial filling and/or pressure (ICP), reduce the translaminar cribrosa pressure gradient, and impair glymphatic clearance (Lawley et al., 2017; Mathieu et al., 2017; Seidler et al., 2024a; Wostyn & De Deyn, 2018). Additional contributors may include elevated CO₂, dietary composition, radiation exposure, and in-flight resistance exercise (Lee et al., 2020; J. Ong et al.,
2023). However, reliable in-flight monitoring of ICP remains elusive, and while non-invasive estimates exist, gold standard measurements such as lumbar puncture or ventriculostomy remain impractical during missions. Thus, most data are acquired post-flight, limiting insights into in-mission dynamics and individual variability (Stern et al., 2023).

Understanding how these environmental and physiological stressors influence cerebral structure and function is critical. While many findings to date stem from ~6-month missions aboard the International Space Station (ISS), future interplanetary travel will expose astronauts to longer mission durations, isolation, and limited communication and medical support. This highlights the importance of
advancing brain health monitoring, identifying early indicators of dysfunction, and implementing effective countermeasures.

To address this challenge, the Brains in Space conference convened NASA medical and behavioral operations personnel, international researchers, and industry leaders. The goal was to align operational needs with emerging technologies in brain assessment and stimulation. The following sections summarize current risks and priorities in medical and psychological domains, before highlighting new approaches to brain monitoring and intervention that may support crew health and performance during long-duration exploration missions.