Neurological complications in microgravity and long duration spaceflight

Abstract

Long-duration spaceflight produces structural, functional, and hemodynamic brain changes driven by microgravity, radiation, elevated CO2, and isolation. Consequences include Spaceflight-Associated Neuro-Ocular Syndrome, vestibular imbalance, orthostatic intolerance, and cognitive disturbance. We consolidate current evidence, present a cerebrovascular physiologic framework, and discuss emerging countermeasures—including lower body negative pressure, artificial gravity, advanced neuromonitoring, and synthetic torpor—needed to safeguard neurological health on exploration-class missions.

Introduction

The brain is responsible for the most crucial and tightly calibrated functions in the human body. It is also the most susceptible to changes in the conditions of the internal and external environment^1–3. Therefore, it is reasonable to expect that the brain will be particularly affected by the vastly different conditions to be encountered in deep space^1–3.

Structural and functional brain changes have been documented in astronauts returning from missions in the International Space Station (ISS), but still little is known about the potential consequences of more prolonged and pronounced exposure to the risk factors that could produce neurological complications during deep space travel^3–7. This article will review those risk factors, the brain changes that have been noted after exposure to microgravity, the neurological problems that may be expected during long space travel, and what preventive strategies might help diminish their impact.

Risk factors for neurological complications in microgravity

The main risk factors for neurological complications in deep space are anticipated to be microgravity, cosmic radiation, increased CO2, confinement and social isolation, and disruption of the circadian rhythm (Fig. 4)^2–5.

Fig. 4. Functional changes.

A Major physiologic and neurological challenges of zero gravity and longer-duration missions beyond Earth, including loss of magnetospheric radiation protection and long-term SANS risk with impact on astronaut visual function. B SANS ocular findings (upper right). Image credit: NASA (public domain). Composite figure prepared by the authors.

Among these factors, microgravity has been the most studied – though our knowledge of the consequences of prolonged exposure to microgravity remains rudimentary. As discussed in the next section, morphological and connectivity changes have been observed with magnetic resonance imaging (MRI) and functional MRI (fMRI) in astronauts returning from missions at the ISS, particularly those lasting 6 months or more^1–4. These brain changes are thought to be primarily related to cephalic fluid shifts because of the absence of the usual fluctuations in intracranial pressure that we experience on Earth with changes in body position (i.e., lower intracranial pressure in erect compared with supine position)⁵. Yet, several other mechanisms may also be at play, including vestibular adaptation and reweighing of sensorimotor networks in response to weightlessness and deprivation of proprioceptive inputs⁶.

Less is known about the effects of cosmic radiation because no human has yet been exposed to the type and intensity of radiation present in deep space. It is estimated that astronauts on a Mars mission may be exposed to radiation levels up to ten times higher than those experienced during missions on the International Space Station⁷. Cosmic radiation includes high-charge, high-energy (HZE) particles with high linear energy transfer, which produce complex biological damage not seen with terrestrial radiation sources⁸. These limitations significantly constrain risk prediction for long-duration missions and highlight uncertainties in modeling radiation-induced neurological injury^7,9,10.

In the ISS the concentration of CO₂ averages 0.5% (vs 0.04% on Earth)¹¹ Though this concentration is much lower than the levels seen in individuals who exhibit symptoms of acute narcosis, persistent exposure to even low degrees of hypercapnia could still be detrimental. Furthermore, it has been suggested that the sensitivity to CO₂-related symptoms (such as headache and mental fogging) may be exacerbated during space missions, perhaps because of an interaction with the effects of microgravity¹². A ground analog study using 6° head-down tilt strict bed rest for 30 days combined with elevated ambient CO₂ has shown widespread changes in functional connectivity (as assessed by serial resting state fMRI) across vestibular, somatosensory, motor and visual centers, with associated reductions in sensorimotor performance¹².

Prolonged confinement and social isolation can negatively affect mental health. In a high-fidelity ground experiment designed to simulate the conditions expected to occur in a mission to Mars, 6 participants were kept confined for 520 days in a 550 m³ pressurized chamber with interconnected habitable modules. There were major differences among the participants in measures of stress, fatigue and depression; some developed severe and protracted psychological symptoms while others tolerated the experiment without negative psychological consequences¹³. Sleep disruption and alterations in the circadian rhythm were common, and they correlated with the degree of individual sedentariness¹⁴ Sleep problems, particularly insomnia, are very prevalent during ISS missions and astronauts report frequent use of sleep-inducing medications¹⁵.

Cerebral changes in microgravity and deep space

Multiple studies have reported morphological and functional brain changes using pre- and post-spaceflight neuroimaging^2,4,16–22. Structural and connectivity alterations have also been documented in studies with brain analogs²³. While the findings across these studies have been variable (due at least in part to differences in measurement techniques)³, they demonstrate that long-duration spaceflights can provoke microstructural, macrostructural and functional modifications in the brain, primarily from prolonged exposure to microgravity.

Structural changes

Cephalad movement of body fluids is thought to play a large role in accumulation of cerebrospinal fluid (CSF) in the head. Measurement of cerebral blood flow (CBF) changes in microgravity remains poorly understood with relation to intracranial pressure (ICP) changes well described physiologically on Earth (Fig. 1). Transcranial Doppler (TCD) is an easy, compact way to measure CBF non-invasively using ultrasound over the temporal bone area of the human skull and it can provide non-invasive information about brain compliance/elastance via waveform and pulsatility and resistance indices (Fig. 2).

Fig. 1. Cerebrovascular relationship of cerebral perfusion pressure (CPP) on the x-axis versus cerebral blood flow (CBF) on the y-axis.

In normal states, cerebrovascular resistance (CVR) varies inversely to maintain CBF across a wide range of CPP values, a process termed cerebrovascular autoregulation (F). In chronic hypertension, this curve is rightward-shifted (F*); in brain injury (BI*), CBF becomes linearly dependent on CPP. The relationship parallels Ohm’s law (V = I×R), where current = CBF and voltage difference = CPP − ICP. Mean arterial pressure (MAP) ≈ 1/3 SBP + 2/3 DBP is measured non-invasively or via arterial line. Figure created by the authors.

Fig. 2. Non-invasive intracranial CBF monitoring via Transcranial Doppler (TCD) of the major intracranial arteries.

R = right; L = left; ACA = anterior cerebral artery; ICA = internal carotid artery; MCA = middle cerebral artery; PCA = posterior cerebral artery; BA = basilar artery; VA = vertebral artery. TCD assessments can be performed on Earth and in microgravity to evaluate vessel patency and to derive non-invasive indicators of the intracranial pressure–volume relationship (elastance/compliance) from waveform analysis. Elevated ICP and altered pressure–volume relationships produce increased Pulsatility Index (Gosling) approaching 2.0 and Resistance Index (Pourcelot) approaching 0.8, with triangular or biphasic waveforms as CPP approaches zero. Figure created by the authors.

Increased volume of the lateral and third ventricles is probably the most consistent finding across studies^{1,2,4,17,18,24}. Cephalad fluid redistribution because of the lack of intracranial pressure fluctuations normally induced by gravity is most likely the major factor responsible for the increase in cerebrospinal fluid volume that occurs over the course of long-duration spaceflight^25,26. Concomitant upward brain shift with twisting of the cerebral aqueduct (that communicates the third with the fourth ventricles) may also contribute to the accumulation of fluid in the lateral and third ventricles, with relative preservation of the volume of the fourth ventricle^1,17,18. Ventricular size improves after return to Earth but may remain abnormal even after 12 months⁴. Fluid redistribution would also explain the observed increase in free water content in frontopolar, temporal and occipital regions^4,17 which has been accompanied by alterations in water diffusivity along and across white matter pathways documented by diffusion tensor imaging (Fig. 3)^16,17,22.

Fig. 3. Zero-gravity and spaceflight-related CNS/brain changes.

(1) Upward cephalad migration of the brain; (2) narrowing of the central sulcus and (3) reduced CSF spaces at the vertex; (4) increased sensorimotor cortex volume (homunculus, shown in pink); (5) widening of the third ventricle and (6) the anterior horn of the lateral ventricle; (7) rotation of the cerebral aqueduct, a critical pathway for CSF pulsations into the foramina of Magendie and Luschka for CSF reabsorption; (8) cephalad migration of the optic chiasm with optic disc edema (shown in Fig. 4); (9) stretching of the pituitary stalk; (10) global reduction of cerebral white matter volume; and (11) increased periventricular white matter hyperintensity volume on MRI. Figure created by the authors.

Functional changes

Neuroimaging studies longitudinally evaluating gray and white matter changes have produced more variable results. Transient focal gray matter volume changes (decrease in orbitofrontal and temporal regions and increase in basal ganglia, pre- and post-central gyri and supplementary motor cortex) have been noted in the context vertical brain shift and increased ventricular volumes^19,22,25. Reversible changes in white matter have also been reported, such as increased white matter volume in cerebellar and corticospinal tracts (which control motor function), the superior longitudinal fasciculus (integrally involved in visual processing), and vestibular pathways (that regulate balance)^16,22. Complex alterations in connectivity across various brain regions have been described with serial fMRI, but understanding the significance of these findings will demand further investigation^20,27 (Figs. 4 and 5).

Fig. 5. Cerebrovascular (CV), metabotropic brain, and cardiovascular physiology in relation to Ohm’s equation.

Image adapted and modified from “Cerebral Autoregulation Large.jpg” by Shieak Tzeng, licensed under CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0/); adaptation and annotation by the authors. Note on figure sources. All figures are original works by the authors except the NASA-sourced SANS image in Fig. 4B (NASA public domain) and the base image in Fig. 5, which is adapted from a CC BY-SA 3.0 licensed source (attributed above). No BioRender assets are used.

It is still unclear whether these structural and functional brain changes represent adaptive or maladaptive responses. Some of these neuroimaging findings have been shown to be associated with neurological symptoms or impairment in neurological functions. For instance, astronauts with greater cerebral changes on MRI had poorer postural control and worse cognitive performance upon return to Earth in the minority of studies that included those clinical assessments^16,17. Most, if not all, of the documented cerebral changes appear to be reversible based on available evidence. However, whether permanent alterations in brain morphology or connections could happen with much longer spaceflights remains unknown. Beyond ventricular enlargement and upward brain shift, long-duration spaceflight appears to affect other compartments involved in brain fluid homeostasis. Recent MRI studies demonstrate changes in visible perivascular spaces, suggesting altered glymphatic and perivascular fluid clearance in microgravity²¹. White matter alterations are also more anatomically specific than previously recognized, with diffusion-based analyses identifying changes in sensorimotor, cerebellar, and association tracts after long-duration missions²². These findings indicate that structural brain adaptation extends beyond cerebrospinal fluid redistribution to include remodeling of white matter architecture and fluid transport pathways, which may influence both neurologic function and post-flight recovery.

Functional and physiologic adaptations further expand the spectrum of cerebral changes in spaceflight. Vestibular and cerebellar systems undergo sensory reweighting in microgravity, with altered neural responses and connectivity patterns^28,29. In parallel, autonomic dysfunction and altered cerebrovascular regulation may impair cerebral autoregulation and contribute to orthostatic intolerance^29,30. Radiation exposure represents an additional concern, as experimental models demonstrate that high-energy particle irradiation can induce persistent cognitive deficits through hippocampal and cortical injury⁹. Emerging data from commercial spaceflight missions such as Inspiration 4 suggest that even short-duration missions may produce measurable neurovestibular and physiologic changes, although detailed neuroimaging correlates remain limited³¹. Together, these mechanisms highlight that neurological risk during long-duration spaceflight is multifactorial, involving structural, functional, hemodynamic, and radiation-related processes.

Spaceflight-associated neuro-ocular syndrome (SANS)

Cerebral changes on neuroimaging have been observed in individuals with spaceflight-associated neuro-ocular syndrome (SANS)^17,32. This ophthalmological complication causes loss of near vision (hyperopic shift) and occurs quite frequently during prolonged space missions^33,34. Ocular morphological correlates include optic disc edema, choroidal folds and nerve layer infarcts on funduscopic examination, and posterior globe flattening on orbital imaging (MRI, optical coherence tomography or ultrasound)^33,34. While vision typically recovers after weeks or months, the ocular changes sometimes subsist³⁵. The presence of optic disc edema and the association of visual changes with vertical brain shift on MRI initially led to the hypothesis that SANS was caused by intracranial hypertension. Yet, astronauts with symptoms of SANS do not have other features of intracranial hypertension (such as headaches, nausea, diplopia or transient visual obscurations) and the ocular findings of SANS are frankly asymmetric, when not strictly unilateral. Moreover, a recent study showed only a modest association between greater peripapillary retinal thickness (indicative of edema) and larger lateral ventricle volume on brain MRI (and indirect measure of increased cerebrospinal fluid pressure) and no association with white matter or total cerebral volumes³⁶. Thus, while the precise pathophysiology of SANS remains unclear, available evidence suggests that SANS is more likely related to a process of intraocular CSF compartmentalization with increase in the local pressure around the optic nerve, rather than intracranial hypertension³⁴. More recent reviews and methodology studies support a multifactorial pathophysiology and highlight the need for standardized ocular measurements in spaceflight research^37,38.

Hemodynamic changes

Lastly, cerebral hemodynamic changes also occur during long-duration spaceflight. Most notably, stagnant and retrograde blood flow in the internal jugular vein have been shown by ultrasound studies conducted aboard the ISS; one astronaut even had thrombosis of the internal jugular vein^39,40. Therefore, venous hypertension with its accompanying effects on glymphatic drainage⁴¹ may contribute to the pathogenesis of neurological complications in deep space.

Brain and neurologic equations

Understanding the quantitative relationships governing cerebrovascular physiology is essential for predicting and monitoring the neurological effects of microgravity described above. These relationships provide a mechanistic framework linking systemic cardiovascular adaptations, intracranial pressure dynamics, and cerebral blood flow regulation. The following equations therefore serve as a physiological foundation for interpreting neuroimaging findings, guiding real-time monitoring strategies, and informing the development of targeted countermeasures for maintaining cerebral perfusion and metabolic homeostasis during long-duration spaceflight.

There are at least 4 important equations for cerebrovascular physiology relevant to Earth and microgravity physiology undergoing research (Fig. 5). The first equation (Eq. 1) is Mean Arterial Pressure (MAP), which is equal to the Pulse Pressure (PP) added to the Diastolic Blood Pressure (DBP). While MAP has different algebraic forms, we find that the simplified one below (Eq. 1) is easiest to remember. Pulse Pressure (Eq. 2) is the Systolic Blood Pressure (SBP) minus the Diastolic Blood Pressure (DBP). Cerebral Perfusion Pressure (Eq. 3) therefore is the forward pressure (MAP) minus the intracranial backpressure (ICP), which is relevant given the cephalad fluid shifts intracranially and potential effects on CPP and CBF. Cerebral Blood Flow (CBF) (Eq. 4) is similar to Ohm’s law (Eq. 5, where I = current or CBF, V is CPP or voltage difference, and R = Resistance is CVR or CerebroVascular Resistance). Validation of Eq. 4 has been performed using non-invasive TCD (CBF) in normal subjects (auto-adjusting CVR variable) and using multimodal software in brain-injured subjects which shows CVR becomes a constant, and thus CPP linearly dependent on MAP. Oxygen Extraction Fraction (OEF) of brain tissue (Eq. 5) is proportional to the Cerebral Metabolic Consumption of Oxygen (CMRO2) divided by the CBF times the O2-carrying capacity of arterial blood (CaO2) (Eq. 6). These equations are important especially for the brain’s metabolic or metabotropic considerations on CBF and energy consumption. For example, the brain’s CMRO2 and OEF (O2 metabolism) are linearly related to core body temperature. For longer spaceflight missions into deeper space (e.g., Mars and beyond) considerations for reducing and controlling body and brain metabolism or torpor will become increasingly relevant. The brain’s metabolism not only varies with temperature but functional activation and CMRO2 (Tables 1 and 2).

Table 1.

Physical characteristics of cerebral compartments relevant to intracranial dynamics in microgravity

Compartment	Elastance (Pa)	Volume at rest (cc)
Arteries	27.3 × 10⁴	30
Arterioles	40.0 × 10⁴	16
Capillaries	44.0 × 10⁴	20
Brain parenchyma	(1.0–10.0) × 10³	1400
Cerebral SAS	8.0 × 10⁴ (estimated)	30
Venules	117.0 × 10⁴	70–80
Veins	(5.0–27.3) × 10⁴	—
Venous sinus	2.6 × 10⁴	13
Spinal SAS / canal	1.0 × 10⁶	90–100

In microgravity, cephalad fluid shifts increase intracranial blood and CSF volumes, promoting venous congestion, reduced buffering capacity, and altered intracranial dynamics. These changes contribute to impaired glymphatic drainage, SANS, and displacement of brain structures. Data adapted from the NASA Human Research Roadmap and related technical reports^48–51.

Table 2.

Brain physiologic parameters relevant to cerebral hemodynamics and CSF dynamics in microgravity

Parameter	Value
Blood density	1050 kg/m³
Blood viscosity	0.004 kg/m·s
Arterial flow (max/min)	1194 / 588 mL/min
Venous flow (max/min)	882 / 630 mL/min
Central venous pressure (CVP)	5–6 seated; 10–12 supine; 15–17 launch; 0–3 in microgravity
Cerebral blood flow	738 mL/min
Gray matter flow	80–100 mL/100 g/min
White matter flow	~50 mL/100 g/min
CSF density	998.2 kg/m³
CSF viscosity	0.001 kg/m·s
CSF production	0.35 mL/min
Brain porosity	0.3
Permeability	0.7 × 10⁻¹⁵ m²
CSF reabsorption resistance	Normal: 16; Hydrocephalus: 88.9
Phase lag	12–13%

Microgravity alters hydrostatic gradients, promoting cephalad fluid shifts, impaired venous outflow, and reduced CSF reabsorption. Data adapted from the NASA Human Research Roadmap and related technical reports^48–51.

Equations

$$\mathrm{Mean\; Arterial\; Pressure}:\mathrm{MAP}=\mathrm{PP}+\mathrm{DBP}$$ 1

Given the cardiovascular adaptations to microgravity, including reduced plasma volume and altered autonomic tone, MAP (Eq. 1) becomes a key upstream determinant of cerebral perfusion under these shifting conditions.

$$\mathrm{Pulse\; Pressure}:\mathrm{PP}=\mathrm{SBP}-\mathrm{DBP}$$ 2

Because PP reflects arterial compliance and stroke volume, changes observed during spaceflight—such as vascular remodeling and decreased preload—may directly influence PP and thus indirectly affect MAP and downstream cerebral hemodynamics.

$$\mathrm{Cerebral\; Perfusion\; Pressure}:\mathrm{CPP}=\mathrm{MAP}-\mathrm{ICP}$$ 3

Given the cephalad fluid shifts described above, the CPP equation (Eq. 3) becomes particularly relevant because even modest increases in ICP may reduce effective cerebral perfusion despite preserved or mildly altered MAP.

$$\mathrm{Cerebral\; Blood\; Flow}:\mathrm{CBF}=\mathrm{CPP}/\mathrm{CVR}(\mathrm{analogous\; to\; Ohm}\mathrm{’}\mathrm{s\; law},\mathrm{I}=\mathrm{V}/\mathrm{R})$$ 4

In the context of altered autoregulation in microgravity or disease states, Eq. 4 highlights how impaired CVR adaptability may render CBF increasingly pressure-passive and dependent on fluctuations in CPP.

$$\mathrm{Oxygen\; Extraction\; Fraction}:\mathrm{OEF}=\mathrm{CMRO}2/(\mathrm{CBF}\times \mathrm{CaO}2)$$ 5

As microgravity and prolonged spaceflight may alter both cerebral metabolism and perfusion, Eq. 5 underscores the compensatory role of OEF in maintaining oxygen delivery when CBF is reduced or redistributed.

$$\mathrm{Arterial\; Oxygen\; Content}:\mathrm{CaO}2=(1.34\times \mathrm{Hb}\times \mathrm{SaO}2)+(0.003\times \mathrm{PaO}2)$$ 6

Given spaceflight-associated changes such as “space anemia” and shifts in oxygenation dynamics, Eq. 6 becomes critical for interpreting how systemic adaptations influence cerebral oxygen delivery and metabolic balance.

Expected neurological complications

In addition to the visual impairment related to SANS (an ophthalmological rather than a neurological complication), astronauts returning from spaceflight missions often have diminished postural balance, reduced manual dexterity, and impaired reaction times and executive function^16,17,42. Balance problems are related to vestibular dysfunction, which can be transiently severe. Changes in various cerebral areas known to contribute to balance control through connections with the peripheral vestibular system have been noted after prolonged spaceflight and the degree of these changes correlates with the severity and duration of the postural imbalance upon return to Earth^16,20. Of note, these central changes may be adaptations to the weightless environment: decreased vestibular input may serve to ameliorate symptoms of space motion sickness during the spaceflight. Yet, once back on Earth this reduction in vestibular afference to the brain causes imbalance and demands reliance on compensatory proprioceptive and visual sensory inputs until readjustment to gravity occurs. Early imbalance in returning astronauts is exacerbated because proprioceptive function also needs time to undergo reprogramming after prolonged exposure to microgravity (deprivation of proprioceptive inputs occurs in the absence of gravity)⁴³. Meanwhile, judgment of subjective visual vertical is also temporarily degraded after long-duration space missions⁴⁴.

Postural imbalance only becomes a problem once space travelers are back on Earth. The same cannot be said of the cognitive and behavioral problems that may manifest themselves during spaceflight. Unfortunately, we do not have enough information about cognitive function during space missions. However, it is unlikely that the impaired performance on tasks of spatial working memory, dual motor tasks, and reaction time tests observed in post-flight assessments^16,17 would not also be present during the spaceflight. Some of the neuroimaging findings discussed in the previous section would be expected to have consequences in fine motor and higher cortical functions. A battery of neurocognitive tests (called Cognition) was specifically developed and validated for use in the high-performing cohort of astronauts⁴⁵. As information on the results of these cognitive testing becomes available, we will better understand the magnitude of the problem.

Any cognitive impairment during long-duration missions will be magnified by behavioral problems that may develop because of confinement and isolation and by the deleterious consequences of insomnia and disruptions of the sleep-wake cycle^15,45. Executive dysfunction is common in individuals with sleep disorders (such as insomnia)⁴⁶ and depression⁴⁷. Thus, multiple factors could contribute to impair the execution of complex cognitive tasks vital to the success of long-duration space missions.

Other non-neurological symptoms, such as fatigue and deconditioning could further affect mental and physical performance in deep space. A list of these possible complications is presented in Table 3.

Table 3.

Neurological and ophthalmological complications associated with spaceflight and potential countermeasures

Neurological complication	Pathophysiology/prevalence in microgravity	Countermeasures
Spaceflight-Associated Neuro-Ocular Syndrome (SANS)	Affects >60% of astronauts; associated with cephalad fluid shift and ocular structural changes	Optical monitoring (fundoscopy, OCT), TCD, LBNP
Neurovestibular / postural imbalance	Altered vestibular input and sensorimotor adaptation in microgravity	Vestibular training devices, adaptation protocols
Orthostatic intolerance	>50% post-flight; impaired autonomic/vascular adaptation	Fluids/salt, compression garments, exercise, midodrine
Neuromuscular deconditioning	Muscle atrophy and reduced motor control	Resistive exercise, motor training
Cognitive / psychosocial effects	Sleep disruption, fatigue, mood and cognitive changes	Sleep optimization, AI monitoring, behavioral strategies

Preventive Strategies: Monitoring and Countermeasures

Preventive strategies for health maintenance in space can be designed to address specific complications (such as the efforts underway to reduce the risks of SANS) or to ameliorate the effects of the main potential mechanisms (e.g., microgravity or radiation). Given our insufficient knowledge on what health problems can be encountered during long sojourns into deep space, the latter strategy appears particularly appealing. Table 3 provides a high-level summary of NASA countermeasures to these major areas of neurological space challenges.

In addition to systemic countermeasures, neurological-specific strategies are increasingly recognized as essential components of risk mitigation in long-duration spaceflight. Vestibular rehabilitation and sensorimotor re-adaptation protocols, including pre-flight adaptation training and post-flight recalibration exercises, may accelerate recovery of balance and spatial orientation. Cognitive countermeasures should incorporate structured neurocognitive monitoring and training using validated tools such as NASA’s Cognition battery, enabling early detection of performance decline and targeted interventions. Neuroprotective strategies are also under investigation, including the use of antioxidants and anti-inflammatory agents to mitigate radiation-induced central nervous system injury, particularly in the context of exposure to high-energy particles.

Advanced neurological monitoring will play a central role in future missions. Techniques such as transcranial Doppler (TCD) allow real-time assessment of cerebral hemodynamics and autoregulation, while electroencephalography (EEG) can provide continuous evaluation of sleep architecture and cognitive states. Measurement of optic nerve sheath diameter offers a non-invasive surrogate for intracranial pressure monitoring, which may be particularly relevant for early detection of SANS-related changes. In parallel, targeted intracranial pressure management strategies, including lower body negative pressure, venous outflow optimization, and potential pharmacologic modulation of CSF dynamics may help mitigate cephalad fluid shifts and their neurological consequences.

Within the NASA Human Research Program framework, these interventions align with a risk-based model that categorizes neurological risks across domains including sensorimotor performance, cognitive function, and neuro-ocular health, emphasizing integrated monitoring and countermeasure development across mission phases^48–52.

Negative pressure applied to the lower body has been proposed to diminish the effects of microgravity on fluid distribution. Early data appear promising. In studies relying on head-down tilt to simulate microgravity, the application of lower body negative pressure induced reductions in estimated intracranial pressure (by non-invasive measures)⁵³ and optic nerve sheath diameter⁵⁴. Application of moderate lower body negative pressure (30 minutes of −25 mmHg) during spaceflight has been shown to reduce jugular vein volume (making it comparable to the volume found in preflight supine position), with associated increases in middle cerebral vein velocity and portal vein cross-sectional area⁴⁰. However, these measurements were only obtained twice during the spaceflight and it is unknown whether frequent application of lower body negative pressure can afford persistent beneficial effects on venous volume and pressure.

Another possible countermeasure against the deleterious effects of prolonged exposure to microgravity could be the use of centrifuge-generated artificial gravity. While multiple potential beneficial effects from the application of artificial gravity have been posited^55,56 its implementation in deep space represents an enormous engineering challenge. Gradual adaptation to the rotation of the centrifuge would be necessary to prevent severe motion sickness⁵⁷

Inducing synthetic torpor through hypothermia is theoretically a very appealing alternative. In a state of torpor, metabolic demands can be considerably reduced: brain oxygen consumption declines by 10% for each degree Celsius below normal (e.g., down to 50% of baseline at 32°C)⁵⁸ Furthermore, based on data from hibernating animals, it has been estimated that humans could reach a minimum metabolic rate of 10%–20% of baseline even while maintaining body temperatures slightly above 30°C⁵⁹. Natural hibernators can go into torpor for months without any major loss of body mass or bone density, despite consuming no food. Torpor protects them from tissue damage by suppressing mechanisms of autophagy and apoptosis⁶⁰ Notably, torpor also generates resistance to radiation injury⁶¹ To make things even more ideal, space travelers undergoing torpor could be kept upright under moderate lower body negative pressure to minimize cephalad fluid shifts. The big problem is that we do not know how to induce synthetic torpor in humans safely or how to unlock our genetic code to allow for the occurrence of natural torpor. Clinical experience with induction of hypothermia (for instance, in survivors of cardiac arrest) is not very informative: those patients require mechanical ventilation, sedation to prevent shivering, artificial nutrition, and very close monitoring to prevent serious complications. The engineering aspects of synthetic torpor induction can be handled⁶² but the biology requires much more investigation⁵⁹.

Shielding of the spacecraft can theoretically protect humans from cosmic radiation. However, shielding has drawbacks because of its added weight and the risk of provoking spallation (fragmentation of particle radiation) that could potentially worsen the effects of cosmic radiation exposure¹⁰. Future advances in engineering might increase the efficiency of shielding, but it is unlikely that shielding alone will be sufficient to eliminate the health risks related to exposure to cosmic radiation during interplanetary missions.

Close monitoring of physiologic parameters will be essential to detect both anticipated and unexpected health changes during long-duration spaceflight. Current capabilities aboard the International Space Station include ultrasound-based vascular assessments, optical coherence tomography for evaluation of SANS, and ambulatory physiologic monitoring such as Holter electrocardiography. These tools reflect ongoing efforts within NASA’s Human Research Program to develop compact, reliable monitoring systems suitable for spaceflight, although significant limitations remain for deep-space missions where real-time ground support is not feasible^40,48–51.

Lastly, we need to learn how to screen and select those individuals at the lowest risk for health problems in deep space. Experience with SANS¹⁷ and long confinement¹³ have already offered proof that there is great variability in the susceptibility to the medical complications that can be encountered during prolonged spaceflight. Genetic, metabolic, endocrine, and behavioral factors may need to be considered in the future to identify ideal candidates for interplanetary missions.

Conclusion

Although our knowledge of the neurological complications in deep space is just incipient, there is already evidence that long-duration spaceflight can produce changes in brain function and morphology. In turn, these changes can result in symptoms that could compromise the physical and mental performance of space travelers. Therefore, much more research needs to be conducted to identify ways to mitigate the risks of the various environmental factors that may imperil brain health in deep space.

Author contributions

GC (Giselle Coelho): Conceived the study, performed the literature review, drafted the manuscript, and contributed to revisions.AR (Alejandro Rabinstein) : Conceived the study, conducted the literature review, drafted the manuscript, contributed to data interpretation, prepared figures, performed technical review, and participated in revisions.WF (William Freeman): Participated in all phases of manuscript production, including conceptualization, drafting, critical revisions, and final approval.All authors read and approved the final version of the manuscript.

Funding

No specific grant or funding was received from any agency in the public, commercial, or not-for-profit sectors for the preparation of this manuscript.

Data availability

No datasets were generated or analysed during the current study.

Competing interests

The authors declare no competing interests.