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Year : 2019  |  Volume : 67  |  Issue : 8  |  Page : 182--187

Current trends and future perspectives of space neuroscience towards preparation for interplanetary missions

Christos A Frantzidis1, Evangelia Kontana2, Aliki Karkala2, Vasilis Nigdelis3, Maria Karagianni3, Christiane M Nday3, Krishnan Ganapathy4, Chrysoula Kourtidou-Papadeli1,  
1 Laboratory of Medical Physics, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece; Greek AeroSpace Medical Association-Space Research (GASMA-SR), Greece
2 Greek AeroSpace Medical Association-Space Research (GASMA-SR), Greek
3 Laboratory of Medical Physics, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
4 Apollo Telemedicine Networking Foundation, Chennai, Tamil Nadu, India

Correspondence Address:
Dr. Christos A Frantzidis
Laboratory of Medical Physics, Medical School, Aristotle University of Thessaloniki, Thessaloniki 54124


This review addresses central nervous system (CNS) physiological changes during inter-planetary missions, specifically sensorimotor processing and sleep disorders. Isolation, confinement and induced stress factors also have a detrimental effect on cognitive and mental well-being, which could jeopardize mission accomplishment. Although countermeasures have been proposed, they mostly focus on cardiovascular and/or musculoskeletal systems. Long-term space flights require optimal cognitive performance of crew members during weightlessness for longer time periods independent of ground support. The present study describes various countermeasures trends in neuroscientific data acquisition and future perspectives of advanced analysis through functional connectivity and graph theory. These could be used to identify early deterioration patterns and evaluate the robustness of countermeasures employed.

How to cite this article:
Frantzidis CA, Kontana E, Karkala A, Nigdelis V, Karagianni M, Nday CM, Ganapathy K, Kourtidou-Papadeli C. Current trends and future perspectives of space neuroscience towards preparation for interplanetary missions.Neurol India 2019;67:182-187

How to cite this URL:
Frantzidis CA, Kontana E, Karkala A, Nigdelis V, Karagianni M, Nday CM, Ganapathy K, Kourtidou-Papadeli C. Current trends and future perspectives of space neuroscience towards preparation for interplanetary missions. Neurol India [serial online] 2019 [cited 2022 Jul 4 ];67:182-187
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Full Text

Space neuroscience investigates the physiology of the central nervous system (CNS) in weightlessness and analogue environments. Information processing is a function of the human body interacting with its physical environment.[1] Earth gravity has formulated cerebral functions related with motion, posture and navigation through a two-dimensional representation. However, weightlessness encountered within the International Space Station (ISS) and during space flights forces the brain to evolve in a three-dimensional (3D) environment. Reference points, due to specific gravitational constraints, do not exist anymore. The latter implies differences in posture and sensorimotor coordination.[2] Weightlessness is combined with living within an extreme—both isolated and confined—environment.[3] Crew members should maintain an optimal status of cognitive functioning for performing complex mental tasks with circadian rhythm alterations.[4] These factors may induce stress, sleep disorders and fatigue—which contribute to detrimental effects on cognitive and mental well-being with the risk of jeopardizing inter-crew relationships.[5] Space neuroscience primarily aims at 1) providing a better understanding of how reduced gravity affects brain functions, and 2) exploring countermeasures to ameliorate the detrimental effects of weightlessness to promote the success of space exploration missions.[6]

 Low Earth Orbit (LEO)

Ground stations can communicate with Low Earth Orbit (LEO) satellites only when the satellite is in their visibility region. Contact communication time could take 5-15 minutes with an average frequency of 6-8 times a day. A full orbit (24 hours earth time) takes 90-110 minutes. Every satellite carries special instruments and the satellite coverage area is defined as a region of the Earth, where the satellite is seen at a minimum predefined elevation angle. Reduced time delay in communication makes scientific applications and communications networking easier.[7]

In LEO, space crews are exposed to high ionizing radiation levels that can lead to severe cellular damage or even late-occurring cancer. To reduce radiation exposure of astronauts, the composition of radiation fields and particle directions needs to be understood.[8]

 Interplanetary Missions

Evolving on Earth has made humans perfectly adapted to its gravity and atmospheric conditions. Leaving the Earth results in degradation of a number of human systems. Long duration stays on the International Space Station (ISS) are accompanied by significant effects on crew's cardiovascular, vestibular and musculoskeletal systems. Bone loss and muscle atrophy occur at 1-3% and 5% per month, respectively. Oxygen consumption is reduced by about 25% after a few weeks in space.

Interplanetary missions raise health issues. These are due to long-term exposure to microgravity, and prolonged stay of unpredictable duration on board a spacecraft without direct contact with Earth. Living in a team with a risk of psychological incompatibility and the impossibility of urgent return to Earth add to the issue. A highly-trained medical person within the crew, diagnostic tools and equipment, psychophysiological support, countermeasures, and provisions for urgent, including surgical, treatment on board are necessary.[9]

Manned planetary missions took place between 1969 and 1972, during the Apollo program when 12 astronauts walked on the moon surface. During the initial Apollo-11 lunar landing mission, the crew remained in the one-sixth G environment of the moon for less than one day, and conducted a single excursion of less than 3 hours, during which they ventured only about 50m from the Lunar Module. Scientific experiments carried out on the Apollo missions provided important information about the moon as well as the solar system. NASA and its international partners are currently focusing on extending the human presence beyond earth orbit in support of human exploration and scientific discovery.[6]

When arriving on Mars, considerable biomechanical alterations may occur. Optimum walking speed may be 30% lower. Peak vertical forces may be reduced by 50%, while stride length, stride time and airborne time may increase. On Mars, half as much energy will be required to travel the equivalent distance on Earth and it will be 65% more economical to run than to walk.[10]

A round-trip Mars journey would require nearly 3 years away from Earth. On a Mars trip, most of the time will be spent on a third of Earth's gravity environment, and either intermittent or continuous artificial gravity should be provided for the transit between planets.[11]

 Ground Based Analogues

Research in the microgravity setting is indispensable to disclose the impact of gravity on biological processes and organisms. At the same time, research in the near-Earth orbit is severely constrained by the limited number of flight opportunities. The term “microgravity” is frequently used as a synonym for “weightlessness” and “zero-G,” which indicates that the G-forces are not actually zero but just “very small”. “True” weightlessness can only be achieved in space.

Ground-based simulators of microgravity are valuable tools for preparing space flight experiments. They also facilitate stand-alone studies and cost-efficient platforms for gravitational research.[12] The main reasons why ground-based analogues are of great importance are as follows:

Not all experiments can be done in flightThe ISS has a limited lifeLimited resources (crew time, funds) are available in flightSignificantly longer times are required to complete studies (multiple flights are needed to achieve the required sample size)ISS may not be the best platform for conducting the studyThe ground-based analogues allow for the selection of the best candidate and countermeasures before testing them in flightThese analogues save time and money as studies can be completed more quickly and less expensively on the ground.[13]

Space flight analogues as used for human research create a situation that produces physiological and behavioural effects on the human body similar to those experienced in spaceflight. The analogue selection should take into consideration either the current ISS operations (Low Earth Orbit) or the future explorations (Moon, Mars).[6]

The notion of space analogues is not new. NASA has used such sites for a long time.

Facilities are located in remote locations with extreme environments. Travel to these destinations can be difficult with little or no opportunity for emergency evacuation once the crew arrive. The goal of these missions is typically field research such as geological, environmental, or marine science. Human research is an adjunct to these missions. Therefore, crew responses to isolation and stress are studied.

In principle, organisms of all evolutionary levels can be used with ground based facilities: sessile organisms like plants or moving/swimming ones (e.g., small animals, protists, or bacteria) and cell cultures.[12] Earth-based analogues to simulate the effects of the space flight environment include the following:

Human models

Bed rest—both with and without head-down tilt—has been extensively used as an earth-bound analogue to study the physiologic effects mimicking those occurring in weightlessness during spaceflight.[14] HDTBR (head down tilt bed rest) has become by far the most commonly used method, especially for longer studies.[15] During HDTBR, a subject lies in a bed that is inclined with the head down (6° in most cases) typically for a period of 1 week, 1 month, or even longer. This causes a cephalic fluid shift and the absolute restriction to the bed replicates immobilization, isolation, and monotony of activities. However, the gravitational and vestibular input remains.[16] Long-duration bed rest is widely employed to simulate the effects of microgravity on various physiological systems, especially for studies of the musculoskeletal and cardiovascular systems. At present, HDTBR with normal volunteers is the most common analogue for microgravity simulation and to test countermeasures for bone loss, muscle and cardiac atrophy, orthostatic intolerance, and reduced muscle strength/exercise capacity. Recent results suggest that the HDT bed rest analogue is less reliable as an analogue for other important physiological problems of long-duration space flight such as radiation hazards [17]Dry immersion involves immersing the subject in thermo-neutral water while being covered in an elastic waterproof fabric to keep the subject dry. By doing so, there is no direct contact with water. Immersion is an adequate space flight alternative, since it mimics several space flight features, such as “supportlessness” (i.e., lack of a supporting structure against the body), centralization of body fluids, confinement, immobilization, and hypokinesia.[16] This technique is not difficult and is also cost effective, but in the control of aircraft models, movements need to overcome force and torque generated by the liquid.[18] Immersion in water proved impractical because remaining in water for more than a day brought on unpleasant consequences. With the dry immersion model, studies of up to 57 days have been conducted [19]Parabolic Flight (PF) or free fall capsule on the ground facility: The aircraft flies parabolic arcs that produce approximately 25 seconds of freefall (0 g) followed by 40 seconds of enhanced force (1.8 g), repeated 30-60 times.[20] The sensation of weightlessness is caused when the aircraft is in free fall, because during that time it does not exert any ground reaction force on its contents. PF consists of gravity transitions, (microgravity, hyper gravity and normal gravity phases) generated during 31 parabolas. An entire flight lasts around 3-3.5 hours. During a PF—especially during the microgravity phase—the vestibular input is largely disturbed. This might cause an incongruity with the normal terrestrial expectations regarding verticality and spatial orientation.[21] A major advantage of parabolic flight is the ready access for investigators and subjects. A disadvantage is that 0 G phases of 25 seconds each (or other hypo-G phases) are interspersed with hyper-G phases. In long duration missions, significant adaptive and compensatory effects take place.

Animal models

A rat model has been developed to simulate on earth some aspects of weightlessness alterations experienced in space, i.e., unloading and fluid shifts. Comparison of data collected from space flight and from the head-down rat suspension model suggests that this model system reproduces many of the physiological alterations induced by space flight. The effects of weightlessness on micromechanical properties of bone tissue were investigated using rat tail suspension. Data from various versions of the rat model are virtually identical for the same parameters; thus, modifications of the model for acute, chronic, or metabolic studies do not alter the results as long as the critical components of the model are maintained, i.e., a cephalad shift of fluids and/or unloading of the rear limbs.[22],[23]

 Sleep and Neurocognitive Performance

Understanding how space flight affects the human brain is essential to future space exploration. Several studies have reported anatomical and biochemical alterations, deterioration of the astronauts' performance and mental health, as well as disturbances in cortical activity and sleep. Important factors contributing to impairments in alertness and performance during space missions,[24] include sleep disturbances and alterations of circadian rhythms, as one night of sleep deprivation could deteriorate motivation, concentration, and increase cortisol levels.[25]

In space and bed rest simulations, there are a number of factors that may influence circadian rhythms and sleep. These include microgravity (gravitational force of 10−4-10−6 G (Newton), light flashes (light-dark cycles of approximately 90 minutes), light exposure (two-thirds of the time), low light intensity (below the threshold of efficiently entraining the human circadian clock), motion sickness, emotional stress, a high work load, an abnormal work/rest schedule,[26] noise,[27] thermal discomfort, muscle pain and confinement.[26]

Polysomnographic recordings and subjective assessment of sleep quality demonstrated a shorter duration of sleep by 27% of the subjects [25] with inconstant structural changes occurring due to intra-sleep wakefulness,[25],[27] more awakenings and decrease in slow wave sleep (SWS), rapid eye movement (REM) sleep by 50% and REM latency, during the flight.[25] Specifically for the N2 sleep in extreme environments, the global networks characteristics and connectivity are impaired.[27] The N2 sleep is referring to the deep sleep stage and is presenting with sleep spindles (frequency range of waves from the electroencephalography signal: 12-14 Hz) and K-complexes (frequency range: 0.5-1.5 Hz).[28] Simultaneous orbital sleep disturbances, with the estimated circadian phase being outside the sleep episode 19% of the time, lead to depression, anxiety, personality changes, and intra-crew conflicts.[25] Returning to earth, sleep latency and REM latency are very short and REM is amplified, particularly during the first sleep recording after landing,[26] although insomnia was reported. Space missions of a short duration demonstrated short sleep patterns and SWS, while the latter increased on long-term missions, with the proportion of REM being within normal intervals.[27]

Reduction in cognitive function is most likely to occur one week before the launch or just prior to leaving space.[29] Deteriorations in performance were often monitored in the transition phases of missions, suggesting a possible impact of stress.[30] A further reduction in flight and a slow recovery after flight were related to circadian and REM sleep disturbances,[26] including decreased response time, increased error, impaired working memory and perception.[25] Use of the emotional Stroop task (presentation of mission-related emotionally loaded stimuli) and the Stroop colour-word task (presentation of emotionally loaded stimuli related to personal concerns) found reductions in executive control of cognitive functions, conflict, clique formation, self- or group-imposed isolation.[3] Supportively, under a simulated long-duration spaceflight environment (SLSE) with rats, their axodendrite and cortical synapses were significantly reduced in number, and the cross-sectional synaptic length and the density of the apoptotic cells were significantly larger.[31]

In humans, diffusion magnetic resonance imaging (dMRI) that measures white matter components has demonstrated spaceflight-associated increase in periventricular white matter hyper-intensities, responsible for impairment in cognitive and motor performance, declines in balance, locomotion, and manual control, as well as cerebrospinal fluid (CSF) redistribution following global and local gray matter tissue shifts. Other displays of neuroimaging include an increased somatosensory cortex volume, decreases in frontal and temporal gray matter volumes, an upward displacement of the brain within the skull and ventricular volume expansion.[32] Thalamic gray matter volume appeared significantly reduced, with consecutive decrease in visual alertness.[25]

Electroencephalography (EEG) combined with low-resolution brain electromagnetic tomography (LORETA) and near infrared spectroscopy (NIRS) demonstrated an increased cortical activity in the Brodmann area 6 and premotor cortex, a decreased activity in the temporal and occipital cortex utilizing the 2000-2350 ms manoeuvre, and an increase in the Brodmann area 9 of the dorsolateral prefrontal cortex [29],[33] after the onset of weightlessness in a parabolic flight. Neural processing in microgravity improved, with reference to the reaction time in answering. Observations on cognitive performance in selected individuals in these environments should not be generalised.[34]

 Sensorimotor Performance

Sensorimotor performance of astronauts appears to worsen during space missions,[27] suggesting disrupted structural connectivity in multiple tracts, expressed as a variety of disorders. A major risk for manned flight is VIIP-Syndrome (visual impairment/intracranial pressure syndrome) due to hypoxic exposure, microgravity and reduced atmospheric pressure. This aggravates the symptoms of hypoxia leading to vision impairment, edema of the visual nerve papilla and increased intracranial pressure. Disruption of the blood brain barrier, upward repositioning of the optic nerves and globe flattening, affect the brain and other neuronal tissues such as the retina and larger nerves such as the optic nerve.[32],[35] Additionally, spaceflight-associated neuro-ocular syndrome is a concern that has affected about one-third of long-duration astronauts.[32] This presents a unilateral or bilateral optic disc edema, globe flattening, choroidal and retinal folds, hyperopic refractive error shifts, and nerve fiber layer infarcts.[36]

More abnormalities include top-down modulation of visual processing, problematic sound localization in binaural hearing and tracking of unpredictable targets.[27] This destruction of the endogenous attentional system implicates sleep deprivation.[25] Processes requiring prefrontal multimodal integration of sensory inputs, such as the visuomotor control and higher-order visuospatial processing, coordination of body posture and body spatial representation with respect to the environment, may be at risk.[32] Sensorimotor areas are activated by non-consciously processed stimuli. The latter integrates interoceptive and exteroceptive signals and is implicated in temporal processing.[37]


A countermeasure is the action that we take to prevent all the changes of the human body induced by the loss of gravity (e.g., fluid loss, loss of muscle tissue, loss of bone mass) when entering the microgravity environment, in order to keep the body healthy with the least of deteriorations.

The main countermeasure types are 1) lower body negative pressure (LBNP), 2) exercise, 3) artificial gravity, and 4) loading suits.[2]

Lower Body Negative Pressure (LBNP) is regarded as a cardiovascular countermeasure, which employs a vacuum tube. It is isolated to the hips and pulls body fluids down to the legs. However, it is extremely uncomfortable.[38]

Exercise countermeasures focus on attenuation of bone and/or muscle loss and at preserving optimal cardiovascular and brain function. They employ resistance or aerobic training. Though successful in maintaining the cardiovascular stability, the results in the musculoskeletal and central nervous system are still not satisfactory.[39]

Artificial gravity, as implemented through human centrifuges, creates a gravitational gradient, which provides loading on the musculoskeletal system at the foot level. This countermeasure may be implemented as a) a short-arm radius, b) centrifugation of a part of the space vehicle, and c) whole vehicle centrifugation, which (i) is the most realistic from an engineering point of view, (ii) is implemented as a rotating module of the spacecraft and thus its negative effect on the vestibular system is minimized, and (iii) implies spinning of the entire vehicle, which involves many unresolved technical issues and a huge energy requirement.[40]

Loading suits are characterized by their low cost and mass. They apply a compressive loading down the body. The “Penguin” allows 70% axial loading during aerobic (treadmill) training and 40 kg loading during walking when combined with specially designed shoes. It results in lower bone mineral density loss at the lumbar vertebrae during space missions. It was also validated in a bed-rest study through a 10 Kg loading for 10 hours and was effective in preserving the size of the soleus muscle. Despite its effectiveness, it is uncomfortable and thermally unviable when worn for the recommended 8 hours. It does not efficiently replicate gravity or provide appropriate body loading. The Gravity Loading Countermeasure Skinsuit (GLCS) utilizes a specialized and tailored material strain for creating gravitational loading, which is not constant at every joint but cumulative.[2]


Although space medicine has studied the cardiovascular and musculoskeletal systems during the spaceflights and simulated microgravity, there is limited knowledge regarding the physiology of the central nervous system in space. It is mainly focused on quantifying the neuro-vestibular, posture, visual and spatial orientation disorders. However, the neural substrates of these changes, in terms of functional and/or structural connectivity, are largely unknown. These need to be investigated towards the preparation of inter-planetary space missions [Figure 1]a.{Figure 1}

Recent advances facilitated the use of electroencephalographic (EEG) data acquisition for providing an unobtrusive and good temporal resolution window of brain functioning [Figure 1]b. Reconstruction of cortical activity overcomes the spatial EEG limitations enabling quantification of the cortical activity during the task performance or resting-state. The latter enables estimation of the cortical functional connectivity during drowsiness and sleep and estimation of neuroplasticity to adapt to novel environments [Figure 1]c (e.g., microgravity).[27]

To sum up, the aforementioned modern neuroscientific tools may boost a better understanding of the microgravity-related disorders and facilitate an evaluation of the countermeasure efficacy. Specifically, the exact quantification of the countermeasure impact on the functional connectivity of cortical resting-state networks would result in development of novel countermeasures (e.g., artificial gravity equipped with aerobic and/or resistance training) for facilitating implementation of long-term interplanetary (e.g., Mars) missions.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


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