The comparison of HRV behavior of a healthy astronaut monitored on two long-duration space missions indicates improvement in the process of neural adaptation on the second spaceflight. Results assessed around day 20 after launch indicate that microgravity-induced brain-plasticity or well-being, including life satisfaction, may have contributed to the improved adaptation. During nighttime, sleep improved, and HRV activity co-varying with brain neural activity in the SN accelerated, while decelerating during daytime. HRV endpoints reflecting DMN activity showed no differences between the 2 space missions.
Stimulating environment and brain plasticity
Brain plasticity refers to the capacity of neurons and of neural circuits in the brain to change, structurally and functionally, in response to experience. This property is fundamental for the adaptability of behavior, for learning and memory processes, brain development, and brain repair. The environment can greatly affect brain function. Exposure to stimulating environments has repeatedly been shown to strongly influence brain plasticity. Thus, it is a crucial underlying component of the enormous challenge of space adaptation for astronauts. Neural plasticity can take place at several levels, from synaptic plasticity at the (sub)cellular level to plasticity at the system and network levels [23, 24]. Brain plasticity can be studied with a number of methods, such as electroencephalography (EEG)/evoked potentials (ERPs), structural and functional MRI and transcranial magnetic stimulation (TMS). Herein, it was assessed in a healthy astronaut as changes in sleep performance and HRV behavior in specific frequency regions for interpretation in terms of functional brain networks, as done in previous studies [10, 20, 11, 13].
Our observation of improved sleep should show beneficial consequences of brain adaptation. Indeed, previous investigations reported shorter sleep duration and inadequate sleep quality of astronauts during spaceflight aboard the ISS. These results were attributed to environmental factors, including exposure to microgravity, the 90-min light-dark cycle from the skylight, weightlessness itself, excitement, and workload scheduled by operational demands [25, 26].
Effect of nighttime HRV changes on brain plasticity in space
Despite increased interest in the effect of spaceflight on the human central nervous system (CNS) , not much is known thus far about the functional and morphological effects of microgravity on the human CNS. Previous studies have shown that CNS changes occur during and after spaceflight in the form of neuro-vestibular problems, alterations in cognitive function and sensory perception, problems with motor function, cephalic fluid shift, and psychological disturbances [28, 29]. In the past few years, advances in structural and functional neuroimaging techniques have shown spaceflight-induced neuroplasticity in humans in several brain regions, including the insular cortex, the temporo-parietal junction, and the thalamus, in relation to short- and long-duration spaceflight [1, 2, 4]. However, this investigation did not show any accelerated DMN activity, reflected by Baria’s LF-band  or Chang’s LF-component  between the two spaceflights, either during daytime or nighttime.
We did observe a statistically significant increase in HRV indices that co-vary with SN activity. The SN is linked to the autonomic nervous system function in that both are sensitive to environmental challenges. The SN is mainly centered on the dorsal anterior cingulate, extending into the perigenual anterior cingulate cortex, and orbital fronto-insular cortices, but it also encompasses the limbic and brainstem areas. Relevance to HF-HRV is suggested by the inclusion of known autonomic nervous system control areas in the SN, and by this vagal marker’s putative role in switching between rest and activity and between internal and external focus of attention.
Acceleration of SN activity started with nighttime sleep, suggesting that brain plasticity may have been initiated at night. The sensitivity of vagally-induced heart rate reactions to event salience might further suggest relationships between the SN and HF-HRV, as might the apparent overlap between nodes of the SN and areas related to autonomic control.
Identified as related to HF-HRV, the mPFC is important both as a node in the DMN and in the SN . Anatomically, the mPFC is known to connect to pre-autonomic cell groups in the hypothalamus, periaqueductal gray, and brainstem [31, 32]. If diffuse attention is a major aspect of the functionality of the DMN, then the overlapping membership of the mPFC in the two networks would provide an anatomical site for shifting from DMN activation to SN activation. Some evidence supports the view that DMN activation is switched to SN activation when an interoceptive or environmental stimulus is encoded as significant .
Daytime HRV fluctuations associated with brain resilience in space
Because HRV may be associated with neural structures that are involved in the appraisal of threat and safety, HRV can be considered a potential marker of stress. HRV reflects the status of one’s ongoing adjustment to constantly changing environmental demands. Previously, under stressful environments, such as performing tasks during a spaceflight mission, HRV was found to be decreased . Increased HF-HRV is considered to be associated with a positive mood, absence of negative affect, and an alert readiness to engage with the physical and social environment [34, 35].
Much recent research has found that psychological resilience, including subjective well-being and life satisfaction, is mediated by spontaneous brain activity measured with resting-state functional MRI. Although Waugh et al.  found that when facing with a threat, participants had prolonged changed activity in the insula in response to aversive stimuli, psychological resilience is a complex construct that likely involves different brain functions. Other studies provided evidence that brain resilience is related not only to the insula, but also to the mPFC, OFC, PCC, ACC, and thalamus [37, 38, 39, 40, 41, 42, 43]. In the extant literature, the most consistent brain area related to psychological resilience is the ACC, perhaps because the ACC is associated with many important emotional functions, including motivation, emotion regulation, and attention or adaptation to a novel environment, such as space [44, 45, 46, 47]. Previous investigations on resilience speculated that local activity in the ACC (such as fractional amplitude of low-frequency fluctuations measured by fMRI) would be negatively associated with psychological resilience [8, 47, 48].
The bi-directional connections between heart and brain enunciated by Claude Bernard can be studied by analyzing HRV [5, 49]. Over the past several years, many neuroimaging studies examined the association of HRV endpoints with fluctuations in brain functional connectivity [6, 7, 22, 50, 51]. They confirmed the existence of intimate connections between the different brain regions and HRV endpoints. They also posited that any changes in brain functional networks, which dynamically adjust the structure of their global and local network connectivity, should affect and change HRV activities in their respective frequency bands. “HRV is like a mirror reflecting the strength of activities of humans’ brain and mind” .
Astronauts’ vocation aboard the ISS is also expected to reflect changed activities in the respective HRV frequency bands. Several investigations reported a relation between levels of psychological well-being and HRV [52, 53], which confirmed a statistically significant negative correlation between life satisfaction and HF-HRV activities . Our observation of decreased spectral power of HF-HRV, HF-component, and the series of the HF-band groups, and of lowered r-MSSD, pNN50 and Lorenz plot’s measures (Table 1, left and Fig. 2, left) thus suggests psychological resilience of the astronaut during the second space mission. It likely reflects increased well-being, a feeling of satisfaction or fulfillment during daytime on second compared to the first spaceflight.
Role of biological rhythms in the adaptation to the space environment
Whereas the circadian system plays a key role in the adaptation to a novel environment, such as microgravity in space [7, 10, 11, 12, 13], ultradian components provided an evolutionary advantage for almost all life forms, from bacteria to humans [54, 55, 56, 57, 58].
These ultradian rhythms can be expected to be important for the rapid adaptation to microgravity in space. The 12-hour (circasemidian) component in particular may be involved [59, 60, 61, 62, 63, 64]. It may reflect the function of two stress response pathways reacting to unfolded protein in the endogenous endoplasmic reticulum (ER) and mitochondria. A 12-hour (circasemidian) component characterizes the ER- and mitochondria-associated “unfolded protein response (UPR) cycle” [62, 63, 64, 65, 66, 67]. Several potential roles of the circasemidian clock in coordinating human health have been proposed, such as maintaining metabolic homeostasis , coordinating sleep quality of slow wave sleep [68, 69], and mediating aging, especially in the prevention of aging-related metabolic decline [61, 62, 70, 71].
Based on our observations herein, the following hypothesis comes to mind. First, when faced with a new environment in space, the 12-hour response appeared faster and was larger than the circadian response (Table 2). Second, strong 12-hour clock regulation might help repair circadian desynchrony (Table 3 and Fig. 3). The more severe internal desynchrony is (Table 3, Flight 1), the larger is the activation of the 12-hour component (Table 2 and Fig. 3, Flight 1). Third, the circasemidian response was milder during the second than during the first mission, suggesting that spaceflight-induced neuroplasticity was present in the astronaut’s brain during the second mission.
In conclusion, harmonic oscillations of 24 and 12 hours likely provide evolutionarily adaptive advantages. The 12-hour (circasemidian) component contributes to consolidating a strong circadian system in space, and may contribute to the better adaptation in space by taking advantage of brain plasticity at night and psychological resilience during daytime.
This investigation has several limitations. First, the study is limited to a single astronaut, and space adaptation of human neural cardiovascular coordination remains a challenge, as mechanisms are diverse and complex. Second, brain oscillatory activity data are lacking. Several studies, however, showed that HRV is associated with structures and functions of the neural network, and HRV is a biomarker reflecting activities of the brain integration system. These associations are extremely complex, however, and have not yet been fully confirmed. Future investigations are needed to directly assess the brain’s oscillatory activity in space.