Impaired Attentional Processing During Parabolic Flight.

Previous studies suggest that altered gravity levels during parabolic flight maneuvers affect spatial updating. Little is known about the impact of the experimental setting and psychological stressors associated with parabolic flight experiments on attentional processes. To address this gap, we investigated the level of alertness, selective and sustained attention in 1 and 0 g using a Go/No-Go Continuous Performance Task. We also identified several parameters associated with the experimental set-up of a parabolic flight that could be expected to affect attentional processing. These included the use of scopolamine, sleep quality prior to the flight day, participant's stress level as well as mood and anxiety state before and after the parabolic flight. We observed a deterioration in attentional processing prior to the first parabola that was further aggravated in weightlessness and returned to baseline after the last parabola. Reaction Time, Hit and False Alarm Rate were moderately correlated with self-reported anxiety state, but not cortisol levels or emotional states. The use of scopolamine had minor effects on Reaction Time. Our results confirm previous studies reporting impairments of cognitive performance in 0 g, and highlight important aspects that should be considered for the design of behavioral research experiments in future parabolic flight campaigns.

Long-Term Bed Rest Delays the Circadian Phase of Core Body Temperature.

Spaceflight can be associated with sleep loss and circadian misalignment as a result of non-24 h light-dark cycles, operational shifts in work/rest cycles, high workload under pressure, and psychological factors. Head-down tilt bed rest (HDBR) is an established model to mimic some of the physiological and psychological adaptions observed in spaceflight. Data on the effects of HDBR on circadian rhythms are scarce. To address this gap, we analyzed the change in the circadian rhythm of core body temperature (CBT) in two 60-day HDBR studies sponsored by the European Space Agency [n = 13 men, age: 31.1 ± 8.2 years (M ± SD)]. CBT was recorded for 36 h using a non-invasive and validated dual-sensor heatflux technology during the 3rd and the 8th week of HDBR. Bed rest induced a significant phase delay from the 3rd to the 8th week of HDBR (16.23 vs. 16.68 h, p = 0.005, g = 0.85) irrespective of the study site (p = 0.416, g = -0.46), corresponding to an average phase delay of about 0.9 min per day of HDBR. In conclusion, long-term bed rest weakens the entrainment of the circadian system to the 24-h day. We attribute this effect to the immobilization and reduced physical activity levels associated with HDBR. Given the critical role of diurnal rhythms for various physiological functions and behavior, our findings highlight the importance of monitoring circadian rhythms in circumstances in which gravity or physical activity levels are altered.

Effects of two months of bed rest and antioxidant supplementation on attentional processing.

Physical inactivity across the lifespan is a growing public health concern affecting the cardiovascular, musculoskeletal, and central nervous system. Data on the effects of dietary antioxidants as neuroprotective treatments when physical activity levels are impaired are lacking. In this randomized controlled study, twenty young healthy men underwent 60 days of bed rest. Participants were randomly assigned to a treatment group (n = 10) receiving a daily antioxidant supplement comprising polyphenols, omega-3 fatty acids, vitamin E, and selenium or a control group (n = 10). Event-related potentials (ERPs) and behavioral data from a three-stimulus oddball paradigm were collected eight days before bed rest, after 60 days of immobilization, and after eight days of recovery. After two months of bed rest, we found a significant decrease in task efficiency irrespective of the treatment that was corroborated by lower ERPs in fronto-central and parietal brain regions. Neither behavioral nor electrocortical data returned to baseline values after eight days of recovery. Our results provide support for the adverse and persistent neurobehavioral effects of prolonged bed rest, which could not be mitigated by antioxidant supplementation. These findings raise important implications for situations in which physical activity levels become severely restricted such as medical conditions or sedentary lifestyles.

Head-Down Tilt Position, but Not the Duration of Bed Rest Affects Resting State Electrocortical Activity.

Adverse cognitive and behavioral conditions and psychiatric disorders are considered a critical and unmitigated risk during future long-duration space missions (LDSM). Monitoring and mitigating crew health and performance risks during these missions will require tools and technologies that allow to reliably assess cognitive performance and mental well-being. Electroencephalography (EEG) has the potential to meet the technical requirements for the non-invasive and objective monitoring of neurobehavioral conditions during LDSM. Weightlessness is associated with fluid and brain shifts, and these effects could potentially challenge the interpretation of resting state EEG recordings. Head-down tilt bed rest (HDBR) provides a unique spaceflight analog to study these effects on Earth. Here, we present data from two long-duration HDBR experiments, which were used to systematically investigate the time course of resting state electrocortical activity during prolonged HDBR. EEG spectral power significantly reduced within the delta, theta, alpha, and beta frequency bands. Likewise, EEG source localization revealed significantly lower activity in a broad range of centroparietal and occipital areas within the alpha and beta frequency domains. These changes were observed shortly after the onset of HDBR, did not change throughout HDBR, and returned to baseline after the cessation of bed rest. EEG resting state functional connectivity was not affected by HDBR. The results provide evidence for a postural effect on resting state brain activity that persists throughout long-duration HDBR, indicating that immobilization and inactivity per se do not affect resting state electrocortical activity during HDBR. Our findings raise an important issue on the validity of EEG to identify the time course of changes in brain function during prolonged HBDR, and highlight the importance to maintain a consistent body posture during all testing sessions, including data collections at baseline and recovery.

Exercise-induced changes in brain activity during memory encoding and retrieval after long-term bed rest.

Episodic memory depends decisively on the hippocampus and the parahippocampal gyrus, brain structures that are also prone to exercise-induced neuroplasticity and cognitive improvement. We conducted a randomized controlled trial to investigate the effects of a high-intensity exercise program in twenty-two men resting in bed for 60 days on episodic memory and its neuronal basis. All participants were exposed to 60 days of uninterrupted bed rest. Eleven participants were additionally assigned to a high-intensity interval training that was performed five to six times weekly for 60 days. Episodic memory and its neural basis were determined four days prior to and on the 58th day of bed rest using functional magnetic resonance imaging (fMRI). We found increased BOLD signal in the left hippocampus and parahippocampal gyrus in the non-exercising group compared to the exercising bed rest group whereas the mnemonic performance did not differ significantly. These findings indicate a higher neuronal efficiency in the training group during memory encoding and retrieval and may suggest a dysfunctional mechanism in the non-exercising bed rest group induced by two months of physical inactivity. Our results provide further support for the modulating effects of physical exercise and adverse implications of a sedentary lifestyle and bedridden patients.

Spatial Updating Depends on Gravity.

As we move through an environment the positions of surrounding objects relative to our body constantly change. Maintaining orientation requires spatial updating, the continuous monitoring of self-motion cues to update external locations. This ability critically depends on the integration of visual, proprioceptive, kinesthetic, and vestibular information. During weightlessness gravity no longer acts as an essential reference, creating a discrepancy between vestibular, visual and sensorimotor signals. Here, we explore the effects of repeated bouts of microgravity and hypergravity on spatial updating performance during parabolic flight. Ten healthy participants (four women, six men) took part in a parabolic flight campaign that comprised a total of 31 parabolas. Each parabola created about 20-25 s of 0 g, preceded and followed by about 20 s of hypergravity (1.8 g). Participants performed a visual-spatial updating task in seated position during 15 parabolas. The task included two updating conditions simulating virtual forward movements of different lengths (short and long), and a static condition with no movement that served as a control condition. Two trials were performed during each phase of the parabola, i.e., at 1 g before the start of the parabola, at 1.8 g during the acceleration phase of the parabola, and during 0 g. Our data demonstrate that 0 g and 1.8 g impaired pointing performance for long updating trials as indicated by increased variability of pointing errors compared to 1 g. In contrast, we found no support for any changes for short updating and static conditions, suggesting that a certain degree of task complexity is required to affect pointing errors. These findings are important for operational requirements during spaceflight because spatial updating is pivotal for navigation when vision is poor or unreliable and objects go out of sight, for example during extravehicular activities in space or the exploration of unfamiliar environments. Future studies should compare the effects on spatial updating during seated and free-floating conditions, and determine at which g-threshold decrements in spatial updating performance emerge.

Electrocortical Evidence for Impaired Affective Picture Processing after Long-Term Immobilization.

The neurobehavioral risks associated with spaceflight are not well understood. In particular, little attention has been paid on the role of resilience, social processes and emotion regulation during long-duration spaceflight. Bed rest is a well-established spaceflight analogue that combines the adaptations associated with physical inactivity and semi-isolation and confinement. We here investigated the effects of 30 days of 6 degrees head-down tilt bed rest on affective picture processing using event-related potentials (ERP) in healthy men. Compared to a control group, bed rest participants showed significantly decreased P300 and LPP amplitudes to pleasant and unpleasant stimuli, especially in centroparietal regions, after 30 days of bed rest. Source localization revealed a bilateral lower activity in the posterior cingulate gyrus, insula and precuneus in the bed rest group in both ERP time frames for emotional, but not neutral stimuli.

High-Intensity Exercise Mitigates Cardiovascular Deconditioning During Long-Duration Bed Rest.

Head-down-tilt bed rest (HDT) mimics the changes in hemodynamics and autonomic cardiovascular control induced by weightlessness. However, the time course and reciprocal interplay of these adaptations, and the effective exercise protocol as a countermeasure need further clarification. The overarching aim of this work (as part of a European Space Agency sponsored long-term bed rest study) was therefore to evaluate the time course of cardiovascular hemodynamics and autonomic control during prolonged HDT and to assess whether high-intensity, short-duration exercise could mitigate these effects. A total of n = 23 healthy, young, male participants were randomly allocated to two groups: training (TRAIN, n = 12) and non-training (CTRL, n = 11) before undergoing a 60-day HDT. The TRAIN group underwent a resistance training protocol using reactive jumps (5-6 times per week), whereas the CTRL group did not perform countermeasures. Finger blood pressure (BP), heart rate (HR), and stroke volume were collected beat-by-beat for 10 min in both sitting and supine positions 7 days before HDT (BDC-7) and 10 days after HDT (R+10), as well as on the 2nd (HDT2), 28th (HDT28), and 56th (HDT56) day of HDT. We investigated (1) the isolated effects of long-term HDT by comparing all the supine positions (including BDC-7 and R+10 at 0 degrees), and (2) the reactivity of the autonomic response before and after long-term HDT using a specific postural stimulus (i.e., supine vs. sitting). Two-factorial linear mixed models were used to assess the time course of HDT and the effect of the countermeasure. Starting from HDT28 onwards, HR increased (p < 0.02) and parasympathetic tone decreased exclusively in the CTRL group (p < 0.0001). Moreover, after 60-day HDT, CTRL participants showed significant impairments in increasing cardiac sympathovagal balance and controlling BP levels during postural shift (supine to sitting), whereas TRAIN participants did not. Results show that a 10-day recovery did not compensate for the cardiovascular and autonomic deconditioning following 60-day HDT. This has to be considered when designing rehabilitation programs-not only for astronauts but also in general public healthcare. High-intensity, short-duration exercise training effectively minimized these impairments and should therefore deserve consideration as a cardiovascular deconditioning countermeasure for spaceflight.

Gender-Specific Cardiovascular Reactions to +Gz Interval Training on a Short Arm Human Centrifuge.

Cardiovascular deconditioning occurs in astronauts during microgravity exposure, and may lead to post-flight orthostatic intolerance, which is more prevalent in women than men. Intermittent artificial gravity is a potential countermeasure, which can effectively train the cardiovascular mechanisms responsible for maintaining orthostatic integrity. Since cardiovascular responses may differ between women and men during gravitational challenges, information regarding gender specific responses during intermittent artificial gravity exposure plays a crucial role in countermeasure strategies. This study implemented a +Gz interval training protocol using a ground based short arm human centrifuge, in order to assess its effectiveness in stimulating the components of orthostatic integrity, such as diastolic blood pressure, heart rate and vascular resistance amongst both genders. Twenty-eight participants (12 men/16 women) underwent a two-round graded +1/2/1 Gz profile, with each +Gz phase lasting 4 min. Cardiovascular parameters from each phase (averaged last 60 sec) were analyzed for significant changes with respect to baseline values. Twelve men and eleven women completed the session without interruption, while five women experienced an orthostatic event. These women had a significantly greater height and baseline mean arterial pressure than their counterparts. Throughout the +Gz interval session, women who completed the session exhibited significant increases in heart rate and systemic vascular resistance index throughout all +Gz phases, while exhibiting increases in diastolic blood pressure during several +Gz phases. Men expressed significant increases from baseline in diastolic blood pressure throughout the session with heart rate increases during the +2Gz phases, while no significant changes in vascular resistance were recorded. Furthermore, women exhibited non-significantly higher heart rates over men during all phases of +Gz. Based on these findings, this protocol proved to consistently stimulate the cardiovascular systems involved in orthostatic integrity to a larger extent amongst women than men. Thus the +Gz gradients used for this interval protocol may be beneficial for women as a countermeasure against microgravity induced cardiovascular deconditioning, whereas men may require higher +Gz gradients. Lastly, this study indicates that gender specific cardiovascular reactions are apparent during graded +Gz exposure while no significant differences regarding cardiovascular responses were found between women and men during intermittent artificial gravity training.

Short tandem repeats in the inhibitory domain of the mineralocorticoid receptor: prediction of a ß-solenoid structure.

BACKGROUND: The human mineralocorticoid receptor (MR) is one of the main components of the renin-angiotensin-aldosterone system (RAAS), the system that regulates the body exchange of water and sodium. The evolutionary origins of this protein predate those of renin and the RAAS; accordingly it has other roles, which are being characterized. The MR has two trans-activating ligand independent domains and one inhibitory domain (ID), which modulates the activity of the former. The structure of the ID is currently unknown. RESULTS: Here we report that the ID contains at least 15 tandem repeats of around 10 amino acids, which we computationally characterize in the human MR and in selected orthologs. This ensemble of repeats seems to have emerged around 450 million years ago, after the divergence of the MR from its close homolog, the glucocorticoid receptor, which does not possess the repeats. The region would have quickly expanded by successive duplication of the repeats stabilizing at its length in human MR shortly after divergence of tetrapoda from bony fishes 400 million years ago. Structural predictions, in combination with molecular dynamics simulations suggest that the repeat ensemble forms a ß-solenoid, namely a ß-helical fold with a polar core, stabilized by hydrogen-bonded ladders of polar residues. Our 3D-model, in conjunction with previous experimental data, implies a role of the ß-helical fold as a scaffold for multiple intra-and inter-molecular interactions and that these interactions are modulated via phosphorylation-dependent conformational changes. CONCLUSIONS: We, thus, propose that the structure of the repeat ensemble plays an important role in the coordination and sequential interactions of various MR partners and therefore in the functionality and specificity of MR.