Spaceflight exposes astronauts to unique environmental conditions, including radiation, altered atmospheric parameters, and microgravity. While the effects of spaceflight on the body are extensively studied, the impact on brain function remains relatively unknown. Previous research has shown changes in brain structure in astronauts post-flight, such as an upward shift of the brain and changes in cerebrospinal fluid spaces. However, acute brain changes in weightlessness have been largely unexplored. Transcranial magnetic stimulation (TMS) offers a portable, non-invasive method for measuring cortical excitability. By delivering electromagnetic pulses to the brain, TMS depolarizes neurons, causing a quantifiable motor response. The resting motor threshold (rMT), the minimum intensity needed to elicit a response, is a sensitive measure of corticospinal excitability. The development of custom head-worn TMS systems enabled the researchers to assess rMT in zero gravity. This parabolic flight study aimed to determine the feasibility and safety of administering TMS in zero gravity and to investigate whether rMT changes as a function of gravity state. The hypothesis was that the amount of electromagnetism required for rMT would be altered in zero gravity due to acute central nervous system changes.

Existing literature demonstrates structural changes in the brains of astronauts after prolonged spaceflight, including an upward shift of the brain and alterations in cerebrospinal fluid spaces. However, there is a paucity of research on the acute effects of microgravity on brain physiology. While TMS has been used extensively to study cortical excitability on Earth, its application in microgravity had not been thoroughly investigated prior to this study. Studies have shown that rMT is sensitive to various factors including cortical excitability and distance from the TMS coil to the cortex. Previous non-TMS studies during parabolic flight have reported changes in EEG activity in zero gravity, but the relationship to TMS-measured cortical excitability was unknown.

Ten healthy adults (5 men, mean age 41) participated in the study. They underwent two baseline visits, followed by a parabolic flight. Participants were divided into two teams. Custom-designed head-worn TMS systems were used, ensuring consistent coil placement and reliable TMS delivery. The systems used closed-loop TMS/EMG analysis to determine rMT via a PEST protocol. A total of three rMT measurements were acquired at each of three time points: pre-flight at Earth gravity (1G), during zero gravity (0G) periods of parabolic flight, and post-flight at 1G. A maximum of 5 PEST steps were used at each time point, with an interstimulus interval of 3.0-3.5 seconds. Subjective emotional arousal was also assessed using a 1-10 scale. Parabolic flight induced alternating periods of hypergravity (1.8G) and microgravity (0G). TMS was administered only during the approximately 20-second 0G periods. Data analysis involved a linear mixed model accounting for factors like team, age, gender, emotional arousal, and rMT assessment number. The model assessed the effect of gravity state (1G, 0G) on TMS motor threshold, while controlling for other variables.

The study found no adverse events associated with TMS administration in zero gravity. There was a significant effect of gravity state on the TMS motor threshold (F(2, 85.21) = 18.56, p < 0.0001). Specifically, rMT values were significantly lower during zero gravity (mean 48.1 points) compared to Earth gravity (mean 55.0 points pre-flight and 55.4 points post-flight). This represented a 12.6% reduction in rMT during 0G. The reduction was transient, and rMT values returned to baseline levels immediately after the flight. Analysis of individual data showed a consistent reduction in rMT during zero gravity for all participants. The study found no significant effect of emotional arousal on motor threshold values.

The significant decrease in rMT during zero gravity suggests acute neurophysiological changes. Several possible explanations were considered. One is the physical movement of the brain within the skull due to altered gravitational forces. Calculations based on previous research suggest a plausible upward brain shift of approximately 2.3 mm could account for the observed rMT change. Another possibility is altered cerebral hemodynamics, impacting cortical excitability. Changes in intracranial pressure and internal jugular venous pressure during parabolic flight could contribute. Peripheral nervous system changes such as neuromuscular junction alterations or differences in signal propagation might also play a role. However, peripheral effects were not directly measured in this study. The findings contrast with some previous research using EEG but align with limited prior TMS work in microgravity.

This study demonstrated that administering TMS in zero gravity is feasible and safe. The significant and transient decrease in rMT during zero gravity highlights the need for further research into the neurophysiological adaptations to altered gravity. Future studies could incorporate additional TMS measures (e.g., MEP latency, paired pulse TMS) and investigate the effects during hypergravity periods as well. Understanding the interplay between gravity, brain structure, and function is crucial for astronaut health and for future exploration of space.

Several limitations should be considered. The study only collected motor threshold values; other TMS measures could provide a more complete picture of cortical excitability. Data were collected only during zero gravity and not during hypergravity periods, limiting causal interpretations. The magnetic field strength of the TMS machine was not quantified, and potential effects of the parabolic flight environment itself (beyond changes in gravity) were not fully addressed. The findings pertain only to brief periods of zero gravity, potentially not fully representative of the effects of prolonged spaceflight.