Brain stimulation in zero gravity: transcranial magnetic stimulation (TMS) motor threshold decreases during zero gravity induced by parabolic flight

We are just beginning to understand how spaceflight may impact brain function. As NASA proceeds with plans to send astronauts to the Moon and commercial space travel interest increases, it is critical to understand how the human brain and peripheral nervous system respond to zero gravity. Here, we developed and refined head-worn transcranial magnetic stimulation (TMS) systems capable of reliably and quickly determining the amount of electromagnetism each individual needs to detect electromyographic (EMG) threshold levels in the thumb (called the resting motor threshold (rMT)). We then collected rMTs in 10 healthy adult participants in the laboratory at baseline, and subsequently at three time points onboard an airplane: (T1) pre-flight at Earth gravity, (T2) during zero gravity periods induced by parabolic flight and (T3) post-flight at Earth gravity. Overall, the subjects required 12.6% less electromagnetism applied to the brain to cause thumb muscle activation during weightlessness compared to Earth gravity, suggesting neurophysiological changes occur during brief periods of zero gravity. We discuss several candidate explanations for this finding, including upward shift of the brain within the skull, acute increases in cortical excitability, changes in intracranial pressure, and diffuse spinal or neuromuscular system effects. All of these possible explanations warrant further study. In summary, we documented neurophysiological changes during brief episodes of zero gravity and thus highlighting the need for further studies of human brain function in altered gravity conditions to optimally prepare for prolonged microgravity exposure during spaceflight.


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Software and code
Policy information about availability of computer code Data collection The EMG recording (sensors placed on the right abductor pollicis bevis) is real-time analyzed using a companion Spike 2 software that uses prewritten software to determine whether muscle activation occurred (>150uV) and changes the output of the TMS capacitor to the next probabilistic intensity based on parametric estimation via sequential testing (PEST) protocol.

Data analysis
All statistics were completed in IBM SPSS 25.
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Study description
Quantitative study design exploring the effects of zero gravity on the brain. This was a longitudinal, multi-visit trial investigating cortical excitability in various gravity states.

Research sample
We recruited 10 healthy adults (5 men, mean age = 41.0) in this multi-visit TMS cortical excitability experiment conducted in simulated zero gravity (0G) environment induced by parabolic flight (Zero Gravity Corporation, USA). Inclusion/exclusion criteria were as follows: Age between 25-61 years old, familiarity with TMS equipment, a baseline resting motor threshold lower than 90% of total machine output, no personal or familial history of seizures, no medications that would reduce seizure threshold, no metal implanted in the body above the level of the neck, no motion sickness on Earth. One of the 10 participants had prior zero gravity experienced. All others were unexperienced fliers who had limited to expert levels of TMS training and familiarity with the onboard TMS and MEP acquisition equipment. Nine out of 10 participants were right handed; handedness was not anticipated to impact rMT values as we used a within-subjects, repeated-measures design.

Sampling strategy
We enrolled 10 individuals due to the limitation on the number of zero gravity fliers. 10 participants was the maximum number of seats we had on the parabolic flight airplane.

Data collection
All data collection was recorded in real-time on the computers that administered the stimulation paradigm. Back-up data was recorded using pen and paper in case there were technical issues on the flight.

Timing
We collected data on three separate days. The first two days served as baseleine confirmation of stable neurophysiological signatures at earth gravity. These baselines were spread one week apart. The third visit was conducted on flight day, with three repeated meas

Data exclusions
No data was excluded during any of the Earth gravity rMT attempts (100 baseline attempts (5 per subject/visit), 30 pre-flight attempts (3 per subject), and 30 post-flight attempts (3 per subject)). During Zero Gravity, 10 of the 50 rMT attempts were rejected in-flight due to poor quality acquisition determined by the computer operator and secondarily confirmed digitally post-flight by one rater trained in Spike 2 software. Each participant had at least 3, and up to 5, clean zero gravity rMT acquisitions.
Non-participation N/A Randomization Participants were divided into two teams of 5 individuals (Team A and B) and each team was assigned their own closed-loop TMS system. Both systems had identical hardware and software. The two teams were roughly equivalent in age (Team A -mean = 42.8 years, Team B -mean = 39.2) and gender (Team A -2 female, Team B -3 female).

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