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www.nature.com/npjmgrav ARTICLE OPEN Brain stimulation in zero gravity: transcranial magnetic stimulation (TMS) motor threshold decreases during zero gravity induced by parabolic ﬂight 1 1 1 1 1,2,4 1 1 Bashar W. Badran , Kevin A. Caulﬁeld , Claire Cox , James W. Lopez , Jeffrey J. Borckardt , William H. DeVries , Philipp Summers , 1 1 1,2 1,2 3 Suzanne Kerns , Colleen A. Hanlon , Lisa M. McTeague , Mark S. George and Donna R. Roberts 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. npj Microgravity (2020) 6:26 ; https://doi.org/10.1038/s41526-020-00116-6 INTRODUCTION depends on several factors, including cortical excitability and scalp to cortex distance. The minimum amount of electromagnetic During spaceﬂight, astronauts onboard the International Space power required to move the thumb is known as the resting motor Station (ISS) experience unique environmental conditions includ- threshold (rMT) . The rMT is a standard measure of corticospinal ing radiation exposure, altered atmospheric parameters, and excitability and is sensitive to various factors at the synaptic level microgravity. Understanding the effects of spaceﬂight on human 8,9 (such as pharmacological agents) and morphological level health is important as more opportunities become available to 10,11 (distance of TMS coil on the scalp to motor cortex) . TMS can send humans into space including the near-term reality of 1,2 thus indirectly and noninvasively measure cortical excitability and commercial suborbital and orbital ﬂights . Extensive research is able to capture acute CNS changes, making it a potential tool to has documented that adaptive responses occur throughout the 3 measure brain changes in microgravity. body during exposure to the spaceﬂight environment . However, We built custom, head-worn TMS systems that enable the relatively little is known concerning the effects of microgravity on exploration of TMS effects in zero gravity . We then conducted a human brain function and health. Our group and others have parabolic ﬂight study in which we collected rMTs in 10 individuals demonstrated changes in brain structure on post-ﬂight MRI in ISS before- during- and after parabolic ﬂight to investigate whether astronauts and cosmonauts including a global upward positioning TMS is feasible and safe to administer in zero gravity. Additionally, shift of the brain coupled with narrowing of the central sulcus and we aimed to determine whether the rMT changes as a function of 4–6 vertex cerebrospinal ﬂuid spaces, and ventricular enlargement . gravity state. Our a priori hypothesis was that the amount of Although anatomical changes would be expected to result in electromagnetism required for the rMT would be altered in zero changes in brain physiology, there have been virtually no studies gravity compared to Earth gravity due to acute changes in the of acute brain changes in weightlessness. central nervous system. Transcranial magnetic stimulation (TMS) is a portable, non- invasive method for measuring cortical excitability by delivering electromagnetic pulses to the brain. When applied over the motor RESULTS cortex, TMS depolarizes neurons in the corticospinal tract that Safety of TMS in zero gravity result in an observable and quantiﬁable motor response in the muscles of the contralateral hand. The intensity of the TMS There were no adverse events caused by the single pulse TMS electromagnetic pulse required to activate the motor cortex administered in this experiment, irrespective of gravity state. Anti- 1 2 Brain Stimulation Division, Department of Psychiatry & Behavioral Sciences, Medical University of South Carolina, Charleston, SC 29425, USA. Ralph H. Johnson VA Medical 3 4 Center, Charleston, SC 29401, USA. Department of Radiology, Medical University of South Carolina, Charleston, SC 29425, USA. Department of Anesthesia and Perioperative Medicine, Medical University of South Carolina, Charleston, SC 29425, USA. email: firstname.lastname@example.org; email@example.com Published in cooperation with the Biodesign Institute at Arizona State University, with the support of NASA 1234567890():,; B.W. Badran et al. nausea medications were not used in order to avoid confounding the model: team, emotional arousal, age, gender, motor threshold effects on cortical excitability. Three of the 10 participants or assessment number. experienced transient nausea with vomiting during ﬂight. When We further investigated the consistency and reliability of these it occurred, the nausea was after each participant’s rMT was overall group ﬁndings by looking at the individual effects of each acquired (parabola numbers: 22, 25, and 26, respectively) with no of the 10 individuals on the ﬂight. These ﬁndings are presented in participant reports of nausea during their rMT recording. There Fig. 2 which demonstrate a consistent reduction in the resting were no other adverse consequences of rMT assessment during motor threshold during zero-g time points compared to pre- and zero gravity. post ﬂight. For all 10 individual ﬂiers, the mean zero-g resting motor threshold value was lower than the pre- and post- ﬂight motor threshold, suggesting this is a true biologic effect. Motor threshold in zero gravity Furthermore, the standard error for each of the individual We recorded the motor thresholds of 10 participants working in measurements are similar at each time point. two teams of ﬁve people. Three to ﬁve rMTs were successfully acquired for each participant before (1 Gravity or G), during (0 G), Subjective emotional arousal rating and after (1 G) parabolic ﬂight. The recordings during parabolic ﬂight were measured during the zero gravity portions of each We analyzed informal, self-reported subjective emotional arousal parabola, lasting approximately 20 s each. We found a signiﬁcant on a scale of 1 (lowest) to 10 (highest) at each motor threshold effect of gravity state on TMS motor threshold (F (2,85.21) = 18.56, time point to determine whether emotional arousal may inﬂuence p < 0.0001) using a linear mixed-model, accounting for team motor threshold levels. There was an overall main effect of time (A or B), age, gender, subjective emotional arousal at the outset of comparing pre- (mean 5.2, SEM 0.55), during- (mean 6.0, SEM motor threshold measurement, and rMT assessment number 0.25), and post- (mean 3.7, SEM 0.63) ﬂight emotional arousal (F (1 to 5). Earth pre-ﬂight (1 G) motor thresholds were a mean of 55.0 (1.540, 13.86) = 9.92, p = 0.0035). This effect was driven by the points (SE= 3.61). Parabolic ﬂight (0 G) motor thresholds were a post-ﬂight reduction of emotional arousal, and post-hoc compar- mean of 48.1 points (SE= 2.38). Upon return to Earth, the mean isons revealed no signiﬁcant difference between pre- and during- post-ﬂight motor threshold was 55.4 points (SE= 3.50) (Fig. 1). ﬂight emotional arousal. Overall, zero gravity motor thresholds were 6.6 (SE = 1.08) We used a linear mixed model with unstructured covariance points lower than were Earth motor thresholds collapsed across matrix to examine the effects of subjective emotional arousal pre- and post-ﬂight timepoints (t (86.18) = 6.13, p < 0.0001). The ratings and found no signiﬁcant effect of emotional arousal on the immediately pre-ﬂight motor thresholds were 6.6 points (SE = motor threshold values analyzed in this experiment (F (1,85.79) = 1.11) higher than in 0 G (t (85.09) = 5.98, p < 0.0001), equating to a 0.61, ns). 12.6% reduction in motor threshold value. This reduction recovered immediately post-ﬂight as the Earth post-ﬂight (1 G) DISCUSSION thresholds were 6.5 points (SE = 1.48) higher than in zero gravity Using custom helmets and closed-loop, real-time EMG analysis (t (85.41) = 4.39, p < 0.0001), and roughly the same as before the software, we have demonstrated the feasibility of determining ﬂight. No signiﬁcant difference was found between the pre- and rMT during brief episodes of zero gravity induced by parabolic post-ﬂight Earth sessions (F (1,47.35) = 0.772, ns) and no ﬂight. Supporting our a priori hypothesis that the gravity state signiﬁcant effects were found for any of the other variables in alters neurophysiology, we found that rMT levels were 6.6 points (or 12.6%) lower in zero gravity than they were pre- and post-ﬂight in Earth gravity. These rMT changes were transient and did not persist after ﬂight, and were not related to age, gender, or subjective emotional arousal at the time of data acquisition. Under normal conditions, the rMT is fairly consistent within an individual 13–16 over time and is used as a standard measure in TMS treatment protocols to determine individual dosing. Therefore, the assessment of rMT in the zero gravity condition is an important baseline data point in understanding the response of the brain to acutely altered gravity and will facilitate investigators in designing TMS treatment protocols for use on future spaceﬂight missions. The magnitude of the changes found are considered large when compared to pharmacologic methods of modulating cortical excitability such as the anticonvulsant medication lamotrigine , with a similar range of effect size however opposite directional effect. However, there are many factors that can inﬂuence the magnitude of rMT changes, such as equipment (TMS machine and coil), the determination method of rMT (visual or EMG based), targeted muscle, participant characteristics (e.g. age, gender, etc.) and others . Therefore, the mechanisms underlying the magnitude of change we observed in rMT during parabolic ﬂight however are still unclear. These ﬁndings suggest that physical movement of the brain within the skull during the alternating gravitational loads of parabolic ﬂight may have been a contributing factor to our Fig. 1 Motor threshold changes as a function of gravity state. (A) observed effects on rMT. TMS rMT varies widely between On Earth motor thresholds for the group (n = 10) remain stable at individuals, however, is extremely reliable within individual. Nearly baseline and maintain the same average level through pre-ﬂight 60% of the between individual variance is due to differences in measurements on the airplane. During Zero Gravity, a signiﬁcant, the scalp to cortex distance . As the scalp to cortex distance 6.6 point reduction in motor threshold level was observed, which recovered post-ﬂight (p < 0.0001). increases a greater amount of electromagnetism is required to npj Microgravity (2020) 26 Published in cooperation with the Biodesign Institute at Arizona State University, with the support of NASA 1234567890():,; B.W. Badran et al. Fig. 2 Individual resting motor threshold data across all measured time points demonstrating a reduction in motor threshold value for each individual during Zero-G periods compared to 1G onboard parabolic ﬂight. induce cortical activation. Kozel et al. have suggested that within a 2.8 times . Intracranial pressure (ICP) is known to change with narrow range, every 1 mm increase of scalp to cortex distance changes in position as well as during parabolic ﬂight. Lawley et al. would result in a 2.9 point increase in TMS motor threshold .If found that ICP during parabolic ﬂight is reduced in 0 G while lying brain movement does occur acutely during parabolic ﬂight, it in the supine position compared to 1 G . Internal jugular venous could result in altered rMTs. Applying Kozel’s ﬁndings to our pressure increases during parabolic ﬂight compared with the current study suggests that the 6.6-point reduction of rMT in zero supine position (23.9 ± 5.6 vs. 9.9 ± 5.1 mm Hg) . A change in gravity which we documented would have required an upward body position results in arterial baroreceptor stimulation which shift in the brain of approximately 2.3 mm. This magnitude of shift alters cortical activity and studies have shown that the supine 28–30 is plausible, as the average distance at the vertex between the position results in cortical inhibition . It is possible that the surface of the brain and the endocast is, on average, 3–7mm . dynamics of ICP or these physiological changes or both during The brain is a deformable tissue and is not rigidly ﬁxed in place. parabolic ﬂight altered cortical excitability and contributed to the During each cardiac cycle, the brain undergoes a deformation decrease in rMT. with the largest displacements occurring at the level of the brain Interestingly, a prior, non-TMS parabolic ﬂight experiment stem. At the level of the cortex, peak displacements are conducted in 2008 by Schneider and colleagues recorded 20,21 approximately 0.1 mm . Few studies have examined how resting electroencephalogram (EEG) activity in seven participants much the brain may instantaneously shift under the altered before, during, and after zero gravity which suggested that frontal directional gravity gradients experienced during normal daily lobe excitably might change in zero gravity. In contrast to our position changes, and those studies have reported shifts on the study, they found EEG suppression of frontal cortical excitability, order of the typical voxel size (1 mm). Mikkonen and Laakso rather than an increase during zero gravity. On the other hand, reported an upward and backward shift of the brain in the supine Chéron et al. found an increase in power of spontaneous 10-Hz position with the greatest shifts of up to 1.6 mm involving the oscillation on EEG in the parieto-occipital and sensorimotor areas parietal regions, although alignment errors were 0.4 ± 0.1 mm. in 5 cosmonauts during spaceﬂight . It is not clear how these EEG Other investigators have also suggested that the brain may shift measures relate to our TMS rMT ﬁndings. Cortical excitability of by approximately 1 mm when moving between the supine, lateral the motor system has also been investigated previously by Davey recumbent and prone positions, however these measurements and colleagues in 2004 , who were perhaps the ﬁrst to use TMS were made by indirectly estimating brain movement based on to explore corticospinal excitability in zero gravity. Davey 23,24 estimating the thickness of the surrounding CSF . It is unknown administered TMS to the bilateral motor cortices to investigate how much the brain may shift in position upon moving from motor changes in the lower extremities of three healthy supine to the upright position or during parabolic ﬂight. Roberts individuals. They were only able to acquire valid data in one and colleagues have previously demonstrated an upward shift of subject, however they found that this subject had transient the brain in astronauts following months in space aboard the ISS, increases in motor evoked potential amplitude recorded from the however, the chronic effects of exposure to weightlessness lower extremity in microgravity compared to Earth gravity measured in 1 G would not be equivalent to the transient consistent with our results. changes we describe here. However, we did not actually measure An alternative explanation for our observed reduction in motor the brain’s position during parabolic ﬂight so this is only one threshold during zero-G could be changes in the periphery. Since possible explanation for our results. acquiring rMT requires activation of cortex, which secondarily In addition to the physical movement of the brain, body activates the musculoskeletal system (measured from recordings position is known to acutely affect cerebral hemodynamics. For on the anterior pollicis brevis of the contralateral hand), the rMT example, Alperin et al. has previously shown that compared with changes could be due to biomechanics of the periphery that are 7,8,34 the supine position, CSF outﬂow through the foramen magnum more sensitive to motor cortex outputs in zero gravity . This while upright is decreased by 50%, cerebral blood ﬂow is could be due to neuromuscular junction changes, differences in decreased by 12% and intracranial compliance is increased by propagation of efferent motor signal, or a combination of the two. Published in cooperation with the Biodesign Institute at Arizona State University, with the support of NASA npj Microgravity (2020) 26 B.W. Badran et al. Generally, a muscle that is partially activated pushing against 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 gravity will have a lower rMT than will the same muscle when it is zero gravity experienced. All others were unexperienced ﬂiers who had completely at rest . We thus assumed that with respect to muscle limited to expert levels of TMS training and familiarity with the onboard activation affecting our measurements, in zero gravity there is less TMS and MEP acquisition equipment. Nine out of 10 participants were gravity to push against, so the muscle would be fully ‘at rest’ and right handed; handedness was not anticipated to impact rMT values as we the amount of electricity needed to cause changes in it would used a within-subjects, repeated-measures design. All research conducted increase. Our ﬁndings of decreased electricity needed in zero in this study complied with ethical regulations for work with human gravity are in the opposite direction predicted by this reasoning. participants, and all subjects signed written informed consent approved by However, in our study, we did not explore the peripheral effects of the MUSC IRB. Furthermore, the authors afﬁrm that human research zero gravity, and therefore it is not possible to fully control for participants provided informed consent for publication of the images in all potential gravitational effects on the musculoskeletal system. ﬁgures and in supplemental materials. We made custom TMS helmets for Future studies could include EMG recordings of several muscles each subject using the methods described in Badran et al. . This simple method allows for reliable administration of TMS in mobile or extreme throughout the ﬂight to determine if there is a general muscle environments during which TMS coil placement needs to be ﬁxed outside activating effect of entering zero gravity . of the laboratory. These helmets produce consistent and reliable TMS- induced motor evoked potentials in the contralateral abductor pollicis Limitations and future considerations brevis (APB) muscle. Participants attended 2 baseline visits followed by one parabolic ﬂight This study is a ﬁrst attempt to investigate the use of TMS in zero (see the study timeline in Fig. 1). The baseline visits were conducted the gravity and has several limitations that should be considered for week before the parabolic ﬂight. Participants were divided into two teams future parabolic ﬂight experiments that utilize TMS as an of 5 individuals (Team A and B) and each team was assigned their own investigational tool. First, we only collected motor threshold closed-loop TMS system. Both systems had identical hardware and values, as determined by a parametric estimation via sequential software. The two teams were roughly equivalent in age (Team A— testing. However other TMS electrophysiological values that may mean= 42.8 years, Team B—mean= 39.2) and gender (Team A—2 female, better elucidate brain changes and excitability such as MEP Team B—3 female). Both teams performed 5 closed-loop TMS motor latency, paired pulse TMS, cortical silent period and input output thresholds on each other in a round robin fashion at three different time curves were not collected. Future experiments assessing the points: T1—in the airplane while stationary on the runway pre-ﬂight, T2— in the airplane during 0 G, T3—in the airplane while stationary on the effects of zero gravity on motor physiology could consider adding runway post-ﬂight. some of these additional measurements to further assess the effects observed in this study. Second, we only collected information during zero gravity periods and not during hyper- Closed-loop TMS/EMG paradigm gravity, which limits the interpretation of the ﬁndings as to TMS was administered using two identical closed-loop TMS/EMG systems. whether gravity state was the underlying cause of the changes The TMS component used was the Magstim BiStim capacitor with a D70 rather than simply being on the ﬂight. Third, we did not quantify remote coil and the EMG component used was the Cambridge Electronics EMG system (CED 1401, 1902), which uses electromyography (EMG) to the magnetic ﬁeld (Tesla) emitted from the TMS machine, and measure the amplitude of the TMS motor evoked potential. The EMG although highly unlikely, since the systems used were intended recording (sensors placed on the right abductor pollicis bevis) is real-time for use in 1 G, the magnetic ﬁeld strength produced by the TMS analyzed using a companion Spike 2 software that uses prewritten coil might conceivably have changed. Lastly, it is important to software to determine whether muscle activation occurred (>150 μV) and recognize that these preliminary ﬁndings are for brief periods of changes the output of the TMS capacitor to the next probabilistic intensity zero gravity and are difﬁcult to translate to long-term spaceﬂight. 35,36 based on parametric estimation via sequential testing (PEST) protocol . Future studies could use TMS to investigate neurophysiological We used a threshold of >150 μV at all timepoints in anticipation of changes in subjects exposed to zero gravity for longer periods. increased latent electrical noise in the on-plane environment. Therefore, all We have demonstrated that administering TMS in zero gravity laboratory earth data collection was also conducted at the 150uV threshold aboard a parabolic ﬂight in a team environment is safe and to maintain a controlled, uniﬁed threshold through all data acquisition feasible, leading the way for future studies of brain physiology in points. At the three timepoints included in our statistical analysis (Pre- Flight 1 G, During Flight 0 G, Post-Flight 1 G), we used a maximum of 5 zero gravity environments. We found that the rMT, a fundamental 37,38 PEST steps using an interstimulus interval of 3.0–3.5 s . We did not measurement in the application of TMS, signiﬁcantly decreases in formally assess how the conventional lab-based TMS PEST protocol rMTs zero gravity induced by parabolic ﬂight and restores to baseline compared to the on-plane PEST protocol rMTs as the only rMTs included in levels post-ﬂight. It is difﬁcult to elucidate the underlying the statistical analysis were acquired using the 5 PEST step method. mechanism of our ﬁndings; however potential etiologies include All TMS was administered to the left motor cortex using custom, upward brain shift, increased cortical excitability, changes in individualized, helmets designed to administer TMS in non-laboratory intracranial pressure, peripheral nervous system changes in the environments (Fig. 3) in a seated upright position. We did not collect roll, musculoskeletal system, or some combination of all of these. As pitch, or yaw coordinate changes to track helmet stability as the helmets TMS and other brain stimulation methods grow in their clinical were custom cast to each individual’s head using ﬁberglass . This tight ﬁt utility, and likely need for use in space, further studies are needed greatly reduced the roll, pitch, and yaw of the helmet and had greater than 95% reliability of capturing accurate motor thresholds on two days. to build on these ﬁndings. In addition, TMS rMT is an important Furthermore, we minimized the risk of helmets ﬂoating in the superior tool to directly measure brain activity in zero gravity and more direction during 0 G by attaching chin straps to each helmet and having studies are needed to understand how the human brain adapts to the TMS administrator apply downward pressure to the TMS coil during zero gravity. the 0 G portions. All participants were additionally strapped into their seats with seatbelts. All motor thresholds were resting motor thresholds, with the participant’s right-hand resting palm-down on a foam pad with no MATERIALS AND METHODS 39 muscles working against gravity as described in Badran et al. . During the Study overview in-ﬂight acquisitions, this foam pad was attached to the participants thigh to keep it from ﬂoating away and an elastic band was strapped to it to We recruited 10 healthy adults (5 men, mean age= 41.0, SD= 11.0) in this ensure the arm was in an identical position to all Earth motor thresholds. multi-visit TMS cortical excitability experiment conducted in simulated zero We collected baseline rMT data to ensure repeatability and stability of gravity (0 G) environment induced by parabolic ﬂight (Zero Gravity Corporation, USA). Inclusion/exclusion criteria were as follows: Age the rMT of each participant. During each of the baseline visits, we collected between 25–61 years old, familiarity with TMS equipment, a baseline ﬁve separate rMTs spread 1 min apart. The automated PEST system started resting motor threshold lower than 90% of total machine output, no at 50% maximum stimulation output (MSO) for each participant and used a personal or familial history of seizures, no medications that would reduce series of incremental steps to determine the motor threshold. npj Microgravity (2020) 26 Published in cooperation with the Biodesign Institute at Arizona State University, with the support of NASA B.W. Badran et al. Fig. 3 The TMS helmets used in in this experiment were custom casted to all participant’s head. We created 10 of these helmets, one for each ﬂier. As visualized in this ﬁgure, helmets minimized any movement that could have been caused by weightlessness or shift in position. Fig. 4 Overview of our TMS experiment in parabolic ﬂight. a This diagram describes how the in-ﬂight data collection was conducted. Each team had a computer operator, TMS operator, and a participant. Participants were rotated every 5 parabolas during level ﬂight and received TMS using custom fabricated helmets that ﬁx the TMS coil to the scalp. All TMS and EMG equipment was strapped to the ﬂoor of the airplane ahead of the computer operator and plugged into the airplane power circuit. b Parabolic ﬂight simulates zero gravity by ﬂying parabolas that alternate ﬂiers between 1.8G and 0G. We administered TMS only during the 30 0G portions which each lasted approximately 20 seconds. Parabolic ﬂight TMS lab setup an rMT, shortening the time to <25 s, matching the limited time of microgravity induced during parabolic ﬂight (<25 s). A MOVIE has been Parabolic ﬂight was carried out in a modiﬁed Boeing 727 airplane prepared included that shows the research team A conducting the experiment in by Zero Gravity Corporation ﬂying out of Sanford Airport in Sanford, real time in footage from the ﬂight. Florida. We outﬁtted the plane with two mobile TMS laboratories capable For on-plane rMT collection while on the runway (pre- and post-ﬂight), of conducting closed-loop TMS with EMG recording and calculating an we collected 3 separate MTs for each participant spread 1 min apart. automated motor threshold in less than 20 s (Fig. 4a). The pattern of ﬂight During each 25 s period of microgravity, we collected one rMT per team. consisted of 30 parabolas, alternating between 1.8 G and 0 G as shown in We attempted to collect 5 rMT/subject. We collected a minimum of 3 MTs Fig. 4b. per participant (one rMT per parabola) and up to 5 MTs per participant All on-plane rMT collections used the same modiﬁed rMT script for depending on quality of acquisition. All on-plane MTs were conducted closed loop rMT determination. This modiﬁed script is a truncated version with the participant seated upright in a standard airplane seat. After 5 of the one used at the baseline the week before the ﬂight, and rather than parabolas, participants rotated from receiving TMS to a different study- starting at 50%, was started at each individual’s average baseline related task. determined rMT. This reduced the number of steps required to determine Published in cooperation with the Biodesign Institute at Arizona State University, with the support of NASA npj Microgravity (2020) 26 B.W. Badran et al. Emotional arousal ratings 9. Paulus, W. et al. 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Neurophysiol. 126, 1071–1107 (2015). npj Microgravity (2020) 26 Published in cooperation with the Biodesign Institute at Arizona State University, with the support of NASA B.W. Badran et al. 39. Badran, B. W. et al. Are EMG and visual observation comparable in determining ADDITIONAL INFORMATION resting motor threshold? A reexamination after twenty years. Brain Stimul. 12, Supplementary information is available for this paper at https://doi.org/10.1038/ 364–366 (2019). s41526-020-00116-6. Correspondence and requests for materials should be addressed to B.W.B. or D.R.R. ACKNOWLEDGEMENTS Reprints and permission information is available at http://www.nature.com/ We would like to acknowledge Dr. Nick Davey, a British neuroscientist who was likely reprints the ﬁrst researcher to conduct TMS in zero gravity aboard the Novospace A300 airbus parabolic ﬂight in 2003. We also would like to acknowledge Dr. Tony Barker, the Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional afﬁliations. inventor of modern TMS for his insight into the discussion. We thank Minnie Dobbins for her time in organizing the behind-the-scenes details required for successful science, and Dr. Christian Finetto for his last minute coding and technical support. This work is supported by the Translational Research Institute through NASA through NASA NNX16AO69A, National Center of Neuromodulation for Rehabilitation (NC Open Access This article is licensed under a Creative Commons NM4R) (5P2CHD086844–03), COBRE Brain Stimulation Core (5P20GM109040-04). Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party AUTHOR CONTRIBUTIONS material in this article are included in the article’s Creative Commons license, unless B.W.B., K.A.C., J.W.L., C.C., J.J.B., W.H.D., P.S., S.K., C.H., L.M., M.S.G., and D.R. contributed to indicated otherwise in a credit line to the material. If material is not included in the the planning, data collection, data analysis, interpretation, and writing of this manuscript. article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons. org/licenses/by/4.0/. COMPETING INTERESTS B.W.B. is listed as an inventor on a provisional patent related to the helmets described in this manuscript, which is assigned to the Medical University of South Carolina. © The Author(s) 2020 Published in cooperation with the Biodesign Institute at Arizona State University, with the support of NASA npj Microgravity (2020) 26
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