Transcranial magnetic stimulation in non-human primates: A systematic review.

Transcranial magnetic stimulation (TMS) is widely employed as a tool to investigate and treat brain diseases. However, little is known about the direct effects of TMS on the brain. Non-human primates (NHPs) are a valuable translational model to investigate how TMS affects brain circuits given their neurophysiological similarity with humans and their capacity to perform complex tasks that approach human behavior. This systematic review aimed to identify studies using TMS in NHPs as well as to assess their methodological quality through a modified reference checklist. The results show high heterogeneity and superficiality in the studies regarding the report of the TMS parameters, which have not improved over the years. This checklist can be used for future TMS studies with NHPs to ensure transparency and critical appraisal. The use of the checklist would improve methodological soundness and interpretation of the studies, facilitating the translation of the findings to humans. The review also discusses how advancements in the field can elucidate the effects of TMS in the brain.

Effect of galvanic vestibular stimulation applied at the onset of stance on muscular activity and gait cycle duration in healthy individuals.

Locomotion requires the complex involvement of the spinal and supraspinal systems. So far, the role of vestibular input in gait has been assessed mainly with respect to gait stability. The noninvasive technique of galvanic vestibular stimulation (GVS) has been reported to decrease gait variability and increase gait speed, but the extent of its effect on spatiotemporal gait parameters is not fully known. Objective: Characterize vestibular responses during gait and determine the influence of GVS on cycle duration in healthy young participants. Methods: Fifteen right-handed individuals participated in the study. Electromyography (EMG) recordings of the bilateral soleus (SOL) and tibialis anterior muscles (TA) were performed. First, to determine stimulation intensity, an accelerometer placed on the vertex recorded the amplitude of the head tilts evoked by the GVS (1-4 mA, 200 ms) to establish a motor threshold (T). Second, while participants walked on a treadmill, GVS was applied at the onset of the stance phase during the treadmill gait with an intensity of 1 and 1.5 T with the cathode behind the right (RCathode) or left ear (LCathode). EMG traces were rectified, averaged (n = 30 stimuli), and analyzed. Latency, duration, and amplitude of vestibular responses as well as the mean duration of the gait cycles were measured. Results: GVS mainly induced long-latency responses in the right SOL, right TA and left TA. Only short-latency responses were triggered in the left SOL. Responses in the right SOL, left SOL and left TA were polarity dependent, being facilitatory with RCathode and inhibitory with LCathode, whereas responses in the right TA remained facilitatory regardless of the polarity. With the RCathode configuration, the stimulated cycle was prolonged compared with the control cycle at both 1 and 1.5 T, due to prolonged left SOL and TA EMG bursts, but no change was observed in right SOL and TA. With LCathode, GVS did not modify the cycle duration. Conclusion: During gait, a brief, low-intensity GVS pulse delivered at the right stance onset induced mainly long-latency polarity-dependent responses. Furthermore, a RCathode configuration increased the duration of the stimulated gait cycle by prolonging EMG activity on the anodic side. A similar approach could be explored to influence gait symmetry in individuals with neurological impairment.

Assessing head acceleration to identify a motor threshold to galvanic vestibular stimulation.

Galvanic vestibular stimulation (GVS) is used to assess vestibular system function, but vestibulospinal responses can exhibit variability depending on protocols or intensities used. Here, we measured head acceleration in healthy subjects to identify an objective motor threshold on which to base GVS intensity when assessing standing postural responses. Thirteen healthy right-handed subjects stood on a force platform, eyes closed, and head facing forward. An accelerometer was placed on the vertex to detect head acceleration, and electromyography activity of the right soleus was recorded. GVS (200 ms; current steps 0.5, from 1 mA to 4 mA) was applied in a binaural and bipolar configuration. 1) GVS induced a biphasic accelerometer response at a latency of 15 ms. Based on response amplitude, we constructed a recruitment curve for all participants and determined the motor threshold. In parallel, the method of limits was used to devise a more rapid approach to determine motor threshold. 2) We observed significant differences between motor threshold based on a recruitment curve and all perceptual thresholds reported either by the subject (sensation of movement) or a standing experimenter observing the participant (perception of movement). No significant difference was observed between the motor threshold based on the method of limits and perceptual thresholds of movement. 3) Using orthogonal polynomial contrasts, we observed a linear progression between multiples of the objective motor threshold (0.5, 0.75, 1, 1.5× motor threshold) and the 95% confidence ellipse area, the first peak of center of pressure displacement velocity, and the short and medium latency responses in the soleus. Hence, an objective motor threshold for GVS based on head acceleration was identified in standing participants and a recruitment curve could be constructed for all participants. These novel approaches could enable better understanding of changes in the vestibular system in different conditions or over time.NEW & NOTEWORTHY Galvanic vestibular stimulation (GVS) has been used to assess the vestibular system, but the significant interindividual variability in the responses makes it difficult to quantitatively compare them between individuals or conditions. Using an accelerometer to quantify head movement induced by GVS, we were able to determine an objective motor threshold and construct a recruitment curve for all participants. These methods could help assess changes in the vestibular system under different conditions.

Assessment of vestibulocortical interactions during standing in healthy subjects.

The vestibular system is essential to produce adequate postural responses enabling voluntary movement. However, how the vestibular system influences corticospinal output during postural tasks is still unknown. Here, we examined the modulation exerted by the vestibular system on corticospinal output during standing. Healthy subjects (n = 25) maintained quiet standing, head facing forward with eyes closed. Galvanic vestibular stimulation (GVS) was applied bipolarly and binaurally at different delays prior to transcranial magnetic stimulation (TMS) which triggered motor evoked potentials (MEPs). With the cathode right/anode left configuration, MEPs in right Soleus (SOL) muscle were significantly suppressed when GVS was applied at ISI = 40 and 130ms before TMS. With the anode right/cathode left configuration, no significant changes were observed. Changes in the MEP amplitude were then compared to changes in the ongoing EMG when GVS was applied alone. Only the decrease in MEP amplitude at ISI = 40ms occurred without change in the ongoing EMG, suggesting that modulation occurred at a premotoneuronal level. We further investigated whether vestibular modulation could occur at the motor cortex level by assessing changes in the direct corticospinal pathways using the short-latency facilitation of the SOL Hoffmann reflex (H-reflex) by TMS. None of the observed modulation occurred at the level of motor cortex. Finally, using the long-latency facilitation of the SOL H-reflex, we were able to confirm that the suppression of MEP at ISI = 40ms occurred at a premotoneuronal level. The data indicate that vestibular signals modulate corticospinal output to SOL at both premotoneuronal and motoneuronal levels during standing.