Neuromodulatory effects and reproducibility of the most widely used repetitive transcranial magnetic stimulation protocols.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is widely used in both research and clinical settings to modulate human brain function and behavior through the engagement of the mechanisms of plasticity. Based upon experiments using single-pulse TMS as a probe, the physiologic mechanism of these effects is often assumed to be via changes in cortical excitability, with 10 Hz rTMS increasing and 1 Hz rTMS decreasing the excitability of the stimulated region. However, the reliability and reproducibility of these rTMS protocols on cortical excitability across and within individual subjects, particularly in comparison to robust sham stimulation, have not been systematically examined. OBJECTIVES: In a cohort of 28 subjects (39 ± 16 years), we report the first comprehensive study to (1) assess the neuromodulatory effects of traditional 1 Hz and 10 Hz rTMS on corticospinal excitability against both a robust sham control, and two other widely used patterned rTMS protocols (intermittent theta burst stimulation, iTBS; and continuous theta burst stimulation, cTBS), and (2) determine the reproducibility of all rTMS protocols across identical repeat sessions. RESULTS: At the group level, neither 1 Hz nor 10 Hz rTMS significantly modulated corticospinal excitability. 1 Hz and 10 Hz rTMS were also not significantly different from sham and both TBS protocols. Reproducibility was poor for all rTMS protocols except for sham. Importantly, none of the real rTMS and TBS protocols demonstrated greater neuromodulatory effects or reproducibility after controlling for potential experimental factors including baseline corticospinal excitability, TMS coil deviation and the number of individual MEP trials. CONCLUSIONS: These results call into question the effectiveness and reproducibility of widely used rTMS techniques for modulating corticospinal excitability, and suggest the need for a fundamental rethinking regarding the potential mechanisms by which rTMS affects brain function and behavior in humans.

Phase matters when there is power: Phasic modulation of corticospinal excitability occurs at high amplitude sensorimotor mu-oscillations.

Prior studies have suggested that oscillatory activity in cortical networks can modulate stimulus-evoked responses through time-varying fluctuations in neural excitation-inhibition dynamics. Studies combining transcranial magnetic stimulation (TMS) with electromyography (EMG) and electroencephalography (EEG) can provide direct measurements to examine how instantaneous fluctuations in cortical oscillations contribute to variability in TMS-induced corticospinal responses. However, the results of these studies have been conflicting, as some reports showed consistent phase effects of sensorimotor mu-rhythms with increased excitability at the negative mu peaks, while others failed to replicate these findings or reported unspecific mu-phase effects across subjects. Given the lack of consistent results, we systematically examined the modulatory effects of instantaneous and pre-stimulus sensorimotor mu-rhythms on corticospinal responses with offline EEG-based motor evoked potential (MEP) classification analyses across five identical visits. Instantaneous sensorimotor mu-phase or pre-stimulus mu-power alone did not significantly modulate MEP responses. Instantaneous mu-power analyses showed weak effects with larger MEPs during high-power trials at the overall group level analyses, but this trend was not reproducible across visits. However, TMS delivered at the negative peak of high magnitude mu-oscillations generated the largest MEPs across all visits, with significant differences compared to other peak-phase combinations. High power effects on MEPs were only observed at the trough phase of ongoing mu oscillations originating from the stimulated region, indicating site and phase specificity, respectively. More importantly, such phase-dependent power effects on corticospinal excitability were reproducible across multiple visits. We provide further evidence that fluctuations in corticospinal excitability indexed by MEP amplitudes are partially driven by dynamic interactions between the magnitude and the phase of ongoing sensorimotor mu oscillations at the time of TMS, and suggest promising insights for (re)designing neuromodulatory TMS protocols targeted to specific cortical oscillatory states.

Coordination of reach-to-grasp in physical and haptic-free virtual environments.

BACKGROUND: Virtual reality (VR) offers unprecedented opportunity as a scientific tool to study visuomotor interactions, training, and rehabilitation applications. However, it remains unclear if haptic-free hand-object interactions in a virtual environment (VE) may differ from those performed in the physical environment (PE). We therefore sought to establish if the coordination structure between the transport and grasp components remain similar whether a reach-to-grasp movement is performed in PE and VE. METHOD: Reach-to-grasp kinematics were examined in 13 healthy right-handed young adults. Subjects were instructed to reach-to-grasp-to-lift three differently sized rectangular objects located at three different distances from the starting position. Object size and location were matched between the two environments. Contact with the virtual objects was based on a custom collision detection algorithm. Differences between the environments were evaluated by comparing movement kinematics of the transport and grasp components. RESULTS: Correlation coefficients, and the slope of the regression lines, between the reach and grasp components were similar for the two environments. Likewise, the kinematic profiles of the transport velocity and grasp aperture were strongly correlated across the two environments. A rmANOVA further identified some similarities and differences in the movement kinematics between the two environments - most prominently that the closure phase of reach-to-grasp movement was prolonged when movements were performed in VE. CONCLUSIONS: Reach-to-grasp movement patterns performed in a VE showed both similarities and specific differences compared to those performed in PE. Additionally, we demonstrate a novel approach for parsing the reach-to-grasp movement into three phases- initiation, shaping, closure- based on established kinematic variables, and demonstrate that the differences in performance between the environments are attributed to the closure phase. We discuss this in the context of how collision detection parameters may modify hand-object interactions in VE. Our study shows that haptic-free VE may be a useful platform to study reach-to-grasp movements, with potential implications for haptic-free VR in neurorehabilitation.

Building knowledge of healthy eating in hospitalized youth: a self-regulated campaign.

BACKGROUND: Data from the World Health Organization shows obesity has more than doubled worldwide since 1980. Childhood obesity is mainly associated with external and modifiable factors, as eating habits, existing room for promoting healthy lifestyles. Additionally, learning can take place in contexts other than schools, as the hospital, potentiating the time of hospitalization. Self-regulated learning framework is suited to train the skills necessary for self-management processes and behavioral changes. The aim was to describe and evaluate a campaign designed to increase knowledge about healthy eating by hospitalized school-aged youth. METHOD: A quasi-experimental design was used. Participants were randomly distributed between the experimental and control groups, each one with 15 participants aged between six and 16 years-old. Information about healthy eating was not provided directly; participants had to reflect and work to build knowledge through activities inspired in the self-regulated learning framework. RESULTS: Results showed that the experimental group when compared with their counterparts significantly improved their knowledge on healthy eating after taking part in the campaign. CONCLUSIONS: Campaigns that increase knowledge on healthy eating based on the promotion of self-regulated learning strategies could be incorporated in health promotion programs not only in pediatric units but also in other educational contexts.