Inhibiting corticospinal excitability by entraining ongoing mu-alpha rhythm in motor cortex

AbstractsSensorimotor mu-alpha rhythm reflects the state of cortical excitability. Repetitive transcranial magnetic stimulation (rTMS) can modulate neural synchrony by inducing periodic electric fields (E-fields) in the cortical networks. We hypothesized that the increased synchronization of mu-alpha rhythm would inhibit the corticospinal excitability reflected by decreased motor evoked potentials (MEP). In seventeen healthy participants, we applied rhythmic, arrhythmic, and sham rTMS over the left M1. The stimulation intensity was individually adapted to 35 mV/mm using prospective E-field estimation. This intensity corresponded to ca. 40% of the resting motor threshold. We found that rhythmic rTMS increased the synchronization of mu-alpha rhythm, increased mu-alpha/beta power, and reduced MEPs. On the other hand, arrhythmic rTMS did not change the ongoing mu-alpha synchronization or MEPs, though it increased the alpha/beta power. We concluded that low intensity, rhythmic rTMS can synchronize mu-alpha rhythm and modulate the corticospinal excitability in M1.HighlightsWe studied the effect of rhythmic rTMS induced E-field at 35 mV/mm in the M1Prospective electric field modeling guided the individualized rTMS intensitiesRhyhtmic rTMS entrained mu-alpha rhythm and modulated mu-alpha/beta powerArrhythmic rTMS did not synchronize ongoing activity though increased mu-alpha/beta power.Rhythmic but not arrhythmic or sham rTMS inhibited the cortical excitability in M1

Download Full-text

Cerebellar rTMS and PAS effectively induce cerebellar plasticity

Scientific Reports ◽

10.1038/s41598-021-82496-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Martje G. Pauly ◽

Annika Steinmeier ◽

Christina Bolte ◽

Feline Hamami ◽

Elinor Tzvi ◽

...

Keyword(s):

Motor Cortex ◽

Healthy Subjects ◽

Primary Motor Cortex ◽

Cortical Excitability ◽

Motor Evoked Potentials ◽

Repetitive Transcranial Magnetic Stimulation ◽

Premotor Cortex ◽

Motor Pathways ◽

Non Invasive ◽

Cerebellar Plasticity

AbstractNon-invasive brain stimulation techniques including repetitive transcranial magnetic stimulation (rTMS), continuous theta-burst stimulation (cTBS), paired associative stimulation (PAS), and transcranial direct current stimulation (tDCS) have been applied over the cerebellum to induce plasticity and gain insights into the interaction of the cerebellum with neo-cortical structures including the motor cortex. We compared the effects of 1 Hz rTMS, cTBS, PAS and tDCS given over the cerebellum on motor cortical excitability and interactions between the cerebellum and dorsal premotor cortex / primary motor cortex in two within subject designs in healthy controls. In experiment 1, rTMS, cTBS, PAS, and tDCS were applied over the cerebellum in 20 healthy subjects. In experiment 2, rTMS and PAS were compared to sham conditions in another group of 20 healthy subjects. In experiment 1, PAS reduced cortical excitability determined by motor evoked potentials (MEP) amplitudes, whereas rTMS increased motor thresholds and facilitated dorsal premotor-motor and cerebellum-motor cortex interactions. TDCS and cTBS had no significant effects. In experiment 2, MEP amplitudes increased after rTMS and motor thresholds following PAS. Analysis of all participants who received rTMS and PAS showed that MEP amplitudes were reduced after PAS and increased following rTMS. rTMS also caused facilitation of dorsal premotor-motor cortex and cerebellum-motor cortex interactions. In summary, cerebellar 1 Hz rTMS and PAS can effectively induce plasticity in cerebello-(premotor)-motor pathways provided larger samples are studied.

Download Full-text

Low-intensity repetitive transcranial magnetic stimulation decreases motor cortical excitability in humans

Journal of Applied Physiology ◽

10.1152/japplphysiol.01399.2005 ◽

2006 ◽

Vol 101 (2) ◽

pp. 500-505 ◽

Cited By ~ 29

Author(s):

Gabrielle Todd ◽

Stanley C. Flavel ◽

Michael C. Ridding

Keyword(s):

Transcranial Magnetic Stimulation ◽

Magnetic Stimulation ◽

Cortical Excitability ◽

Repetitive Transcranial Magnetic Stimulation ◽

Motor Threshold ◽

Sham Stimulation ◽

Motor Cortical Excitability ◽

Resting Motor Threshold ◽

Active Motor ◽

Motor Cortical

Repetitive transcranial magnetic stimulation of the motor cortex (rTMS) can be used to modify motor cortical excitability in human subjects. At stimulus intensities near to or above resting motor threshold, low-frequency rTMS (∼1 Hz) decreases motor cortical excitability, whereas high-frequency rTMS (5–20 Hz) can increase excitability. We investigated the effect of 10 min of intermittent rTMS on motor cortical excitability in normal subjects at two frequencies (2 or 6 Hz). Three low intensities of stimulation (70, 80, and 90% of active motor threshold) and sham stimulation were used. The number of stimuli were matched between conditions. Motor cortical excitability was investigated by measurement of the motor-evoked potential (MEP) evoked by single magnetic stimuli in the relaxed first dorsal interosseus muscle. The intensity of the single stimuli was set to evoke baseline MEPs of ∼1 mV in amplitude. Both 2- and 6-Hz stimulation, at 80% of active motor threshold, reduced the magnitude of MEPs for ∼30 min ( P < 0.05). MEPs returned to baseline values after a weak voluntary contraction. Stimulation at 70 and 90% of active motor threshold and sham stimulation did not induce a significant group effect on MEP magnitude. However, the intersubject response to rTMS at 90% of active motor threshold was highly variable, with some subjects showing significant MEP facilitation and others inhibition. These results suggest that, at low stimulus intensities, the intensity of stimulation may be as important as frequency in determining the effect of rTMS on motor cortical excitability.

Download Full-text

Sham-derived effects and the minimal reliability of theta burst stimulation

Scientific Reports ◽

10.1038/s41598-021-98751-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

P. O. Boucher ◽

R. A. Ozdemir ◽

D. Momi ◽

M. J. Burke ◽

A. Jannati ◽

...

Keyword(s):

Motor Evoked Potentials ◽

Repetitive Transcranial Magnetic Stimulation ◽

Brain Activity ◽

Corticospinal Excitability ◽

Therapeutic Effects ◽

Theta Burst Stimulation ◽

Burst Stimulation ◽

Similar Time ◽

Repeat Visit ◽

Theta Burst

AbstractTheta-burst stimulation (TBS) is a patterned form of repetitive transcranial magnetic stimulation (rTMS) that has been used to induce long-term modulation (plasticity) of corticospinal excitability in a drastically shorter duration protocol than conventional rTMS protocols. In this study we tested the reliability of the effects of two well defined TBS protocols, continuous TBS (cTBS) and intermittent TBS (iTBS), especially in relation to sham TBS, within and across the same 24 participants. All TBS protocols were repeated after approximately 1 month to assess the magnitude and reliability of the modulatory effects of each TBS protocol. Baseline and post-TBS changes in motor evoked potentials (MEP—measure of corticospinal excitability) amplitudes were compared across the cTBS, iTBS and sham TBS protocols and between the initial and retest visits. Overall, across participants, at the initial visit, iTBS facilitated MEPs as compared to baseline excitability, with sham eliciting the same effect. cTBS did not show a significant suppression of excitability compared to baseline MEPs at either visit, and even facilitated MEPs above baseline excitability at a single time point during the repeat visit. Otherwise, effects of TBS were generally diminished in the repeat visit, with iTBS and sham TBS replicating facilitation of MEPs above baseline excitability at similar time points. However, no protocol demonstrated consistent intra-individual modulation of corticospinal excitability upon retest. As the first study to test both iTBS and cTBS against sham TBS across repeat visits, our findings challenge the efficacy and reliability of TBS protocols and emphasize the importance of accounting for sham effects of TBS. Furthermore, given that therapeutic effects of TBS are hypothetically derived from consistent and repeated modulation of brain activity, the non-replicability of plasticity and sham effects call into question these basic mechanisms.

Download Full-text

Weak rTMS-induced electric fields produce neural entrainment in humans

10.31234/osf.io/k2z8u ◽

2019 ◽

Author(s):

Elina Zmeykina ◽

Matthias Mittner ◽

Walter Paulus ◽

Zsolt Turi

Keyword(s):

Field Strength ◽

Electric Field ◽

Electric Field Strength ◽

Electric Fields ◽

Repetitive Transcranial Magnetic Stimulation ◽

Current Standard ◽

Conventional Dose ◽

Novel Approach ◽

Resting Motor Threshold ◽

Field Strengths

Repetitive transcranial magnetic stimulation (rTMS) is a potent tool for modulating endogenous oscillations in humans. The current standard dosing method for rTMS defines the electric field strength only indirectly. A better characterization of the electric field strength induced by a given rTMS protocol is necessary in order to improve the understanding of the neural mechanisms of rTMS. In this study we used a novel approach, in which individualized prospective computational modeling of the induced electric field guided the choice of stimulation intensity. We consistently found that rhythmic rTMS protocols increased neural synchronization in the posterior alpha frequency band when measured simultaneously with scalp electroencephalography. We observed this effect already at electric field strengths of roughly half the lowest conventional dose, which is 80% of the resting motor threshold. We conclude that rTMS can induce immediate electrophysiological effects at much weaker electric field strengths than previously thought.

Download Full-text

Changes in TMS measures induced by repetitive TMS

10.1093/oxfordhb/9780198832256.013.19 ◽

2021 ◽

Author(s):

Joseph Classen ◽

Ying-Zu Huang ◽

Christoph Zrenner

Keyword(s):

Primary Motor Cortex ◽

Motor Evoked Potentials ◽

Repetitive Transcranial Magnetic Stimulation ◽

Low Frequency ◽

Corticospinal Excitability ◽

After Effects ◽

Before And After ◽

Neurophysiological Mechanisms ◽

Synaptic Changes ◽

Theta Burst

Commonly used repetitive transcranial magnetic stimulation (rTMS) protocols, including regular rTMS, intermittent and continuous theta-burst stimulation (TBS) and quadripulse stimulation (QPS) are presented with respect to their induced neuromodulatory after-effects and the underlying cellular and synaptic neurophysiological mechanisms. The anatomical target is typically primary motor cortex since motor evoked potentials (MEPs) before and after the intervention can be used to assess effects of the respective rTMS protocol. High-frequency regular rTMS and intermittent TBS protocols tend to increase corticospinal excitability as indexed by MEP amplitude, whereas low-frequency regular rTMS and continuous TBS protocols tend to reduce corticospinal excitability. These effects are primarily due to LTP-like and LTD-like synaptic changes mediated by GABA and NMDA receptors. Changes in the balance between excitatory and inhibitory cortical microcircuits play a secondary role, with inconsistent effects as determined by paired-pulse TMS protocols. Finally, the challenge of large inter-subject response variability, and current directions of research to optimize rTMS effects through EEG-dependent personalized TMS are discussed.

Download Full-text

Acute Changes in Motor Cortical Excitability During Slow Oscillatory and Constant Anodal Transcranial Direct Current Stimulation

Journal of Neurophysiology ◽

10.1152/jn.00437.2009 ◽

2009 ◽

Vol 102 (4) ◽

pp. 2303-2311 ◽

Cited By ~ 35

Author(s):

Til Ole Bergmann ◽

Sergiu Groppa ◽

Markus Seeger ◽

Matthias Mölle ◽

Lisa Marshall ◽

...

Keyword(s):

Direct Current ◽

Transcranial Direct Current Stimulation ◽

Cortical Excitability ◽

Motor Evoked Potentials ◽

Corticospinal Excitability ◽

Slow Oscillation ◽

Facilitatory Effect ◽

Endogenous Rhythms ◽

Direct Current Stimulation ◽

On Line

Transcranial oscillatory current stimulation has recently emerged as a noninvasive technique that can interact with ongoing endogenous rhythms of the human brain. Yet, there is still little knowledge on how time-varied exogenous currents acutely modulate cortical excitability. In ten healthy individuals we used on-line single-pulse transcranial magnetic stimulation (TMS) to search for systematic shifts in corticospinal excitability during anodal sleeplike 0.8-Hz slow oscillatory transcranial direct current stimulation (so-tDCS). In separate sessions, we repeatedly applied 30-s trials (two blocks at 20 min) of either anodal so-tDCS or constant tDCS (c-tDCS) to the primary motor hand area during quiet wakefulness. Simultaneously and time-locked to different phase angles of the slow oscillation, motor-evoked potentials (MEPs) as an index of corticospinal excitability were obtained in the contralateral hand muscles 10, 20, and 30 s after the onset of tDCS. MEPs were also measured off-line before, between, and after both stimulation blocks to detect any lasting excitability shifts. Both tDCS modes increased MEP amplitudes during stimulation with an attenuation of the facilitatory effect toward the end of a 30-s tDCS trial. No phase-locking of corticospinal excitability to the exogenous oscillation was observed during so-tDCS. Off-line TMS revealed that both c-tDCS and so-tDCS resulted in a lasting excitability increase. The individual magnitude of MEP facilitation during the first tDCS trials predicted the lasting MEP facilitation found after tDCS. We conclude that sleep slow oscillation-like excitability changes cannot be actively imposed on the awake cortex with so-tDCS, but phase-independent on-line as well as off-line facilitation can reliably be induced.

Download Full-text

Transcranial static magnetic stimulation over the motor cortex can facilitate the contralateral cortical excitability in human

Scientific Reports ◽

10.1038/s41598-021-84823-4 ◽

2021 ◽

Vol 11 (1) ◽

Cited By ~ 2

Author(s):

Yasuyuki Takamatsu ◽

Satoko Koganemaru ◽

Tatsunori Watanabe ◽

Sumiya Shibata ◽

Yoshihiro Yukawa ◽

...

Keyword(s):

Motor Cortex ◽

Magnetic Stimulation ◽

Primary Motor Cortex ◽

Cortical Excitability ◽

Motor Evoked Potentials ◽

Single Pulse ◽

Brain Network ◽

Corticospinal Excitability ◽

Double Blind ◽

The Right

AbstractTranscranial static magnetic stimulation (tSMS) has been focused as a new non-invasive brain stimulation, which can suppress the human cortical excitability just below the magnet. However, the non-regional effects of tSMS via brain network have been rarely studied so far. We investigated whether tSMS over the left primary motor cortex (M1) can facilitate the right M1 in healthy subjects, based on the hypothesis that the functional suppression of M1 can cause the paradoxical functional facilitation of the contralateral M1 via the reduction of interhemispheric inhibition (IHI) between the bilateral M1. This study was double-blind crossover trial. We measured the corticospinal excitability in both M1 and IHI from the left to right M1 by recording motor evoked potentials from first dorsal interosseous muscles using single-pulse and paired-pulse transcranial magnetic stimulation before and after the tSMS intervention for 30 min. We found that the corticospinal excitability of the left M1 decreased, while that of the right M1 increased after tSMS. Moreover, the evaluation of IHI revealed the reduced inhibition from the left to the right M1. Our findings provide new insights on the mechanistic understanding of neuromodulatory effects of tSMS in human.

Download Full-text

Low-Frequency Repetitive Transcranial Magnetic Stimulation for Stroke-Induced Upper Limb Motor Deficit: A Meta-Analysis

Neural Plasticity ◽

10.1155/2017/2758097 ◽

2017 ◽

Vol 2017 ◽

pp. 1-12 ◽

Cited By ~ 16

Author(s):

Lan Zhang ◽

Guoqiang Xing ◽

Shiquan Shuai ◽

Zhiwei Guo ◽

Huaping Chen ◽

...

Keyword(s):

Transcranial Magnetic Stimulation ◽

Upper Limb ◽

Magnetic Stimulation ◽

Cortical Excitability ◽

Repetitive Transcranial Magnetic Stimulation ◽

Meta Analysis ◽

Low Frequency ◽

Motor Evoked Potential ◽

Motor Deficit ◽

Resting Motor Threshold

Background and Purpose. This meta-analysis aimed to evaluate the therapeutic potential of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) over the contralesional hemisphere on upper limb motor recovery and cortex plasticity after stroke.Methods. Databases of PubMed, Medline, ScienceDirect, Cochrane, and Embase were searched for randomized controlled trials published before Jun 31, 2017. The effect size was evaluated by using the standardized mean difference (SMD) and a 95% confidence interval (CI). Resting motor threshold (rMT) and motor-evoked potential (MEP) were also examined.Results. Twenty-two studies of 1 Hz LF-rTMS over the contralesional hemisphere were included. Significant efficacy was found on finger flexibility (SMD = 0.75), hand strength (SMD = 0.49), and activity dexterity (SMD = 0.32), but not on body function (SMD = 0.29). The positive changes of rMT (SMD = 0.38 for the affected hemisphere and SMD = −0.83 for the unaffected hemisphere) and MEP (SMD = −1.00 for the affected hemisphere and SMD = 0.57 for the unaffected hemisphere) were also significant.Conclusions. LF-rTMS as an add-on therapy significantly improved upper limb functional recovery especially the hand after stroke, probably through rebalanced cortical excitability of both hemispheres. Future studies should determine if LF-rTMS alone or in conjunction with practice/training would be more effective.Clinical Trial Registration Information. This trial is registered with unique identifierCRD42016042181.

Download Full-text

Repetitive transcranial magnetic stimulation on the modulation of cortical and spinal cord excitability in individuals with spinal cord injury

Restorative Neurology and Neuroscience ◽

10.3233/rnn-211167 ◽

2021 ◽

pp. 1-11

Author(s):

Thyciane Mendonça ◽

Rodrigo Brito ◽

Plínio Luna ◽

Mayara Campêlo ◽

Lívia Shirahige ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Transcranial Magnetic Stimulation ◽

Magnetic Stimulation ◽

Cortical Excitability ◽

Repetitive Transcranial Magnetic Stimulation ◽

Sham Stimulation ◽

Resting Motor Threshold ◽

Cord Injury ◽

Spinal Excitability

Background: Repetitive transcranial magnetic stimulation (rTMS) has been applied for modulating cortical excitability and treating spasticity in neurological lesions. However, it is unclear which rTMS frequency is most effective in modulating cortical and spinal excitability in incomplete spinal cord injury (SCI). Objective: To evaluate electrophysiological and clinical repercussions of rTMS compared to sham stimulation when applied to the primary motor cortex (M1) in individuals with incomplete SCI. Methods: A total of 11 subjects (35±12 years) underwent three experimental sessions of rTMS (10 Hz, 1 Hz and sham stimulation) in a randomized order at 90%intensity of the resting motor threshold and interspersed by a seven-day interval between sessions. The following outcome measures were evaluated: M1 and spinal cord excitability and spasticity in the moments before (baseline), immediately after (T0), 30 (T30) and 60 (T60) minutes after rTMS. M1 excitability was obtained through the motor evoked potential (MEP); spinal cord excitability by the Hoffman reflex (H-reflex) and homosynaptic depression (HD); and spasticity by the modified Ashworth scale (MAS). Results: A significant increase in cortical excitability was observed in subjects submitted to 10 Hz rTMS at the T0 moment when compared to sham stimulation (p = 0.008); this increase was also significant at T0 (p = 0.009), T30 (p = 0.005) and T60 (p = 0.005) moments when compared to the baseline condition. No significant differences were observed after the 10 Hz rTMS on spinal excitability or on spasticity. No inter-group differences were detected, or in the time after application of 1 Hz rTMS, or after sham stimulation for any of the assessed outcomes. Conclusions: High-frequency rTMS applied to M1 was able to promote increased cortical excitability in individuals with incomplete SCI for at least 60 minutes; however, it did not modify spinal excitability or spasticity.

Download Full-text

Enhanced corticospinal excitability with physiologically heightened sympathetic nerve activity

Journal of Applied Physiology ◽

10.1152/japplphysiol.01586.2011 ◽

2013 ◽

Vol 114 (4) ◽

pp. 429-435 ◽

Cited By ~ 12

Author(s):

Vasiliy E. Buharin ◽

Andrew J. Butler ◽

Justin K. Rajendra ◽

Minoru Shinohara

Keyword(s):

Sympathetic Nerve ◽

Sympathetic Nerve Activity ◽

Lower Body Negative Pressure ◽

Motor Evoked Potentials ◽

Corticospinal Excitability ◽

Control Group ◽

Nerve Activity ◽

Healthy Humans ◽

Resting Motor Threshold ◽

Experimental Group

Corticospinal excitability is modulated differently with norepinephrine and dopamine agonists, although both monoamines are released with heightened sympathetic nerve activity. The purpose of this study was to investigate the influence of physiological heightening of sympathetic nerve activity on corticospinal excitability in healthy humans. Subjects were divided into control and experimental groups. In each participant, motor-evoked potentials (MEPs) were measured from the resting first dorsal interosseous muscle of the right hand with transcranial magnetic stimulation (TMS) in two trials separated by 1 h. In the experimental group, sympathetic nerve activity was physiologically heightened during the second trial by applying lower body negative pressure (LBNP). In the control group, sympathetic nerve activity was not altered between the two trials. MEP peak-to-peak amplitude increased from trial 1 to trial 2 in the experimental group only. This increase was evident at a TMS intensity of 130% resting motor threshold and higher. It was concluded that physiological heightening of sympathetic nerve activity with LBNP enhances corticospinal excitability.

Download Full-text