Online corticomotor modulations in action inhibition: Insights from TMS studies.

Control of digit forces for grasping relies on sensorimotor memory gained from prior experience with the same or similar objects and on online sensory feedback. However, little is known about neural mechanisms underlying digit force planning. We addressed this question by quantifying the temporal evolution of corticospinal excitability (CSE) using single-pulse transcranial magnetic stimulation (TMS) during two reach-to-grasp tasks. These tasks differed in terms of the magnitude of force exerted on the same points on the object to isolate digit force planning from reach and grasp planning. We also addressed the role of intracortical circuitry within primary motor cortex (M1) by quantifying the balance between short intracortical inhibition and facilitation using paired-pulse TMS on the same tasks. Eighteen right-handed subjects were visually cued to plan digit placement at predetermined locations on the object and subsequently to exert either negligible force ("low-force" task, LF) or 10% of their maximum pinch force ("high-force" task, HF) on the object. We found that the HF task elicited significantly smaller CSE than the LF task, but only when the TMS pulse coincided with the signal to initiate the reach. This force planning-related CSE modulation was specific to the muscles involved in the performance of both tasks. Interestingly, digit force planning did not result in modulation of M1 intracortical inhibitory and facilitatory circuitry. Our findings suggest that planning of digit forces reflected by CSE modulation starts well before object contact and appears to be driven by inputs from frontoparietal areas other than M1.

The motor system displays strong changes in neural activity during action preparation. In the past decades, several techniques, including transcranial magnetic stimulation (TMS), electroencephalography (EEG) and functional magnetic resonance imaging (fMRI), have allowed us to gain insights into the functional role of such preparatory activity in humans. More recently, new TMS tools have been proposed to study the mechanistic principles underlying the changes in corticospinal excitability during action preparation. The aim of the present review is to provide a comprehensive description of these advanced methods and to discuss the new knowledge they give access to, relative to other existing approaches. We start with a brief synthesis of the work that has been achieved so far using classic TMS protocols during action preparation, such as the so-called single-pulse and paired-pulse techniques. We then highlight three new approaches that recently arose in the field of action preparation, including (1) the exploitation of TMS current direction, known as directional TMS, which enables investigating different subsets of neurons in the primary motor cortex, (2) the use of paired-pulse TMS to study the suppressive influence of the cerebellum on corticospinal excitability and (3) the development of a double-coil TMS approach, which facilitates the study of bilateral changes in corticospinal excitability. The aim of the present article is twofold: we seek to provide a comprehensive description of these advanced TMS tools and to discuss their bearings for the field of action preparation with respect to more traditional TMS approaches, as well as to neuroimaging techniques such as EEG or fMRI. Finally, we point out perspectives for fundamental and clinical research that arise from the combination of these methods, widening the horizon of possibilities for the investigation of the human motor system, both in health and disease.

Modulation of corticospinal excitability by repetitive transcranial magnetic stimulation

PurposeAcute intermittent hypoxia (AIH) is a safe and non-invasive treatment approach that uses brief, repetitive periods of breathing reduced oxygen air alternated with normoxia. While AIH is known to affect spinal circuit excitability, the effects of AIH on cortical excitability remain largely unknown. We investigated the effects of AIH on cortical excitability within the primary motor cortex.MethodsEleven healthy, right-handed participants completed two testing sessions: (1) AIH (comprising 3 min in hypoxia [fraction of inspired oxygen ~ 10%] and 2 min in normoxia repeated over five cycles) and (2) normoxia (NOR) (equivalent duration to AIH). Single- and paired-pulse transcranial magnetic stimulations were delivered to the primary motor cortex, before and 0, 25, and 50 min after AIH and normoxia.ResultsThe mean nadir in arterial oxygen saturation was lower (p < 0.001) during the cycles of AIH (82.5 ± 4.9%) than NOR (97.8 ± 0.6%). There was no significant difference in corticospinal excitability, intracortical facilitation, or intracortical inhibition between AIH and normoxia conditions at any time point (all p > 0.05). There was no association between arterial oxygen saturation and changes in corticospinal excitability after AIH (r = 0.05, p = 0.87).ConclusionOverall, AIH did not modify either corticospinal excitability or excitability of intracortical facilitatory and inhibitory circuits within the primary motor cortex. Future research should explore whether a more severe or individualised AIH dose would induce consistent, measurable changes in corticospinal excitability.

Decoding corticospinal excitability changes during a force tracking task

This study examined the effect of temporal changes in corticospinal excitability in motor imagery (MI) and the effect of real-time guides for MI on excitability changes. The MI task involved wrist flexion and motor evoked potentials using transcranial magnetic stimulation were recorded and examined from the flexor carpi radialis. Ballistic (momentary MI) and tonic (continuous MI) conditions were used, and the duration of each MI was different. In Experiment 1, each MI task was performed using an acoustic trigger. In Experiment 2, a real-time guide was presented on a computer screen, which provided a visual indication of the onset and duration of the MI task through via moving dots on the screen. The results indicate that the corticospinal excitability changed differently, depending on the duration of MI. Additionally, with real-time guides, the change in corticospinal excitability became clearer. Thus, corticospinal excitability changes due to the temporal specificities of MI, as well as with actual motor output. Moreover, if MI is actively performed without a guide, it is likely to show an unintended change in corticospinal excitability. It is suggested that when MI is performed with visual guide, the excitatory changes of the corticospinal tract might be different from the actual motor output. Therefore, when using MI for mental practices, it is possible to improve the effect of a guide for MI, such as a visual indicator for motor output. Additionally, when examining neural activities in MI, it may be necessary to consider the characteristics of motion performed by MI.

IntroductionStudies using transcranial magnetic stimulation and electromyography suggest that disrupted functional corticospinal connectivity significantly contributes to difficulty in initiating and controlling voluntary movements such as walking. In individuals with Cerebral Palsy (CP), the corticospinal tract (CST) may therefore be identified as a potential target for improving gait control. Increasing corticospinal excitability may enhance voluntary control of lower-limb muscles and improve selective activation patterns during gait. However, it remains uncertain whether this pathway can be further activated given the damage caused by the brain lesion. Moreover, muscle synergies, a cooperative activation of groups of muscles, play an essential role in efficient and adaptive locomotion. Disrupted CST projections may reduce the specificity and strength of descending commands, which can lead to the fusion or splitting of muscle synergies. This impaired descending modulation could explain the reduced number of synergies and lower variance often reported in people with CP. Understanding and improving the modulation of these synergies could lead to better rehabilitation strategies for individuals with CP. The objective of this study was to assess whether a visuomotor walking task promotes an increase in corticospinal excitability and a modulation of muscle synergies compared to a simple walking task in individuals with CP.MethodsSixteen individuals with CP were initially recruited, muscle synergy analyses were conducted in 14 participants and TMS-based corticospinal excitability assessments in 11 participants, due to contraindications to TMS or technical issues. In addition, 14 control subjects took part in this study. Each participant performed a simple walking task and a visuomotor walking task (i.e., stepping onto virtual targets) at comfortable speed, in counterbalanced order. Transcranial magnetic stimulations were delivered during walking at approximately 40% of the gait cycle (late stance phase), corresponding to minimal tibialis anterior activity. Muscle synergies were extracted from full gait cycles recorded throughout each condition. Motor evoked potentials (MEPs) in the tibialis anterior muscle were induced using transcranial magnetic stimulation. Muscle synergies were extracted from surface electromyography signals acquired from six key lower-limb muscles during both tasks. Values were expressed as (median [Q1–Q3]).ResultsIn the visuomotor task, MEPs increased by 59.4% in the CP group (simple task MEP = 1.89 [1.00–3.09] a.u vs. visuomotor task MEP = 2.70 [1.59–4.80] a.u; p ≤ 0.01) and 113.8% in the control group (simple task MEP = 1.95 [0.99–2.72] a.u vs. visuomotor task MEP = 2.91 [1.97–3.66] a.u; p ≤ 0.01). An increase in the number of synergies was observed during visuomotor task in CP group (p = 0.018).ConclusionThese results suggest that performing a visuomotor walking task allows to enhance the corticospinal excitability in both individuals with CP and control subjects. Moreover, CP individuals showed that either the number or the structure of synergies are modulated by the visuomotor task, in comparison to control subjects. Longitudinal studies are recommended to assess the impact of the integration of complex tasks in gait rehabilitation interventions.

Recent transcranial magnetic stimulation studies have shown that the motor output pathway shows a profound inhibition during the preparation of an action. This phenomenon, called “preparatory inhibition”, remains incompletely understood, as it is still unclear which neural structures support it and what function it exactly serves during action preparation. In the current study, we tested this preparatory inhibition in Parkinson’s disease (PD) patients and matched healthy control subjects. The aim was to better understand the role of basal ganglia (which are dysfunctional in PD) and the influence of dopamine replacement therapy on motor inhibition during action preparation.

Action observation (AO) and motor imagery (MI) are used for the rehabilitation of patients who face difficulty walking. Rehabilitation involving AO, MI, and AO combined with MI (AO+MI) facilitates gait recovery after neurological disorders. However, the mechanism by which it positively affects gait function is unclear. We previously examined the neural mechanisms underlying AO and MI of walking, focusing on AO+MI and corticospinal and spinal motor neuron excitability, which play important roles in gait function. Herein, we investigated the effects of a short intervention using AO+MI of walking on the corticospinal and spinal motor neuron excitability and MI ability of participants. Twelve healthy individuals participated in this study, which consisted of a 20 min intervention. Before the experiment, we measured MI ability using the Vividness of Movement Imagery Questionnaire-2 (VMIQ-2). We used motor evoked potential and F-wave measurements to evaluate the corticospinal and spinal motor neuron excitability at rest, pre-intervention, 0 min, and 15 min post-intervention. We also measured corticospinal excitability during MI of walking and the participant’s ability to perform MI using a visual analog scale (VAS). There were no significant changes in corticospinal and spinal motor neuron excitability during and after the intervention using AO+MI (p>0.05). The intervention temporarily increased VAS scores, thus indicating clearer MI (p<0.05); however, it did not influence corticospinal excitability during MI of walking (p>0.05). Furthermore, there was no significant correlation between the VMIQ-2 and VAS scores and changes in corticospinal and spinal motor neuron excitability. Therefore, one short intervention using AO+MI increased MI ability in healthy individuals; however, it was insufficient to induce plastic changes at the cortical and spinal levels. Moreover, the effects of intervention using AO+MI were not associated with MI ability. Our findings provide information about intervention using AO+MI in healthy individuals and might be helpful in planning neurorehabilitation strategies.

Acute Exercise Modulates the Excitability of Specific Interneurons in Human Motor Cortex

Exploring the links between gut microbiota and excitatory and inhibitory brain processes in alcohol use disorder: A TMS study

Modulation of Corticospinal Excitability with Contralateral Arm Cycling

Background: Past studies of neurophysiological differences between the dominant (dM1) and non-dominant (NdM1) motor hemispheres in response to motor training have had equivocal results, possibly due to a lack of training task novelty. Understanding differences between brain hemispheres in the capacity for neural plasticity in response to motor learning is important for rehabilitation and occupational settings. Objective: Our first objective was to develop an index finger tracking task that was equally challenging to both hands. The second objective was to measure neurophysiological changes in the dM1 and NdM1 in response to task performance. Methods: In the first experiment, 12 right-handed males (mean age: 22.3, ±0.4 years; laterality index [LI] of 81.25±5.22) completed two training sessions of a tracing task designed to be equally novel and challenging for each hand, separated by 24 hours. In the second experiment, 20 right-handed males (M: 21.6 ±.0.4 years; [LI]=83.24±4.1) were randomly assigned to perform this training task with either hand. The slope of transcranial magnetic stimulation (TMS) input-output (IO) curves, was used to measure change in corticospinal excitability. Results: Both hands had similar improvement of motor performance across two days of training (40% decrease in motor error for dM1 and 41% decrease for NdM1). Only the right hand significantly decreased IO curve slope over time (F (1, 18)= 1.319 with p=0.034). Conclusion: This work suggests that the dM1 may adapt more quickly to tasks equally novel for each hand which has implications for the design of rehabilitation programs and devices. Keywords: Asymmetry, Motor Training, Handedness, Motor Performance, Primary Motor Cortex, Corticospinal excitability.

This study aimed to assess the effects of thoracic anodal and cathodal transcutaneous spinal direct current stimulation (tsDCS) on upper and lower limb corticospinal excitability. Although there have been studies assessing how thoracic tsDCS influences the spinal ascending tract and reflexes, none has assessed the effects of this technique over upper and lower limb corticomotor neuronal connections. In 14 healthy subjects we recorded motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) from abductor hallucis (AH) and hand abductor digiti minimi (ADM) muscles before (baseline) and at different time points (0 and 30 min) after anodal or cathodal tsDCS (2.5 mA, 20 min, T9-T11 level). In 8 of the 14 subjects we also tested the soleus H reflex and the F waves from AH and ADM before and after tsDCS. Both anodal and cathodal tsDCS left the upper limb MEPs and F wave unchanged. Conversely, while leaving lower limb H reflex unchanged, they oppositely affected lower limb MEPs: whereas anodal tsDCS increased resting motor threshold [(mean ± SE) 107.33 ± 3.3% increase immediately after tsDCS and 108.37 ± 3.2% increase 30 min after tsDCS compared with baseline] and had no effects on MEP area and latency, cathodal tsDCS increased MEP area (139.71 ± 12.9% increase immediately after tsDCS and 132.74 ± 22.0% increase 30 min after tsDCS compared with baseline) without affecting resting motor threshold and MEP latency. Our results show that tsDCS induces polarity-specific changes in corticospinal excitability that last for >30 min after tsDCS offset and selectively affect responses in lower limb muscles innervated by lumbar and sacral motor neurons.

Combined non-invasive brain stimulation (NIBS) and rehabilitation interventions have the potential to improve function in children with unilateral cerebral palsy (UCP), however their effects on developing brain function are not well understood. In a proof-of-principle study, we used single-pulse transcranial magnetic stimulation (TMS) to measure changes in corticospinal excitability and relationships to motor performance following a randomized controlled trial consisting of 10 days of combined constraint-induced movement therapy (CIMT) and cathodal transcranial direct current stimulation (tDCS) applied to the contralesional motor cortex. Twenty children and young adults (mean age = 12 years, 9 months, range = 7 years, 7 months, 21 years, 7 months) with UCP participated. TMS testing was performed before, after, and 6 months after the intervention to measure motor evoked potential (MEP) amplitude and cortical silent period (CSP) duration. The association between neurophysiologic and motor outcomes and differences in excitability between hemispheres were examined. Contralesional MEP amplitude decreased as hypothesized in five of five participants receiving active tDCS immediately after and 6 months after the intervention, however no statistically significant differences between intervention groups were noted for MEP amplitude [mean difference = −323.9 μV, 95% CI = (−989, 341), p = 0.34] or CSP duration [mean difference = 3.9 ms, 95% CI = (−7.7, 15.5), p = 0.51]. Changes in corticospinal excitability were not statistically associated with improvements in hand function after the intervention. Across all participants, MEP amplitudes measured in the more-affected hand from both contralesional (mean difference = −474.5 μV) and ipsilesional hemispheres (−624.5 μV) were smaller compared to the less-affected hand. Assessing neurophysiologic changes after tDCS in children with UCP provides an understanding of long-term effects on brain excitability to help determine its potential as a therapeutic intervention. Additional investigation into the neurophysiologic effects of tDCS in larger samples of children with UCP are needed to confirm these findings.