Decoding corticospinal excitability changes during a force tracking task

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.

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.

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.

Anodal transcranial direct current stimulation enhances time to task failure of a submaximal contraction of elbow flexors without changing corticospinal excitability

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.

Transient motor evoked potential suppression following a complex sensorimotor task

The relationship of corticospinal excitability with pain, motor performance and disability in subjects with chronic wrist/hand pain

Human motor cortex is capable of rapid and long-lasting reorganization, evident globally, as shifts in body part representations, and at the level of individual muscles as changes in corticospinal excitability. Representational shifts provide an overview of how various body parts reorganize relative to each other but do not tell us whether all muscles in a given body part reorganize in the same manner and to the same extent. Transcranial magnetic stimulation (TMS) provides information about individual muscles and can therefore inform us about the uniformity of plastic changes within a body part. We used TMS to investigate changes in corticospinal excitability of forearm flexors and extensors after inflation of a tourniquet around the wrist. Motor evoked potential (MEP) amplitudes and input/output (I/O) curves were obtained from wrist flexors and extensors simultaneously before and during block. TMS was delivered to the optimal site for eliciting MEPs in flexors in experiment 1, extensors in experiment 2, and both flexors and extensors in experiment 3. In all experiments flexor MEP amplitude increased during block while extensor MEP amplitude showed no systematic change, and the slope of flexor but not extensor I/O curves increased. Flexor H-reflex amplitude normalized to maximal M wave showed negligible changes during block, suggesting that the increase in corticospinal excitability in the flexors cannot be completely explained by increased excitability at the spinal cord level. These findings show that forearm flexors and extensors differ in their potential for plastic changes, highlight the importance of investigating how experimentally induced plasticity affects anatomically close, but functionally distinct, muscle groups, and suggest that rehabilitation interventions aiming to alter cortical organization should consider the differential sensitivity of various muscle groups to plasticity processes.

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.

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.

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.

While previous studies assessed corticospinal excitability changes during and after motor imagery (MI) or action observation (AO) combined with peripheral nerve electrical stimulation (ES), we examined, for the first time, the time course of corticospinal excitability changes for MI during AO combined with ES (AO-MI + ES) using transcranial magnetic stimulation to measure motor evoked potentials (MEPs) in healthy individuals. Fourteen healthy volunteers participated in the following three sessions on different days: AO-MI alone, ES alone, and AO-MI + ES. In the AO-MI task, participants imagined squeezing and relaxing a ball, along with the respective actions shown in a movie, while passively holding the ball. We applied ES (intensity, 90% of the motor threshold) to the ulnar nerve at the wrist, which innervates the first dorsal interosseous (FDI) muscle. We assessed the FDI muscle MEPs at baseline and after every 5min of the task for a total of 20min. Additionally, participants completed the Vividness of Movement Imagery Questionnaire-2 (VMIQ-2) at the beginning of the experiment. Compared to baseline, AO-MI + ES significantly increased corticospinal excitability after 10min, while AO-MI or ES alone had no effect on corticospinal excitability after 20min. Moreover, the AO-MI + ES-induced cortical excitability changes were correlated with the VMIQ-2 scores for visual and kinaesthetic imagery. Collectively, our findings indicate that AO-MI + ES induces cortical plasticity earlier than does AO-MI or ES alone and that an individual's imagery ability plays an important role in inducing cortical excitability changes following AO-MI + ES.

BackgroundNovel non-invasive brain stimulation techniques such as transcranial direct current stimulation (tDCS) have been developed in recent years. TDCS-induced corticospinal excitability changes depend on two important factors current intensity and stimulation duration. Despite clinical success with existing tDCS parameters, optimal protocols are still not entirely set.Objective/hypothesisThe current study aimed to investigate the effects of four different anodal tDCS (a-tDCS) current densities on corticospinal excitability.MethodsFour current intensities of 0.3, 0.7, 1.4 and 2 mA resulting in current densities (CDs) of 0.013, 0.029, 0.058 and 0.083 mA/cm2 were applied on twelve right-handed (mean age 34.5±10.32 yrs) healthy individuals in different sessions at least 48 hours apart. a-tDCS was applied continuously for 10 minute, with constant active and reference electrode sizes of 24 and 35 cm2 respectively. The corticospinal excitability of the extensor carpi radialis muscle (ECR) was measured before and immediately after the intervention and at 10, 20 and 30 minutes thereafter.ResultsPost hoc comparisons showed significant differences in corticospinal excitability changes for CDs of 0.013 mA/cm2 and 0.029 mA/cm2 (P = 0.003). There were no significant differences between excitability changes for the 0.013 mA/cm2 and 0.058 mA/cm2 (P = 0.080) or 0.013 mA/cm2 and 0.083 mA/cm2 (P = 0.484) conditions.ConclusionThis study found that a-tDCS with a current density of 0.013 mA/cm2 induces significantly larger corticospinal excitability changes than CDs of 0.029 mA/cm2. The implication is that might help to avoid applying unwanted amount of current to the cortical areas.

BackgroundRecent studies have shown that neurophysiological outcomes of transcranial direct current stimulation (TDCS) are influenced by current flow in brain regions between the electrodes, and in particular the orientation of current flow relative to the cortical surface. ObjectiveWe asked whether the directional effects of TDCS on physiological measures in the motor system would also be observed on motor behaviours. MethodsWe applied TDCS during the practice of a ballistic movement task to test whether it affected learning or the retention of learning 48 h later. TDCS electrodes were oriented perpendicular to the central sulcus and two current orientations were used (posterior-anterior, TDCSPA; and anterior-posterior, TDCSAP). Transcranial magnetic stimulation (TMS) was used to assess whether changes in corticospinal excitability reflected any behavioural changes. ResultsDirectional TDCSAP impaired the retention of learning on the ballistic movement task compared to TDCSPA and a sham condition. Although TDCSPA had no effect on learning or retention, it blocked the typical increase in corticospinal excitability after a period of motor practice. ConclusionsOur results extend on previous reports of TDCS producing directionally specific changes in neurophysiological outcomes by showing that current direction through a cortical target also impacts upon behavioural outcomes. In addition, changes in corticospinal excitability after a period of motor practice are not causally linked to behavioural learning.

Previous research has demonstrated a lack of neuroplasticity induced by acute exercise in low fit individuals, but the influence of exercise intensity is unclear. In the present study, we assessed the effect of acute high-intensity (HI) or moderate-intensity (MOD) interval exercise on neuroplasticity in individuals with low fitness, as determined by a peak oxygen uptake (VO2peak) test (n = 19). Transcranial magnetic stimulation (TMS) was used to assess corticospinal excitability via area under the motor evoked potential (MEP) recruitment curve before and following training. Corticospinal excitability was unchanged after HI and MOD, suggesting no effect of acute exercise on neuroplasticity as measured via TMS in sedentary, young individuals. Repeated bouts of exercise, i.e., physical training, may be required to induce short-term changes in corticospinal excitability in previously sedentary individuals.