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BACKGROUND: In Parkinson's disease (PD), neurophysiological abnormalities within the primary motor cortex (M1) have been shown to contribute to bradykinesia, but exact modalities are still uncertain. We propose that such motor slowness could involve alterations in mechanisms underlying movement preparation, especially the suppression of corticospinal excitability-called "preparatory suppression"-which is considered to propel movement execution by increasing motor neural gain in healthy individuals. METHODS: On two consecutive days, 29 PD patients (on and off medication) and 29 matched healthy controls (HCs) underwent transcranial magnetic stimulation over M1, eliciting motor-evoked potentials (MEPs) in targeted hand muscles, while they were either at rest or preparing a left- or right-hand response in an instructed-delay choice reaction time task. Preparatory suppression was assessed by expressing MEP amplitudes during movement preparation relative to rest. RESULTS: Contrary to HCs, PD patients showed a lack of preparatory suppression when the side of the responding hand was analyzed, especially when the latter was the most affected one. This deficit, which did not depend on dopamine medication, increased with disease duration and also tended to correlate with motor impairment, as measured by the Movement Disorder Society Unified Parkinson's Disease Rating Scale, Part III (both total and bradykinesia scores). CONCLUSIONS: Our novel findings indicate that preparatory suppression fades in PD, in parallel with worsening motor symptoms, including bradykinesia. Such results suggest that an alteration in this marker of intact movement preparation could indeed cause motor slowness and support its use in future studies on the relation between M1 alterations and motor impairment in PD. © 2022 International Parkinson and Movement Disorder Society.

Reinforcement feedback can improve motor learning, but the underlying brain mechanisms remain underexplored. Especially, the causal contribution of specific patterns of oscillatory activity within the human striatum is unknown. To address this question, we exploited an innovative, non-invasive deep brain stimulation technique called transcranial Temporal Interference Stimulation (tTIS) during reinforcement motor learning with concurrent neuroimaging, in a randomised, sham-controlled, double-blind study. Striatal tTIS applied at 80Hz, but not at 20Hz, abolished the benefits of reinforcement on motor learning. This effect was related to a selective modulation of neural activity within the striatum. Moreover, 80Hz, but not 20Hz tTIS increased the neuromodulatory influence of the striatum on frontal areas involved in reinforcement motor learning. These results show for the first time that tTIS can non-invasively and selectively modulate a striatal mechanism involved in reinforcement learning, opening new horizons for the study of causal relationships between deep brain structures and human behaviour.

Vassiliadis P, Derosiere G, Grandjean J, Duque J. Motor training strengthens corticospinal suppression during movement preparation. J Neurophysiol 124: 1656-1666, 2020. First published September 30, 2020; doi:10.1152/jn.00378.2020.-Training can improve motor skills and modify neural activity at rest and during movement execution. Learning-related modulations may also concern motor preparation but the neural correlates and the potential behavioral relevance of such adjustments remain unclear. In humans, preparatory processes have been largely investigated using transcranial magnetic stimulation (TMS) with several studies reporting decreased corticospinal excitability (CSE) relative to a baseline measure at rest; a phenomenon called preparatory suppression. Here, we investigated the effect of motor training on such preparatory suppression, in relation to resting CSE, in humans. We trained participants to initiate quick movements in an instructed-delay reaction time (RT) task and used TMS to investigate changes in CSE over the practice blocks. Training on the task speeded up RTs, with no repercussion on error rates. Training also increased resting CSE. Most interestingly, we found that CSE during action preparation did not mirror the training-related increase observed at rest. Rather, compared with the rising baseline, the degree of preparatory suppression strengthened with practice. This training-related change in preparatory suppression (but not the changes in baseline CSE) predicted RT gains: the subjects showing a greater strengthening of preparatory suppression were also those exhibiting larger gains in RTs. Finally, such a relationship between RTs and preparatory suppression was also evident at the single-trial level, though only in the nonselected effector: RTs were generally faster in trials where preparatory suppression was deeper. These findings suggest that training induces changes in motor preparatory processes that are linked to an enhanced ability to initiate fast movements., NEW & NOTEWORTHY Movement preparation involves a broad suppression in the excitability of the corticospinal pathway, a phenomenon called preparatory suppression. Here, we show that motor training strengthens preparatory suppression and that this strengthening is associated with faster reaction times. Our findings highlight a key role of preparatory suppression in training-driven behavioral improvements.

Previous studies suggest that humans are capable of coregulating the speed of decisions and movements if promoted by task incentives. It is unclear however whether such behavior is inherent to the process of translating decisional information into movements, beyond posing a valid strategy in some task contexts. Therefore, in a behavioral online study we imposed time constraints to either decision- or movement phases of a sensorimotor task, ensuring that coregulating decisions and movements was not promoted by task incentives. We found that participants indeed moved faster when fast decisions were promoted and decided faster when subsequent finger tapping movements had to be executed swiftly. These results were further supported by drift diffusion modelling and inspection of psychophysical kernels: Sensorimotor delays related to initiating the finger tapping sequence were shorter in fast-decision as compared to slow-decision blocks. Likewise, the decisional speed-accuracy tradeoff shifted in favor of faster decisions in fast-tapping as compared to slow-tapping blocks. These findings suggest that decisions not only impact movement characteristics, but that properties of movement impact the time taken to decide. We interpret these behavioral results in the context of embodied decision-making, whereby shared neural mechanisms may modulate decisions and movements in a joint fashion.

In Parkinson’s disease, neurophysiological abnormalities within the primary motor cortex have been shown to contribute to cardinal symptoms such as bradykinesia, but the exact modalities are still uncertain. Here, we propose that such impairment could involve alterations of mechanisms shaping motor activity specifically during voluntary movement preparation. Indeed, several past studies in healthy populations have suggested that a strong suppression of corticospinal excitability called “preparatory suppression” – propels movement execution by increasing motor neural gain. Thus, we hypothesized that a gradual alteration to this mechanism may contribute to progressive motor slowness in Parkinson’s disease. We also predicted a benefit of dopamine medication in restoring correct motor neural activity during action preparation.To test these hypotheses, we investigated preparatory suppression on two consecutive days in 29 Parkinson’s disease patients (ON and OFF medication) and 29 matched healthy controls. Single-pulse transcranial magnetic stimulation was applied over both primary motor cortices, eliciting concurrent motor-evoked potentials in the two hands, while subjects were either at rest or prepared a left- or right-hand response in an instructed-delay choice reaction time task. Preparatory suppression was assessed by expressing the amplitude of motor potentials evoked during movement preparation relative to those obtained at rest. These neurophysiological measures were cross-analysed with task behaviour and clinical data.Contrary to healthy controls, Parkinson’s disease patients showed a lack of preparatory suppression, which appeared to depend on disease progression, but not on dopamine medication. Indeed, in relatively early disease stages, patients still exhibited partial preparatory suppression, while in later stages, they lacked it completely and even exhibited a tendency for corticospinal facilitation in the hand selected for movement execution. As expected, patients also showed increasing motor handicap with disease progression as well as a decreased movement velocity during the task, but such findings did not directly correlate with levels of preparatory suppression in our cohort. While dopamine medication had no effect on the latter, it did however globally reduce raw corticospinal excitability in the dominant hand.Taken together, our results are in line with the idea that a lack of corticospinal suppression during movement preparation in Parkinson’s disease slows down response execution and illustrate the importance of considering disease stages in such investigations; they also suggest differential roles of dopamine in shaping corticospinal output in those patients. Our findings thus support the use of task-related functional markers such as preparatory suppression in future studies on motor impairment in Parkinson’s disease.

Reward can improve motor learning and the consolidation of motor memories. Identifying the features of reward feedback that are critical for motor learning is a necessary step for successful integration into rehabilitation programs. One central feature of reward feedback that may affect motor learning is its timing – that is, the delay after which reward is delivered following movement execution. In fact, research on associative learning has shown that short and long reward delays (e.g., 1 and 6 s following action execution) activate preferentially the striatum and the hippocampus, respectively, which both contribute with varying degrees to motor learning. Given the distinct functional role of these two areas, we hypothesized that reward timing could modulate how people learn and consolidate a new motor skill. In sixty healthy participants, we found that delaying reward delivery by a few seconds influenced motor learning dynamics. Indeed, training with a short reward delay (i.e., 1 s) induced slow, yet continuous gains in performance, while a long reward delay (i.e., 6 s) led to initially high learning rates that were followed by an early plateau in the learning curve and a lower endpoint performance. Moreover, participants who successfully learned the skill with a short reward delay displayed overnight consolidation, while those who trained with a long reward delay exhibited an impairment in the consolidation of the motor memory. Overall, our data show that reward timing affects motor learning, potentially by modulating the engagement of different learning processes, a finding that could be exploited in future rehabilitation programs.

SummaryHumans and other animals are able to adjust their speed-accuracy tradeoff (SAT) at will depending on the urge to act, favoring either cautious or hasty decision policies in different contexts. An emerging view is that SAT regulation relies on influences exerting broad changes on the motor system, tuning its activity up globally when hastiness is at premium. The present study aimed to test this hypothesis. Fifty subjects performed a task involving choices between left and right index fingers, in which incorrect choices led either to a high or to a low penalty in two contexts, inciting them to emphasize either cautious or hasty policies. We applied transcranial magnetic stimulation on multiple motor representations, eliciting motor evoked potentials (MEP) in nine finger and leg muscles. MEP amplitudes allowed us to probe activity changes in the corresponding finger and leg representations, while subjects were deliberating about which index to choose. Our data indicate that hastiness entails a broad amplification of motor activity, though this amplification was limited to the chosen side. On top of this effect, we identified a local suppression of motor activity, surrounding the chosen index representation. Hence, a decision policy favoring speed over accuracy appears to rely on overlapping processes producing a broad (but not global) amplification and a surround suppression of motor activity. The latter effect may help to increase the signal-to-noise ratio of the chosen representation, as supported by single-trial correlation analyses indicating a stronger differentiation of activity changes in finger representations in the hasty context.

Humans and other animals often need to balance the desire to gather sensory information (to make the best choice) with the urgency to act, facing a speed-accuracy tradeoff (SAT). Given the ubiquity of SAT across species, extensive research has been devoted to understanding the computational mechanisms allowing its regulation at different timescales, including from one context to another, and from one decision to another. However, animals must frequently change their SAT on even shorter timescales – i.e., over the course of an ongoing decision – and little is known about the mechanisms that allow such rapid adaptations. The present study aimed at addressing this issue. Human subjects performed a decision task with changing evidence. In this task, subjects received rewards for correct answers but incurred penalties for mistakes. An increase or a decrease in penalty occurring halfway through the trial promoted rapid SAT shifts, favoring speeded decisions either in the early or in the late stage of the trial. Importantly, these shifts were associated with stage-specific adjustments in the accuracy criterion exploited for committing to a choice. Those subjects who decreased the most their accuracy criterion at a given decision stage exhibited the highest gain in speed, but also the highest cost in terms of performance accuracy at that time. Altogether, the current findings offer a unique extension of previous work, by suggesting that dynamic changes in accuracy criterion allow the regulation of the SAT within the timescale of a single decision.New and noteworthyExtensive research has been devoted to understanding the mechanisms allowing the regulation of the speed-accuracy tradeoff (SAT) from one context to another and from one decision to another. Here, we show that humans can voluntarily change their SAT on even shorter timescales – i.e., over the course of a decision. These rapid SAT shifts are associated with dynamic adjustments in the accuracy criterion exploited for committing to a choice.

By applying transcranial magnetic stimulation (TMS) over primary motor cortex (M1) to elicit motor-evoked potentials (MEPs) in muscles of the contralateral hand during reaction time (RT) tasks, many studies have reported a strong global suppression of motor excitability during action preparation, a phenomenon called preparatory inhibition. Several hypotheses have been put forward regarding the role of this broad suppression, with the predominant view that it reflects inhibitory processes assisting action selection. However, this assumption is still a matter of debate. Here, we aimed at directly addressing this idea by comparing MEPs in a task that required subjects to select a finger response within a set of predefined options (choice RT task: left or right index finger abduction) or when subjects simply had to provide the same finger response on every trial, in the absence of choice (simple RT task). Moreover, we minimized any effect that could be associated with other forms of inhibition. In both versions of the task, TMS was applied on both M1 (double-coil protocol) at several time points between the go signal and the left or right index finger response, eliciting MEPs bilaterally in the prime mover (index finger agonist) and in an irrelevant muscle (pinky agonist). Overall, MEP suppression was moderate in this study compared to past research; it was only found for the irrelevant muscle. As such, MEPs in the index agonist were facilitated when elicited in a responding hand (e.g. left MEPs preceding left responses) and remained mostly unchanged in a non-responding hand (e.g. left MEPs preceding right responses). In contrast, MEPs were almost always suppressed in the pinky muscle when elicited in the non-responding hand. This finding contrasts with previous studies where preparatory inhibition usually concerns both relevant and irrelevant muscles. Yet importantly, the suppression was more consistent in the choice than in the simple RT task, supporting the view that preparatory inhibition may assist action selection.

Summary Besides relying heavily on sensory and reinforcement feedback, motor skill learning may also depend on the level of motivation experienced during training. Yet, how motivation by reward modulates motor learning remains unclear. In 90 healthy subjects, we investigated the net effect of motivation by reward on motor learning while controlling for the sensory and reinforcement feedback received by the participants. Reward improved motor skill learning beyond performance-based reinforcement feedback. Importantly, the beneficial effect of reward involved a specific potentiation of reinforcement-related adjustments in motor commands, which concerned primarily the most relevant motor component for task success and persisted on the following day in the absence of reward. We propose that the long-lasting effects of motivation on motor learning may entail a form of associative learning resulting from the repetitive pairing of the reinforcement feedback and reward during training, a mechanism that may be exploited in future rehabilitation protocols., Graphical abstract, Highlights • Reward improves motor learning beyond performance-based reinforcement feedback • Reward boosts specifically reinforcement-based adjustments in motor commands • These effects persist on the following day, in the absence of reward, Neuroscience; Behavioral neuroscience; Sensory neuroscience; Cognitive neuroscience

Highlights: • Excessive preparatory excitatory drive is associated with hazardous drinking. • Deficient preparatory inhibitory drive only concerns severe alcohol use disorders. • Immersion in a virtual alcohol-related environment can increase craving. • Craving does not affect the strength of preparatory excitatory or inhibitory drive., Action preparation relies on the operation of control processes that modulate the excitability of the corticospinal tract. On the one hand, excitatory processes prepare the motor system for the forthcoming response; the stronger these influences, the stronger the tendency to act. On the other hand, inhibitory influences allow to suppress inappropriate actions and, more generally, to ensure some sort of impulse control. Because an impairment in these processes could foster inappropriate drinking behavior, the present study aimed at evaluating the motor correlates of such excitatory and inhibitory influences in non-treatment seeking heavy drinkers (HDs) and inpatients suffering from severe alcohol use disorder (SAUDs). Besides, as cue-elicited craving might further alter these processes, we also assessed the impact of an alcohol-related exposure. To do so, 15 healthy controls (HCs), 15 HDs and 15 SAUDs performed a choice reaction time task after having been immersed in a neutral or an alcohol-related environment, using virtual reality videos. Importantly, single-pulse transcranial magnetic stimulation was applied over the left and the right primary motor cortex during the task to elicit motor-evoked potentials in a set of hand muscles allowing us to specifically probe the impact of excitatory and inhibitory processes on motor activity. Our data indicate that excitatory influences are particularly high in both HDs and SAUDs, especially in the dominant hand, an effect that was not observed in HCs. By contrast, inhibitory influences were found to be perfectly normal in HDs, while they were lacking in SAUDs. Furthermore, the alcohol-related exposure enhanced the level of self-reported craving, but this effect only arose in HDs and did not significantly alter the strength of excitatory and inhibitory influences. Overall, although these results have to be taken with caution due to the small sample sizes, this study suggests that enhanced excitatory processes characterize both HDs and SAUDs, while weaker inhibitory influences only concern SAUDs. Hence, an abnormally strong tendency to act could represent a common feature of hazardous drinking, leading individuals to excessive alcohol consumption, whereas deficient impulse control would be a hallmark of more severe forms of AUD, potentially due to the chronic neurotoxic effects of alcohol. Finally, although an alcohol-related exposure does not seem to affect excitatory and inhibitory processes at play during action preparation per se, future works should evaluate changes in corticospinal excitability during the preparation of responses specifically targeting alcohol-related cues.

Prospective judgments about one’s capability to perform an action are assumed to involve mental simulation of the action. Previous studies of motor imagery suggest this simulation is supported by a large fronto-parietal network including the motor system. Experiment 1 used fMRI to assess the contribution of this fronto-parietal network to judgments about one’s capacity to grasp objects of different sizes between index and thumb. The neural network underlying prospective graspability judgments overlapped the fronto-parietal network involved in explicit motor imagery of grasping. However, shared areas were located in the right hemisphere, outside the motor cortex, and were also activated during perceptual length judgments, suggesting a contribution to object size estimate rather than motor simulation. Experiment 2 used TMS over the motor cortex to probe transient excitability changes undetected with fMRI. Results show that graspability judgments elicited a selective increase of excitability in the thumb and index muscles, which was maximal before the object display and intermediate during the judgment. Together, these findings suggest that prospective action judgments do not rely on the motor system to simulate the action per se but to refresh the memory of one’s maximal grip aperture and facilitate its comparison with object size in right fronto-parietal areas.

Inhibitory control underlies the ability to inhibit inappropriate responses and involves processes that suppress motor excitability. Such motor modulatory effect has been largely described during action preparation but very little is known about the neural circuit responsible for its implementation. Here, we addressed this point by studying the degree to which the extent of preparatory suppression relates to brain morphometry. We investigated this relationship in patients suffering from severe alcohol use disorder (AUD) because this population displays an inconsistent level of preparatory suppression and major structural brain damage, making it a suitable sample to measure such link. To do so, 45 detoxified patients underwent a structural magnetic resonance imaging (MRI) and performed a transcranial magnetic stimulation (TMS) experiment, in which the degree of preparatory suppression was quantified. Besides, behavioral inhibition and trait impulsivity were evaluated in all participants. Overall, whole-brain analyses revealed that a weaker preparatory suppression was associated with a decrease in cortical thickness of a medial prefrontal cluster, encompassing parts of the anterior cingulate cortex and superior-frontal gyrus. In addition, a negative association was observed between the thickness of the supplementary area (SMA)/pre-SMA and behavioral inhibition abilities. Finally, we did not find any significant correlation between preparatory suppression, behavioral inhibition and trait impulsivity, indicating that they represent different facets of inhibitory control. Altogether, the current study provides important insight on the neural regions underlying preparatory suppression and allows highlighting that the excitability of the motor system represents a valuable read-out of upstream cognitive processes.

Recent transcranial magnetic stimulation (TMS) research indicated that the ability of the dorsolateral prefrontal cortex (DLPFC) to disinhibit the contralateral primary motor cortex (M1) during motor preparation is an important predictor for bimanual motor performance in both young and older healthy adults. However, this DLPFC-M1 disinhibition is reduced in older adults. Here, we transiently suppressed left DLPFC using repetitive TMS (rTMS) during a cyclical bimanual task and investigated the effect of left DLPFC suppression: (1) on the projection from left DLPFC to the contralateral M1; and (2) on motor performance in 21 young (mean age ± SD = 21.57 ± 1.83) and 20 older (mean age ± SD = 69.05 ± 4.48) healthy adults. As predicted, without rTMS, older adults showed compromised DLPFC-M1 disinhibition as compared to younger adults and less preparatory DLPFC-M1 disinhibition was related to less accurate performance, irrespective of age. Notably, rTMS-induced DLPFC suppression restored DLPFC-M1 disinhibition in older adults and improved performance accuracy right after the local suppression in both age groups. However, the rTMS-induced gain in disinhibition was not correlated with the gain in performance. In sum, this novel rTMS approach advanced our mechanistic understanding of how left DLPFC regulates right M1 and allowed us to establish the causal role of left DLPFC in bimanual coordination. FUNDING This work was supported by the Hercules fund AUHL/11/01 (R-3987) awarded to RM, the Internal Research Fund KU Leuven (C16/15/070), the Research Foundation Flanders (Fonds Wetenschappelijk Onderzoek; FWO) grant (G089818N) and Excellence of Science grant (EOS 30446199, MEMODYN) awarded to SS and colleagues. ACKNOWLEDGMENTS We are thankful to R. Clerckx for his support in programming the bimanual tracking task and for his help in preprocessing the acquired task data. We additionally thank E. Ghasemian Shivran and several master students of KU Leuven and UHasselt who assisted with data collection. Helpful comments on the latest version of the manuscript were given by S. Depestele.

Interactive behaviors rely on the operation of several processes allowing the control of actions, including their selection, withholding, and cancellation. The corticospinal system provides a unique route through which multiple brain circuits can exert control over bodily motor acts. In humans, the influence of these modulatory circuits on the corticospinal system can be probed using various transcranial magnetic stimulation (TMS) protocols. Here, we review neural data from TMS studies at the basis of our current understanding of how diverse pathways—including intra-cortical, trans-cortical, and subcortico-cortical circuits—contribute to action control by tuning the activity of the corticospinal system. Critically, when doing so, we point out important caveats in the field that arise from the fact that these circuits, and their impact on the corticospinal system, have not been considered equivalently for action selection, withholding, and cancellation. This has led to the misleading view that some circuits or regions are specialized in specific control processes and that they produce particular modulatory changes in corticospinal excitability (e.g., generic vs. specific modulation of corticospinal excitability). Hence, we point to the need for more transversal research approaches in the field of action control.

Many behaviors require choosing between conflicting options competing against each other in visuomotor areas. Such choices can benefit from top-down control processes engaging frontal areas in advance of conflict when it is anticipated. Yet, very little is known about how this proactive control system shapes the visuomotor competition. Here, we used electroencephalography in human subjects (male and female) to identify the visual and motor correlates of conflict expectation in a version of the Eriksen Flanker task that required left or right responses according to the direction of a central target arrow surrounded by congruent or incongruent (conflicting) flankers. Visual conflict was either highly expected (it occurred in 80% of trials; mostly incongruent blocks) or very unlikely (20% of trials; mostly congruent blocks). We evaluated selective attention in the visual cortex by recording target- and flanker-related steady-state visual-evoked potentials (SSVEPs) and probed action selection by measuring response-locked potentials (RLPs) in the motor cortex. Conflict expectation enhanced accuracy in incongruent trials, but this improvement occurred at the cost of speed in congruent trials. Intriguingly, this behavioral adjustment occurred while visuomotor activity was less finely tuned: target-related SSVEPs were smaller while flanker-related SSVEPs were higher in mostly incongruent blocks than in mostly congruent blocks, and incongruent trials were associated with larger RLPs in the ipsilateral (nonselected) motor cortex. Hence, our data suggest that conflict expectation recruits control processes that augment the tolerance for inappropriate visuomotor activations (rather than processes that downregulate their amplitude), allowing for overflow activity to occur without having it turn into the selection of an incorrect response.SIGNIFICANCE STATEMENTMotor choices made in front of discordant visual information are more accurate when conflict can be anticipated, probably due to the engagement of top-down control from frontal areas. How this control system modulates activity within visual and motor areas is unknown. Here, we show that, when control processes are recruited in anticipation of conflict, as evidenced by higher midfrontal theta activity, visuomotor activity is less finely tuned: visual processing of the goal-relevant location was reduced and the motor cortex displayed more inappropriate activations, compared with when conflict was unlikely. We argue that conflict expectation is associated with an expansion of the distance-to-selection threshold, improving accuracy while the need for online control of visuomotor activity is reduced.

Impaired inhibitory control contributes to the development, maintenance, and relapse of alcohol-dependence, but the neural correlates of this deficit are still unclear. Because inhibitory control has been labeled as an executive function, most studies have focused on prefrontal areas, overlooking the contribution of more “primary” structures, such as the motor system. Yet, appropriate neural inhibition of the motor output pathway has emerged as a central aspect of healthy behavior. Here, we tested the hypothesis that this motor inhibition is altered in alcohol-dependence. Neural inhibitory measures of motor activity were obtained in 20 detoxified alcohol-dependent (AD) patients and 20 matched healthy subjects, using a standard transcranial magnetic stimulation procedure whereby motor-evoked potentials (MEPs) are elicited in a choice reaction time task. Moreover, behavioral inhibition and trait impulsivity were evaluated in all participants. Finally, the relapse status of patients was assessed 1 year after the experiment. As expected, AD patients displayed poorer behavioral inhibition and higher trait impulsivity than controls. More importantly, the MEP data revealed a considerable shortage of neural motor inhibition in AD patients. Interestingly, this neural defect was strongest in the patients who ended up relapsing during the year following the experiment. Our data suggest a strong motor component in the neural correlates of altered inhibitory control in AD patients. They also highlight an intriguing relationship with relapse and the perspective of a new biomarker to follow strategies aiming at reducing relapse in AD patients.

Transcranial magnetic stimulation (TMS) studies in humans have shown that many behaviors engage processes that suppress excitability within the corticospinal tract. Inhibition of the motor output pathway has been extensively studied in the context of action stopping, where a planned movement needs to be abruptly aborted. Recent TMS work has also revealed markers of motor inhibition during the preparation of movement. Here, we review the evidence for motor inhibition during action stopping and action preparation, focusing on studies that have used TMS to monitor changes in the excitability of the corticospinal pathway. We discuss how these physiological results have motivated theoretical models of how the brain selects actions, regulates movement initiation and execution, and switches from one state to another.

Decisions about actions typically involve a period of deliberation that ends with the commitment to a choice and the motor processes overtly expressing that choice. Previous studies have shown that neural activity in sensorimotor areas, including the primary motor cortex (M1), correlates with deliberation features during action selection. However, the causal contribution of these areas to the decision process remains unclear. Here, we investigated whether M1 determines choice commitment or whether it simply reflects decision signals coming from upstream structures and instead mainly contributes to the motor processes that follow commitment. To do so, we tested the impact of a disruption of M1 activity, induced by continuous theta burst stimulation (cTBS), on the behavior of human subjects in 1) a simple reaction time (SRT) task allowing us to estimate the duration of the motor processes and 2) a modified version of the tokens task (Cisek P, Puskas GA, El-Murr S. J Neurosci 29: 11560–11571, 2009), which allowed us to estimate subjects’ time of commitment as well as accuracy criterion. The efficiency of cTBS was attested by a reduction in motor evoked potential amplitudes following M1 disruption compared with those following a sham stimulation. Furthermore, M1 cTBS lengthened SRTs, indicating that motor processes were perturbed by the intervention. Importantly, all of the behavioral results in the tokens task were similar following M1 disruption and sham stimulation, suggesting that the contribution of M1 to the deliberation process is potentially negligible. Taken together, these findings favor the view that M1 contribution is downstream of the decision process. NEW & NOTEWORTHY Decisions between actions are ubiquitous in the animal realm. Deliberation during action choices entails changes in the activity of the sensorimotor areas controlling those actions, but the causal role of these areas is still often debated. With the use of continuous theta burst stimulation, we show that disrupting the primary motor cortex (M1) delays the motor processes that follow instructed commitment but does not alter volitional deliberation, suggesting that M1 contribution may be downstream of the decision process.

Motor-evoked potentials (MEPs), elicited by Transcranial Magnetic Stimulation (TMS) over the motor cortex, are reduced during the preparatory period in delayed response tasks. Here we examine how MEP suppression varies as a function of the anatomical organization of the motor cortex. MEPs were recorded from a left index muscle while participants prepared a hand or leg movement in Experiment 1, or prepared an eye or mouth movement in Experiment 2. In this manner, we assessed if the level of MEP suppression in a hand muscle varied as a function of the anatomical distance between the agonist for the forthcoming movement and the muscle targeted by TMS. MEPs suppression was attenuated when the cued effector was anatomically distant from the hand (e.g., leg or facial movement compared to finger movement). A similar effect was observed in Experiment 3 in which MEPs were recorded from a muscle in the leg and the forthcoming movement involved the upper limb or face. These results demonstrate an important constraint on preparatory inhibition: It is sufficiently broad to be manifest in a muscle that is not involved in the task, but is not global, showing a marked attenuation when the agonist muscle belongs to a different segment of the body.New & NoteworthyUsing TMS, we examine changes in corticospinal excitability as people prepare to move. Consistent with previous work, we observe a reduction in excitability during the preparatory period, an effect observed in both task relevant and task irrelevant muscles. However, this preparatory inhibition is anatomically constrained, attenuated in muscles belonging to a different body segment than the agonist of the forthcoming movement.

Motor decisions entails a buildup of choice-selective activity in the motor cortex. The rate of this buildup crucially depends on the amount of evidence favoring the selection of each action choice in the visual environment. Though numerous studies have characterized how sensory evidence drives motor activity when processed consciously, very little is known about the neural mechanisms that underlie the integration of implicit sources of information. Here, we used electroencephalography to investigate the impact of implicit visual cues on response-locked potentials and oscillatory activity in the motor cortex during decision-making. Subjects were required to select between left and right index finger responses according to the motion direction of a cloud of dots presented in one of three possible colors. Unbeknown to the participants, the color cue could bring evidence either in favor of or against the selection of the correct response. Implicit color cues tuned choice-selective oscillatory activity in the low beta range (16–25 Hz), boosting the buildup of contralateral activity when evidence favored the selection of the correct action, while weakening it when evidence biased against the correct response. This modulation of oscillatory activity influenced the speed at which the correct action was eventually chosen. Implicit cues also altered oscillatory activity in a non-selective way in the low frequency oscillation (1–7 Hz) and high beta ranges (25–35 Hz), impacting both contralateral and ipsilateral activity. The current findings yield a critical extension of prior observations by indicating that the integration of both explicit and implicit sources of evidence tunes oscillatory motor activity during decision-making.

The role of the dorsolateral prefrontal cortex (DLPFC) in the regulation of bimanual coordination appears to become crucial with aging. Age-related changes in the involvement of the DLPFC in bimanual coordination were studied by using disruptive repetitive TMS (rTMS), inducing a transient lesion in this brain structure. Neurophysiological as well as behavioral effects of suppressing DLPFC during the preparation and execution of a bimanual task were studied in 41 healthy adults (young and old). Specifically, we combined short-train rTMS with single pulse TMS to examine the effect of DLPFC suppression on the interhemispheric projection to the contralateral primary motor cortex (M1) during motor preparation. Findings revealed that compromised interhemispheric DLPFC-M1 disinhibition during motor preparation in older adults resulted in less accurate bimanual performance. The altered DLPFC-M1 interaction in older adults appeared to result from a decline in local inhibitory mechanisms in the DLPFC. In addition, the induction of DLPFC suppression affected task accuracy, but not movement stability in both age groups. Taken together, these results suggest that DLPFC acts as a key regulator in the control of bimanual movement coordination.

By applying transcranial magnetic stimulation (TMS) over the primary motor cortex (M1) to elicit motor-evoked potentials (MEPs) in muscles of the contralateral hand during reaction time (RT) tasks, many studies have reported a strong suppression of MEPs during action preparation, a phenomenon called preparatory inhibition. Several hypotheses have been put forward regarding the role of this inhibition, with the predominant view suggesting that it would help action selection. However, this assumption is still a matter of debate. Here, we aimed at directly addressing this idea by comparing MEPs in a task that required subjects to select a finger response within a set of predefined options (choice RT task: left or right index finger abduction) or when subjects simply had to provide the same finger response on every trial, in the absence of choice (simple RT task). Moreover, we minimized any effect that could be associated with other forms of inhibition. In both versions of the task, TMS was applied on both M1 (double-coil protocol) at several time points between the go signal and the left or right index finger response, eliciting MEPs bilaterally in the prime mover (index finger agonist) and in an irrelevant muscle (pinky agonist). Overall, MEP suppression was moderate in this study; it was only found for the irrelevant muscle. As such, MEPs in the index agonist were facilitated when elicited in a responding hand (e.g. left MEPs preceding left responses) and remained mostly unchanged in a non-responding hand (e.g. left MEPs preceding right responses). In contrast, MEPs were almost always suppressed in the pinky muscle when elicited in the non-responding hand and sometimes also in the responding hand. Importantly, this effect was more consistent in the choice than in the simple RT task, supporting the view that preparatory inhibition may assist action selection. Moreover, the fact that it sometimes concerned the responding hand is coherent with the idea of a global process, suppressing broadly the motor system.

Decisions about actions typically involve a period of deliberation that ends with the commitment to a choice and the motor processes overtly expressing that choice. Previous studies have shown that neural activity in sensorimotor areas, including the primary motor cortex (M1), correlates with deliberation features during action selection. Yet, the causal contribution of these areas to the decision process remains unclear. Here, we investigated whether M1 determines choice commitment, or whether it simply reflects decision signals coming from upstream structures and instead mainly contributes to the motor processes that follow commitment. To do so, we tested the impact of a disruption of M1 activity, induced by continuous theta burst stimulation (cTBS), on the behavior of human subjects in (1) a simple reaction time (SRT) task allowing us to estimate the duration of the motor processes and (2) a modified version of the tokens task (Cisek et al., 2009), which allowed us to estimate subjects’ time of commitment as well as accuracy criterion. The efficiency of cTBS was attested by a reduction in motor evoked potential amplitudes following M1 disruption, as compared to those following a sham stimulation. Furthermore, M1 cTBS lengthened SRTs, indicating that motor processes were perturbed by the intervention. Importantly, all of the behavioral results in the tokens task were similar following M1 disruption and sham stimulation, suggesting that the contribution of M1 to the deliberation process is potentially negligible. Taken together, these findings favor the view that M1 contribution is downstream of the decision process.New and noteworthyDecisions between actions are ubiquitous in the animal realm. Deliberation during action choices entails changes in the activity of the sensorimotor areas controlling those actions, but the causal role of these areas is still often debated. Using continuous theta burst stimulation, we show that disrupting the primary motor cortex (M1) delays the motor processes that follow instructed commitment but does not alter volitional deliberation, suggesting that M1 contribution may be downstream of the decision process.

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.

Transcranial magnetic stimulation (TMS) applied over the primary motor cortex (M1), elicits motor-evoked potentials (MEPs) in contralateral limb muscles which are valuable indicators of corticospinal excitability (CSE) at the time of stimulation. So far, most studies have used single-coil TMS over one M1, yielding MEPs in muscles of a single limb—usually the hand. However, tracking CSE in the two hands simultaneously would be useful in many contexts. We recently showed that, in the resting state, double-coil stimulation of the two M1 with a 1 ms inter-pulse interval (double-coil1 ms TMS) elicits MEPs in both hands that are comparable to MEPs obtained using single-coil TMS. To further evaluate this new technique, we considered the MEPs elicited by double-coil1 ms TMS in an instructed-delay choice reaction time task where a prepared response has to be withheld until an imperative signal is displayed. Single-coil TMS studies have repetitively shown that in this type of task, the motor system is transiently inhibited during the delay period, as evident from the broad suppression of MEP amplitudes. Here, we aimed at investigating whether a comparable inhibitory effect can be observed with MEPs elicited using double-coil1 ms TMS. To do so, we compared the amplitude as well as the coefficient of variation (CV) of MEPs produced by double-coil1 ms or single-coil TMS during action preparation. We observed that MEPs were suppressed (smaller amplitude) and often less variable (smaller CV) during the delay period compared to baseline. Importantly, these effects were equivalent whether single-coil or double-coil1 ms TMS was used. This suggests that double-coil1 ms TMS is a reliable tool to assess CSE, not only when subjects are at rest, but also when they are involved in a task, opening new research horizons for scientists interested in the corticospinal correlates of human behavior.

A fundamental function of nociception is to trigger defensive motor responses to threatening events. Here, we explored the effects of phasic pain on the motor excitability of ipsilateral and contralateral arms. We reasoned that the occurrence of a short-lasting nociceptive stimulus should result in a specific modulation of motor excitability for muscles involved in the withdrawal of the stimulated limb. This was assessed using transcranial magnetic stimulation (TMS) of the left and right primary motor cortex to elicit motor-evoked potentials (MEPs) in three flexor and two extensor muscles of both arms. To assess the time-course of nociception-motor interactions, TMS pulses were triggered 50–2000 ms after delivering short-lasting nociceptive laser stimuli to the left or right hand. We made three main observations. First, nociceptive stimuli induced an early-latency (100 ms) enhancement of MEPs in flexor muscles of the stimulated hand. Considering its latency, this modulation is likely consequent to nociceptive-motor interactions at spinal level. This early and lateralized enhancement was followed by a later (150–400 ms) MEP reduction in extensor muscles of the stimulated hand and flexor muscles of both hands, predominant at the stimulated hand. Finally, we observed a long-lasting (600–2000 ms) MEP enhancement in muscles of the non-stimulated hand. These later effects of the nociceptive stimulus could reflect nociception-motor interactions occurring at cortical level.

Summary Objectives Motor-evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) show a profound suppression when elicited during the instructed-delay of reaction time (RT) tasks. One predominant hypothesis is that this phenomenon, called “preparatory inhibition”, reflects the operation of processes that suppress motor activity to withhold prepared (but delayed) responses, a form of impulse control. In addition, a startling acoustic stimulus (SAS) – a loud and narrow sound – can trigger the release of prepared responses in RT tasks. We predicted that, if such premature release is clearly forbidden, then anticipating a SAS during delay periods may be associated with increased preparatory inhibition for greater impulse control. Methods Subjects performed a behavioural (n = 16) and TMS (n = 11) experiment. Both used a choice RT task that required subjects to choose a response based on a preparatory cue but to only release it after an imperative signal. SAS and TMS pulses were elicited at the end of the delay period and subjects were asked to do their best to only release their response after the imperative signal, even in the presence of SAS. SAS could be either rare or frequent, in separate blocks. Results Consistent with the literature, SAS shortened RTs, especially when they occurred frequently. Moreover, MEPs were suppressed when subjects delayed prepared responses but this preparatory inhibition did not depend on whether SAS were frequent or rare. Discussion The stronger RT shortening with frequent rather than rare SAS may be due to increased attention and/or reduced reactive inhibition to SAS, leaving preparatory inhibition unaffected.