The role of dorsal premotor cortex in joint action inhibition.

Behavioral interpersonal coordination requires smooth negotiation of actions in time and space (joint action-JA). Inhibitory control may play a role in fine-tuning appropriate coordinative responses. To date, little research has been conducted on motor inhibition during JA and on the modulatory influence that premotor areas might exert on inhibitory control. Here, we used an interactive task in which subjects were required to reach and open a bottle using one hand. The bottle was held and stabilized by a co-actor (JA) or by a mechanical holder (vice clamp, no-JA). We recorded two TMS-based indices of inhibition (short-interval intracortical inhibition-sICI; cortical silent period-cSP) during the reaching phase of the task. These reflect fast intracortical (GABAa-mediated) and slow corticospinal (GABAb-mediated) inhibition. Offline continuous theta burst stimulation (cTBS) was used to interfere with dorsal premotor cortex (PMd), ventral premotor cortex (PMv), and control site (vertex) before the execution of the task. Our results confirm a dissociation between fast and slow inhibition during JA coordination and provide evidence that premotor areas drive only slow inhibitory mechanisms, which in turn may reflect behavioral co-adaptation between trials. Exploratory analyses further suggest that PMd, more than PMv, is the key source of modulatory drive sculpting movements, according to the socio-interactive context.

Stop affordance task: a measure of the motor interference effect.

The term affordance refers to the property or quality of an object that indicates the ways in which it could potentially be used. Affordances elicit automatic motor representations that sometimes differ from the current action representation, resulting in behavioural interference effects. This affordance-induces interference could result in automatic and involuntary behavioural inhibition, probably according to the same mechanism that controls the voluntary motor inhibition. Nevertheless, few studies have considered how voluntary response inhibition is modulated by affordance. In this study, we assess the effect of affordance on voluntary action inhibition using a stop-signal task with an affordance object as a Stop Signal. An image of a mug, with the handle orientated in the same or in the opposite direction of the hand recruited to respond at the target, was used as Stop Signal. Our results showed a reduction of the time necessary to withhold the response when the handle of the mug was pointed toward the hand pre-activated to respond. This effect indicates an increased inhibition due to the mismatch between the motor representation elicited by the affordance and the motor representation pre-activated by the target. This suggests a specific interference effect, reflected in an enhanced ability to inhibit an ongoing action.

Cortico-cortical paired associative stimulation conditioning superficial ventral premotor cortex-primary motor cortex connectivity influences motor cortical activity during precision grip.

The ventral premotor cortex (PMv) and primary motor cortex (M1) represent critical nodes of a parietofrontal network involved in grasping actions, such as power and precision grip. Here, we investigated how the functional PMv-M1 connectivity drives the dissociation between these two actions. We applied a PMv-M1 cortico-cortical paired associative stimulation (cc-PAS) protocol, stimulating M1 in both postero-anterior (PA) and antero-posterior (AP) directions, in order to induce long-term changes in the activity of different neuronal populations within M1. We evaluated the motor-evoked potential (MEP) amplitude, MEP latency and cortical silent period, in both PA and AP, during the isometric execution of precision and power grip, before and after the PMv-M1 cc-PAS. The repeated activation of the PMv-M1 cortico-cortical network with PA orientation over M1 did not change MEP amplitude or cortical silent period duration during both actions. In contrast, the PMv-M1 cc-PAS stimulation of M1 with an AP direction led to a specific modulation of precision grip motor drive. In particular, MEPs tested with AP stimulation showed a selective increase of corticospinal excitability during precision grip. These findings suggest that the more superficial M1 neuronal populations recruited by the PMv input are involved preferentially in the execution of precision grip actions. KEY POINTS: Ventral premotor cortex (PMv)-primary motor cortex (M1) cortico-cortical paired associative stimulation (cc-PAS) with different coil orientation targets dissociable neural populations. PMv-M1 cc-PAS with M1 antero-posterior coil orientation specifically modulates corticospinal excitability during precision grip. Superficial M1 populations are involved preferentially in the execution of precision grip. A plasticity induction protocol targeting the specific PMv-M1 subpopulation might have important translational value for the rehabilitation of hand function.

Mechanisms of Hebbian-like plasticity in the ventral premotor - primary motor network.

The functional connection between ventral premotor cortex (PMv) and primary motor cortex (M1) is critical for the organization of goal-directed actions. Repeated activation of this connection by means of cortico-cortical paired associative stimulation (cc-PAS), a transcranial magnetic stimulation (TMS) protocol, may induce Hebbian-like plasticity. However, the physiological modifications produced by Hebbian-like plasticity in the PMv-M1 network are poorly understood. To fill this gap, we investigated the effects of cc-PAS on PMv-M1 circuits. We hypothesized that specific interactions would occur with I2 -wave interneurons as measured by the short intracortical facilitation protocol (SICF). We used different paired-pulse TMS protocols to examine the effects of PMv-M1 cc-PAS on SICF, on GABAergic circuits as measured by short (SICI) and long (LICI) intracortical inhibition protocols, and varied the current direction in M1 to target different M1 neuronal populations. Finally, we examined the effects of cc-PAS on PMv-M1 connectivity using a dual coil approach. We found that PMv-M1 cc-PAS induces both a long-term potentiation (LTP)- or long-term depression (LTD)-like after-effect in M1 neuronal activity that is strongly associated with a bidirectional-specific change in I2 -wave activity (SICF = 2.5 ms ISI). Moreover, cc-PAS induces a specific modulation of the LICI circuit and separately modulates PMv-M1 connectivity. We suggest that plasticity within the PMv-M1 circuit is mediated by a selective mechanism exerted by PMv on M1 by targeting I2 -wave interneurons. These results provide new mechanistic insights into how PMv modulates M1 activity that are relevant for the design of brain stimulation protocols in health and disease. KEY POINTS: The I2 -wave is specifically modulated by the induction of ventral premotor cortex - primary motor cortex (PMv-M1) plasticity. After PMv-M1 cortico-cortical paired associative stimulation (cc-PAS), corticospinal excitability correlates negatively with I2 -wave amplitude. Different cc-PAS coil orientations can lead to a long-term potentiation- or long-term depression-like after-effect in M1.

The role of dorsal premotor cortex in joint action stopping.

Human sensorimotor interaction requires mutual behavioral adaptation as well as shared cognitive task representations (Joint Action, JA). Yet, an under-investigated aspect of JA is the neurobehavioral mechanisms employed to stop actions if the context calls for it. Sparse evidence points to the possible contribution of the left dorsal premotor cortex (lPMd) in sculpting movements according to the socio-interactive context. To clarify this issue, we ran two experiments integrating a classical stop signal paradigm with an ecological JA task. The first behavioral study shows longer Stop performance in the JA condition. In the second, we use transcranial magnetic stimulation to inhibit the lPMd or a control site (vertex). Results show that lPMd modulates the JA stopping performance. Action stopping is an important component of JA coordination, and here we provide evidence that lPMd is a key node of a brain network recruited for online mutual co-adaptation in social contexts.

Parallel fast and slow motor inhibition processes in Joint Action coordination.

Motor inhibition is essential to adapt to an ever-changing environment and to noise in state prediction. As a consequence, inhibitory motor control must also play a key role during Joint Action (JA) tasks, where the motor system has to further integrate inferences about others' action. Yet, very little research has been carried out on the contribution of motor inhibition in JA tasks. Here, we used an interactive task in which subjects were required to open a bottle with one hand. The bottle was held and stabilized by a co-actor (JA) or by a mechanical holder (vice clamp, no-JA). A first motion capture study characterized the reaching and grasping kinematics of the two conditions. In a second study, by means of Transcranial Magnetic Stimulation (TMS), we measured (i) corticospinal excitability (CSE), (ii) cortical silent period (cSP) and (iii) short-interval intracortical inhibition (sICI), during the reaching phase of the task. These latter two indexes respectively reflect slow corticospinal (GABAb-mediated) and fast intracortical (GABAa-mediated) inhibition. We found no modulation for CSE, while cSP was increased and intracortical inhibition was downregulated during JA. Interestingly, the cSP correlated with partners' predictability as a whole and with partners' behaviour in the previous trial. These results, beside showing clear dissociation between fast and slow inhibition during JA, also shed new light on the predictive role played by corticospinal inhibitory mechanisms in online mutual behavioural co-adaptation.

Beta Rebound as an Index of Temporal Integration of Somatosensory and Motor Signals.

Modulation of cortical beta rhythm (15-30 Hz) is present during preparation for and execution of voluntary movements as well as during somatosensory stimulation. A rebound in beta synchronization is observed after the end of voluntary movements as well as after somatosensory stimulation and is believed to describe the return to baseline of sensorimotor networks. However, the contribution of efferent and afferent signals to the beta rebound remains poorly understood. Here, we applied electrical median nerve stimulation (MNS) to the right side followed by transcranial magnetic stimulation (TMS) on the left primary motor cortex after either 15 or 25 ms. Because the afferent volley reaches the somatosensory cortex after about 20 ms, TMS on the motor cortex was either anticipating or following the cortical arrival of the peripheral stimulus. We show modulations in different beta sub-bands and in both hemispheres, following a pattern of greater resynchronization when motor signals are paired with a peripheral one. The beta rebound in the left hemisphere (stimulated) is modulated in its lower frequency range when TMS precedes the cortical arrival of the afferent volley. In the right hemisphere (unstimulated), instead, the increase is limited to higher beta frequencies when TMS is delivered after the arrival of the afferent signal. In general, we demonstrate that the temporal integration of afferent and efferent signals plays a key role in the genesis of the beta rebound and that these signals may be carried in parallel by different beta sub-bands.

Motor cortical inhibition during concurrent action execution and action observation.

Action Execution (AE) and Action Observation (AO) share an extended cortical network of activated areas. During coordinative action these processes also overlap in time, potentially giving rise to behavioral interference effects. The neurophysiological mechanisms subtending the interaction between concurrent AE and AO are substantially unknown. To assess the effect of AO on observer's corticomotor drive, we run one electromyography (EMG) and three Transcranial Magnetic Stimulation (TMS) studies. Participants were requested to maintain a steady hand opening or closing posture while observing the same or a different action (hand opening and closing in the main TMS study). By measuring Cortical Silent Periods (CSP), an index of GABAB-mediated corticospinal inhibitory strength, we show a selective reduction of inhibitory motor drive for mismatching AE-AO pairs. The last two TMS experiments, show that this mismatch is computed according to a muscle-level agonist-antagonist representation. Combined, our results suggest that corticospinal inhibition may be the central neurophysiological mechanism by which one's own motor execution is adapted to the contextual visual cues provided by other's actions.