Excitatory/inhibitory motor balance reflects individual differences during joint action coordination.

Joint action (JA) is a continuous process of motor co-regulation based on the integration of contextual (top-down) and kinematic (bottom-up) cues from partners. The fine equilibrium between excitation and inhibition in sensorimotor circuits is, thus, central to such a dynamic process of action selection and execution. In a bimanual task adapted to become a unimanual JA task, the participant held a bottle (JA), while a confederate had to reach and unscrew either that bottle or another stabilized by a mechanical clamp (No_JA). Prior knowledge was manipulated in each trial such that the participant knew (K) or not (No_K) the target bottle in advance. Online transcranial magnetic stimulation (TMS) was administered at action-relevant landmarks to explore corticospinal excitability (CSE) and inhibition (cortical silent period [cSP]). CSE was modulated early on before the action started if prior information was available. In contrast, cSP modulation emerged later during the reaching action, regardless of prior information. These two indexes could thus reflect the concurrent elaboration of contextual priors (top-down) and the online sampling of partner's kinematic cues (bottom-up). Furthermore, participants selected either one of two possible behavioural strategies, preferring early or late force exertion on the bottle. One translates into a reduced risk of motor coordination failure and the other into reduced metabolic expenditure. Each strategy was characterised by a specific excitatory/inhibitory profile. In conclusion, the study of excitatory/inhibitory balance paves the way for the neurophysiological determination of individual differences in the combination of top-down and bottom-up processing during JA coordination.

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.

Modulatory Effects of Communicative Gaze on Attentional Orienting Are Driven by Dorsomedial Prefrontal Cortex but Not Right Temporoparietal Junction.

Communicative gaze (e.g., mutual or averted) has been shown to affect attentional orienting. However, no study to date has clearly separated the neural basis of the pure social component that modulates attentional orienting in response to communicative gaze from other processes that might be a combination of attentional and social effects. We used TMS to isolate the purely social effects of communicative gaze on attentional orienting. Participants completed a gaze-cueing task with a humanoid robot who engaged either in mutual or in averted gaze before shifting its gaze. Before the task, participants received either sham stimulation (baseline), stimulation of right TPJ (rTPJ), or dorsomedial prefrontal cortex (dmPFC). Results showed, as expected, that communicative gaze affected attentional orienting in baseline condition. This effect was not evident for rTPJ stimulation. Interestingly, stimulation to rTPJ also canceled out attentional orienting altogether. On the other hand, dmPFC stimulation eliminated the socially driven difference in attention orienting between the two gaze conditions while maintaining the basic general attentional orienting effect. Thus, our results allowed for separation of the pure social effect of communicative gaze on attentional orienting from other processes that are a combination of social and generic attentional components.

The value of corticospinal excitability and intracortical inhibition in predicting motor skill improvement driven by action observation.

The observation of other's actions represents an essential element for the acquisition of motor skills. While action observation is known to induce changes in the excitability of the motor cortices, whether such modulations may explain the amount of motor improvement driven by action observation training (AOT) remains to be addressed. Using transcranial magnetic stimulation (TMS), we first assessed in 41 volunteers the effect of action observation on corticospinal excitability, intracortical inhibition, and transcallosal inhibition. Subsequently, half of the participants (AOT-group) were asked to observe and then execute a right-hand dexterity task, while the controls had to observe a no-action video before practicing the same task. AOT participants showed greater performance improvement relative to controls. More importantly, the amount of improvement in the AOT group was predicted by the amplitude of corticospinal modulation during action observation and, even more, by the amount of intracortical inhibition induced by action observation. These relations were specific for the AOT group, while the same patterns were not found in controls. Taken together, our findings demonstrate that the efficacy of AOT in promoting motor learning is rooted in the capacity of action observation to modulate the trainee's motor system excitability, especially its intracortical inhibition. Our study not only enriches the picture of the neurophysiological effects induced by action observation onto the observer's motor excitability, but linking them to the efficacy of AOT, it also paves the way for the development of models predicting the outcome of training procedures based on the observation of other's actions.

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.

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.

Attentional bias on motor control: is motor inhibition influenced by attentional reorienting?

Motor inhibition and attentional processing are tightly linked. Recent neurophysiological studies have shown that both processes might rely on similar cognitive and neural mechanisms (Wessel and Aron, Neuron 93:259-280, 2017). However, it remains unclear whether attentional reorientation influences inhibition of a subsequent action. Therefore, we combined two tasks that are commonly used in the motor inhibition and visual attention reorientation field [respectively: the stop-signal task (Logan and Cowan, Psychol Rev 91:295-327, 1984) and the Posner endogenous cueing paradigm (Posner, Q J Exp Psychol 32(1):3-25, 1980)] to investigate how different aspects of visual attention modulate subsequent voluntary inhibition. Our results showed an increase in stopping-reaction time after a reorientation of attention only. This suggests a specific impairment of inhibitory control when a reorientation of visual attention is needed. These findings support the idea of a selective influence of attention reorientation on subsequent motor inhibition (stop signal). This may be linked to the "circuit breaker" hypothesis, proposing that attention reorientation toward an unexpected event "resets" the ongoing processes to allow the analysis of the potentially behaviorally relevant visual events (Corbetta et al., Neuron 58(3):306-324, 2008).

Characterization of network structure in stereoEEG data using consensus-based partial coherence.

Coherence is a widely used measure to determine the frequency-resolved functional connectivity between pairs of recording sites, but this measure is confounded by shared inputs to the pair. To remove shared inputs, the 'partial coherence' can be computed by conditioning the spectral matrices of the pair on all other recorded channels, which involves the calculation of a matrix (pseudo-) inverse. It has so far remained a challenge to use the time-resolved partial coherence to analyze intracranial recordings with a large number of recording sites. For instance, calculating the partial coherence using a pseudoinverse method produces a high number of false positives when it is applied to a large number of channels. To address this challenge, we developed a new method that randomly aggregated channels into a smaller number of effective channels on which the calculation of partial coherence was based. We obtained a 'consensus' partial coherence (cPCOH) by repeating this approach for several random aggregations of channels (permutations) and only accepting those activations in time and frequency with a high enough consensus. Using model data we show that the cPCOH method effectively filters out the effect of shared inputs and performs substantially better than the pseudo-inverse. We successfully applied the cPCOH procedure to human stereotactic EEG data and demonstrated three key advantages of this method relative to alternative procedures. First, it reduces the number of false positives relative to the pseudo-inverse method. Second, it allows for titration of the amount of false positives relative to the false negatives by adjusting the consensus threshold, thus allowing the data-analyst to prioritize one over the other to meet specific analysis demands. Third, it substantially reduced the number of identified interactions compared to coherence, providing a sparser network of connections from which clear spatial patterns emerged. These patterns can serve as a starting point of further analyses that provide insight into network dynamics during cognitive processes. These advantages likely generalize to other modalities in which shared inputs introduce confounds, such as electroencephalography (EEG) and magneto-encephalography (MEG).

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.

Individual differences in intracortical inhibition predict action control when facing emotional stimuli.

Efficient inhibitory control in the context of prepotent actions is vital. However, such action inhibition may be profoundly influenced by affective states. Interestingly, research indicates that action control can be either impaired or improved by emotional stimuli. Thus, a great deal of confusion surrounds our knowledge of the complex dynamics subtending emotions and action control. Here, we aimed to investigate whether negative stimuli, even when non-consciously presented and task-irrelevant, can affect action control relative to neutral stimuli. Additionally, we tested whether individual differences in intracortical excitability may predict action control capabilities. To address these issues, we asked participants to complete a modified version of the Stop Signal Task (SST) in which fearful or neutral stimuli were subliminally presented before the go signals as primes. Moreover, we assessed participants' resting-state corticospinal excitability, short intracortical inhibition (SICI), and intracortical facilitation (ICF). Results demonstrated better action control capabilities when fearful stimuli were subliminally presented and interindividual SICI predicted stronger action inhibition capabilities. Taken together, these results shed new light on the intricate dynamics between action, consciousness, and motor control, suggesting that intracortical measures can be used as potential biomarkers of reduced motor inhibition in research and clinical settings.

When the heart inhibits the brain: Cardiac phases modulate short-interval intracortical inhibition.

The phasic cardiovascular activity influences the central nervous system through the systolic baroreceptor inputs, inducing widespread inhibitory effects on behavior. Through transcranial magnetic stimulation (TMS) delivered during resting-state over the left primary motor cortex and across the different cardiac phases, we measured corticospinal excitability (CSE) and distinct indices of intracortical motor inhibition: short (SICI) and long (LICI) interval, corresponding to GABAA and GABAB neurotransmission, respectively. We found a significant effect of the cardiac phase on short-intracortical inhibition, without any influence on LICI. Specifically, SICI was stronger at systole compared to diastole. These results show a tight relationship between the cardiac cycle and the inhibitory neurotransmission within M1, and in particular with GABAA-ergic-mediated motor inhibition. We hypothesize that this process requires greater motor control via the gating mechanism and that this, in turn, needs to be recalibrated through the modulation of intracortical inhibition.

Stopping in (e)motion: Reactive action inhibition when facing valence-independent emotional stimuli.

Emotions are able to impact our ability to control our behaviors. However, it is not clear whether emotions play a detrimental or an advantageous effect on action control and whether the valence of the emotional stimuli differently affects such motor abilities. One way to measure reactive inhibitory control is the stop-signal task (SST), which estimates the ability to cancel outright a response to the presentation of a stop signal by means of the stop signal reaction times (SSRT). Impaired as well as facilitated action control has been found when faced with emotional stimuli such as stop signals in SSTs and mixed results were observed for positive versus negative stimuli. Here, we aimed to investigate these unresolved issues more deeply. Action control capabilities were tested in 60 participants by means of a SST, in which the stop signals were represented by a fearful and a happy body posture together with their neutral counterpart. Results showed that both positive and negative body postures enhanced the ability to suppress an ongoing action compared to neutral body postures. These results demonstrate that emotional valence-independent emotional stimuli facilitate action control and suggest that emotional stimuli may trigger increased sensory representation and/or attentional processing that may have promote stop-signal processing and hence improved inhibitory performance.

The Influence of Vicarious Fear-Learning in "Infecting" Reactive Action Inhibition.

Since the dawn of cognitive neuroscience, emotions have been recognized to impact on several executive processes, such as action inhibition. However, the complex interplay between emotional stimuli and action control is not yet fully understood. One way to measure inhibitory control is the stop-signal task (SST), which estimates the ability to cancel outright an action to the presentation of a stop signal by means of the stop-signal reaction times (SSRTs). Impaired as well as facilitated action control has been found when faced with intrinsic emotional stimuli as stop signals in SSTs. Here, we aimed at investigating more deeply the power of negative stimuli to influence our action control, testing the hypothesis that a previously neutral stimulus [i.e., the image of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)], which has been conditioned through vicarious fear learning, has the same impact on reactive action inhibition performance as an intrinsically negative stimulus (i.e., a fearful face or body). Action control capabilities were tested in 90 participants by means of a SST, in which the stop signals were represented by different negative stimuli. Results showed that the SARS-CoV-2 image enhanced the ability to suppress an ongoing action similarly to observing fearful facial expressions or fearful body postures. Interestingly, we found that this effect was predicted by impulsivity traits: for example, the less self-control the participants had, the less they showed emotional facilitation for inhibitory performance. These results demonstrated that vicarious fear learning has a critical impact on cognitive abilities, making a neutral image as threatening as phylogenetically innate negative stimuli and able to impact on our behavioral control.

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.

Weaker implicit interoception is associated with more negative body image: Evidence from gastric-alpha phase amplitude coupling and the heartbeat evoked potential.

Interoception refers to the processing of internal bodily stimuli, while body image refers to appearance-related perceptions, affect, and cognitions. Previous research has found that body image is associated with self-reported and behavioural indices of interoception. Here, we extended this research by examining associations between measures of positive (i.e., body appreciation, functionality appreciation) and negative body image (i.e., body shame, weight preoccupation) and two electrophysiological indices of interoceptive processing, namely the heartbeat evoked potential (HEP) and gastric-alpha phase-amplitude coupling (PAC), in a sample of 36 adults. Significant negative associations were identified between the indices of negative body image and the interoception variables. Specifically, more negative HEP amplitude and lower gastric-alpha PAC were both associated with greater body shame and weight preoccupation. However, no significant associations were identified for the indices of positive body image. These findings extend previous work by demonstrating that there are significant associations between negative body image and previously unexplored components of cardiac and gastric interoception. This, in turn, could have important clinical applications, such as the HEP and gastric-alpha PAC both serving as biomarkers of negative body image.

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.

Human stereoEEG recordings reveal network dynamics of decision-making in a rule-switching task.

The processing steps that lead up to a decision, i.e., the transformation of sensory evidence into motor output, are not fully understood. Here, we combine stereoEEG recordings from the human cortex, with single-lead and time-resolved decoding, using a wide range of temporal frequencies, to characterize decision processing during a rule-switching task. Our data reveal the contribution of rostral inferior parietal lobule (IPL) regions, in particular PFt, and the parietal opercular regions in decision processing and demonstrate that the network representing the decision is common to both task rules. We reconstruct the sequence in which regions engage in decision processing on single trials, thereby providing a detailed picture of the network dynamics involved in decision-making. The reconstructed timeline suggests that the supramarginal gyrus in IPL links decision regions in prefrontal cortex with premotor regions, where the motor plan for the response is elaborated.

Altered bodily self-consciousness and peripersonal space in autism.

There is some evidence that disordered self-processing in autism spectrum disorders is linked to the social impairments characteristic of the condition. To investigate whether bodily self-consciousness is altered in autism spectrum disorders as a result of multisensory processing differences, we tested responses to the full body illusion and measured peripersonal space in 22 adults with autism spectrum disorders and 29 neurotypical adults. In the full body illusion set-up, participants wore a head-mounted display showing a view of their 'virtual body' being stroked synchronously or asynchronously with respect to felt stroking on their back. After stroking, we measured the drift in perceived self-location and self-identification with the virtual body. To assess the peripersonal space boundary we employed an audiotactile reaction time task. The results showed that participants with autism spectrum disorders are markedly less susceptible to the full body illusion, not demonstrating the illusory self-identification and self-location drift. Strength of self-identification was negatively correlated with severity of autistic traits and contributed positively to empathy scores. The results also demonstrated a significantly smaller peripersonal space, with a sharper (steeper) boundary, in autism spectrum disorders participants. These results suggest that bodily self-consciousness is altered in participants with autism spectrum disorders due to differences in multisensory integration, and this may be linked to deficits in social functioning.

Early modulation of intra-cortical inhibition during the observation of action mistakes.

Errors while performing an action are fundamental for learning. During interaction others' errors must be monitored and taken into account to allow joint action coordination and imitation learning. This monitoring relies on an action observation network (AON) mainly based on parietofrontal recurrent circuits. Although different studies suggest that inappropriate actions may rapidly be inhibited during execution, little is known about the modulation of the AON when an action misstep is shown. Here we used single and paired pulse transcranial magnetic stimulation to assess corticospinal excitability, intracortical facilitation and intracortical inhibition at different time intervals (120, 180, 240 ms) after the visual presentation of a motor execution error. Results show a specific and early (120 ms) decrease of intracortical inhibition likely because of a significant mismatch between the observed erroneous action and observer's expectations. Indeed, as proposed by the top-down predictive framework, the motor system may be involved in the generation of these error signals and our data show that this mechanism could rely on the early decrease of intracortical inhibition within the corticomotor system.