Amplified engagement of prefrontal cortex during control of voluntary action in Tourette syndrome.

Tourette syndrome is characterized by 'unvoluntary' tics, which are compulsive, yet often temporarily suppressible. The inferior frontal gyrus is implicated in motor control, including inhibition of pre-potent actions through influences on downstream subcortical and motor regions. Although tic suppression in Tourette syndrome also engages the inferior frontal gyrus, it is unclear whether such prefrontal control of action is also dysfunctional: Tic suppression studies do not permit comparison with control groups, and neuroimaging studies of motor inhibition can be confounded by the concurrent expression or suppression of tics. Here, patients with Tourette syndrome were directly compared to control participants when performing an intentional inhibition task during functional MRI. Tic expression was recorded throughout for removal from statistical models. Participants were instructed to make a button press in response to Go cues, withhold responses to NoGo cues, and decide whether to press or withhold to 'Choose' cues. Overall performance was similar between groups, for both intentional inhibition rates (% Choose-Go) and reactive NoGo inhibition commission errors. A subliminal face prime elicited no additional effects on intentional or reactive inhibition. Across participants, the task activated prefrontal and motor cortices and subcortical nuclei, including pre-supplementary motor area, inferior frontal gyrus, insula, caudate nucleus, thalamus and primary motor cortex. In Tourette syndrome, activity was elevated in the inferior frontal gyrus, insula and basal ganglia, most notably within the right inferior frontal gyrus during voluntary action and inhibition (Choose-Go and Choose-NoGo), and reactive inhibition (NoGo-correct). Anatomically, the locus of this inferior frontal gyrus hyperactivation during control of voluntary action matched that previously reported for tic suppression. In Tourette syndrome, activity within the caudate nucleus was also enhanced during both intentional (Choose-NoGo) and reactive (NoGo-correct) inhibition. Strikingly, despite the absence of overt motor behaviour, primary motor cortex activity increased in patients with Tourette syndrome but decreased in controls during both reactive and intentional inhibition. Additionally, severity of premonitory sensations scaled with functional connectivity of the pre-supplementary motor area to the caudate nucleus, globus pallidus and thalamus when choosing to respond (Choose-Go). Together, these results suggest that patients with Tourette syndrome use equivalent prefrontal mechanisms to suppress tics and withhold non-tic actions, but require greater inferior frontal gyrus engagement than controls to overcome motor drive from hyperactive downstream regions, notably primary motor cortex. Moreover, premonitory sensations may cue midline motor regions to generate tics through interactions with the basal ganglia.

Effect of alcohol on the sense of agency in healthy humans.

Even at low to moderate doses, ingestion of the widely used recreational drug alcohol (ethanol) can impact cognitive and emotional processing. Recent studies show that the sense of agency (SoA; ie, the subjective experience of voluntary control over actions) can be modulated by specific pharmacological manipulations. The SoA, as quantified by the intentional binding (IB) paradigm, is enhanced by direct or indirect dopaminergic agonists in patients with Parkinson's disease and by ketamine (an N-methyl-D-aspartate (NMDA) receptor antagonist) in healthy individuals. These findings implicate dopaminergic and glutamatergic neurotransmission in mechanisms underlying SoA. Alcohol has a complex set of actions, including disinhibition of dopaminergic neurotransmission and allosteric antagonism at NMDA receptors. Here, we tested the hypothesis that low to moderate doses of alcohol would enhance SoA, and impact impulsivity and subjective emotional state. We conducted two experiments in 59 healthy male and female social drinkers, who ingested either a placebo "vehicle," or one of two doses of ethanol: 0.4 and 0.6 g/kg. In both experiments, we observed increased SoA/IB at both doses of alcohol exposure, relative to the placebo condition. We found no correlation between the effects of alcohol on IB and on impulsivity or subjective emotional state. Our findings might have implications for social and legal responsibility related to alcohol use, particularly in states prior to overt intoxication. Further studies are necessary to investigate the effects of alcohol and other addictive substances on the SoA.

Face perception enhances insula and motor network reactivity in Tourette syndrome.

Tourette syndrome is a neurodevelopmental disorder, characterized by motor and phonic tics. Tics are typically experienced as avolitional, compulsive, and associated with premonitory urges. They are exacerbated by stress and can be triggered by external stimuli, including social cues like the actions and facial expressions of others. Importantly, emotional social stimuli, with angry facial stimuli potentially the most potent social threat cue, also trigger behavioural reactions in healthy individuals, suggesting that such mechanisms may be particularly sensitive in people with Tourette syndrome. Twenty-one participants with Tourette syndrome and 21 healthy controls underwent functional MRI while viewing faces wearing either neutral or angry expressions to quantify group differences in neural activity associated with processing social information. Simultaneous video recordings of participants during neuroimaging enabled us to model confounding effects of tics on task-related responses to the processing of faces. In both Tourette syndrome and control participants, face stimuli evoked enhanced activation within canonical face perception regions, including the occipital face area and fusiform face area. However, the Tourette syndrome group showed additional responses within the anterior insula to both neutral and angry faces. Functional connectivity during face viewing was then examined in a series of psychophysiological interactions. In participants with Tourette syndrome, the insula showed functional connectivity with a set of cortical regions previously implicated in tic generation: the presupplementary motor area, premotor cortex, primary motor cortex, and the putamen. Furthermore, insula functional connectivity with the globus pallidus and thalamus varied in proportion to tic severity, while supplementary motor area connectivity varied in proportion to premonitory sensations, with insula connectivity to these regions increasing to a greater extent in patients with worse symptom severity. In addition, the occipital face area showed increased functional connectivity in Tourette syndrome participants with posterior cortical regions, including primary somatosensory cortex, and occipital face area connectivity with primary somatosensory and primary motor cortices varied in proportion to tic severity. There were no significant psychophysiological interactions in controls. These findings highlight a potential mechanism in Tourette syndrome through which heightened representation within insular cortex of embodied affective social information may impact the reactivity of subcortical motor pathways, supporting programmed motor actions that are causally implicated in tic generation. Medicinal and psychological therapies that focus on reducing insular hyper-reactivity to social stimuli may have potential benefit for tic reduction in people with Tourette syndrome.

Don't make me angry, you wouldn't like me when I'm angry: Volitional choices to act or inhibit are modulated by subliminal perception of emotional faces.

Volitional action and self-control-feelings of acting according to one's own intentions and in being control of one's own actions-are fundamental aspects of human conscious experience. However, it is unknown whether high-level cognitive control mechanisms are affected by socially salient but nonconscious emotional cues. In this study, we manipulated free choice decisions to act or withhold an action by subliminally presenting emotional faces: In a novel version of the Go/NoGo paradigm, participants made speeded button-press responses to Go targets, withheld responses to NoGo targets, and made spontaneous, free choices to execute or withhold the response for Choice targets. Before each target, we presented emotional faces, backwards masked to render them nonconscious. In Intentional trials, subliminal angry faces made participants more likely to voluntarily withhold the action, whereas fearful and happy faces had no effects. In a second experiment, the faces were made supraliminal, which eliminated the effects of angry faces on volitional choices. A third experiment measured neural correlates of the effects of subliminal angry faces on intentional choice using EEG. After replicating the behavioural results found in Experiment 1, we identified a frontal-midline theta component-associated with cognitive control processes-which is present for volitional decisions, and is modulated by subliminal angry faces. This suggests a mechanism whereby subliminally presented "threat" stimuli affect conscious control processes. In summary, nonconscious perception of angry faces increases choices to inhibit, and subliminal influences on volitional action are deep seated and ecologically embedded.

Illusory Temporal Binding in Meditators.

We investigate conditions in which more accurate metacognition may lead to greater susceptibility to illusion and thus conditions under which mindfulness meditation may lead to less accurate perceptions. Specifically, greater awareness of intentions may lead to an illusory compression of time between a voluntary action and its outcome ("intentional binding"). Here, we report that experienced Buddhist mindfulness meditators rather than non-meditators display a greater illusory shift of the timing of an outcome toward an intentional action. Mindfulness meditation involves awareness of causal connections between different mental states, including intentions. We argue that this supports improvements in metacognition targeted at motor intentions. Changes in metacognitive ability may result in an earlier and less veridical experience of the timing of action outcomes either through increased access to sensorimotor pre-representations of an action outcome or by affording greater precision to action timing judgements. Furthermore, as intentional binding is an implicit measure of the sense of agency; these results also provide evidence that mindfulness meditators experience a stronger sense of agency.

Choosing to Stop: Responses Evoked by Externally Triggered and Internally Generated Inhibition Identify a Neural Mechanism of Will.

Inhibiting inappropriate action is key to human behavioral control. Studies of action inhibition largely investigated external stop signals, yet these are rare in everyday life. Instead healthy adults exert "self-control," implying an ability to decide internally to stop actions. We added "choose for yourself" stimuli to a conventional go/no-go task to compare reactive versus intentional action and inhibition. No-go reactions showed the N2 EEG potential characteristic of inhibiting prepotent motor responses, whereas go reactions did not. Interestingly, the N2 component was present for intentional choices both to act and also to inhibit. Thus, free choices involved a first step of intentionally inhibiting prepotent responses before generating or withholding an action. Intentional inhibition has a crucial role breaking the flow of stimulus-driven responding, allowing expression of volitional decisions. Even decisions to initiate self-generated actions require this prior negative form of volition, ensuring the "freedom from immediacy" characteristic of human behavior.

Subliminal priming of intentional inhibition.

Intentional choice is an important process underlying human behaviour. Intentional inhibition refers to the capacity to endogenously cancel an about-to-be-executed action at the last moment. Previous research suggested that such intentional inhibitory control requires conscious effort and awareness. Here we show that intentional decisions to inhibit are nevertheless influenced by unconscious processing. In a novel version of the Go/No-Go task, participants made speeded keypress actions to a Go target, or withheld responses to a No-Go target, or made free, spontaneous choices whether to execute or inhibit a keypress when presented with a free-choice target. Prior to each target, subliminal masked prime arrows were presented. Primes could be congruent with the Go or No-Go arrows, or neutral. Response times and proportion of action choices were measured. Primes were presented at latencies that would give either positive or negative compatibility effects (PCE, Experiment 1, and NCE, Experiment 2, respectively), based on previous literature. Go-primes at positive-compatibility latencies facilitated speeded response times as expected, but did not influence number of choices to act on free-choice trials. However, when Go primes were presented at negative-compatibility latencies, "free" decisions to inhibit were significantly increased. Decisions to act or not can be unconsciously manipulated, at least by inhibitory mechanisms. The cognitive mechanisms for intentionally withholding an action can be influenced by unconscious processing. We discuss possible moral and legal implications of these findings.

Hedonic value of intentional action provides reinforcement for voluntary generation but not voluntary inhibition of action.

Intentional inhibition refers to stopping oneself from performing an action at the last moment, a vital component of self-control. It has been suggested that intentional inhibition is associated with negative hedonic value, perhaps due to the frustration of cancelling an intended action. Here we investigate hedonic implications of the free choice to act or inhibit. Participants gave aesthetic ratings of arbitrary visual stimuli that immediately followed voluntary decisions to act or to inhibit action. We found that participants for whom decisions to act produced a strong positive hedonic value for the immediately following visual stimulus made more choices to act than those with weaker hedonic value for action. This finding is consistent with reinforcement learning of action decisions. However, participants who experienced inhibition as generating more positive hedonic value did not choose to inhibit more than other participants. Thus, voluntary inhibition of action did not act as reinforcement for future inhibitory behaviour. Our finding that inhibition of action lacks motivational capacity may explain why self-control is both difficult and limited.

Action simulation: time course and representational mechanisms.

The notion of action simulation refers to the ability to re-enact foreign actions (i.e., actions observed in other individuals). Simulating others' actions implies a mirroring of their activities, based on one's own sensorimotor competencies. Here, we discuss theoretical and experimental approaches to action simulation and the study of its representational underpinnings. One focus of our discussion is on the timing of internal simulation and its relation to the timing of external action, and a paradigm that requires participants to predict the future course of actions that are temporarily occluded from view. We address transitions between perceptual mechanisms (referring to action representation before and after occlusion) and simulation mechanisms (referring to action representation during occlusion). Findings suggest that action simulation runs in real-time; acting on newly created action representations rather than relying on continuous visual extrapolations. A further focus of our discussion pertains to the functional characteristics of the mechanisms involved in predicting other people's actions. We propose that two processes are engaged, dynamic updating and static matching, which may draw on both semantic and motor information. In a concluding section, we discuss these findings in the context of broader theoretical issues related to action and event representation, arguing that a detailed functional analysis of action simulation in cognitive, neural, and computational terms may help to further advance our understanding of action cognition and motor control.

The influence of visual training on predicting complex action sequences.

Linking observed and executable actions appears to be achieved by an action observation network (AON), comprising parietal, premotor, and occipitotemporal cortical regions of the human brain. AON engagement during action observation is thought to aid in effortless, efficient prediction of ongoing movements to support action understanding. Here, we investigate how the AON responds when observing and predicting actions we cannot readily reproduce before and after visual training. During pre- and posttraining neuroimaging sessions, participants watched gymnasts and wind-up toys moving behind an occluder and pressed a button when they expected each agent to reappear. Between scanning sessions, participants visually trained to predict when a subset of stimuli would reappear. Posttraining scanning revealed activation of inferior parietal, superior temporal, and cerebellar cortices when predicting occluded actions compared to perceiving them. Greater activity emerged when predicting untrained compared to trained sequences in occipitotemporal cortices and to a lesser degree, premotor cortices. The occipitotemporal responses when predicting untrained agents showed further specialization, with greater responses within body-processing regions when predicting gymnasts' movements and in object-selective cortex when predicting toys' movements. The results suggest that (1) select portions of the AON are recruited to predict the complex movements not easily mapped onto the observer's body and (2) greater recruitment of these AON regions supports prediction of less familiar sequences. We suggest that the findings inform both the premotor model of action prediction and the predictive coding account of AON function.

The perception of prototypical motion: synchronization is enhanced with quantitatively morphed gestures of musical conductors.

Aesthetic theories have long suggested perceptual advantages for prototypical exemplars of a given class of objects or events. Empirical evidence confirmed that morphed (quantitatively averaged) human faces, musical interpretations, and human voices are preferred over most individual ones. In this study, biological human motion was morphed and tested for prototype effects in task-specific actions, perceptual judgments, and kinematic characteristics. A motion capture system recorded the movements of six novice and six expert orchestral conductors while they performed typical beat patterns in time with a metronome. Point-light representations of individual conductors and morphs of experts, novices, and a grand average morph were generated. In a repeated-measures sensorimotor synchronization paradigm, participants tapped a finger in time with the conducting and provided evaluations of the gestures' characteristics. Quantitatively averaged conducting motion resulted in reduced jerk (i.e., smoother motion) as well as higher synchronization accuracy and tapping consistency. Perceived beat clarity and quality of the gestures correlated with the timing of vertical acceleration in the conductors' movements. While gestures of individual conductors were perceived to be more expressive, morphs appeared more conventional. Thus, due to smoother spatiotemporal profiles of morphs, perception and action advantages were observed for prototypes that are presumably based both on motor resonance mechanisms and cognitive representations.

Movement kinematics affect action prediction: comparing human to non-human point-light actions.

The influence of movement kinematics on the accuracy of predicting the time course of another individual's actions was studied. A human point-light shape was animated with human movement (natural condition) and with artificial movement that was more uniform regarding velocity profiles and trajectories (artificial condition). During brief occlusions, the participants predicted the actions in order to judge after occlusion whether the actions were continued coherently in time or shifted to an earlier or later frame. Error rates and reaction times were increased in the artificial compared to the natural condition. The findings suggest a perceptual advantage for movement with a human velocity profile, corresponding to the notion of a close interaction between observed and executed movement. The results are discussed in the framework of the simulation account and alternative interpretations are provided on the basis of correlations between the velocity profiles of natural and artificial movements with prediction performance.

Before, during and after you disappear: aspects of timing and dynamic updating of the real-time action simulation of human motions.

The detailed dynamics of action simulation was investigated using the occluder paradigm: a point light actor (PLA) was shown, then briefly occluded from view, during which period action simulation was generated. Following occlusion, the PLA reappeared, either a progression of the motion as it should be post-occlusion or temporally shifted earlier/later. Participants made judgements on whether the reappearing PLA was too early or too late to be a correct continuation (Experiments 1 and 3) or whether it was a veridical continuation or not (Experiment 2). Over three experiments we asked how action simulation is affected by motion information before, during and after occlusion. Reducing motion presented before occlusion retained the accuracy of action simulation judgements. Presenting 4 frames (67 ms) of PLA motion during the occluder duration dynamically updates or altogether regenerates the action simulation. Reducing the duration of the test motion after the occluder decreases judgement precision, which we interpret as a limitation in the process of postdictive motion judgments. Overall, this is further evidence that the action simulation process is remarkably adapted to making human motion predictions.

Robotic movement preferentially engages the action observation network.

As humans, we gather a wide range of information about other people from watching them move. A network of parietal, premotor, and occipitotemporal regions within the human brain, termed the action observation network (AON), has been implicated in understanding others' actions by means of an automatic matching process that links observed and performed actions. Current views of the AON assume a matching process biased towards familiar actions; specifically, those performed by conspecifics and present in the observer's motor repertoire. In this study, we test how this network responds to form and motion cues when observing natural human motion compared to rigid robotic-like motion across two independent functional neuroimaging experiments. In Experiment 1, we report the surprising finding that premotor, parietal, occipitotemporal regions respond more robustly to rigid, robot-like motion than natural human motion. In Experiment 2, we replicate and extend this finding by demonstrating that the same pattern of results emerges whether the agent is a human or a robot, which suggests the preferential response to robot-like motion is independent of the agent's form. These data challenge previous ideas about AON function by demonstrating that the core nodes of this network can be flexibly engaged by novel, unfamiliar actions performed by both human and non-human agents. As such, these findings suggest that the AON is sensitive to a broader range of action features beyond those that are simply familiar.

Can you see me in the snow? Action simulation aids the detection of visually degraded human motion.

Using a novel paradigm, we demonstrate that action simulation can directly facilitate ongoing perception of people's movements. Point-light actors (PLAs) representing common human motions were shown embedded in a visual noise reminiscent of "TV snow". At first, the PLAs were perceived clearly, then occluded from view for a short duration, during which it was hypothesized that a real-time action simulation was generated tracking the motion's course. The PLA then reappeared in motion at variable visibility against the noise, whilst detection thresholds for the reappearance were measured. In the crucial manipulation, the test motion was either temporally congruent with the motion as it would have continued during occlusion, and thus temporally matching the simulation, or temporally incongruent. Detection thresholds were lower for congruent than for incongruent reappearing motions, suggesting that reappearing motion that temporally matched the internal action simulation was more likely to be detected.

Line by line: the ERP correlates of stroke order priming in letters.

The perception of written letters reflects the action sequences that produce them. Faster recognition is observed for letters presented as sequences of strokes in a temporal order consistent with letter writing, compared to an inconsistent order. During a speeded letter identification task, parietal event-related potential (ERP) components were analysed separately for each stroke-frame in action-consistent and inconsistent stimulus sequences, during both passive and active (task-engaged) viewing. Electrophysiological data provided unique insights into stroke order priming by comparing local neural organisation during early, response-independent stages with later response-dependent stages. ERPs over posterior scalp areas revealed speeded visual processing for action-consistent stroke sequences prior to, and upon, letter completion. These signatures of perceptually facilitated letter processing were present in both active and passive viewing conditions, indicating that priming was not response-contingent, but rather an inherent part of visual letter perception. Stroke order priming is discussed in terms of matching stored letter production action codes, which upon activation provide top-down facilitation for visual processing of letters.

Temporal order of strokes primes letter recognition.

Does the perception of objects that are the result of human actions reflect the underlying temporal structure of the actions that gave rise to them? We tested whether the temporal order of letter strokes influences letter recognition. In three experiments, participants were asked to identify letters that temporally unfolded as an additive sequence of letter strokes, either consistent or inconsistent with common writing action. Participants were significantly faster to identify letters from consistent temporal sequences, indicating that the initial part of the sequence contained sufficient information to prime letter recognition. We suggest that letter perception reflects the temporal structure of letter production; in other words, Simon sees as Simon does.