Conscious awareness of motor fluidity improves performance and decreases cognitive effort in sequence learning.

Motor skill learning is improved when participants are instructed to judge after each trial whether their performed movements have reached maximal fluidity. Consequently, the conscious awareness of this maximal fluidity can be classified as a genuine learning factor for motor sequences. However, it is unknown whether this effect of conscious awareness on motor learning could be mediated by the increased cognitive effort that may accompany such judgment making. The main aim of this study was to test this hypothesis in comparing two groups with, and without, the conscious awareness of the maximal fluidity. To assess the possible involvement of cognitive effort, we have recorded the pupillary dilation to the task, which is well-known to increase in proportion to cognitive effort. Results confirmed that conscious awareness indeed improved motor sequence learning of the trained sequence specifically. Pupil dilation was smaller during trained than during novel sequence performance, indicating that sequence learning decreased the cognitive cost of sequence execution. However, we found that in the group that had to judge on their maximal fluidity, pupil dilation during sequence production was smaller than in the control group, indicating that the motor improvement induced by the fluidity judgment does not involve additional cognitive effort. We discuss these results in the context of motor learning and cognitive effort theories.

Electrophysiological Correlates of a Versatile Executive Control System in the Monkey Anterior Cingulate Cortex.

When a subject faces conflicting situations, decision-making becomes uncertain. The human dorsal anterior cingulate cortex (dACC) has been repeatedly implicated in the monitoring of such situations, and its neural activity is thought to be involved in behavioral adjustment. However, this hypothesis is mainly based on neuroimaging results and is challenged by animal studies that failed to report any neuronal correlates of conflict monitoring. This discrepancy is thought be due either to methodological or more fundamental cross-species differences. In this study, we eliminated methodological biases and recorded single-neuron activity in monkeys performing a Stroop-like task. We found specific changes in dACC activity during incongruent trials but only in a small subpopulation of cells. Critically, these changes were not related to reaction time and were absent before any incorrect action was taken. A larger fraction of neurons exhibited sustained activity during the whole decision period, whereas another subpopulation of neurons was modulated by reaction time, with a gradual increase in their firing rate that peaked at movement onset. Most of the neurons found in these subpopulations exhibited activity after the delivery of an external negative feedback stimulus that indicated an error had been made. These findings, which are consistent with an executive control role, reconcile various theories of prefrontal cortex function and support the homology between human and monkey cognitive architectures.

Creating semantics in tool use.

This article presents the first evidence for a functional link between tool use and the processing of abstract symbols like Arabic numbers. Participants were required to perform a tool-use task after the processing of an Arabic number. These numbers represented either a small (2 or 3) or a large magnitude (8 or 9). The tool-use task consisted in using inverse pliers for gripping either a small or a large object. The inverse pliers enable to dissociate the hand action from the tool action in relation to the object (i.e., closing the hand led to an opening of the tool and vice versa). The number/tool hypothesis predicts that the quantity representation associated with Arabic numbers will interact with the action of the tool toward the object. Conversely, the number/hand hypothesis predicts that the quantity associated with numbers will interact with the action of the hand toward the tool. Results confirmed the first hypothesis and rejected the second. Indeed, large numbers interacted with the action of the tool, such that participants were longer to perform an "opening-hand/closing-tool" action after the processing of large numbers. Moreover, no effect was detected for small numbers, confirming previous studies which used only finger movements. Altogether, our finding suggests that the well-known finger/number interaction can be reversed with tool use.

Dorsal premotor cortex: neural correlates of reach target decisions based on a color-location matching rule and conflicting sensory evidence.

We recorded single-neuron activity in dorsal premotor (PMd) and primary motor cortex (M1) of two monkeys in a reach-target selection task. The monkeys chose between two color-coded potential targets by determining which target's color matched the predominant color of a multicolored checkerboard-like Decision Cue (DC). Different DCs contained differing numbers of colored squares matching each target. The DCs provided evidence about the correct target ranging from unambiguous (one color only) to very ambiguous and conflicting (nearly equal number of squares of each color). Differences in choice behavior (reach response times and success rates as a function of DC ambiguity) of the monkeys suggested that each applied a different strategy for using the target-choice evidence in the DCs. Nevertheless, the appearance of the DCs evoked a transient coactivation of PMd neurons preferring both potential targets in both monkeys. Reach response time depended both on how long it took activity to increase in neurons that preferred the chosen target and on how long it took to suppress the activity of neurons that preferred the rejected target, in both correct-choice and error-choice trials. These results indicate that PMd neurons in this task are not activated exclusively by a signal proportional to the net color bias of the DCs. They are instead initially modulated by the conflicting evidence supporting both response choices; final target selection may result from a competition between representations of the alternative choices. The results also indicate a temporal overlap between action selection and action initiation processes in PMd and M1.

Neuronal activity correlated with checking behaviour in the subthalamic nucleus of patients with obsessive-compulsive disorder.

Doubt, and its behavioural correlate, checking, is a normal phenomenon of human cognition that is dramatically exacerbated in obsessive-compulsive disorder. We recently showed that deep brain stimulation in the associative-limbic area of the subthalamic nucleus, a central core of the basal ganglia, improved obsessive-compulsive disorder. To understand the physiological bases of symptoms in such patients, we recorded the activity of individual neurons in the therapeutic target during surgery while subjects performed a cognitive task that gave them the possibility of unrestricted repetitive checking after they had made a choice. We postulated that the activity of neurons in this region could be influenced by doubt and checking behaviour. Among the 63/87 task-related neurons recorded in 10 patients, 60% responded to various combinations of instructions, delay, movement or feedback, thus highlighting their role in the integration of different types of information. In addition, task-related activity directed towards decision-making increased during trials with checking in comparison with those without checking. These results suggest that the associative-limbic subthalamic nucleus plays a role in doubt-related repetitive thoughts. Overall, our results not only provide new insight into the role of the subthalamic nucleus in human cognition but also support the fact that subthalamic nucleus modulation by deep brain stimulation reduced compulsive behaviour in patients with obsessive-compulsive disorder.

Check or Go? Impact of Doubt on the Hierarchical Organization of the Mediofrontal Area.

BACKGROUND: Based on numerous imaging and electrophysiological studies, the presupplementary motor area (pre-SMA) and the rostral cingulate motor area are cortical regions considered to be essential to voluntary movement initiation and behavioral control. However, their respective roles and functional interactions remain a long-standing and still debated question. METHODS: Here, we trained 2 rhesus monkeys (Macaca mulatta) in a complex cognitive task to compare the neuronal activity of these 2 regions on the medial wall during both perceptual and internally guided decisions. RESULTS: We confirmed the implication of both areas throughout the decision process. Critically, we demonstrate that instead of a stable invariant role, the pre-SMA and rostral cingulate motor area manifested a versatile hierarchical relationship depending on the mode of movement initiation. Whereas pre-SMA neurons were primarily engaged in decisions based on perceptual information, rostral cingulate motor area neurons preempted the decision process in case of an internally doubt-driven checking behavior, withholding pre-SMA recruitment during the time spent inhibiting the habitual action. CONCLUSIONS: We identified a versatile hierarchical organization of the mediofrontal area that may substantially affect normal and pathological decision processes because adaptive behaviors, such as doubt-checking and its compulsive counterpart, rely on this subtle equilibrium in controlling action initiation.

Primate models of dystonia.

Several models of dystonia have emerged from clinical studies providing a comprehensive explanation for the pathophysiology of this movement disorder. However, several points remain unclear notably concerning the specific role of brainstem, basal ganglia nuclei and premotor cortex. We review data collected in sub-human primate to see whether they might provide new insights into the pathophysiology of dystonia. As in human patients, lesions of the putamen induce dystonia, as well as pharmacological manipulations of the dopaminergic system. In addition, primate studies revealed that lesions in brain stem areas involved in the control of muscular tone and GABAergic manipulations in various basal ganglia nuclei or thalamus also lead to dystonia. Moreover, there is a dramatic disruption in the processing of proprioceptive information with abnormal large receptive fields in the basal ganglia, thalamus, primary somesthetic cortex and premotor cortex of dystonic monkeys. These data highlight the idea that dystonia is associated with aberrant sensory representations interfering with motor control. Considering that the supplementary motor area (SMAp) is the target of basal ganglia projections within the motor loop, we propose a model of dystonia in which abnormal excitability, associated with alteration in sensory receptive fields within the SMAp, leads to an abnormal synchronization between primary motor cortex columns. Such a phenomenon might account for the co-contractions of antagonist muscles favored by action and the abnormal postures observed in dystonia.

Competition, Conflict and Change of Mind: A Role of GABAergic Inhibition in the Primary Motor Cortex.

Deciding between different voluntary movements implies a continuous control of the competition between potential actions. Many theories postulate a leading role of prefrontal cortices in this executive function, but strong evidence exists that a motor region like the primary motor cortex (M1) is also involved, possibly via inhibitory mechanisms. This was already shown during the pre-movement decision period, but not after movement onset. For this pilot experiment we designed a new task compatible with the dynamics of post-onset control to study the silent period (SP) duration, a pause in electromyographic activity after single-pulse transcranial magnetic stimulation that reflects inhibitory mechanisms. A careful analysis of the SP during the ongoing movement indicates a gradual increase in inhibitory mechanisms with the level of competition, consistent with an increase in mutual inhibition between alternative movement options. However, we also observed a decreased SP duration for high-competition trials associated with change-of-mind inflections in their trajectories. Our results suggest a new post-onset adaptive process that consists in a transient reduction of GABAergic inhibition within M1 for highly conflicting situations. We propose that this reduced inhibition softens the competition between concurrent motor options, thereby favoring response vacillation, an adaptive strategy that proved successful at improving behavioral performance.

Response competition in the primary motor cortex: corticospinal excitability reflects response replacement during simple decisions.

It has been suggested that, during decisions about actions, multiple options are initially specified in parallel and then gradually eliminated in a competition for overt execution. To further test this hypothesis, we studied the modulation of human corticospinal excitability during the reaction time of the Eriksen flanker task. In the task, subjects responded with finger flexion or extension to a central arrow while ignoring congruent or incongruent flanker arrows. Single-pulse transcranial magnetic stimulation (TMS) was applied over primary motor cortex (M1) at one of five different latencies after stimulus onset, and motor-evoked potentials (MEPs) were measured in the contralateral index finger. During the control (no flankers) and congruent conditions, MEP size in the agonist increased gradually over the course of reaction time, indicating an increase in corticospinal excitability. Conversely, when the same muscle acted as an antagonist, MEP size decreased, suggesting inhibition. Critically, in the incongruent condition, MEPs briefly increased in the muscle corresponding to an initial default response to the flanker arrows and were later replaced by MEPs corresponding to the correct response to the central arrow. Finally, we found that the gradually growing MEPs for the three conditions reached a constant maximum level just before movement initiation. We propose that this dynamic modulation in corticospinal excitability reflects the competition process, leading to the selection of one response and the rejection of the other. Our results suggest that response competition influences activity in primary motor cortex and that its timing directly influences motor output latency.

Impact of commitment on performance evaluation in the rostral cingulate motor area.

Performance evaluation is a prerequisite for behavioral adaptation. Although the anterior cingulate cortex (ACC) is thought to play a central role in error detection, little is known about the electrophysiological activity of this structure during the performance-monitoring process. We directly addressed this issue by training monkeys to perform a Stroop-like task and then recorded neuronal activity in the rostral cingulate motor area (CMAr), a relatively unexplored region of the ACC known to be involved in motor processing. We found that most CMAr neurons responded during the evaluation period to both positive and negative feedback, but neuronal changes were more important after an error than after a successful trial. Interestingly, this performance-monitoring activity was not directly modulated by the degree of difficulty of the cognitive situation because changes in discharge frequency were similar whatever the level of attentional control imposed on the monkey. Firing activity during the evaluation period increased more, however, in erroneously completed than in incompleted trials and when the reward was delivered in an active rather than passive context, indicating that performance evaluation was conditioned by the degree of commitment of the animal to the task. It would thus seem that CMAr neurons could constitute a system for the evaluation of behavioral performance contingent on the subject's commitment to the task.

A safety mechanism for observational learning.

This empirical article presents the first evidence of a "safety mechanism" based on an observational-learning paradigm. It is accepted that during observational learning, a person can use different strategies to learn a motor skill, but it is unknown whether the learner is able to circumvent the encoding of an uncompleted observed skill. In this study, participants were tested in a dyadic protocol in which an observer watched a participant practicing two different motor sequences during a learning phase. During this phase, one of the two motor sequences was interrupted by a stop signal that precluded motor learning. The results of the subsequent retention test revealed that both groups learned the two motor sequences, but only the physical practice group showed worse performance for the interrupted sequence. The observers were consequently able to use a safety strategy to learn both sequences equally. Our findings are discussed in light of the implications of the action observation network for sequence learning and the cognitive mechanisms of error-based observation.

Checking behavior in rhesus monkeys is related to anxiety and frontal activity.

When facing doubt, humans can go back over a performed action in order to optimize subsequent performance. The present study aimed to establish and characterize physiological doubt and checking behavior in non-human primates (NHP). We trained two rhesus monkeys (Macaca mulatta) in a newly designed "Check-or-Go" task that allows the animal to repeatedly check and change the availability of a reward before making the final decision towards obtaining that reward. By manipulating the ambiguity of a visual cue in which the reward status is embedded, we successfully modulated animal certainty and created doubt that led the animals to check. This voluntary checking behavior was further characterized by making EEG recordings and measuring correlated changes in salivary cortisol. Our data show that monkeys have the metacognitive ability to express voluntary checking behavior similar to that observed in humans, which depends on uncertainty monitoring, relates to anxiety and involves brain frontal areas.

[The anterior cingulate cortex in error detection and conflict monitoring. Unitary neuronal activity in monkeys]. / Le cortex cingulaire antérieur dans la détection des erreurs et la gestion des conflits. Analyse de l'activité neuronale chez le singe.

Using a Stroop-like visuo-motor task in monkeys, we studied the unitary neuronal activity of the anterior cingulate cortex (ACC, CMAr : 24c) during error detection and conflict monitoring. A high percentage of cingular neurons modified their firing frequency during both attentional and evaluation periods. During the latter period, however, changes in discharge rates were always much more pronounced for erroneous responses than for successful movements that induced reward delivery. Moreover, some neurons responded more markedly to the warning stimulus when a previous trial failed In this case, the probability of a subsequent correct response increased. Such a neuronal apparatus could represent an error compensation system that serves to adapt a subject's behavioral response following an unfavorable and unexpected outcome. Abnormal activity of these neurons, which appear to take advantage of past errors, could contribute to the genesis of obsessive-compulsive disorders (OCD).

Neuronal Circuits for Fear Expression and Recovery: Recent Advances and Potential Therapeutic Strategies.

Recent technological developments, such as single unit recordings coupled to optogenetic approaches, have provided unprecedented knowledge about the precise neuronal circuits contributing to the expression and recovery of conditioned fear behavior. These data have provided an understanding of the contributions of distinct brain regions such as the amygdala, prefrontal cortex, hippocampus, and periaqueductal gray matter to the control of conditioned fear behavior. Notably, the precise manipulation and identification of specific cell types by optogenetic techniques have provided novel avenues to establish causal links between changes in neuronal activity that develop in dedicated neuronal structures and the short and long-lasting expression of conditioned fear memories. In this review, we provide an update on the key neuronal circuits and cell types mediating conditioned fear expression and recovery and how these new discoveries might refine therapeutic approaches for psychiatric conditions such as anxiety disorders and posttraumatic stress disorder.

Single medial prefrontal neurons cope with error.

Learning from mistakes is a key feature of human behavior. However, the mechanisms underlying short-term adaptation to erroneous action are still poorly understood. One possibility relies on the modulation of attentional systems after an error. To explore this possibility, we have designed a Stroop-like visuo-motor task in monkeys that favors incorrect action. Using this task, we previously found that single neurons recorded from the anterior cingulate cortex (ACC) were closely tuned to behavioral performance and, more particularly, that the activity of most neurons was biased towards the evaluation of erroneous action. Here we describe single neurons engaged in both error detection and response alertness processing, whose activation is closely associated with the improvement of subsequent behavioral performance. Specifically, we show that the effect of a warning stimulus on neuronal firing is enhanced after an erroneous response rather than a successful one and that this outcome is correlated with an error rate decrease. Our results suggest that the anterior cingulate cortex, which exhibits this activity, serves as a powerful computational locus for rapid behavioral adaptation.

Disruption of the proprioceptive mapping in the medial wall of parkinsonian monkeys.

Parkinsonian patients present an impairment of proprioceptor-guided movement that could imply abnormal processing in the frontal mesial cortex. To test this hypothesis, we compared neuronal response to joint displacement in the supplementary and presupplementary motor areas of two monkeys, before and after the progressive establishment of an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonian syndrome. After MPTP administration, neurons were activated by the passive movement of numerous joints in various directions and no longer simply by one or two joints in one direction. This impairment of the focused selection of proprioceptive inputs, imputable to dopamine depletion, could impede motor planning and thus contribute to akinesia.