暂无摘要。

Predictive learning can engage a selective form of cognitive control that biases choice between actions based on information about future outcomes that the learning provides. This influence has been hypothesized to depend on a feedback circuit in the brain through which the basal ganglia modulate activity in the prefrontal cortex; however, direct evidence for this functional circuit has proven elusive. Here, using an animal model of cognitive control, we found that the influence of predictive learning on decision making is mediated by an inhibitory feedback circuit linking the medial ventral pallidum and the mediodorsal thalamus, the activation of which causes disinhibition of the orbitofrontal cortex via reduced activation of inhibitory parvalbumin interneurons during choice. Thus, we found that, for this function, the mediodorsal thalamus serves as a pallidal-cortical relay through which predictive learning controls action selection, which has important implications for understanding cognitive control and its vicissitudes in various psychiatric disorders and addiction.

Goal-directed acting requires the integration of sensory information but can also be performed without direct sensory input. Examples of this can be found in sports and can be conceptualized by feedforward processes. There is, however, still a lack of understanding of the temporal neural dynamics and neuroanatomical structures involved in such processes. In the current study, we used EEG beamforming methods and examined 37 healthy participants in two well-controlled experiments varying the necessity of anticipatory processes during goal-directed action. We found that alpha and beta activity in the medial and posterior cingulate cortex enabled feedforward predictions about the position of an object based on the latest sensorimotor state. On this basis, theta band activity seems more related to sensorimotor representations, while beta band activity would be more involved in setting up the structure of the neural representations themselves. Alpha band activity in sensory cortices reflects an intensified gating of the anticipated perceptual consequences of the to-be-executed action. Together, the findings indicate that goal-directed acting through the anticipation of the predicted state of an effector is based on accompanying processes in multiple frequency bands in midcingulate and sensory brain regions.

Evidence suggests that dopamine activity provides a US-related prediction error for Pavlovian conditioning and the reinforcement signal supporting the acquisition of habits. However, its role in goal-directed action is less clear. There are currently few studies that have assessed dopamine release as animals acquire and perform self-paced instrumental actions. Here we briefly review the literature documenting the psychological, behavioral and neural bases of goal-directed actions in rats and mice, before turning to describe recent studies investigating the role of dopamine in instrumental learning and performance. Plasticity in dorsomedial striatum, a central node in the network supporting goal-directed action, clearly requires dopamine release, the timing of which, relative to cortical and thalamic inputs, determines the degree and form of that plasticity. Beyond this, bilateral release appears to reflect reward prediction errors as animals experience the consequences of an action. Such signals feedforward to update the value of the specific action associated with that outcome during subsequent performance, with dopamine release at the time of action reflecting the updated predicted action value. More recently, evidence has also emerged for a hemispherically lateralised signal associated with the action; dopamine release is greater in the hemisphere contralateral to the spatial target of the action. This effect emerges over the course of acquisition and appears to reflect the strength of the action-outcome association. Thus, during goal-directed action, dopamine release signals the action, the outcome and their association to shape the learning and performance processes necessary to support this form of behavioral control.

The acquisition and performance of goal-directed actions has long been argued to depend on the integration of glutamatergic inputs to the posterior dorsomedial striatum (pDMS) under the modulatory influence of dopamine. Nevertheless, relatively little is known about the dynamics of striatal dopamine during goal-directed actions. To investigate this, we chronically recorded dopamine release in the pDMS as rats acquired two actions for distinct outcomes as these action-outcome associations were incremented and then subsequently degraded or reversed. We found that bilateral dopamine release scaled with action value, whereas the lateralized dopamine signal, i.e., the difference in dopamine release ipsilaterally and contralaterally to the direction of the goal-directed action, reflected the strength of the action-outcome association independently of changes in movement. Our results establish, therefore, that striatal dopamine activity during goal-directed action reflects both bilateral moment-to-moment changes in action value and the long-term action-outcome association.

Instrumental behavior can reflect the influence of goal-directed and habitual systems. Contemporary research suggests that stress may facilitate control by the habitual system under conditions where the behavior would otherwise reflect control by the goal-directed system. However, it is unclear how stress modulates the influence of these systems on instrumental responding to achieve this effect, particularly in females. Here, we examine whether a mild psychogenic stressor experienced before acquisition training (Experiment 1), or prior to the test of expression (Experiment 2) would influence goal-directed and habitual control of instrumental responding in female rats. In both experiments, rats acquired an instrumental nose-poke response for a sucrose reward. This was followed by a reinforcer devaluation phase in which half the rats in Stressed and Non-Stressed conditions received pairings of the sucrose pellet with illness induced by lithium chloride until they rejected the pellet when offered. The remaining rats received a control treatment consisting of pellets and illness on separate days (Unpaired). Control by goal-directed and habitual systems was evaluated in a subsequent nonreinforced test of nose poking. The results of Experiment 1 indicated that the Non-Stressed Paired group reduced nose-poking compared to the Unpaired controls, identifying the response as goal directed, whereas the Stressed Paired and Unpaired groups made a similar number of nose pokes identifying the response as habitual despite a similar amount of training. Results from Experiment 2 indicated habitual control of nose-poke responding was present when stress was experienced just prior to the test. Collectively, these data suggest that stress may facilitate habitual control by altering the relative influence of goal-directed and habitual processes underpinning instrumental behavior. These results may be clinically relevant for understanding the contributions of stress to dysregulated instrumental behavior in compulsive pathologies.

Operant behavior can reflect the influence of goal-directed and habitual processes. These can be distinguished by changes to response rate following devaluation of the reinforcing outcome. Whether a response is goal directed or habitual depends on whether devaluation affects response rate. Response rate can be decomposed into frequencies of bouts and pauses by analyzing the distribution of interresponse times. This study sought to characterize goal-directed and habitual behaviors in terms of bout-initiation rate, within-bout response rate, bout length, and bout duration. Data were taken from three published studies that compared sensitivity to devaluation following brief and extended training with variable-interval schedules. Analyses focused on goal-directed and habitual responding, a comparison of a habitual response to a similarly trained response that had been converted back to goal-directed status after a surprising event, and a demonstration of contextual control of habit and goal direction in the same subjects. Across experiments and despite responses being clearly distinguished as goal directed and habitual by total response rate, analyses of bout-initiation rate, within-bout rate, bout length, and bout duration did not reveal a pattern that distinguished goal-directed from habitual responding.

Children with developmental coordination disorder (DCD) show deficits in motor-cognitive coupling. However, it remains unclear whether such deficits depend on the severity of DCD. The aim of this study was to examine cognitive-motor coupling under different levels of inhibitory control in children with severe (s-DCD) or moderate DCD (m-DCD), compared with typically-developing children (TDC). The performance of 29 primary-school children aged 6-12 years with s-DCD (Mage = 9.12 ± 1.56 years), 53 m-DCD (Mage = 8.78 ± 1.67 years), and 201 TDC (Mage = 9.20 ± 1.50 years) was compared on a double jump reaching task (DJRT) paradigm, presented on a large 42-inch touchscreen. The task display had a circular home-base, centred at the bottom of the display, and three target locations at radials of -20°, 0°, and 20°, 40 cm above the home-base circle. For the standard double-jump reaching task (DJRT), children moved their index finger from home-base circle to touch the target stimulus as fast as possible; 20% were jump trials where the target shifted left or right at lift-off. For the anti-jump reaching task (AJRT), 20% of trials required an anti-jump movement, touching the contralateral target location. While no group differences were shown on the DJRT, the DCD group were slower to complete reaching movements than the TDC group on AJRT; on the latter, the two DCD sub-groups were not shown to differ. Results confirm the presence of motor inhibition deficits in DCD which may not be dependent on the motor severity of the disorder.

Obsessive compulsive disorder (OCD) can occur comorbidly with epilepsy; both are complex, disruptive disorders that lower quality of life. Both OCD and epilepsy are disorders of hyperexcitable circuits, but it is unclear whether common circuit pathology may underlie the co-occurrence of these two neuropsychiatric disorders. Here, we induced early-life seizures (ELS) in rats to examine habit formation as a model for compulsive behaviors. Compulsive, repetitive behaviors in OCD utilize the same circuitry as habit formation. We hypothesized that rats with ELS could be more susceptible to habit formation than littermate controls, and that altered behavior would correspond to altered signaling in fronto-striatal circuits that underlie decision-making and action initiation. Here, we show instead that rats with ELS were significantly less likely to form habit behaviors compared with control rats. This behavioral difference corresponded with significant alterations to temporal coordination within and between brain regions that underpin the action to habit transition: 1) phase coherence between the lateral orbitofrontal cortex and dorsomedial striatum (DMS) and 2) theta-gamma coupling within DMS. Finally, we used cortical electrical stimulation as a model of transcranial magnetic stimulation (TMS) to show that temporal coordination of fronto-striatal circuits in control and ELS rats are differentially susceptible to potentiating and suppressive stimulation, suggesting that altered underlying circuit physiology may lead to altered response to therapeutic interventions such as TMS.

BACKGROUND: The endocannabinoid system makes critical contributions to reward processing, motivation, and behavioral control. Repeated exposure to THC or other cannabinoid drugs can cause persistent adaptions in the endocannabinoid system and associated neural circuitry. It remains unclear how such treatments affect the way rewards are processed and pursued.
OBJECTIVE: We examined if repeated THC exposure (5 mg/kg/day for 14 days) during adolescence or adulthood led to long-term changes in rats\' capacity to flexibly encode and use action-outcome associations for goal-directed decision making. Effects on hedonic feeding and progressive ratio responding were also assessed.
RESULTS: THC exposure had no effect on rats\' ability to flexibly select actions following reward devaluation. However, instrumental contingency degradation learning, which involves avoiding an action that is unnecessary for reward delivery, was augmented in rats with a history of adult but not adolescent THC exposure. THC-exposed rats also displayed more vigorous instrumental behavior in this study, suggesting a motivational enhancement. A separate experiment found that while THC exposure had no effect on hedonic feeding behavior, it increased rats\' willingness to work for food on a progressive ratio schedule, an effect that was more pronounced when THC was administered to adults. Adolescent and adult THC exposure had opposing effects on the CB1 receptor dependence of progressive ratio performance, decreasing and increasing sensitivity to rimonabant-induced behavioral suppression, respectively.
CONCLUSIONS: Our findings reveal that exposure to a translationally relevant THC exposure regimen induces long-lasting, age-dependent alterations in cognitive and motivational processes that regulate the pursuit of rewards.