A ventral pallidal-thalamocortical circuit mediates the cognitive control of instrumental action.

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.

What Role Does Striatal Dopamine Play in Goal-directed Action?

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.

Adaptation of sequential action benefits from timing variability related to lateral basal ganglia circuitry.

Streamlined action sequences must remain flexible should stable contingencies in the environment change. By combining analyses of behavioral structure with a circuit-specific manipulation in mice, we report on a relationship between action timing variability and successful adaptation that relates to post-synaptic targets of primary motor cortical (M1) projections to dorsolateral striatum (DLS). In a two-lever instrumental task, mice formed successful action sequences by, first, establishing action scaffolds and, second, smoothly extending action duration to adapt to increased task requirements.

Striatal dopamine release tracks the relationship between actions and their consequences.

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.

Action control and selection in social disinhibition following severe TBI: a pavlovian-to-instrumental transfer and outcome devaluation study.

Introduction: Social disinhibition is a significant sequela of severe traumatic brain injury (TBI). Some research suggests that it could reflect a deficiency in goal-directed behavior. The current study aimed to test whether these inappropriate behaviors tend to be deficient in goal-directed control, that is, triggered more by environmental stimuli than by the known consequences of their actions.

Stimulus control of habits: Evidence for both stimulus specificity and devaluation insensitivity in a dual-response task.

Goal-directed and habitual actions are clearly defined by their associative relations. Whereas goal-directed control can be confirmed via tests of outcome devaluation and contingency-degradation sensitivity, a comparable criterion for positively detecting habits has not been established. To confirm habitual responding, a test of control by the stimulus-response association is required while also ruling out goal-directed control.

Immp2l knockdown in male mice increases stimulus-driven instrumental behaviour but does not alter goal-directed learning or neuron density in cortico-striatal circuits in a model of Tourette syndrome and autism spectrum disorder.

Cortico-striatal neurocircuits mediate goal-directed and habitual actions which are necessary for adaptive behaviour. It has recently been proposed that some of the core symptoms of autism spectrum disorder (ASD) and Gilles de la Tourette syndrome (GTS), such as tics and other repetitive behaviours, may emerge because of imbalances in these neurocircuits. We have recently developed a model of ASD and GTS by knocking down Immp2l, a mitochondrial gene frequently associated with these disorders.

Reduced Sensitivity to Background Reward Underlies Apathy After Traumatic Brain Injury: Insights From an Ecological Foraging Framework.

Background: Altered reward processing is increasingly recognised as a crucial mechanism underpinning apathy in many brain disorders. However despite its clinical relevance, little is known about the mechanisms of apathy following moderate-to-severe traumatic brain injury (TBI). In real-life situations, reward representations encompass both foreground (gains from current activity) and background (potential gains from the broader environment) elements.

Cognitive effects of thalamostriatal degeneration are ameliorated by normalizing striatal cholinergic activity.

The loss of neurons in parafascicular thalamus (Pf) and their inputs to dorsomedial striatum (DMS) in Lewy body disease (LBD) and Parkinson's disease dementia (PDD) have been linked to the effects of neuroinflammation. We found that, in rats, these inputs were necessary for both the function of striatal cholinergic interneurons (CINs) and the flexible encoding of the action-outcome (AO) associations necessary for goal-directed action, producing a burst-pause pattern of CIN firing but only during the remapping elicited by a shift in AO contingency. Neuroinflammation in the Pf abolished these changes in CIN activity and goal-directed control after the shift in contingency.

Goal-Directed Action Is Initially Impaired in a hAPP-J20 Mouse Model of Alzheimer's Disease.

Cognitive-behavioral testing in preclinical models of Alzheimer's disease has failed to capture deficits in goal-directed action control. Here, we provide the first comprehensive investigation of goal-directed action in a transgenic mouse model of Alzheimer's disease. Specifically, we tested outcome devaluation performance in male and female human amyloid precursor protein (hAPP)-J20 mice.

What does dopamine release reveal about latent inhibition?

A recent paper by Kutlu et al. (2022) argues that changes in dopamine release during stimulus pre-exposure reflect non-associative changes in attention to the conditioned stimulus that are causally related to latent inhibition effects. Associative accounts of pre-exposure-induced changes in associability suggest, however, that such conclusions may be premature.

The role of the bed nucleus of the stria terminalis in the motivational control of instrumental action.

We review recent studies assessing the role of the bed nucleus of the stria terminalis (BNST) in the motivational control of instrumental conditioning. This evidence suggests that the BNST and central nucleus of the amygdala (CeA) form a circuit that modulates the ventral tegmental area (VTA) input to the nucleus accumbens core (NAc core) to control the influence of Pavlovian cues on instrumental performance. In support of these claims, we found that activity in the oval region of BNST was increased by instrumental conditioning, as indexed by phosphorylated ERK activity (Experiment 1), but that this increase was not due to exposure to the instrumental contingency or to the instrumental outcome (Experiment 2).

The positive valence system, adaptive behaviour and the origins of reward.

Although the hey-day of motivation as an area of study is long past, the issues with which motivational theorists grappled have not grown less important: i.e. the development of deterministic explanations for the particular tuning of the nervous system to specific changes in the internal and external environment and the organisation of adaptive behavioural responses to those changes.

Response-independent outcome presentations weaken the instrumental response-outcome association.

The present article explored the fate of previously formed response-outcome associations when the relation between R and O was disrupted by arranging for O to occur independently of R. In each of three experiments response independent outcome delivery selectively reduced the R earning that O. Nevertheless, in Experiments 1 and 2, the R continued to show sensitivity to outcome devaluation, suggesting that the strength of the R-O association was undiminished by this treatment.

Food for thought: diet-induced impairments to decision-making and amelioration by N-acetylcysteine in male rats.

Rationale: Attempts to lose weight often fail despite knowledge of the health risks associated with obesity and determined efforts. We previously showed that rodents fed an obesogenic diet displayed premature habitual behavioural control and weakened flexible decision-making based on the current value of outcomes produced by their behaviour. Thus, habitual control may contribute to failed attempts to modify eating behaviours.

Contributions of intrinsic and extrinsic reward sensitivity to apathy: Evidence from traumatic brain injury.

Objective: Apathy is a key feature of traumatic brain injury (TBI). However, mechanisms underlying apathy are poorly understood. Evidence suggests that changes in reward may be a crucial factor.

Affective Valence Regulates Associative Competition in Pavlovian Conditioning.

Evidence suggests that, in Pavlovian conditioning, associations form between conditioned stimuli and multiple components of the unconditioned stimulus (US). It is common, for example, to regard USs as composed of sensory and affective components, the latter being either appetitive (e.g.

The Neural Bases of Action-Outcome Learning in Humans.

From an associative perspective the acquisition of new goal-directed actions requires the encoding of specific action-outcome (AO) associations and, therefore, sensitivity to the validity of an action as a predictor of a specific outcome relative to other events. Although competitive architectures have been proposed within associative learning theory to achieve this kind of identity-based selection, whether and how these architectures are implemented by the brain is still a matter of conjecture. To investigate this issue, we trained human participants to encode various AO associations while undergoing functional neuroimaging (fMRI).

Animal models of action control and cognitive dysfunction in Parkinson's disease.

Parkinson's disease (PD) has historically been considered a motor disorder induced by a loss of dopaminergic neurons in the substantia nigra pars compacta. More recently, it has been recognized to have significant non-motor symptoms, most prominently cognitive symptoms associated with a dysexecutive syndrome. It is common in the literature to see motor and cognitive symptoms treated separately and, indeed, there has been a general call for specialized treatment of the latter, particularly in the more severe cases of PD with mild cognitive impairment and dementia.

CRF-receptor1 modulation of the dopamine projection to prelimbic cortex facilitates cognitive flexibility after acute and chronic stress.

Stress reduces cognitive flexibility and dopamine D1 receptor-related activity in the prelimbic cortex (PL), effects hypothesized to depend on reduced corticotropic releasing factor receptor type 1 (CRFr1) regulation of dopamine neurons in the ventral tegmental area (VTA). We assessed this hypothesis in rats by examining the effect of chronic unpredictable restraint stress (CUS), mild acute stress, or their combination on cognitive flexibility, CRFr1 expression in the VTA and D1-related activity in PL. In Experiment 1, rats received either CUS or equivalent handling for 14 days before being trained to press two levers to earn distinct food outcomes.

A novel estimation method for the counting of dendritic spines.

Background: Since Cajal's visualisations of the synaptic spine, this feature of the neuron has been of interest to neuroscientists and has been investigated usually in reference to degeneration or proliferation of dendrites and their neurons. Synaptic spine measurement often forms a critical element of any study investigating neuronal morphology. However, the way researchers have counted spines hasn't changed for almost a century.

Determining the effects of training duration on the behavioral expression of habitual control in humans: a multilaboratory investigation.

It has been suggested that there are two distinct and parallel mechanisms for controlling instrumental behavior in mammals: goal-directed actions and habits. To gain an understanding of how these two systems interact to control behavior, it is essential to characterize the mechanisms by which the balance between these systems is influenced by experience. Studies in rodents have shown that the amount of training governs the relative expression of these two systems: Behavior is goal-directed following moderate training, but the more extensively an instrumental action is trained, the more it becomes habitual.