Nucleus accumbens core and shell are differentially involved in general and outcome‐specific forms of Pavlovian‐instrumental transfer with alcohol and sucrose rewards

Alcohol‐associated stimuli contribute to relapse risk. Therefore, understanding the behavioural and neural mechanisms underlying the ability of such stimuli to promote alcohol‐seeking is important for developing effective treatments for alcohol‐use disorders. The Pavlovian‐instrumental transfer (PIT) paradigm can be used to study the influence of Pavlovian cues on independently‐trained instrumental responses earning reward. The effects can be either general, increasing the vigour of reward‐related behaviours, or specific to responses that earn a common outcome. These different forms of PIT are mediated by distinct neural circuits involving the nucleus accumbens (NAC) core and shell, respectively. Here we examined the effects of pharmacological inactivation of either the NAC core or shell on PIT generated by alcohol‐predictive and sucrose‐predictive stimuli in rats. We found that presentations of a stimulus predicting sucrose enhanced responding for sucrose but not alcohol, suggesting an outcome‐specific effect. In contrast, presentations of an alcohol‐predictive stimulus enhanced responding for both alcohol and sucrose, suggesting a generally arousing effect. Inactivation of the NAC core reduced PIT and, in particular, the effect of the alcohol stimulus. Inactivation of the NAC shell reduced the specificity of the stimulus effects but left the ability of the stimuli to non‐specifically invigorate responding intact, consistent with a role in mediating the specificity of PIT. Together, these results suggest that the NAC core plays a particularly important role in mediating the influence of alcohol‐predictive cues on reward‐seeking behaviours.     

Differential representation of Pavlovian–instrumental transfer by prefrontal cortex subregions and striatum

Environmental cues that once predicted reward can restore extinguished behavior directed toward that reward. This process may be modeled by the Pavlovian–instrumental transfer (PIT) paradigm where a previously learned Pavlovian conditioned stimulus (CS) elicits a representation of the reward associated with that CS, prompts motivation toward the absent reward, and triggers an instrumental action. We recorded in the medial and orbital prefrontal cortex (mPFC and OFC) and dorsal striatum (DS) of freely moving rats during PIT and found that a Pavlovian CS, as compared with neutral or no stimuli, amplified the phasic neuronal responses to instrumental nosepokes ('transfer' event). In mPFC and OFC, but not the DS, representation of the transfer event correlated with the strength of PIT behavior. Neurons in all three regions showed CS-selective amplification of Pavlovian approaches toward the reward delivery site. Whereas striatal neurons represented transfer and approach behavior through mostly segregated neuronal subsets, overlapping subsets represented these events in the mPFC and OFC. These findings suggest that parallel phasic activation of mPFC and OFC neuronal subsets participates in the transfer from Pavlovian incentives to instrumental actions.     

The role of melanin‐concentrating hormone in conditioned reward learning

The orexigenic neuropeptide melanin‐concentrating hormone (MCH) is well positioned to play a key role in connecting brain reward and homeostatic systems due to its synthesis in hypothalamic circuitry and receptor expression throughout the cortico‐striatal reward circuit. Here we examined whether targeted‐deletion of the MCH receptor (MCH‐1R) in gene‐targeted heterozygote and knockout mice (KO), or systemic treatment with pharmacological agents designed to antagonise MCH‐1R in C57BL/6J mice would disrupt two putative consequences of reward learning that rely on different neural circuitries: conditioned reinforcement (CRf) and Pavlovian‐instrumental transfer (PIT). Mice were trained to discriminate between presentations of a reward‐paired cue (CS+) and an unpaired CS?. Following normal acquisition of the Pavlovian discrimination in all mice, we assessed the capacity for the CS+ to act as a reinforcer for new nose‐poke learning (CRf). Pharmacological disruption in control mice and genetic deletion in KO mice impaired CRf test performance, suggesting MCH‐1R is necessary for initiating and maintaining behaviors that are under the control of conditioned reinforcers. To examine a dissociable form of reward learning (PIT), a naïve group of mice were trained in separate Pavlovian and instrumental lever training sessions followed by the PIT test. For all mice the CS+ was capable of augmenting ongoing lever responding relative to CS? periods. These results suggest a role for MCH in guiding behavior based on the conditioned reinforcing value of a cue, but not on its incentive motivational value.     

The role of dopamine in the dorsomedial striatum in general and outcome-selective Pavlovian-instrumental transfer

Pavlovian stimuli predictive of appetitive outcomes can influence the selection and initiation of instrumental behaviour. For instance, Pavlovian stimuli can act to enhance those actions with which they share an outcome, but not others with which they do not share an outcome, a phenomenon termed outcome-selective Pavlovian-instrumental transfer (PIT). Furthermore, Pavlovian stimuli can invigorate an action by inducing a general appetitive arousal that elevates instrumental responding, a phenomenon termed general PIT. The dorsomedial striatum has been implicated in outcome-selective, but not general PIT. However, the role of dopamine (DA) signals in this subregion in mediating PIT is unknown. Here we examined in rats the effects of a 6-hydroxydopamine-induced DA depletion of the anterior (aDMS) or posterior (pDMS) subregion of the dorsomedial striatum on outcome-selective and general PIT as well as on instrumental performance on a FR-5 schedule (five lever presses earned one pellet). Results demonstrate that aDMS and pDMS DA depletions compromised the rate of responding on a FR-5 schedule, suggesting that DA signals in the dorsomedial striatum are necessary to maintain high rates of instrumental responding. By contrast, aDMS and pDMS DA depletions did not affect general PIT, suggesting that DA signals in the dorsomedial striatum do not mediate general activating effects of reward-predictive stimuli to invigorate instrumental responding. Furthermore, aDMS DA depletions did not impair outcome-selective PIT, while pDMS DA depletions had no or only minor effects. Thus, DA signals in the DMS may not be involved in mediating the specific cueing effects of reward-predictive stimuli.     

Modulation of cue‐triggered reward seeking by cholinergic signaling in the dorsomedial striatum

The dorsomedial striatum (DMS) has been strongly implicated in flexible, outcome‐based decision making, including the outcome‐specific Pavlovian‐to‐instrumental transfer effect (PIT), which measures the tendency for a reward‐predictive cue to preferentially motivate actions that have been associated with the predicted reward over actions associated with different rewards. Although the neurochemical underpinnings of this effect are not well understood, there is growing evidence that striatal acetylcholine signaling may play an important role. This study investigated this hypothesis by assessing the effects of intra‐DMS infusions of the nicotinic antagonist mecamylamine or the muscarinic antagonist scopolamine on expression of specific PIT in rats. These treatments produced dissociable behavioral effects. Mecamylamine infusions enhanced rats’ tendency to use specific cue‐elicited outcome expectations to select whichever action was trained with the predicted outcome, relative to their performance when tested after vehicle infusions. In contrast, scopolamine infusions appeared to render instrumental performance insensitive to this motivational influence of reward‐paired cues. These drug treatments had no detectable effect on conditioned food cup approach behavior, indicating that they selectively perturbed cue‐guided action selection without producing more wide‐ranging alterations in behavioral control. Our findings reveal an important role for DMS acetylcholine signaling in modulating the impact of cue‐evoked reward expectations on instrumental action selection.     

On the relationship between anticipatory behaviour in a Pavlovian paradigm and Pavlovian-to-Instrumental Transfer in rats (Rattus norvegicus)

The present rat study assessed the relationship between, and the sensitivity of, two different tests for appetitive conditioned responding to differences in the contingency between a conditioned stimulus (CS) and an unconditioned stimulus (US), and to differences in US magnitude. The first test used a Pavlovian-to-Instrumental Transfer (PIT) paradigm, assessing the capacity of the CS to enhance instrumental responding for food. The second test employed a Pavlovian conditioning paradigm with an extended CS-US interval, and total number of behavioural elements in this interval as a dependent measure. The PIT test proved to be sensitive to contingency but not reward magnitude differences, whereas the reverse was true for the Pavlovian test. Although there was a significant correlation between tests in the magnitude of the CS-induced increase of food-magazine entries, the main dependent measure from PIT (number of lever presses) and that from the Pavlovian test (total number of behavioural elements) did not correlate. It is suggested that in the PIT procedure, the CS induces a chain of behavioural responses of which lever pressing is just a single element and that the Pavlovian test, in principle, is more sensitive.     

Effects of ventral striatal lesions on first‐ and second‐order appetitive conditioning

Rats with bilateral lesions of the ventral striatal nucleus accumbens failed to acquire Pavlovian second‐order conditioning to auditory stimuli paired with visual stimuli that had previously received first‐order pairings with food. This deficit in second‐order conditioning was specific to learning driven by incentive properties of the first‐order cues, and was observed whether the first‐order training had occurred prior to or after lesion surgery. Lesions also produced deficits in the display of conditioned responses to the first‐order conditioned stimulus, but only when they were made after first‐order training. These results suggest a specific role for the ventral striatum in acquiring and expressing incentive properties of conditioned stimuli through second‐order conditioning, as well as a more general role in expressing previously acquired Pavlovian conditioned responses.     

Double dissociation of the effects of lesions of basolateral and central amygdala on conditioned stimulus-potentiated feeding and Pavlovian-instrumental transfer

Pavlovian conditioned stimuli (CSs) for food can enhance both the performance of instrumental responses that earn food (Pavlovian-instrumental transfer; PIT) and the consumption of food itself (CS-potentiated feeding). After a single phase of Pavlovian training, each rat was tested in both PIT and potentiated feeding tasks. Rats with lesions of the central nucleus of the amygdala failed to exhibit PIT but showed normal CS-potentiated feeding. By contrast, rats with lesions of the basolateral amygdala showed normal PIT but failed to display CS-potentiated feeding. Performances in a variety of comparison conditions suggested that both lesion effects reflected impairment of acquired motivational functions, rather than with attentional processes or the display of specific learned responses. Implications of the double dissociation of these two aspects of Pavlovian conditioned incentive motivation for amygdala function in associative learning are considered.     

Pavlovian‐to‐instrumental transfer in Anorexia Nervosa: A pilot study on conditioned learning and instrumental responding to low‐ and high‐calorie food stimuli

Anorexia Nervosa is characterized by persistent restraint eating despite severe negative consequences and often a chronic course of the disease. Recent theoretical models suggest that abnormalities in reward processing and incentive salience of disorder‐compatible stimuli as observed in addictive behaviours contribute to the development and maintenance of Anorexia Nervosa. The aim of the present study was to investigate the process of the acquisition of food‐related conditioned responses and the influence of conditioned low‐calorie and high‐calorie food stimuli on instrumental responding for different foods. A Pavlovian‐to‐instrumental transfer paradigm and questionnaires on eating disorder psychopathology (EDE‐Q, EDI‐2) were administered to patients with Anorexia Nervosa (n = 39) and healthy controls (n = 41). Results indicated that patients with Anorexia Nervosa showed deficits of the acquisition of knowledge of the experimental contingencies. Nevertheless, in patients with Anorexia Nervosa and healthy controls instrumental responding for low‐ and high‐calorie food rewards was affected by stimuli conditioned to these rewards; no group differences were observed. Importantly, in Anorexia Nervosa, instrumental responding for low‐calorie food increased with increasing severity of eating disorder psychopathology suggesting weight‐loss directed behaviour. Future studies are warranted to enhance our understanding of deficits of reward‐associated learning and to replicate and extend findings with regard to the impact of conditioned stimuli on instrumental responding. At present, our findings suggest that cognitive treatment interventions might be warranted that challenge dysfunctional beliefs about weight loss.     

Serotonin modulates the effects of pavlovian aversive predictions on response vigor

Updated theoretical accounts of the role of serotonin (5-HT) in motivation propose that 5-HT operates at the intersection of aversion and inhibition, promoting withdrawal in the face of aversive predictions. However, the specific cognitive mechanisms through which 5-HT modulates withdrawal behavior remain poorly understood. Behavioral inhibition in response to punishments reflects at least two concurrent processes: instrumental aversive predictions linking stimuli, responses, and punishments, and Pavlovian aversive predictions linking stimuli and punishments irrespective of response. In the current study, we examined to what extent 5-HT modulates the impact of instrumental vs Pavlovian aversive predictions on behavioral inhibition. We used acute tryptophan depletion to lower central 5-HT levels in healthy volunteers, and observed behavior in a novel task designed to measure the influence of Pavlovian and instrumental aversive predictions on choice (response bias) and response vigor (response latencies). After placebo treatment, participants were biased against responding on the button that led to punishment, and they were slower to respond in a punished context, relative to a non-punished context. Specifically, participants slowed their responses in the presence of stimuli predictive of punishments. Tryptophan depletion removed the bias against responding on the punished button, and abolished slowing in the presence of punished stimuli, irrespective of response. We suggest that this set of results can be explained by a role for 5-HT in Pavlovian aversive predictions. These findings suggest additional specificity for the influence of 5-HT on aversively motivated behavioral inhibition and extend recent models of the role of 5-HT in aversive predictions.     

Emotion and motivation: the role of the amygdala,ventral striatum,and prefrontal cortex

Emotions are multifaceted, but a key aspect of emotion involves the assessment of the value of environmental stimuli. This article reviews the many psychological representations, including representations of stimulus value, which are formed in the brain during Pavlovian and instrumental conditioning tasks. These representations may be related directly to the functions of cortical and subcortical neural structures. The basolateral amygdala (BLA) appears to be required for a Pavlovian conditioned stimulus (CS) to gain access to the current value of the specific unconditioned stimulus (US) that it predicts, while the central nucleus of the amygdala acts as a controller of brainstem arousal and response systems, and subserves some forms of stimulus-response Pavlovian conditioning. The nucleus accumbens, which appears not to be required for knowledge of the contingency between instrumental actions and their outcomes, nevertheless influences instrumental behaviour strongly by allowing Pavlovian CSs to affect the level of instrumental responding (Pavlovian-instrumental transfer), and is required for the normal ability of animals to choose rewards that are delayed. The prelimbic cortex is required for the detection of instrumental action-outcome contingencies, while insular cortex may allow rats to retrieve the values of specific foods via their sensory properties. The orbitofrontal cortex, like the BLA, may represent aspects of reinforcer value that govern instrumental choice behaviour. Finally, the anterior cingulate cortex, implicated in human disorders of emotion and attention, may have multiple roles in responding to the emotional significance of stimuli and to errors in performance, preventing responding to inappropriate stimuli.     

Neural correlates of Pavlovian-to-instrumental transfer in the nucleus accumbens shell are selectively potentiated following cocaine self-administration

During Pavlovian-to-instrumental transfer (PIT), learned Pavlovian cues significantly modulate ongoing instrumental actions. This phenomenon is suggested as a mechanism under which conditioned stimuli may lead to relapse in addicted populations. Following discriminative Pavlovian learning and instrumental conditioning with sucrose, one group of rats (naive) underwent electrophysiological recordings in the nucleus accumbens core and shell during a single PIT session. Other groups, following Pavlovian and instrumental conditioning, were subsequently trained to self-administer cocaine with nosepoke responses, or received yoked saline infusions and nosepoked for water rewards, and then performed PIT while electrophysiological recordings were taken in the nucleus accumbens. Behaviorally, although both naive and saline-treated groups showed increases in lever pressing during the conditioned stimulus cue, this effect was significantly enhanced in the cocaine-treated group. Neurons in the core and shell tracked these behavioral changes. In control animals, core neurons were significantly more likely to encode general information about cues, rewards and responses than those in the shell, and positively correlated with behavioral PIT performance, whereas PIT-specific encoding in the shell, but not core, tracked PIT performance. In contrast, following cocaine exposure, there was a significant increase in neural encoding of all task-relevant events that was selective to the shell. Given that cocaine exposure enhanced both behavior and shell-specific task encoding, these findings suggest that, whereas the core is important for acquiring the information about cues and response contingencies, the shell is important for using this information to guide and modulate behavior and is specifically affected following a history of cocaine self-administration.     

Long‐lasting contribution of dopamine in the nucleus accumbens core,but not dorsal lateral striatum,to sign‐tracking

The attribution of incentive salience to reward‐paired cues is dependent on dopamine release in the nucleus accumbens core (NAcC). These dopamine signals conform to traditional reward‐prediction error signals and have been shown to diminish with time. Here we examined whether the diminishing dopamine signal in the NAcC has functional implications for the expression of sign‐tracking, a Pavlovian conditioned response indicative of the attribution of incentive salience to reward‐paired cues. Food‐restricted male Sprague Dawley rats were trained in a Pavlovian paradigm in which an insertable lever predicted delivery of food reward in a nearby food cup. After 7 or 14 training sessions, rats received infusions of saline, the dopamine antagonist flupenthixol, or the GABA agonists baclofen and muscimol into the NAcC or the dorsal lateral striatum (DLS). Dopamine antagonism within the NAcC attenuated sign‐tracking, whereas reversible inactivation did not affect sign‐tracking but increased non‐specific food cup checking behaviors. Neither drug in the DLS affected sign‐tracking behavior. Critically, extended training did not alter these effects. Although extended experience with an incentive stimulus may reduce cue‐evoked dopamine in the NAcC, this does not remove the dependence on dopamine in this region to promote Pavlovian cue approach nor result in the recruitment of dorsal lateral striatal systems for this behavior. These data support the notion that dopamine within the mesoaccumbal system, but not the nigrostriatal system, contributes critically to incentive motivational processes independent of the length of training.     

General and outcome-specific forms of Pavlovian-instrumental transfer: the effect of shifts in motivational state and inactivation of the ventral tegmental area

This study compared the contribution of the general activating and specific cueing properties of Pavlovian stimuli to Pavlovian-instrumental transfer (PIT) and the role of the ventral tegmental area (VTA) in mediating these effects. In Experiment 1, hungry rats initially received Pavlovian training, in which three distinct auditory stimuli predicted the delivery of three different food outcomes. Next, the rats were trained to perform two instrumental actions, each earning a unique outcome selected from the three used in Pavlovian conditioning. Finally, the effects of the three stimuli on performance of the two actions were assessed in extinction. Presentation of a stimulus that had been paired with the same outcome as an action increased its performance relative to the other action, demonstrating that PIT effects can be outcome selective. In contrast, presentation of the stimulus that predicted the outcome that was not earned during instrumental training facilitated the performance of both actions indiscriminately. This effect, but not the outcome-selective effect, was abolished by a shift from a hungry to a relatively sated state. Experiment 2 examined the effects of inactivation of the VTA on these two forms of PIT. VTA inactivation was found to attenuate PIT but, unlike satiety, did not appear to differentially affect the general or the outcome-selective forms of PIT. The VTA appears therefore to play an important but general role in the initiation of instrumental actions, enabling cues to influence performance whether they enhance responding by changes in arousal or by retrieving particular actions based on their consequences.     

Involvement of the central nucleus of the amygdala and nucleus accumbens core in mediating Pavlovian influences on instrumental behaviour

Pavlovian conditioned cues exert a powerful influence on instrumental actions directed towards a common reward, this is known as Pavlovian-to-instrumental transfer (PIT). The nucleus accumbens (NAcc) has been hypothesized to function as an interface between limbic cortical structures required for associative conditioning, like the amygdala, and response mechanisms through which instrumental behaviour can be selected and performed. Here we have used selective excitotoxic lesions to investigate the involvement of subnuclei of the amygdala as well as the core and shell regions of the nucleus accumbens on PIT in rats. Within the amygdala, selective lesions of the central nucleus (CeN), but not of the basolateral nucleus (BLA), abolished the PIT effect. In addition, selective lesions of the NAcc core, but not the NAcc shell, also abolished PIT. None of the lesions impaired the acquisition of Pavlovian food cup approaches or instrumental responding itself. These data demonstrate that the CeN and NAcc core are central components of the neural system mediating the impact of Pavlovian cues on instrumental responding. We suggest that this effect may depend upon the regulation of the dopaminergic innervation of the NAcc core by projections from the CeN to the ventral tegmental area.     

Dissociations in dopamine release in medial prefrontal cortex and ventral striatum during the acquisition and extinction of classical aversive conditioning in the rat

Dual perfusion in vivo brain microdialysis was used to monitor extracellular levels of dopamine in the medial prefrontal cortex and ventral striatum during the acquisition and extinction of a classical aversive conditioning paradigm in rats. The main finding was a dissociation in the pattern of release in the two brain areas. The first stimulus–footshock pairing elicited large increases in cortical dopamine over baseline levels that were much greater than the increases elicited by different stimuli of equivalent salience that were unpaired with footshock. In contrast, dopamine levels in ventral striatum were unchanged under these conditions. Over the next two pairings, there was a decline in the cortical response and an increase in the response in ventral striatum. The first presentation of the aversive conditioned stimulus in a separate context elicited the largest response in ventral striatum. Post-conditioning, the cortical response to the conditioned stimulus was smaller than that elicited by the initial stimulus–footshock pairing and was equivalent in magnitude to that elicited by stimuli unpaired with footshock. Over the final two conditioned stimuli presentations, in the absence of the footshock reinforcer (extinction), responses declined in both brain areas. Simultaneous monitoring of behaviour indicated that the neurochemical events were accompanied by effective aversive learning, as indexed by conditioned freezing responses. The data are discussed in terms of the hypothesis that medial prefrontal cortex is especially engaged during novel circumstances which may, potentially, require new learning, whilst ventral striatal dopamine more closely follows the expression of conditioned responding during learning and extinction.     

Hippocampal theta activity is selectively associated with contingency detection but not discrimination in rabbit discrimination‐reversal eyeblink conditioning

The relative power of the hippocampal theta‐band (∼6 Hz) activity (theta ratio) is thought to reflect a distinct neural state and has been shown to affect learning rate in classical eyeblink conditioning in rabbits. We sought to determine if the theta ratio is mostly related to the detection of the contingency between the stimuli used in conditioning or also to the learning of more complex inhibitory associations when a highly demanding delay discrimination‐reversal eyeblink conditioning paradigm is used. A high hippocampal theta ratio was not only associated with a fast increase in conditioned responding in general but also correlated with slow emergence of discriminative responding due to sustained responding to the conditioned stimulus not paired with an unconditioned stimulus. The results indicate that the neural state reflected by the hippocampal theta ratio is specifically linked to forming associations between stimuli rather than to the learning of inhibitory associations needed for successful discrimination. This is in line with the view that the hippocampus is responsible for contingency detection in the early phase of learning in eyeblink conditioning. © 2009 Wiley‐Liss, Inc.     

Amygdala mu‐opioid receptors mediate the motivating influence of cue‐triggered reward expectations

Environmental reward‐predictive stimuli can retrieve from memory a specific reward expectation that allows them to motivate action and guide choice. This process requires the basolateral amygdala (BLA), but little is known about the signaling systems necessary within this structure. Here we examined the role of the neuromodulatory opioid receptor system in the BLA in such cue‐directed action using the outcome‐specific Pavlovian‐to‐instrumental transfer (PIT) test in rats. Inactivation of BLA mu‐, but not delta‐opioid receptors was found to dose‐dependently attenuate the ability of a reward‐predictive cue to selectively invigorate the performance of actions directed at the same unique predicted reward (i.e. to express outcome‐specific PIT). BLA mu‐opioid receptor inactivation did not affect the ability of a reward itself to similarly motivate action (outcome‐specific reinstatement), suggesting a more selective role for the BLA mu‐opioid receptor in the motivating influence of currently unobservable rewarding events. These data reveal a new role for BLA mu‐opioid receptor activation in the cued recall of precise reward memories and the use of this information to motivate specific action plans.     

Orbitofrontal inactivation impairs reversal of Pavlovian learning by interfering with ‘disinhibition’ of responding for previously unrewarded cues

Orbitofrontal cortex (OFC) is critical for reversal learning. Reversal deficits are typically demonstrated in complex settings that combine Pavlovian and instrumental learning. Yet recent work has implicated the OFC specifically in behaviors guided by cues and the features of the specific outcomes they predict. To test whether the OFC is important for reversing such Pavlovian associations in the absence of confounding instrumental requirements, we trained rats on a simple Pavlovian task in which two auditory cues were presented, one paired with a food pellet reward and the other presented without reward. After learning, we reversed the cue–outcome associations. For half the rats, OFC was inactivated prior to each reversal session. Inactivation of OFC impaired the ability of the rats to reverse conditioned responding. This deficit reflected the inability of inactivated rats to develop normal responding for the previously unrewarded cue; inactivation of OFC had no impact on the ability of the rats to inhibit responding to the previously rewarded cue. These data show that OFC is critical to reversal of Pavlovian responding, and that the role of OFC in this behavior cannot be explained as a simple deficit in response inhibition. Furthermore, the contrast between the normal inhibition of responding, reported here, and impaired inhibition of responding during Pavlovian over‐expectation, reported previously, suggests the novel hypothesis that OFC may be particularly critical for learning (or behavior) when it requires the subject to generate predictions about outcomes by bringing together or integrating disparate pieces of associative information.     

Dissociable corticostriatal circuits underlie goal‐directed vs. cue‐elicited habitual food seeking after satiation: evidence from a multimodal MRI study

The present multimodal MRI study advances our understanding of the corticostriatal circuits underlying goal‐directed vs. cue‐driven, habitual food seeking. To this end, we employed a computerized Pavlovian‐instrumental transfer paradigm. During the test phase, participants were free to perform learned instrumental responses (left and right key presses) for popcorn and Smarties outcomes. Importantly, prior to this test half of the participants had been sated on popcorn and the other half on Smarties – resulting in a reduced desirability of those outcomes. Furthermore, during a proportion of the test trials, food‐associated Pavlovian cues were presented in the background. In line with previous studies, we found that participants were able to perform in a goal‐directed manner in the absence of Pavlovian cues, meaning that specific satiation selectively reduced responding for that food. However, presentation of Pavlovian cues biased choice toward the associated food reward regardless of satiation. Functional MRI analyses revealed that, in the absence of Pavlovian cues, posterior ventromedial prefrontal cortex tracked outcome value. In contrast, during cued trials, the BOLD signal in the posterior putamen differentiated between responses compatible and incompatible with the cue‐associated outcome. Furthermore, we identified a region in ventral amygdala showing relatively strong functional connectivity with posterior putamen during the cued trials. Structural MRI analyses provided converging evidence for the involvement of corticostriatal circuits: diffusion tensor imaging data revealed that connectivity of caudate‐seeded white‐matter tracts to the ventromedial prefrontal cortex predicted responding for still‐valuable outcomes; and gray matter integrity in the premotor cortex predicted individual Pavlovian cueing effects.