Thinking Outside the Box: Orbitofrontal Cortex, Imagination, and How We Can Treat Addiction

Schoenbaum, Geoffrey; Chang, Chun Yun; Lucantonio, Federica; Takahashi, Yuji K.

doi:10.1038/npp.2016.147

Cited by 43 publications

(48 citation statements)

References 74 publications

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“…(Verbruggen et al, 2014). Drugs might impair only a specific subcomponent, for example, they might impair capacity to represent competing alternatives to drug rewards, or the beneficial consequences of abstinence (Reiter et al, 2016a;Schoenbaum et al, 2016). In sum then, drug users might be habitual in the natural environment but goal-directed in laboratory tasks, might only show habitual control over specific action sequences, might arbitrate in favour of the habit system only under particular conditions, or might only show deficits in specific components of the control systems.…”

Section: Discussionmentioning

confidence: 99%

Intact goal‐directed control in treatment‐seeking drug users indexed by outcome‐devaluation and Pavlovian to instrumental transfer: critique of habit theory

Hogarth

Lam-Cassettari

Pacitti

et al. 2018

Eur J of Neuroscience

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Animal studies have demonstrated that chronic exposure to drugs of abuse impairs goal-directed control over action selection indexed by the outcome-devaluation and specific Pavlovian to instrumental transfer procedures, suggesting this impairment might underpin addiction. However, there is currently only weak evidence for impaired goal-directed control in human drug users. Two experiments were undertaken in which treatment-seeking drug users and non-matched normative reference samples (controls) completed outcome-devaluation and specific Pavlovian to instrumental transfer procedures notionally translatable to animal procedures (Experiment 2 used a more challenging biconditional schedule). The two experiments found significant outcome-devaluation and specific Pavlovian to instrumental transfer effects overall and there was no significant difference between groups in the magnitude of these effects. Moreover, Bayes factor supported the null hypothesis for these group comparisons. Although limited by non-matched group comparisons and small sample sizes, the two studies suggest that treatment-seeking drug users have intact goal-directed control over action selection, adding uncertainty to already mixed evidence concerning the role of habit learning in human drug dependence. Neuro-interventions might seek to tackle goal-directed drug-seeking rather than habit formation in drug users.

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Section: Discussionmentioning

confidence: 99%

Intact goal‐directed control in treatment‐seeking drug users indexed by outcome‐devaluation and Pavlovian to instrumental transfer: critique of habit theory

Hogarth

Lam-Cassettari

Pacitti

et al. 2018

Eur J of Neuroscience

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“…The orbitofrontal cortex (OFC) is a prime candidate for this because it sends dense glutamatergic innervation to the BLA [18][19][20][21][22] and is itself implicated in reward processing and decision making [32][33][34][35][36][37][38][39][40][41] , including incentive learning 42 . So we next used a chemogenetic approach and the same behavioral task to ask whether OFCBLA projections are necessary for reward value encoding and/or retrieval (Fig.…”

Section: Distinct Ofcbla Projections Are Necessary For Reward Value mentioning

confidence: 99%

Distinct cortical-amygdala projections drive reward value encoding and retrieval

Malvaez

Shieh

Murphy

et al. 2018

Preprint

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The value of an anticipated rewarding event is crucial information in the decision to engage in its pursuit. The networks responsible for encoding and retrieval this value are largely unknown. Using glutamate biosensors and pharmacological manipulations, we found that basolateral amygdala (BLA) glutamatergic activity tracks and mediates both the encoding and retrieval of the hungerstate-dependent value of a palatable food reward. Projection-specific chemogenetic and optogenetic manipulations revealed and it wathe orbitofrontal cortex (OFC) supports the BLA in these processes. Critically, the function of the ventrolateral (lOFC) and medial (mOFC)OFCBLA projections was found to be doubly dissociable. Whereas activity in lOFCBLA projections is necessary for and sufficient to drive encoding of a positive change in the value of a reward, mOFCBLA projections are necessary and sufficient for retrieving this value from memory to guide reward pursuit. These data reveal a new circuit for adaptive reward valuation and pursuit and provide mechanistic insight into the dysfunction in these processes that characterizes myriad psychiatric diseases.. CC-BY-NC-ND 4.0 International license It is made available under a (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/299958 doi: bioRxiv preprint first posted online Apr. 11, 2018; Malvaez et al., 3 Prospective consideration of the outcomes of potential action choices is crucial to adaptive decision making. Chief among these considerations is the value of anticipated rewarding events.This incentive information is state-dependent; e.g., a food reward is more valuable when hungry than when sated. It is also learned. The value of a specific reward is encoded during its experience in a relevant state 1 . Retrieval of the previously-encoded value of an anticipated reward allows adaptive reward pursuit decisions. Dysfunction in either the value encoding or retrieval process will lead to the aberrant reward pursuit and ill-informed decision making─ cognitive symptoms that characterize myriad psychiatric diseases. Despite importance to understanding adaptive and maladaptive behavior, little is known of the neural circuits that support reward value encoding and retrieval.The basolateral amygdala (BLA) has long been known to mediate emotional learning [2][3][4] . Accordingly, this structure is necessary for reward value encoding [5][6][7][8][9][10][11][12][13] . But the circuitry supporting the BLA in this function is unknown. Whether the BLA participates in retrieving reward value is less clear and has been disputed 7,10,11 and its contribution, if any, to active decision making is uncertain.Given the BLA is densely innervated by glutamatergic projections from regions themselves implicated in reward learning and decision making 14,15 , we sought to begin to fill these gaps in knowledge by using electroenzymatic biosensors to characterize...

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“…Inferring future outcomes as in the example above requires the internal representation of relationships between events in the external world [3][4][5][6][7][8][9][10]. This set of relationships is often called a "cognitive map" [11][12][13][14] and may consist of a wide range of content relevant to current goals (e.g., spatial, temporal, and associative). In the current study, we focus on the mental representation of associative information that defines the task environment.…”

Section: Introductionmentioning

confidence: 99%

Interactions between human orbitofrontal cortex and hippocampus support model-based inference

2020

Self Cite

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Internal representations of relationships between events in the external world can be utilized to infer outcomes when direct experience is lacking. This process is thought to involve the orbitofrontal cortex (OFC) and hippocampus (HPC), but there is little evidence regarding the relative role of these areas and their interactions in inference. Here, we used a sensory preconditioning task and pattern-based neuroimaging to study this question. We found that associations among value-neutral cues were acquired in both regions during preconditioning but that value-related information was only represented in the OFC at the time of the probe test. Importantly, inference was accompanied by representations of associated cues and inferred outcomes in the OFC, as well as by increased HPC-OFC connectivity. These findings suggest that the OFC and HPC represent only partially overlapping information and that interactions between the two regions support model-based inference.

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Thinking Outside the Box: Orbitofrontal Cortex, Imagination, and How We Can Treat Addiction

Cited by 43 publications

References 74 publications

Intact goal‐directed control in treatment‐seeking drug users indexed by outcome‐devaluation and Pavlovian to instrumental transfer: critique of habit theory

Intact goal‐directed control in treatment‐seeking drug users indexed by outcome‐devaluation and Pavlovian to instrumental transfer: critique of habit theory

Distinct cortical-amygdala projections drive reward value encoding and retrieval

Interactions between human orbitofrontal cortex and hippocampus support model-based inference

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