Article

Orbitofrontal Cortex, Associative Learning, and Expectancies

Department of Anatomy and Neurobiology, University of Maryland School of Medicine, 20 Penn Street, HSF-2 S251, Baltimore, Maryland 21201, USA.
Neuron (Impact Factor: 15.98). 10/2005; 47(5):633-6. DOI: 10.1016/j.neuron.2005.07.018
Source: PubMed

ABSTRACT Orbitofrontal cortex is characterized by its unique pattern of connections with subcortical areas, such as basolateral amygdala. Here we distinguish between the critical role of these areas in associative learning and the pivotal contribution of OFC to the manipulation of this information to control behavior. This contribution reflects the ability of OFC to signal the desirability of expected outcomes, which requires the integration of associative information with information concerning internal states and goals in representational memory.

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Available from: Geoffrey Schoenbaum, Feb 03, 2014
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    • "The aversive state in drug addiction is partly mediated by activation of corticotropin-releasing factor in prefrontal and limbic brain areas, such as the orbitofrontal cortex (OFC) and the amygdala (Koob and Kreek, 2007; Koob, 2013). The OFC has direct projections to the amygdala (Ghashghaei et al., 2007) and is functionally connected with the amygdala during the integration of emotional and motivational information (Schoenbaum and Roesch, 2005). For example , human neuroimaging studies reveal that the OFC and the amygdala are coactivated during withdrawalinduced craving (Koob and Volkow, 2010), probably through downstream modulation of the OFC on limbic regions (Rolls, 2004). "
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    ABSTRACT: Recent evidence has shown that a single maintenance dose of heroin attenuates psychophysiological stress responses in heroin-dependent patients, probably reflecting the effectiveness of heroin-assisted therapies for the treatment of severe heroin addiction. However, the underlying neural circuitry of these effects has not yet been investigated. Using a cross-over, double-blind, vehicle-controlled design, 22 heroin-dependent and heroin-maintained outpatients from the Centre of Substance Use Disorders at the University Hospital of Psychiatry in Basel were studied after heroin and placebo administration, while 17 healthy controls from the general population were included for placebo administration only. Functional magnetic resonance imaging was used to detect brain responses to fearful faces and dynamic causal modelling was applied to compute fear-induced modulation of connectivity within the emotional face network. Stress responses were assessed by hormone releases and subjective ratings. Relative to placebo, heroin acutely reduced the fear-induced modulation of connectivity from the left fusiform gyrus to the left amygdala and from the right amygdala to the right orbitofrontal cortex in dependent patients. Both of these amygdala-related connectivity strengths were significantly increased in patients after placebo treatment (acute withdrawal) compared to healthy controls, whose connectivity estimates did not differ from those of patients after heroin injection. Moreover, we found positive correlations between the left fusiform gyrus to amygdala connectivity and different stress responses, as well as between the right amygdala to orbitofrontal cortex connectivity and levels of craving. Our findings indicate that the increased amygdala-related connectivity during fearful face processing after the placebo treatment in heroin-dependent patients transiently normalizes after acute heroin maintenance treat-ment. Furthermore, this study suggests that the assessment of amygdala-related connectivity during fear processing may provide a prognostic tool to assess stress levels in heroin-dependent patients and to quantify the efficacy of maintenance treatments in drug addiction.
    Brain 11/2014; 138(1):217-228. DOI:10.1093/brain/awu326 · 10.23 Impact Factor
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    • "Ventral mPFC has a functional role in cognitive and emotional processing (Frysztak and Neafsey, 1994; Vertes, 2006). Rat orbital cortex has been proposed to be involved in associative learning and making predictions about the external environment (Schoenbaum and Roesch, 2005; Schoenbaum and Esber, 2010). Agranular insular cortex has a greater functional role in the processing of sensory information including gustation (Gallagher et al., 1999; Fujita et al., 2011). "
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    ABSTRACT: The connections of prefrontal cortex (PFC) were investigated in the rat brain to determine the order and location of input and output connections to motor and somatosensory cortex. Retrograde (100 nl Fluoro-Gold) and anterograde (100 nl Biotinylated Dextran Amines, BDA; Fluorescein and Texas Red) neuronanatomical tracers were injected into the subdivisions of the PFC (prelimbic, ventral orbital, ventrolateral orbital, dorsolateral orbital) and their projections studied. We found clear evidence for organized input projections from the motor and somatosensory cortices to the PFC, with distinct areas of motor and cingulate cortex projecting in an ordered arrangement to the subdivisions of PFC. As injection location of retrograde tracer was moved from medial to lateral in PFC, we observed an ordered arrangement of projections occurring in sensory-motor cortex. There was a significant effect of retrograde injection location on the position of labelled cells occurring in sensory-motor cortex (dorsoventral, anterior-posterior and mediolateral axes p < 0.001). The arrangement of output projections from PFC also displayed a significant ordered projection to sensory-motor cortex (dorsoventral p < 0.001, anterior-posterior p = 0.002 and mediolateral axes p < 0.001). Statistical analysis also showed that the locations of input and output labels vary with respect to one another (in the dorsal-ventral and medial-lateral axes, p < 0.001). Taken together, the findings show that regions of PFC display an ordered arrangement of connections with sensory-motor cortex, with clear laminar organization of input connections. These results also show that input and output connections to PFC are not located in exactly the same sites and reveal a circuit between sensory-motor and PFC.
    Frontiers in Systems Neuroscience 09/2014; 8(177). DOI:10.3389/fnsys.2014.00177
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    • "We know from previous work that these regions, particularly the VMPFC, are crucial in evaluating the value of stimuli on the basis of context (Blair et al., 2006; Schoenbaum & Roesch, 2005; Schultz & Dickinson, 2000; Tobler, O'Doherty, Dolan, & Schultz, 2006). Human imaging studies have shown that the VMPFC is involved in the extinction of conditioned fear (Phelps, Delgado, Nearing, & LeDoux, 2004) and in skin conductance changes during a risky decision-making paradigm (Critchley, Elliott, Mathias, & Dolan, 2000)—where the VMPFC tracks how the affective representation of a stimulus changes on the basis of context. "
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    ABSTRACT: Stimuli that signal threat show considerable variability in the extents to which they enhance behavior, even among healthy individuals. However, the neural underpinning of this behavioral variability is not well understood. By manipulating expectation of threat in an fMRI study of fearful versus neutral face categorization, we uncovered a network of areas underlying variability in threat processing in healthy adults. We explicitly altered expectations by presenting face images at three different expectation levels: 80 %, 50 %, and 20 %. Subjects were instructed to report as quickly and accurately as possible whether the face was fearful (signaled threat) or not. An uninformative cue preceded each face by 4 s. By taking the difference between reaction times (RTs) to fearful and neutral faces, we quantified an overall fear RT bias (i.e., faster to fearful than to neutral faces) for each subject. This bias correlated positively with late-trial fMRI activation (8 s after the face) during unexpected-fearful-face trials in bilateral ventromedial prefrontal cortex, the left subgenual cingulate cortex, and the right caudate nucleus, and correlated negatively with early-trial fMRI activation (4 s after the cue) during expected-neutral-face trials in bilateral dorsal striatum and the right ventral striatum. These results demonstrate that the variability in threat processing among healthy adults is reflected not only in behavior, but also in the magnitude of activation in medial prefrontal and striatal regions that appear to encode affective value.
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