Schoenbaum G, Nugen SL, Saddoris ML, Setlow B. Orbitofrontal lesions in rats impair reversal but not acquisition of go, no-go odor discriminations. Neuroreport 13: 885-890

Department of Psychological and Brain Sciences, Johns Hopkins University, 3400 North Charles Street, 25 Ames Hall, Baltimore, MD 21218, USA.
Neuroreport (Impact Factor: 1.52). 06/2002; 13(6):885-90. DOI: 10.1097/00001756-200205070-00030
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Recent evidence suggests that orbitofrontal cortex lesions cause an inability to withhold inappropriate responses particularly when learned behavior must be modified to reflect changes in the likely outcome or consequence of responding. By this account, orbitofrontal cortex should not be necessary for acquisition of simple discrimination problems, but should be critical for acquiring reversals of those problems. However, previous work in rats has shown orbitofrontal cortex to be critical for withholding responses even in a simple go, no-go discrimination task. Here we have reexamined the contribution of rat orbitofrontal cortex to acquisition and reversal of go, no-go odor discrimination problems. Contrary to prior reports, we found that rats with lesions of the orbitofrontal cortex acquired novel discrimination problems at the same rate as controls. Impairments were evident in lesioned rats when the response contingencies of the odors in the discrimination problem were reversed. These findings suggest that orbitofrontal cortex is not necessary for inhibiting responses unless responses must be altered to reflect changing relationships between cues and outcomes.

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Available from: Geoffrey Schoenbaum, Oct 04, 2015
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    • "One notable finding in our study was the overall lack of impairment in rats following the OFC and NAc disconnections. Several studies have indicated that these two structures contribute to decision-making by encoding or updating the value of expected rewards (Schoenbaum et al., 2002; Izquierdo et al., 2004; Roesch & Olson, 2004; Kable & Glimcher, 2007; Roesch et al., 2009) and both structures are sensitive to the effects of reward uncertainty (Cardinal et al., 2001; Kheramin et al., 2002; Mobini et al., 2002; Abela & Chudasama, 2013; Stopper et al., 2014; but see St Onge & Floresco , 2010). Our OFC/NAc disconnection did not cause any changes in choice behavior for this type of decision, suggesting that, although both of these structures may independently contribute to such decisions, their intrahemispheric interaction is not critical. "
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    ABSTRACT: Human cognition depends upon the capacity to make decisions in the present that bear upon outcomes in the future. The nucleus accumbens, a recipient of direct projections from both the hippocampus and orbitofrontal cortex, is known to contribute to these aspects of decision-making. Here we demonstrate that interaction of the nucleus accumbens with the hippocampus, but not the orbitofrontal cortex, is critical in shaping decisions that involve time trade-offs. Compared with controls, rats with a disrupted hippocampal-accumbens interaction were strongly biased toward choosing stimuli that led to small and immediate food rewards over large and delayed ones. We show that this pattern of behavior cannot be ascribed to impaired representation of stimulus value, the incapacity to wait, or a general disruption of decision-making. These results identify a hippocampal-accumbens circuit that may underlie a range of problems in which daily decisions are marked by a shift toward immediate gratification. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    European Journal of Neuroscience 06/2015; 42(5). DOI:10.1111/ejn.13009 · 3.18 Impact Factor
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    • "For example, during strategy setshifting , a cue light may initially inform an animal of which of two levers will be rewarded if pressed, but following the set-shift the animal must instead identify the rewarded lever by its location (left or right lever press) and ignore the cue lights. These two forms of flexibility rely in a dissociable manner on different regions of the PFC – the orbitofrontal cortex (OFC) and medial prefrontal cortex (mPFC) respectively [17] [18] [19] [20] [21]. Functional impairment in both set-shifting and reversal learning, and their respective associated regions of the PFC (OFC and mPFC) are implicated in psychiatric symptoms [22]. "
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    ABSTRACT: Exposure to stressful or traumatic events is associated with increased vulnerability to post-traumatic stress disorder (PTSD). This vulnerability may be partly mediated by effects of stress on the prefrontal cortex (PFC) and associated circuitry. The PFC mediates critical cognitive functions, including cognitive flexibility, which reflects an organism's ability to adaptively alter behavior in light of changing contingencies. Prior work suggests that chronic or acute stress exerts complex effects on different forms of cognitive flexibility, via actions on the PFC. Similarly, PFC dysfunction is reported in PTSD, as are executive function deficits. Animal models that permit study of the effects of stress/trauma on cognitive flexibility may be useful in illuminating ways in which stress-linked cognitive changes contribute to PTSD. Here, we examined the behavioral effects of a rodent model of PTSD - single prolonged stress (SPS) - on performance of two forms of cognitive flexibility: reversal learning and strategy set-shifting. SPS did not impair acquisition of either a response or visual-cue discrimination but did cause slight impairments in the retrieval of the visual-cue rule. During response discrimination reversal, SPS rats made more perseverative errors. In comparison, during set-shifting from the visual-cue to response discrimination, SPS rats did not show enhanced perseveration, but did display increased never-reinforced errors, indicative of impairment in selecting a novel strategy. These data demonstrate that SPS leads to a complex and intriguing pattern of deficits in flexible responding and suggest that impairments in executive functioning associated with PTSD could, in part, be a neuro-cognitive consequence of trauma exposure. Copyright © 2015. Published by Elsevier B.V.
    Behavioural Brain Research 03/2015; 286. DOI:10.1016/j.bbr.2015.02.051 · 3.03 Impact Factor
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    • "lever pressing) in olfactory discrimination reversal learning tasks. Using a task in which rats pressed a lever for water reinforcement cued by odor stimuli , Schoenbaum et al. (2002) reported that lesions of LO/VO did not impair initial learning but significantly impaired learning when the odor stimuli were reversed. Thus, the presence of reversal learning deficits following OFC lesions does not appear to be specific to response form (lever pressing vs. digging) or reinforcer type (e.g. "
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    ABSTRACT: Research examining the contribution of genetics to behavior is increasingly focused on higher order behavioral and cognitive processes including the ability to modify behaviors when environmental demands change. The frontal cortices of mammals, including rodents, subserve a diverse set of behavioral and cognitive functions including motor planning, social behavior, evaluation of expected outcomes, and working memory which may be particular sensitive to genetic factors and interactions with experience (e.g. stress). Behavioral flexibility is a core attribute of these functions. This review orients readers to the current landscape of the literature on the frontocortical bases of behavioral flexibility in rodent laboratory experiments. Studies are divided into three broad categories: reversal learning, inhibitory learning, and set-shifting. Functional dissociations within the broader scope of behavioral flexibility are reviewed, followed by discussion of the associations between specific components of frontal cortex and specific aspects of relevant behavioral processes. Finally, the authors identify open questions that need to be addressed to better establish the constituents of frontal cortex underlying behavioral flexibility.
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