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Trevor W Robbins - One of the best experts on this subject based on the ideXlab platform.
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dissociable and paradoxical roles of rat medial and lateral orbitofrontal cortex in visual serial Reversal Learning
Cerebral Cortex, 2020Co-Authors: Mona Elsayed Hervig, Leanne Fiddian, L Piilgaard, Tadej Božic, M Blancopozo, C Knudsen, S F Olesen, Johan Alsio, Trevor W RobbinsAbstract:Much evidence suggests that Reversal Learning is mediated by cortico-striatal circuitries with the orbitofrontal cortex (OFC) playing a prominent role. The OFC is a functionally heterogeneous region, but potential differential roles of lateral (lOFC) and medial (mOFC) portions in visual Reversal Learning have yet to be determined. We investigated the effects of pharmacological inactivation of mOFC and lOFC on a deterministic serial visual Reversal Learning task for rats. For reference, we also targeted other areas previously implicated in Reversal Learning: prelimbic (PrL) and infralimbic (IL) prefrontal cortex, and basolateral amygdala (BLA). Inactivating mOFC and lOFC produced opposite effects; lOFC impairing, and mOFC improving, performance in the early, perseverative phase specifically. Additionally, mOFC inactivation enhanced negative feedback sensitivity, while lOFC inactivation diminished feedback sensitivity in general. mOFC and lOFC inactivation also affected novel visual discrimination Learning differently; lOFC inactivation paradoxically improved Learning, and mOFC inactivation had no effect. We also observed dissociable roles of the OFC and the IL/PrL. Whereas the OFC inactivation affected only perseveration, IL/PrL inactivation improved Learning overall. BLA inactivation did not affect perseveration, but improved the late phase of Reversal Learning. These results support opponent roles of the rodent mOFC and lOFC in deterministic visual Reversal Learning.
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The role of 5-HT2C receptors in touchscreen visual Reversal Learning in the rat: a cross-site study.
Psychopharmacology, 2015Co-Authors: Johan Alsio, Simon R. O. Nilsson, Francois Gastambide, R. A. H. Wang, S. A. Dam, Adam C. Mar, Mark D. Tricklebank, Trevor W RobbinsAbstract:Rationale Reversal Learning requires associative Learning and executive functioning to suppress non-adaptive responding. Reversal-Learning deficits are observed in e.g. schizophrenia and obsessive-compulsive disorder and implicate neural circuitry including the orbitofrontal cortex (OFC). Serotonergic function has been strongly linked to visual Reversal Learning in humans and experimental animals but less is known about which receptor subtypes are involved.
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Dopamine, But Not Serotonin, Regulates Reversal Learning in the Marmoset Caudate Nucleus
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011Co-Authors: Hannah F. Clarke, Trevor W Robbins, Gemma J. Hill, Angela C. RobertsAbstract:Studies of visual discrimination Reversal Learning have revealed striking neurochemical dissociations at the level of the orbitofrontal cortex (OFC) with serotoninergic, but not dopaminergic, integrity being important for successful Reversal Learning. These findings have considerable implications for disorders such as obsessive compulsive disorder and schizophrenia, in which Reversal Learning is impaired, and which are primarily treated with drugs targeting the dopaminergic and serotoninergic systems. Dysfunction in such disorders however, is not limited to the OFC and extends subcortically to other structures implicated in Reversal Learning, such as the medial caudate nucleus. Therefore, because the roles of the serotonin and dopamine within the caudate nucleus are poorly understood, this study compared the effects of selective serotoninergic or selective dopaminergic depletions of the marmoset medial caudate nucleus on serial discrimination Reversal Learning. All monkeys were able to learn novel stimulus–reward associations but, unlike control monkeys and monkeys with selective serotoninergic medial caudate depletions, dopamine-depleted monkeys were markedly impaired in their ability to reverse this association. This impairment was not perseverative in nature. These findings are the opposite of those seen in the OFC and provide evidence for a neurochemical double dissociation between the OFC and medial caudate in the regulation of Reversal Learning. Although the specific contributions of these monoamines within the OFC–striatal circuit remain to be elucidated, these findings have profound implications for the development of drugs designed to remediate some of the cognitive processes underlying impaired Reversal Learning.
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Differential Contributions of the Primate Ventrolateral Prefrontal and Orbitofrontal Cortex to Serial Reversal Learning
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010Co-Authors: Rafal Rygula, Trevor W Robbins, Hannah F. Clarke, Susannah C. Walker, Angela C. RobertsAbstract:The discrimination Reversal paradigm is commonly used to measure a subject's ability to adapt their behavior according to changes in stimulus-reward contingencies. Human functional neuroimaging studies have demonstrated activations in the lateral orbitofrontal cortex (OFC) and the inferior frontal gyrus (IFG) in subjects performing this task. Excitotoxic lesions of analogous regions in marmosets have revealed, however, that although the OFC is indeed critical for Reversal Learning, ventrolateral prefrontal cortex (VLPFC) (analogous to IFG) is not, contributing instead to higher order processing, such as that required in attentional set-shifting and strategy transfer. One major difference between the marmoset and human studies has been the level of training subjects received in Reversal Learning, being far greater in the latter. Since exposure to repeated contingency changes, as occurs in serial Reversal Learning, is likely to trigger the development of higher order, rule-based strategies, we hypothesized a critical role of the marmoset VLPFC in performance of a serial Reversal Learning paradigm. After extensive training in Reversal Learning, marmosets received an excitotoxic lesion of the VLPFC, OFC, or a sham control procedure. In agreement with our prediction, postsurgery, VLPFC lesioned animals were impaired in performing a series of discrimination Reversals, but only when novel visual stimuli were introduced. In contrast, OFC lesioned animals were impaired regardless of whether the visual stimuli were the same or different from those used during presurgery training. Together, these data demonstrate the heterogeneous but interrelated involvement of primate OFC and VLPFC in the performance of serial Reversal Learning.
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selective lesions of the dorsomedial striatum impair serial spatial Reversal Learning in rats
Behavioural Brain Research, 2010Co-Authors: Anna Castane, David E H Theobald, Trevor W RobbinsAbstract:Impairments in Reversal Learning have been attributed to orbitofrontal cortex (OFC) dysfunction in many species. However, the role of subcortical areas interconnected with the OFC such as the striatum remains poorly understood. This study directly evaluated the contribution of core and shell sub-regions of the nucleus accumbens (NAc), dorsomedial (DMS) and dorsolateral (DLS) striatum to Reversal Learning of an instrumental two-lever spatial discrimination task in rats. Selective NAc core, DMS and DLS lesions were achieved with microinjections of quinolinic acid and NAc shell lesions with ibotenic acid. Damage to NAc core or shell did not affect retention of a previously acquired instrumental spatial discrimination. In contrast, DLS and DMS lesions produced changes in aspects of discrimination performance such as the latency to collect earned food pellets. Neither NAc core or shell lesions nor DLS lesions affected the main indices of Reversal performance. Conversely, DMS lesion rats showed a significant impairment in Reversal Learning. DMS damage increased the number of errors to reach criteria that were perseverative in nature. The deficit in Reversal Learning in DMS lesion rats was not associated with an impairment to extinguish instrumental responding. There were no effects on spontaneous locomotor activity. Our data are in agreement with recent work showing that lesions of the medial striatum in marmoset monkeys produce perseverative impairments during a serial visual discrimination Reversal task and support the hypothesis that dorsomedial striatal dysfunction contributes to pathological perseveration, which is a common feature of many psychiatric disorders.
Roshan Cools - One of the best experts on this subject based on the ideXlab platform.
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Greater mindful eating practice is associated with better Reversal Learning
Scientific reports, 2018Co-Authors: Lieneke Janssen, Roshan Cools, Iris Duif, Ilke Van Loon, Jeanne H.m. De Vries, Anne E. M. Speckens, Esther AartsAbstract:Mindfulness-based interventions are thought to reduce compulsive behavior such as overeating by promoting behavioral flexibility. Here the main aim was to provide support for mindfulness-mediated improvements in Reversal Learning, a direct measure of behavioral flexibility. We investigated whether an 8-week mindful eating intervention improved outcome-based Reversal Learning relative to an educational cooking (i.e., active control) intervention in a non-clinical population. Sixty-five healthy participants with a wide BMI range (19-35 kg/m2), who were motivated to change their eating habits, performed a deterministic Reversal Learning task that enabled the investigation of reward- and punishment-based Reversal Learning at baseline and following the intervention. No group differences in Reversal Learning were observed. However, time invested in the mindful eating, but not the educational cooking intervention correlated positively with changes in Reversal Learning, in a manner independent of outcome valence. These findings suggest that greater amount of mindfulness practice can lead to increased behavioral flexibility, which, in turn, might help overcome compulsive eating in clinical populations.
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Acute effects of cocaine and cannabis on Reversal Learning as a function of COMT and DRD2 genotype
Psychopharmacology, 2016Co-Authors: D. B. Spronk, Marieke E. Schaaf, Janelle H. P. Wel, Ellen R. A. De Bruijn, Roshan Cools, Johannes G. Ramaekers, Barbara Franke, Robbert J. VerkesAbstract:RationaleLong-term cannabis and cocaine use has been associated with impairments in Reversal Learning. However, how acute cannabis and cocaine administration affect Reversal Learning in humans is not known.ObjectiveIn this study, we aimed to establish the acute effects of administration of cannabis and cocaine on valence-dependent Reversal Learning as a function of DRD2 Taq1A (rs1800497) and COMT Val108/158Met (rs4680) genotype.MethodsA double-blind placebo-controlled randomized 3-way crossover design was used. Sixty-one regular poly-drug users completed a deterministic Reversal Learning task under the influence of cocaine, cannabis, and placebo that enabled assessment of both reward- and punishment-based Reversal Learning.ResultsProportion correct on the Reversal Learning task was increased by cocaine, but decreased by cannabis. Effects of cocaine depended on the DRD2 genotype, as increases in proportion correct were seen only in the A1 carriers, and not in the A2/A2 homozygotes. COMT genotype did not modulate drug-induced effects on Reversal Learning.ConclusionsThese data indicate that acute administration of cannabis and cocaine has opposite effects on Reversal Learning. The effects of cocaine, but not cannabis, depend on interindividual genetic differences in the dopamine D2 receptor gene.
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Acute effects of cocaine and cannabis on Reversal Learning as a function of COMT and DRD2 genotype
Psychopharmacology, 2015Co-Authors: D. B. Spronk, Ellen R. A. De Bruijn, Roshan Cools, Johannes G. Ramaekers, Barbara Franke, Marieke E. Van Der Schaaf, Janelle H. P. Van Wel, Robbert J. VerkesAbstract:Rationale Long-term cannabis and cocaine use has been associated with impairments in Reversal Learning. However, how acute cannabis and cocaine administration affect Reversal Learning in humans is not known.
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Ventral striatum response during reward and punishment Reversal Learning in unmedicated major depressive disorder.
The American journal of psychiatry, 2012Co-Authors: Oliver J. Robinson, Roshan Cools, Barbara J. Sahakian, Christina O. Carlisi, Wayne C. DrevetsAbstract:Objective:Affective biases may underlie many of the key symptoms of major depressive disorder, from anhedonia to altered cognitive performance. Understanding the cause of these biases is therefore critical in the quest for improved treatments. Depression is associated, for example, with a negative affective bias in Reversal Learning. However, despite the fact that Reversal Learning is associated with striatal response in healthy individuals and depressed individuals exhibit attenuated striatal function on multiple tasks, studies to date have not demonstrated striatal involvement in the negative bias in Reversal Learning in depression. In this study, the authors sought to determine whether this may be because Reversal Learning tasks conventionally used to study behavior examine Reversals only on the basis of unexpected punishment and therefore do not adequately separate reward- and punishment-based behavior. Method:The authors used functional MRI to compare the hemodynamic response to a Reversal Learning t...
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Dissociable responses to punishment in distinct striatal regions during Reversal Learning
NeuroImage, 2010Co-Authors: Oliver J. Robinson, Michael J. Frank, Barbara J. Sahakian, Roshan CoolsAbstract:Adaptive behavior depends on the ability to flexibly alter our choices in response to changes in reward and punishment contingencies. One brain region frequently implicated in such behavior is the striatum. However, this region is functionally diverse and there are a number of apparent inconsistencies across previous studies. For instance, how can significant BOLD responses in the ventral striatum during punishment-based Reversal Learning be reconciled with the frequently demonstrated role of the ventral striatum in reward processing? Here we attempt to address this question by separately examining BOLD responses during Reversal Learning driven by reward and during Reversal Learning driven by punishment. We demonstrate simultaneous valence-specific and valence-nonspecific signals in the striatum, with the posterior dorsal striatum responding only to unexpected reward, and the anterior ventral striatum responding to both unexpected punishment as well as unexpected reward. These data help to reconcile conflicting findings from previous studies by showing that distinct regions of the striatum exhibit dissociable responses to punishment during Reversal Learning.
Jeffrey W. Dalley - One of the best experts on this subject based on the ideXlab platform.
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dorsal and ventral striatal dopamine d1 and d2 receptors differentially modulate distinct phases of serial visual Reversal Learning
Neuropsychopharmacology, 2020Co-Authors: Julia Salabayo, Mona Elsayed Hervig, Leanne Fiddian, Simon R. O. Nilsson, Colin Mckenzie, Alexis Mareschi, Maria Boulos, Peter Zhukovsky, Janet R Nicholson, Jeffrey W. DalleyAbstract:Impaired cognitive flexibility in visual Reversal-Learning tasks has been observed in a wide range of neurological and neuropsychiatric disorders. Although both human and animal studies have implicated striatal D2-like and D1-like receptors (D2R; D1R) in this form of flexibility, less is known about the contribution they make within distinct sub-regions of the striatum and the different phases of visual Reversal Learning. The present study investigated the involvement of D2R and D1R during the early (perseverative) phase of Reversal Learning as well as in the intermediate and late stages (new Learning) after microinfusions of D2R and D1R antagonists into the nucleus accumbens core and shell (NAcC; NAcS), the anterior and posterior dorsomedial striatum (DMS) and the dorsolateral striatum (DLS) on a touchscreen visual serial Reversal-Learning task. Reversal Learning was improved after dopamine receptor blockade in the nucleus accumbens; the D1R antagonist, SCH23390, in the NAcS and the D2R antagonist, raclopride, in the NAcC selectively reduced early, perseverative errors. In contrast, Reversal Learning was impaired by D2R antagonism, but not D1R antagonism, in the dorsal striatum: raclopride increased errors in the intermediate phase after DMS infusions, and increased errors across phases after DLS infusions. These findings indicate that D1R and D2R modulate different stages of Reversal Learning through effects localised to different sub-regions of the striatum. Thus, deficits in behavioral flexibility observed in disorders linked to dopamine perturbations may be attributable to specific D1R and D2R dysfunction in distinct striatal sub-regions.
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Effects of orbitofrontal, infralimbic and prelimbic cortical lesions on serial spatial Reversal Learning in the rat.
Behavioural brain research, 2007Co-Authors: Vasileios Boulougouris, Jeffrey W. Dalley, Trevor W RobbinsAbstract:Abstract Background Recent evidence suggests that the neural correlates of Reversal Learning are localised to the orbitofrontal cortex whereas studies on the contribution of the medial prefrontal cortex to this capacity have produced equivocal results. This study examines the behavioural effects of selective lesions centred on orbitofrontal, infralimbic and prelimbic cortex on serial spatial Reversal Learning in the rat. Methods Rats were trained on a novel instrumental two-lever spatial discrimination and Reversal Learning task, measuring both ‘cognitive flexibility’ and constituent processes including response inhibition. Both levers were presented, only one of which was reinforced. The rat was required to respond on the reinforced lever under a fixed ratio 3 schedule of reinforcement. Following attainment of criterion, a series of Reversals was presented. Results Bilateral excitotoxic lesions of the orbitofrontal cortex did not affect retention of a preoperatively acquired spatial discrimination but did impair Reversal Learning. This deficit manifested as increased perseverative responding on the previously correct lever. Although impairments were evident during Reversal 1, OFC-lesioned animals performed significantly better than controls on Reversal 2. There were no significant effects of infralimbic and prelimbic lesions on the retention of a spatial discrimination or Reversal Learning. Conclusions These results indicate that the orbitofrontal cortex is critical for flexible responding in serial spatial Reversal Learning. The present findings may be relevant to deficits in Reversal Learning and response inhibition in such neuropsychiatric disorders as obsessive-compulsive disorder.
Matthijs G.p. Feenstra - One of the best experts on this subject based on the ideXlab platform.
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Spatial Reversal Learning is robust to total sleep deprivation
Behavioural brain research, 2012Co-Authors: Cathalijn H. C. Leenaars, Matthijs G.p. Feenstra, Ruud N. J. M. A. Joosten, Michiel Kramer, Ger Post, Leslie Eggels, Mark Wuite, Maurice Dematteis, Eus J.w. Van SomerenAbstract:Sleep deprivation affects cognitive functions that depend on the prefrontal cortex (PFC) such as cognitive flexibility, and the consolidation of newly learned information. The identification of cognitive processes that are either robustly sensitive or robustly insensitive to the same experimental sleep deprivation procedure, will allow us to better focus on the specific effects of sleep on cognition, and increase understanding of the mechanisms involved. In the present study we investigate whether sleep deprivation differentially affects the two separate cognitive processes of acquisition and consolidation of a spatial Reversal task. After training on a spatial discrimination between two levers in a Skinner box, male Wistar rats were exposed to a Reversal of the previously learned stimulus-response contingency. We first evaluated the effect of sleep deprivation on the acquisition of Reversal Learning. Performance on Reversal Learning after 12h of sleep deprivation (n=12) was compared to performance after control conditions (n=12). The second experiment evaluated the effect of sleep deprivation on the consolidation of Reversal Learning; the first session of Reversal Learning was followed by 3h of nap prevention (n=8) or undisturbed control conditions (n=8). The experiments had sufficient statistical power (0.90 and 0.81, respectively) to detect differences with medium effect sizes. Neither the acquisition, nor the consolidation, of Reversal Learning was affected by acute sleep deprivation. Together with previous findings, these results help to further delineate the role of sleep in cognitive processing.
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Serial Reversal Learning and acute tryptophan depletion.
Behavioural brain research, 2007Co-Authors: Geoffrey Van Der Plasse, Matthijs G.p. FeenstraAbstract:Cognitive flexibility (i.e. the ability to adapt goal-directed behaviour in response to changed environmental demands) has repeatedly been shown to depend on the prefrontal cortex (PFC). Recent data from primate studies moreover show that depletion of prefrontal 5-HT impairs Reversal Learning of visual stimuli [Clarke HF, Walker SC, Crofts HS, Dalley JW, Robbins TW, Roberts AC. Prefrontal serotonin depletion affects Reversal Learning but not attentional set shifting. J Neurosci 2005;25:532-8; Clarke HF, Walker SC, Dalley JW, Robbins TW, Roberts AC. Cognitive inflexibility after prefrontal serotonin depletion is behaviorally and neurochemically specific. Cereb Cortex 2007;17:18-27]. It is not clear however if 5-HT serves a general role in Reversal Learning or if it is involved only in specific Reversal problems. A first aim of these experiments was to study the role of 5-HT in serial Reversal Learning of a spatial discrimination. Literature has, moreover, repeatedly shown that the PFC is involved in the initial acquisition of a Reversal problem but hardly when the task is well practiced. A second aim concerns the role of 5-HT in early versus late Reversal Learning. With the current experiment, we aim to clarify whether 5-HT is differentially involved in early versus late Reversal Learning. To this end, we tested rats on a serial two-lever Reversal task and induced a temporary reduction of 5-HT availability in these rats by restricting dietary intake of the 5-HT precursor tryptophan at an early and a late Reversal. Our results indicate that acute tryptophan depletion (ATD) did not affect either early or late Reversal Learning, nor extinction and suggest that spatial Reversal Learning, in contrast to visual Reversal Learning, might not be dependent on 5-HT. The data furthermore provide insight in the behavioural strategies employed in serial Reversal Learning and suggests the formation of a Learning-set.
Eus J.w. Van Someren - One of the best experts on this subject based on the ideXlab platform.
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Spatial Reversal Learning is robust to total sleep deprivation
Behavioural brain research, 2012Co-Authors: Cathalijn H. C. Leenaars, Matthijs G.p. Feenstra, Ruud N. J. M. A. Joosten, Michiel Kramer, Ger Post, Leslie Eggels, Mark Wuite, Maurice Dematteis, Eus J.w. Van SomerenAbstract:Sleep deprivation affects cognitive functions that depend on the prefrontal cortex (PFC) such as cognitive flexibility, and the consolidation of newly learned information. The identification of cognitive processes that are either robustly sensitive or robustly insensitive to the same experimental sleep deprivation procedure, will allow us to better focus on the specific effects of sleep on cognition, and increase understanding of the mechanisms involved. In the present study we investigate whether sleep deprivation differentially affects the two separate cognitive processes of acquisition and consolidation of a spatial Reversal task. After training on a spatial discrimination between two levers in a Skinner box, male Wistar rats were exposed to a Reversal of the previously learned stimulus-response contingency. We first evaluated the effect of sleep deprivation on the acquisition of Reversal Learning. Performance on Reversal Learning after 12h of sleep deprivation (n=12) was compared to performance after control conditions (n=12). The second experiment evaluated the effect of sleep deprivation on the consolidation of Reversal Learning; the first session of Reversal Learning was followed by 3h of nap prevention (n=8) or undisturbed control conditions (n=8). The experiments had sufficient statistical power (0.90 and 0.81, respectively) to detect differences with medium effect sizes. Neither the acquisition, nor the consolidation, of Reversal Learning was affected by acute sleep deprivation. Together with previous findings, these results help to further delineate the role of sleep in cognitive processing.
