scholarly journals Dissociable and Paradoxical Roles of Rat Medial and Lateral Orbitofrontal Cortex in Visual Serial Reversal Learning

2019 ◽  
Vol 30 (3) ◽  
pp. 1016-1029 ◽  
Author(s):  
M E Hervig ◽  
L Fiddian ◽  
L Piilgaard ◽  
T Božič ◽  
M Blanco-Pozo ◽  
...  
Keyword(s):  
Reversal Learning ◽  
Orbitofrontal Cortex ◽  
Basolateral Amygdala ◽  
Late Phase ◽  
Learning Task ◽  
Visual Discrimination Learning ◽  
Feedback Sensitivity ◽  
Heterogeneous Region ◽  
Improved Learning ◽  
Serial Reversal

ABSTRACT 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.

scholarly journals Investigation of reward learning and feedback sensitivity in non-clinical participants with a history of early life stress

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0260444
Author(s):  
Matthew Paul Wilkinson ◽  
Chloe Louise Slaney ◽  
Jack Robert Mellor ◽  
Emma Susan Jane Robinson
Keyword(s):  
Reversal Learning ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Learning Task ◽  
Reward Learning ◽  
Feedback Sensitivity ◽  
History Of ◽  
A Current ◽  
Probabilistic Reversal Learning

Early life stress (ELS) is an important risk factor for the development of depression. Impairments in reward learning and feedback sensitivity are suggested to be an intermediate phenotype in depression aetiology therefore we hypothesised that healthy adults with a history of ELS would exhibit reward processing deficits independent of any current depressive symptoms. We recruited 64 adults with high levels of ELS and no diagnosis of a current mental health disorder and 65 controls. Participants completed the probabilistic reversal learning task and probabilistic reward task followed by depression, anhedonia, social status, and stress scales. Participants with high levels of ELS showed decreased positive feedback sensitivity in the probabilistic reversal learning task compared to controls. High ELS participants also trended towards possessing a decreased model-free learning rate. This was coupled with a decreased learning ability in the acquisition phase of block 1 following the practice session. Neither group showed a reward induced response bias in the probabilistic reward task however high ELS participants exhibited decreased stimuli discrimination. Overall, these data suggest that healthy participants without a current mental health diagnosis but with high levels of ELS show deficits in positive feedback sensitivity and reward learning in the probabilistic reversal learning task that are distinct from depressed patients. These deficits may be relevant to increased depression vulnerability.

scholarly journals Cortical and thalamic influences on striatal involvement in instructed, serial reversal learning; implications for the organisation of flexible behaviour.

2021 ◽  
Author(s):  
Brendan Williams ◽  
Anastasia Christakou
Keyword(s):  
Functional Connectivity ◽  
Cognitive Flexibility ◽  
Reversal Learning ◽  
Orbitofrontal Cortex ◽  
Dorsal Striatum ◽  
Response Strategy ◽  
Flexible Control ◽  
The Right ◽  
Serial Reversal

Cognitive flexibility is essential for enabling an individual to respond adaptively to changes in their environment. Evidence from human and animal research suggests that the control of cognitive flexibility is dependent on an array of neural architecture. Cortico-basal ganglia circuits have long been implicated in cognitive flexibility. In particular, the role of the striatum is pivotal, acting as an integrative hub for inputs from the prefrontal cortex and thalamus, and modulation by dopamine and acetylcholine. Striatal cholinergic modulation has been implicated in the flexible control of behaviour, driven by input from the centromedian-parafascicular nuclei of the thalamus. However, the role of this system in humans is not clearly defined as much of the current literature is based on animal work. Here, we aim to investigate the roles corticostriatal and thalamostriatal connectivity in serial reversal learning. Functional connectivity between the left centromedian-parafascicular nuclei and the associative dorsal striatum was significantly increased for negative feedback compared to positive feedback. Similar differences in functional connectivity were observed for the right lateral orbitofrontal cortex, but these were localised to when participants switched to using an alternate response strategy following reversal. These findings suggest that connectivity between the centromedian-parafascicular nuclei and the striatum may be used to generally identify potential changes in context based on negative outcomes, and the effect of this signal on striatal output may be influenced by connectivity between the lateral orbitofrontal cortex and the striatum.

scholarly journals Comparison of conventional and rapid-acting antidepressants in a rodent probabilistic reversal learning task

2020 ◽  
Vol 4 ◽  
pp. 239821282090717 ◽  
Author(s):  
Matthew P. Wilkinson ◽  
John P. Grogan ◽  
Jack R. Mellor ◽  
Emma S. J. Robinson
Keyword(s):  
Reinforcement Learning ◽  
Reversal Learning ◽  
Antidepressant Treatment ◽  
Learning Task ◽  
Reward Processing ◽  
Reward Learning ◽  
Feedback Sensitivity ◽  
Rule Changes ◽  
Reinforcement Learning Model ◽  
Probabilistic Reversal Learning

Deficits in reward processing are a central feature of major depressive disorder with patients exhibiting decreased reward learning and altered feedback sensitivity in probabilistic reversal learning tasks. Methods to quantify probabilistic learning in both rodents and humans have been developed, providing translational paradigms for depression research. We have utilised a probabilistic reversal learning task to investigate potential differences between conventional and rapid-acting antidepressants on reward learning and feedback sensitivity. We trained 12 rats in a touchscreen probabilistic reversal learning task before investigating the effect of acute administration of citalopram, venlafaxine, reboxetine, ketamine or scopolamine. Data were also analysed using a Q-learning reinforcement learning model to understand the effects of antidepressant treatment on underlying reward processing parameters. Citalopram administration decreased trials taken to learn the first rule and increased win-stay probability. Reboxetine decreased win-stay behaviour while also decreasing the number of rule changes animals performed in a session. Venlafaxine had no effect. Ketamine and scopolamine both decreased win-stay probability, number of rule changes performed and motivation in the task. Insights from the reinforcement learning model suggested that reboxetine led animals to choose a less optimal strategy, while ketamine decreased the model-free learning rate. These results suggest that reward learning and feedback sensitivity are not differentially modulated by conventional and rapid-acting antidepressant treatment in the probabilistic reversal learning task.

scholarly journals Value-guided remapping of sensory circuits by lateral orbitofrontal cortex in reversal learning

2020 ◽  
Author(s):  
Abhishek Banerjee ◽  
Giuseppe Parente ◽  
Jasper Teutsch ◽  
Christopher Lewis ◽  
Fabian F. Voigt ◽  
...  
Keyword(s):  
Long Range ◽  
Reversal Learning ◽  
Orbitofrontal Cortex ◽  
Light Sheet ◽  
Learning Task ◽  
Adaptive Behaviour ◽  
Top Down ◽  
Light Sheet Microscopy ◽  
Tactile Stimuli ◽  
Longitudinal Imaging

Flexible decision-making is crucial for adaptive behaviour. Such behaviour in mammals largely relies on the frontal cortex, and specifically, the orbitofrontal cortex (OFC). How OFC neurons encode decision variables and instruct sensory areas to guide adaptive behaviour is a key open question. Here we developed a reversal learning task for head-fixed mice together with two-photon calcium imaging to monitor the activity of lateral OFC neuronal populations and investigated their dynamic interaction with primary somatosensory cortex (S1). Mice trained on this task learned to discriminate go/no-go tactile stimuli and adapt their behaviour upon changes in stimulus–reward contingencies (‘rule-switch’). Longitudinal imaging at cellular resolution across weeks during all behavioural phases revealed a distinct engagement of S1 and lateral OFC neurons: S1 neural activity reflected task learning-related responses, while neurons in the lateral OFC saliently and transiently responded to the rule-switch. A subset of OFC neurons conveyed a value prediction error signal via feedback projections to S1, as direct anatomical long-range projections were revealed by retrograde tracing combined with whole-brain light-sheet microscopy. Top-down signals implemented an update of sensory representations and functionally reconfigured a small subpopulation of S1 neurons that were differentially modulated by reward-history. Functional remapping of these neurons crucially depended on top-down inputs, as chemogenetic silencing of lateral OFC neurons disrupted reversal learning and impaired plastic changes in these outcome-sensitive S1 neurons. Our results reveal the presence of long-range cortical interactions between cellular ensembles in higher and lower-order brain areas specifically recruited during context-dependent learning and task-switching. Such interactions crucially implement history-dependent reward-value computations and error heuristics, which, in turn, help guide adaptive behaviour.

scholarly journals Differential Contributions of the Primate Ventrolateral Prefrontal and Orbitofrontal Cortex to Serial Reversal Learning

2010 ◽  
Vol 30 (43) ◽  
pp. 14552-14559 ◽  
Author(s):  
R. Rygula ◽  
S. C. Walker ◽  
H. F. Clarke ◽  
T. W. Robbins ◽  
A. C. Roberts
Keyword(s):  
Reversal Learning ◽  
Orbitofrontal Cortex ◽  
Serial Reversal
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