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1.
Nat Commun ; 10(1): 4704, 2019 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-31624264

RESUMO

The subjective sense of certainty, or confidence, in ambiguous sensory cues can alter the interpretation of reward feedback and facilitate learning. We trained rats to report the orientation of ambiguous visual stimuli according to a spatial stimulus-response rule that must be learned. Following choice, rats could wait a self-timed delay for reward or initiate a new trial. Waiting times increase with discrimination accuracy, demonstrating that this measure can be used as a proxy for confidence. Chemogenetic silencing of BLA shortens waiting times overall whereas ACC inhibition renders waiting times insensitive to confidence-modulating attributes of visual stimuli, suggesting contribution of ACC but not BLA to confidence computations. Subsequent reversal learning is enhanced by confidence. Both ACC and BLA inhibition block this enhancement but via differential adjustments in learning strategies and consistent use of learned rules. Altogether, we demonstrate dissociable roles for ACC and BLA in transmitting confidence and learning under uncertainty.


Assuntos
Complexo Nuclear Basolateral da Amígdala/fisiologia , Comportamento de Escolha/fisiologia , Giro do Cíngulo/fisiologia , Reversão de Aprendizagem/fisiologia , Incerteza , Animais , Condicionamento Operante/fisiologia , Masculino , Estimulação Luminosa , Ratos Long-Evans , Tempo de Reação/fisiologia , Recompensa
2.
PLoS Comput Biol ; 15(10): e1007341, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31600187

RESUMO

Visual selective attention acts as a filter on perceptual information, facilitating learning and inference about important events in an agent's environment. A role for visual attention in reward-based decisions has previously been demonstrated, but it remains unclear how visual attention is recruited during aversive learning, particularly when learning about multiple stimuli concurrently. This question is of particular importance in psychopathology, where enhanced attention to threat is a putative feature of pathological anxiety. Using an aversive reversal learning task that required subjects to learn, and exploit, predictions about multiple stimuli, we show that the allocation of visual attention is influenced significantly by aversive value but not by uncertainty. Moreover, this relationship is bidirectional in that attention biases value updates for attended stimuli, resulting in heightened value estimates. Our findings have implications for understanding biased attention in psychopathology and support a role for learning in the expression of threat-related attentional biases in anxiety.


Assuntos
Viés de Atenção/fisiologia , Ciências Biocomportamentais/métodos , Percepção Visual/fisiologia , Adulto , Afeto , Ansiedade , Atenção/fisiologia , Tomada de Decisões/fisiologia , Medo , Feminino , Humanos , Masculino , Estimulação Luminosa/métodos , Reversão de Aprendizagem/fisiologia , Recompensa
3.
Behav Processes ; 167: 103936, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31381984

RESUMO

Reversal-learning impairments in the maternal immune activation (MIA) model of schizophrenia risk have been interpreted as being indicative of deficits in reinforcement learning. Here we sought to assess the specific role of cognitive burden in discrimination learning and reversal performance in this model. Control and MIA rats were trained on a visual discrimination task in which responses on either a left or right lever were rewarded depending on the location of a cue light at the beginning of the trial. Groups of MIA and control rats differed in the difficulty of the discrimination rule they initially learned (pressing the lever on the same side vs the opposite side of the cue light). Once the discrimination was learned, performance was tested across four reversals. Across all phases of the experiment, rats in Group Same performed better than rats in Group Opposite. There was no difference in performance of control and MIA rats during acquisition or baseline, but MIA rats displayed impaired performance across reversals, with performance decrements manifesting later in reversals after the new discrimination rule had been learnt. Across reversals, MIA rats also made more perseverative errors than control rats. These results are consistent with others that have shown reversal learning impairments in MIA rats. The results further suggest that impaired behavioural flexibility in the MIA model is not due to a deficit in reinforcement learning, but due to an impaired ability to organize information gained from experience into an accurate and stable representation of the current task requirements.


Assuntos
Cognição/fisiologia , Aprendizagem por Discriminação/fisiologia , Reversão de Aprendizagem/fisiologia , Esquizofrenia/fisiopatologia , Animais , Masculino , Ratos , Ratos Sprague-Dawley , Recompensa , Percepção Visual/fisiologia
4.
Psychopharmacology (Berl) ; 236(8): 2389-2403, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31375849

RESUMO

RATIONALE: According to psychological theories, cognitive distortions play a pivotal role in the aetiology and recurrence of mood disorders. Although clinical evidence for the coexistence of depression and altered sensitivity to performance feedback is relatively coherent, we still do not know whether increased or decreased sensitivity to positive or negative feedback is associated with 'pro-depressive' profile in healthy subjects. OBJECTIVE: Our research has been designed to answer this question, and here, we present the first steps in that direction. METHODS: Using a rat version of the probabilistic reversal-learning (PRL) paradigm, we evaluated how sensitivity to negative and positive feedback influences other cognitive processes associated with mood disorders, such as motivation in the progressive ratio schedule of reinforcement (PRSR) paradigm, hedonic status in the sucrose preference (SP) test, locomotor and exploratory activity in the open field (OF) test, and anxiety in the light/dark box (LDB) test. RESULTS: The results of our study demonstrated for the first time that in rodents, sensitivity to negative and positive feedback could be considered a stable and enduring behavioural trait. Importantly, we also showed that these traits are independent of each other and that trait sensitivity to positive feedback is associated with cognitive flexibility in the PRL test. The computational modelling results also revealed that in animals classified as sensitive to positive feedback, the α learning rates for both positive and negative reward prediction errors were higher than those in animals classified as insensitive. We observed no statistically significant interactions between sensitivity to negative or positive feedback and the parameters measured in the PRSR, SP, OF or LDB tests. CONCLUSIONS: Further studies using animal models of depression based on chronic stress should reveal whether sensitivity to feedback is a latent trait that when interacts with stressful life events, could produce correlates of depressive symptoms in rats.


Assuntos
Retroalimentação Fisiológica/fisiologia , Locomoção/fisiologia , Motivação/fisiologia , Esquema de Reforço , Reversão de Aprendizagem/fisiologia , Recompensa , Animais , Ansiedade/metabolismo , Ansiedade/psicologia , Simulação por Computador , Depressão/metabolismo , Depressão/psicologia , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
5.
J Exp Psychol Anim Learn Cogn ; 45(4): 446-463, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31368765

RESUMO

Three experiments with rats assessed the effects of introducing predictive ambiguity by reversing a Pavlovianly trained discrimination on subsequent context and temporal conditioning. The experience of discrimination reversal did not facilitate context conditioning when the food was presented on a variable time schedule (Experiment 1a). However, in Experiment 1b, discrimination reversal enhanced subsequent learning of a fixed temporal interval associated with unsignaled food presentation in comparison with consistent training. In Experiment 2, temporal discrimination after reversal and consistent training was compared with a naïve control. The experience of discrimination facilitated subsequent temporal conditioning with respect to the naïve control, and discrimination reversal enhanced temporal conditioning even further. In Experiment 3, reversal enhanced learning of the fixed temporal interval, regardless of whether it was relatively short or long (i.e., 30 s or 60 s). Results are discussed in terms of current associative theories of human and nonhuman conditioning and attention. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Assuntos
Comportamento Apetitivo/fisiologia , Condicionamento Clássico/fisiologia , Aprendizagem por Discriminação/fisiologia , Reversão de Aprendizagem/fisiologia , Percepção do Tempo/fisiologia , Animais , Condicionamento Operante/fisiologia , Feminino , Desempenho Psicomotor/fisiologia , Ratos , Ratos Wistar
6.
Psychopharmacology (Berl) ; 236(8): 2337-2358, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31324936

RESUMO

RATIONALE: Disorders of compulsivity such as stimulant use disorder (SUD) and obsessive-compulsive disorder (OCD) are characterised by deficits in behavioural flexibility, some of which have been captured using probabilistic reversal learning (PRL) paradigms. OBJECTIVES: This study used computational modelling to characterise the reinforcement learning processes underlying patterns of PRL behaviour observed in SUD and OCD and to show how the dopamine D2/3 receptor agonist pramipexole and the D2/3 antagonist amisulpride affected these responses. METHODS: We applied a hierarchical Bayesian method to PRL data across three groups: individuals with SUD, OCD, and healthy controls. Participants completed three sessions where they received placebo, pramipexole, and amisulpride, in a double-blind placebo-controlled, randomised design. We compared seven models using a bridge sampling estimate of the marginal likelihood. RESULTS: Stimulus-bound perseveration, a measure of the degree to which participants responded to the same stimulus as before irrespective of outcome, was significantly increased in SUD, but decreased in OCD, compared to controls (on placebo). Individuals with SUD also exhibited reduced reward-driven learning, whilst both the SUD and OCD groups showed increased learning from punishment (nonreward). Pramipexole and amisulpride had similar effects on the control and OCD groups; both increased punishment-driven learning. These D2/3-modulating drugs affected the SUD group differently, remediating reward-driven learning and reducing aspects of perseverative behaviour, amongst other effects. CONCLUSIONS: We provide a parsimonious computational account of how perseverative tendencies and reward- and punishment-driven learning differentially contribute to PRL in SUD and OCD. D2/3 agents modulated these processes and remediated deficits in SUD in particular, which may inform therapeutic effects.


Assuntos
Transtorno Obsessivo-Compulsivo/metabolismo , Receptores de Dopamina D2/metabolismo , Receptores de Dopamina D3/metabolismo , Reversão de Aprendizagem/fisiologia , Transtornos Relacionados ao Uso de Substâncias/metabolismo , Adulto , Estimulantes do Sistema Nervoso Central/uso terapêutico , Cognição/efeitos dos fármacos , Cognição/fisiologia , Agonistas de Dopamina/farmacologia , Agonistas de Dopamina/uso terapêutico , Antagonistas de Dopamina/farmacologia , Antagonistas de Dopamina/uso terapêutico , Antagonistas dos Receptores de Dopamina D2/farmacologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Neurológicos , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Transtorno Obsessivo-Compulsivo/psicologia , Receptores de Dopamina D2/agonistas , Receptores de Dopamina D3/agonistas , Receptores de Dopamina D3/antagonistas & inibidores , Reversão de Aprendizagem/efeitos dos fármacos , Recompensa , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Transtornos Relacionados ao Uso de Substâncias/psicologia , Adulto Jovem
7.
Psychopharmacology (Berl) ; 236(8): 2307-2323, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31218428

RESUMO

RATIONALE: Dopamine D2-like receptors (D2R) are important drug targets in schizophrenia and Parkinson's disease, but D2R ligands also cause cognitive inflexibility such as poor reversal learning. The specific role of D2R in reversal learning remains unclear. OBJECTIVES: We tested the hypotheses that D2R agonism impairs reversal learning by blocking negative feedback and that antagonism of D1-like receptors (D1R) impairs learning from positive feedback. METHODS: Male Lister Hooded rats were trained on a novel visual reversal learning task. Performance on "probe trials", during which the correct or incorrect stimulus was presented with a third, probabilistically rewarded (50% of trials) and therefore intermediate stimulus, revealed individual learning curves for the processes of positive and negative feedback. The effects of D2R and D1R agonists and antagonists were evaluated. A separate cohort was tested on a spatial probabilistic reversal learning (PRL) task after D2R agonism. Computational reinforcement learning modelling was applied to choice data from the PRL task to evaluate the contribution of latent factors. RESULTS: D2R agonism with quinpirole dose-dependently impaired both visual reversal and PRL. Analysis of the probe trials on the visual task revealed a complete blockade of learning from negative feedback at the 0.25 mg/kg dose, while learning from positive feedback was intact. Estimated parameters from the model that best described the PRL choice data revealed a steep and selective decrease in learning rate from losses. D1R antagonism had a transient effect on the positive probe trials. CONCLUSIONS: D2R stimulation impairs reversal learning by blocking the impact of negative feedback.


Assuntos
Retroalimentação Fisiológica/fisiologia , Estimulação Luminosa/métodos , Receptores de Dopamina D2/metabolismo , Reversão de Aprendizagem/fisiologia , Percepção Espacial/fisiologia , Animais , Dopamina/farmacologia , Agonistas de Dopamina/farmacologia , Antagonistas de Dopamina/farmacologia , Antagonistas dos Receptores de Dopamina D2/farmacologia , Retroalimentação Fisiológica/efeitos dos fármacos , Masculino , Ratos , Receptores de Dopamina D1/agonistas , Receptores de Dopamina D1/antagonistas & inibidores , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D2/agonistas , Reversão de Aprendizagem/efeitos dos fármacos , Percepção Espacial/efeitos dos fármacos , Percepção Visual/efeitos dos fármacos , Percepção Visual/fisiologia
8.
Neuron ; 103(4): 734-746.e3, 2019 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-31253468

RESUMO

Adaptive decision making in dynamic environments requires multiple reinforcement-learning steps that may be implemented by dissociable neural circuits. Here, we used a novel directionally specific viral ablation approach to investigate the function of several anatomically defined orbitofrontal cortex (OFC) circuits during adaptive, flexible decision making in rats trained on a probabilistic reversal learning task. Ablation of OFC neurons projecting to the nucleus accumbens selectively disrupted performance following a reversal, by disrupting the use of negative outcomes to guide subsequent choices. Ablation of amygdala neurons projecting to the OFC also impaired reversal performance, but due to disruptions in the use of positive outcomes to guide subsequent choices. Ablation of OFC neurons projecting to the amygdala, by contrast, enhanced reversal performance by destabilizing action values. Our data are inconsistent with a unitary function of the OFC in decision making. Rather, distinct OFC-amygdala-striatal circuits mediate distinct components of the action-value updating and maintenance necessary for decision making.


Assuntos
Córtex Pré-Frontal/fisiologia , Reversão de Aprendizagem/fisiologia , Tonsila do Cerebelo/fisiologia , Animais , Comportamento de Escolha/fisiologia , Toxina Diftérica/farmacologia , Retroalimentação Fisiológica , Masculino , Modelos Neurológicos , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Núcleo Accumbens/fisiologia , Ratos , Recompensa
9.
Neural Plast ; 2019: 1460890, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31191635

RESUMO

Stroke remains a leading cause of disability worldwide. Recently, we have established an animal model of stroke that results in delayed impairment in spatial memory, allowing us to better investigate cognitive deficits. Young and aged brains show different recovery profiles after stroke; therefore, we assessed aged-related differences in poststroke cognition. As neurotrophic support diminishes with age, we also investigated the involvement of brain-derived neurotrophic factor (BDNF) in these differences. Young (3-6 months old) and aged (16-21 months old) mice were trained in operant touchscreen chambers to complete a visual pairwise discrimination (VD) task. Stroke or sham surgery was induced using the photothrombotic model to induce a bilateral prefrontal cortex stroke. Five days poststroke, an additional cohort of aged stroke animals were treated with intracerebral hydrogels loaded with the BDNF decoy, TrkB-Fc. Following treatment, animals underwent the reversal and rereversal task to identify stroke-induced cognitive deficits at days 17 and 37 poststroke, respectively. Assessment of sham animals using Cox regression and log-rank analyses showed aged mice exhibit an increased impairment on VD reversal and rereversal learning compared to young controls. Stroke to young mice revealed no impairment on either task. In contrast, stroke to aged mice facilitated a significant improvement in reversal learning, which was dampened in the presence of the BDNF decoy, TrkB-Fc. In addition, aged stroke control animals required significantly less consecutive days and correction trials to master the reversal task, relative to aged shams, an effect dampened by TrkB-Fc. Our findings support age-related differences in recovery of cognitive function after stroke. Interestingly, aged stroke animals outperformed their sham counterparts, suggesting reopening of a critical window for recovery that is being mediated by BDNF.


Assuntos
Cognição/fisiologia , Recuperação de Função Fisiológica/fisiologia , Reversão de Aprendizagem/fisiologia , Acidente Vascular Cerebral/psicologia , Animais , Aprendizagem por Discriminação/fisiologia , Modelos Animais de Doenças , Masculino , Camundongos , Receptor trkB/metabolismo , Acidente Vascular Cerebral/metabolismo
10.
J Exp Psychol Anim Learn Cogn ; 45(4): 422-430, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31157526

RESUMO

The midsession reversal task involves a simultaneous discrimination between Stimulus 1 (S1) and Stimulus 2 (S2) in which, for the first half of each session, choice of S1 is reinforced and S2 is not, and for the last half of each session, choice of S2 is reinforced and S1 is not. With this task, even after considerable training, pigeons tend to make anticipatory errors as they approach the reversal and they continue to make perseverative errors following the reversal. In the present research, we tested the hypothesis that reversal accuracy would improve by devaluing choice of S2 relative to S1. In Experiment 1, correct choice of S1 was reinforced 100% of the time, whereas correct choice of S2 was reinforced only 20% of the time. This manipulation reduced anticipatory errors but did not increase perseverative errors. In Experiment 2, choice of S1 required a single peck, whereas choice of S2 was devalued by requiring 10 pecks. A similar result was found. In Experiment 3 we devalued S1 by requiring 10 pecks and found decreased accuracy in the form of increased anticipatory errors. Paradoxically, in Experiments 1 and 2, by encouraging the pigeons to avoid using the feedback from choice of S2, and rely solely on feedback from choice of S1, discrimination reversal errors were reduced. The results have implications for attentional theories of learning and theories of behavior change. They also have implications for the conditions responsible for pigeons' tendency to time the occurrence of the change in reinforcement contingencies. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Assuntos
Antecipação Psicológica/fisiologia , Atenção/fisiologia , Comportamento Animal/fisiologia , Comportamento de Escolha/fisiologia , Columbidae/fisiologia , Desempenho Psicomotor/fisiologia , Reversão de Aprendizagem/fisiologia , Animais , Aprendizagem por Discriminação/fisiologia
11.
Neuropharmacology ; 155: 121-130, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31129151

RESUMO

The ability to either erase or update the memories of a previously learned spatial task is an essential process that is required to modify behaviour in a changing environment. Current evidence suggests that the neural representation of such cognitive flexibility involves the balancing of synaptic potentiation (acquisition of memories) with synaptic depression (modulation and updating previously acquired memories). Here we demonstrate that the p38 MAPK/MAPK-activated protein kinase 2 (MK2) cascade is required to maintain the precise tuning of long-term potentiation and long-term depression at CA1 synapses of the hippocampus which is correlated with efficient reversal learning. Using the MK2 knockout (KO) mouse, we show that mGluR-LTD, but not NMDAR-LTD, is markedly impaired in mice aged between 4 and 5 weeks (juvenile) to 7 months (mature adult). Although the amplitude of LTP was the same as in wildtype mice, priming of LTP by the activation of group I metabotropic receptors was impaired in MK2 KO mice. Consistent with unaltered LTP amplitude and compromised mGluR-LTD, MK2 KO mice had intact spatial learning when performing the Barnes maze task, but showed specific deficits in selecting the most efficient combination of search strategies to perform the task reversal. Findings from this study suggest that the mGluR-p38-MK2 cascade is important for cognitive flexibility by regulating LTD amplitude and the priming of LTP.


Assuntos
Hipocampo/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/deficiência , Plasticidade Neuronal/fisiologia , Proteínas Serina-Treonina Quinases/deficiência , Receptores de Glutamato Metabotrópico/metabolismo , Reversão de Aprendizagem/fisiologia , Animais , Potenciais Pós-Sinápticos Excitadores/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/genética , Depressão Sináptica de Longo Prazo/fisiologia , Sistema de Sinalização das MAP Quinases/fisiologia , Camundongos , Camundongos Knockout , Técnicas de Cultura de Órgãos , Proteínas Serina-Treonina Quinases/genética
12.
Brain Stimul ; 12(4): 959-966, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30833215

RESUMO

BACKGROUND: The prefrontal cortex regulates behavioural adaptation in response to feedback. However, the causal role of different prefrontal regions remains unclear, based on indirect evidence derived from functional neuroimaging. Neuroimaging studies show dorsomedial prefrontal activation during feedback monitoring, whereas the ventrolateral prefrontal cortex engages during behavioural adaptation (shifting). OBJECTIVE: We used high-definition transcranial direct current stimulation (HD-tDCS) to elucidate the roles of the ventrolateral prefrontal cortex (vlPFC) and the dorsomedial prefrontal cortex (dmPFC) in behaviour change, using a probabilistic reversal learning task (PRLT). METHOD: Fifty-two healthy adults were randomly assigned to receive cathodal HD-tDCS to inhibit the vlPFC or the dmPFC versus sham stimulation, prior to completing the PRLT. The outcome measures were the number of perseverative errors and the electroencephalography (EEG) signals of feedback-related negativity (FRN) in the PRLT. We hypothesised that inhibition of the vlPFC would be specifically associated with more perseverative errors and weaker FRNs. RESULTS: We found that vlPFC inhibition was associated with higher perseverative errors compared to sham and dmPFC stimulation conditions. Although there were no statistically significant differences in FRN amplitudes, the effect sizes indicate an association between inhibition of the vlPFC and lower FRN amplitudes. CONCLUSION: Our findings support a causal role of the vlPFC on feedback-based behavioural adaptation, which is critical for adaptive goal-driven behaviour.


Assuntos
Eletroencefalografia/métodos , Córtex Pré-Frontal/fisiologia , Aprendizagem por Probabilidade , Reversão de Aprendizagem/fisiologia , Estimulação Transcraniana por Corrente Contínua/métodos , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Neuroimagem/métodos , Adulto Jovem
13.
PLoS One ; 14(3): e0213727, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30893340

RESUMO

Dropouts are a common issue in cognitive tests with non-human primates. One main reason for dropouts is that researchers often face a trade-off between obtaining a sufficiently large sample size and logistic restrictions, such as limited access to testing facilities. The commonly-used opportunistic testing approach deals with this trade-off by only testing those individuals who readily participate and complete the cognitive tasks within a given time frame. All other individuals are excluded from further testing and data analysis. However, it is unknown if this approach merely excludes subjects who are not consistently motivated to participate, or if these dropouts systematically differ in cognitive ability. If the latter holds, the selection bias resulting from opportunistic testing would systematically affect performance scores and thus comparisons between individuals and species. We assessed the potential effects of opportunistic testing on cognitive performance in common marmosets (Callithrix jacchus) and squirrel monkeys (Saimiri sciureus) with a test battery consisting of six cognitive tests: two inhibition tasks (Detour Reaching and A-not-B), one cognitive flexibility task (Reversal Learning), one quantity discrimination task, and two memory tasks. Importantly, we used a full testing approach in which subjects were given as much time as they required to complete each task. For each task, we then compared the performance of subjects who completed the task within the expected number of testing days with those subjects who needed more testing time. We found that the two groups did not differ in task performance, and therefore opportunistic testing would have been justified without risking biased results. If our findings generalise to other species, maximising sample sizes by only testing consistently motivated subjects will be a valid alternative whenever full testing is not feasible.


Assuntos
Cognição/fisiologia , Primatas/fisiologia , Animais , Viés , Callithrix , Feminino , Masculino , Memória/fisiologia , Reversão de Aprendizagem/fisiologia , Saimiri
14.
Neurosci Lett ; 699: 109-114, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-30726715

RESUMO

The dopamine (DA) system is critical for various forms of learning about salient environmental stimuli. Prior work has shown that deletion of the obligatory NR1 subunit of the N-methyl-D-aspartate (NMDA) receptor on neurons expressing the DA transporter (DAT) in mice results in reduced phasic release from DA-containing neurons. To further investigate the contribution of phasic DA release to reward-related learning and cognitive flexibility, the current study evaluated DAT-NR1 null mutant mice in a touchscreen-based pairwise visual discrimination and reversal learning paradigm. Results showed that these mutants were slower to attain a high level of choice accuracy on the discrimination task, but showed improved late reversal performance on sessions where correct choice was above chance. A number of possible interpretations are offered for this pattern of effects, including the opposing possibilities that discrimination memory was either stronger by the completion of training (overtraining effect) or weaker (learning deficit), both of which could potentially produce faster reversal. These data add to the extensive literature ascribing a critical role for DAergic neurotransmission in cognitive functions and the regulation of reward-related behaviors of relevance to addictions.


Assuntos
/fisiologia , Neurônios Dopaminérgicos/metabolismo , Receptores de N-Metil-D-Aspartato/genética , Receptores de N-Metil-D-Aspartato/metabolismo , Reversão de Aprendizagem/fisiologia , Animais , Feminino , Masculino , Camundongos , Camundongos Mutantes Neurológicos , Estimulação Luminosa , Receptores de N-Metil-D-Aspartato/deficiência , Percepção Visual/fisiologia
15.
Neuroscience ; 404: 338-352, 2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30742964

RESUMO

A common feature across neuropsychiatric disorders is inability to discontinue an action or thought once it has become detrimental. Reversal learning, a hallmark of executive control, requires plasticity within cortical, striatal and limbic circuits and is highly sensitive to disruption of N-methyl-D-aspartate receptor (NMDAR) function. In particular, selective deletion or antagonism of GluN2B containing NMDARs in cortical regions including the orbitofrontal cortex (OFC), promotes maladaptive perseveration. It remains unknown whether GluN2B functions to maintain local cortical activity necessary for reversal learning, or if it exerts a broader influence on the integration of neural activity across cortical and subcortical systems. To address this question, we utilized in vivo electrophysiology to record neuronal activity and local field potentials (LFP) in the orbitofrontal cortex and dorsal striatum (dS) of mice with deletion of GluN2B in neocortical and hippocampal principal cells while they performed touchscreen reversal learning. Reversal impairment produced by corticohippocampal GluN2B deletion was paralleled by an aberrant increase in functional connectivity between the OFC and dS. These alterations in coordination were associated with alterations in local OFC and dS firing activity. These data demonstrate highly dynamic patterns of cortical and striatal activity concomitant with reversal learning, and reveal GluN2B as a molecular mechanism underpinning the timing of these processes.


Assuntos
Disfunção Cognitiva/metabolismo , Corpo Estriado/metabolismo , Córtex Pré-Frontal/metabolismo , Receptores de N-Metil-D-Aspartato/deficiência , Reversão de Aprendizagem/fisiologia , Animais , Disfunção Cognitiva/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Receptores de N-Metil-D-Aspartato/genética
16.
Behav Brain Res ; 363: 45-52, 2019 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-30710612

RESUMO

Cognitive flexibility is a term used to describe the brain processes underlying the phenomenon of adaptive change in behaviour in response to changed contingencies in the internal or external environment. Cognitive flexibility is often assessed in complex tasks measuring perceptual attentional shifting or response or task switching, but, arguably, reversal learning is a simple assay of cognitive flexibility. Reversal learning requires the detection of a changed outcome, the cessation of a previously-rewarded response and the selection of an alternative, previously-unrewarded, response. This study addressed the issue of the relationship between reversal learning and cognitive flexibility. In a single testing session, rats completed a series of 2-alternative forced-choice discriminations between digging bowls. The bowls differed according to both the medium within the bowl and the odor of the bowl. Having learned which cue (one of the odors or one of the digging media) indicated the food-baited bowl, half the rats were given additional trials of "over-training". To test reversal learning, the meaning of the cues predictive of reward/non-reward was then switched. There was a robust effect of over-training, with over-trained rats performing reversal learning in fewer trials than rats trained to criterion only. The pattern of errors supported the hypothesis that more rapid reversing results from the formation of an attentional set. This is the same attentional mechanism that results in less rapid shifting or switching. We conclude that the behavioural flexibility demonstrated in reversal learning does not provide a scale on which cognitive flexibility can be measured.


Assuntos
Cognição/fisiologia , Aprendizagem por Discriminação/fisiologia , Reversão de Aprendizagem/fisiologia , Animais , Atenção/fisiologia , Comportamento Animal/fisiologia , Sinais (Psicologia) , Feminino , Córtex Pré-Frontal/fisiologia , Ratos , Ratos Endogâmicos , Recompensa
17.
PLoS Comput Biol ; 15(1): e1006707, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30703108

RESUMO

In our daily lives timing of our actions plays an essential role when we navigate the complex everyday environment. It is an open question though how the representations of the temporal structure of the world influence our behavior. Here we propose a probabilistic model with an explicit representation of state durations which may provide novel insights in how the brain predicts upcoming changes. We illustrate several properties of the behavioral model using a standard reversal learning design and compare its task performance to standard reinforcement learning models. Furthermore, using experimental data, we demonstrate how the model can be applied to identify participants' beliefs about the latent temporal task structure. We found that roughly one quarter of participants seem to have learned the latent temporal structure and used it to anticipate changes, whereas the remaining participants' behavior did not show signs of anticipatory responses, suggesting a lack of precise temporal expectations. We expect that the introduced behavioral model will allow, in future studies, for a systematic investigation of how participants learn the underlying temporal structure of task environments and how these representations shape behavior.


Assuntos
Encéfalo/fisiologia , Tomada de Decisões/fisiologia , Modelos Psicológicos , Modelos Estatísticos , Antecipação Psicológica/fisiologia , Biologia Computacional , Bases de Dados Factuais , Humanos , Imagem por Ressonância Magnética , Reversão de Aprendizagem/fisiologia
18.
Neurochem Int ; 124: 200-214, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30659871

RESUMO

The striatum as the main entry nucleus of the basal ganglia is long known to be critical for motor control. It integrates information from multiple cortical areas, thalamic and midbrain nuclei to refine and control motion. By tackling this incredible variety of input signals, increasing evidences showed a pivotal role, particularly of the dorsal striatum, in executive functions. The complexity of the dorsal striatum (DS) in its compartmentalization and in the nature and origin of its afferent connections, makes it a critical hub controlling dynamics of motor learning and behavioral or cognitive flexibility. The present review summarizes findings from recent studies that utilize optogenetics with complementary technologies including electrophysiology, activity imaging and tracing methods in rodents to elucidate the functioning and role of discrete regions and specific pathways of the DS in behavioral flexibility, with an emphasis on the processes leading to initial action sequence or serial order learning and reversal learning.


Assuntos
Corpo Estriado/química , Corpo Estriado/fisiologia , Locomoção/fisiologia , Reversão de Aprendizagem/fisiologia , Animais , Humanos , Vias Neurais/química , Vias Neurais/fisiologia , Optogenética/métodos
19.
Am J Primatol ; 81(2): e22924, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30281810

RESUMO

The common marmoset (Callithrix jacchus) is uniquely suited for longitudinal studies of cognitive aging, due to a relatively short lifespan, sophisticated cognitive abilities, and patterns of brain aging that resemble those of humans. We examined cognitive function and fine motor skills in male and female marmosets (mean age ∼5 at study entry) followed longitudinally for 2 years. Each year, monkeys were tested on a reversal learning task with three pairs of stimuli (n = 18, 9 females) and a fine motor task requiring them to grasp small rewards from two staircases (Hill and Valley test, n = 12, 6 females). There was little evidence for a decline in cognitive flexibility between the two time points, in part because of practice effects. However, independent of year of testing, females took longer than males to reach criterion in the reversals, indicating impaired cognitive flexibility. Motivation was unlikely to contribute to this effect, as males refused a greater percentage of trials than females in the reversals. With regards to motor function, females were significantly faster than males in the Hill and Valley task. From Year 1 to Year 2, a slight slowing of motor function was observed in both sexes, but accuracy decreased significantly in males only. This study (1) demonstrates that marmosets exhibit sex differences in cognitive flexibility and fine motor function that resemble those described in humans; (2) that changes in fine motor function can already be detected at middle-age; and (3) that males may experience greater age-related changes in fine motor skills than females. Additional data points will determine whether these sex and age differences persist over time.


Assuntos
Envelhecimento , Callithrix/fisiologia , Cognição/fisiologia , Destreza Motora/fisiologia , Animais , Callithrix/psicologia , Feminino , Masculino , Reversão de Aprendizagem/fisiologia , Fatores Sexuais
20.
Q J Exp Psychol (Hove) ; 72(6): 1507-1521, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30091396

RESUMO

The extent to which human outcome-response (O-R) priming effects are automatic or under cognitive control is currently unclear. Two experiments tested the effect of cognitive load on O-R priming to shed further light on the debate. In Experiment 1, two instrumental responses earned beer and chocolate points in an instrumental training phase. Instrumental response choice was then tested in the presence of beer, chocolate, and neutral stimuli. On test, a Reversal instruction group was told that the stimuli signalled which response would not be rewarded. The transfer test was also conducted under either minimal (No Load) or considerable (Load) cognitive load. The Non-Reversal groups showed O-R priming effects, where the reward cues increased the instrumental responses that had previously produced those outcomes, relative to the neutral stimulus. This effect was observed even under cognitive load. The Reversal No Load group demonstrated a reversed effect, where response choice was biased towards the response that was most likely to be rewarded according to the instruction. Most importantly, response choice was at chance in the Reversal Load condition. In Experiment 2, cognitive load abolished the sensitivity to outcome devaluation that was otherwise seen when multiple outcomes and responses were cued on test. Collectively, the results demonstrate that complex O-R priming effects are sensitive to cognitive load, whereas the very simple, standard O-R priming effect is more robust.


Assuntos
Comportamento de Escolha/fisiologia , Sinais (Psicologia) , Função Executiva/fisiologia , Recompensa , Adulto , Feminino , Humanos , Masculino , Reversão de Aprendizagem/fisiologia , Adulto Jovem
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