Biomedical subjects

Anthony Dickinson

Publications and source records attributed to Anthony Dickinson.

At least 19 recordsLinked to original sources

PubMed2006

Dorsomedial prefrontal cortex resolves response conflict in rats.

The capacity for goal-directed behavior requires not only the encoding of the response-outcome relationship but also the ability to resolve conflict induced by competing responses. Recent neuroimaging studies have identified the prefrontal cortex as critical for resolving conflict between competing responses. At present, however, much of this evidence is indirect, and the necessity of dorsomedial prefrontal cortex (dmPFC) function for the resolution of conflict in goal-directed behavior has not been assessed. Here, we develop a rodent paradigm to investigate response conflict caused by the concurrent activation of a correct and incorrect response. In this paradigm, the outcome of one response also acts as a discriminative stimulus signaling that the other response is correct. Whereas rats with a functional dmPFC are able to resolve this conflict, inactivation of dmPFC using an infusion of muscimol produced a deficit by selectively interfering with their ability to inhibit the incorrect, competing response.

Animals↗

PubMed2006

Drug expectancy is necessary for stimulus control of human attention, instrumental drug-seeking behaviour and subjective pleasure.

BACKGROUND: It has been suggested that drug-paired stimuli (S+) control addictive behaviour by eliciting an explicit mental representation or expectation of drug availability. AIMS: The aim of the present study was to test this hypothesis by determining whether the behavioural control exerted by a tobacco-paired S+ in human smokers would depend upon the S+ eliciting an explicit expectation of tobacco. DESIGN: In each trial, human smokers (n=16) were presented with stimuli for which attention was measured with an eyetracker. Participants then reported their cigarette reward expectancy before performing, or not, an instrumental tobacco-seeking response that was rewarded with cigarette gains if the S+ had been presented or punished with cigarette losses if the S- had been presented. Following training, participants rated the pleasantness of stimuli. RESULTS: The S+ only brought about conditioned behaviour in an aware group (those who expected the cigarette reward outcome when presented with the S+). This aware group allocated attention to the S+, performed the instrumental tobacco-seeking response selectively in the presence of the S+ and rated the S+ as pleasant. No conditioned behaviour was seen in the unaware group (those who did not expect the cigarette reward outcome in the presence of the S+). CONCLUSIONS: Drug-paired stimuli control selective attention, instrumental drug-seeking behaviour and positive emotional state by eliciting an explicit expectation of drug availability.

Adult↗

PubMed2006

Frontal responses during learning predict vulnerability to the psychotogenic effects of ketamine: linking cognition, brain activity, and psychosis.

CONTEXT: Establishing a neurobiological account of delusion formation that links cognitive processes, brain activity, and symptoms is important to furthering our understanding of psychosis. OBJECTIVE: To explore a theoretical model of delusion formation that implicates prediction error-dependent associative learning processes in a pharmacological functional magnetic resonance imaging study using the psychotomimetic drug ketamine. DESIGN: Within-subject, randomized, placebo-controlled study. SETTING: Hospital-based clinical research facility, Addenbrooke's Hospital, Cambridge, England. The work was completed within the Wellcome Trust and Medical Research Council Behavioral and Clinical Neuroscience Institute, Cambridge. PARTICIPANTS: Fifteen healthy, right-handed volunteers (8 of whom were male) with a mean +/- SD age of 29 +/- 7 years and a mean +/- SD predicted full-scale IQ of 113 +/- 4 were recruited from within the local community by advertisement. INTERVENTIONS: Subjects were given low-dose ketamine (100 ng/mL of plasma) or placebo while performing a causal associative learning task during functional magnetic resonance imaging. In a separate session outside the scanner, the dose was increased (to 200 ng/mL of plasma) and subjects underwent a structured clinical interview. MAIN OUTCOME MEASURES: Brain activation, blood plasma levels of ketamine, and scores from psychiatric ratings scales (Brief Psychiatric Ratings Scale, Present State Examination, and Clinician-Administered Dissociative States Scale). RESULTS: Low-dose ketamine perturbs error-dependent learning activity in the right frontal cortex (P = .03). High-dose ketamine produces perceptual aberrations (P = .01) and delusion-like beliefs (P = .007). Critically, subjects showing the highest degree of frontal activation with placebo show the greatest occurrence of drug-induced perceptual aberrations (P = .03) and ideas or delusions of reference (P = .04). CONCLUSIONS: These findings relate aberrant prediction error-dependent associative learning to referential ideas and delusions via a perturbation of frontal cortical function. They are consistent with a model of delusion formation positing disruptions in error-dependent learning.

Adult↗

PubMed2006

Motivational control of blocking.

Hungry and thirsty rats lever pressed for food pellets in 1 visual stimulus (V1) and for a saline solution in another stimulus (V2). In a 2nd phase, the rats were made either hungry or thirsty and pressed for a starch solution in 2 stimulus compounds, each containing 1 of the visual cues and an auditory cue, that is, V1A1 and V2A2. On test, rats responded less to A1 than to A2 when hungry but less to A2 than to A1 when thirsty. Two further experiments replicated this selective blocking effect when the rats were both hungry and thirsty during Phase 2 and demonstrated that the magnitude of blocking was comparable to that observed when the reinforcer identity was held constant across the 2 phases.

Animals↗

PubMed2006

Motivational control of heroin seeking by conditioned stimuli associated with withdrawal and heroin taking by rats.

The authors investigated the impact of conditioned withdrawal on drug seeking by training rats to work for a heroin infusion on a seeking-taking schedule, which required responding on a seeking lever in order to gain the opportunity to self-administer the drug by a single response on a taking lever. Following the establishment of opiate dependence, a conditioned stimulus (CS) that had been previously paired with naloxone-precipitated withdrawal suppressed heroin seeking in extinction. However, when the rats had prior experience of heroin taking in the presence of the withdrawal CS, drug seeking was elevated in the presence of this stimulus. The authors conclude that the conditioned motivation of drug seeking in withdrawal depends on previous association of the CS with drug taking.

Animals↗

PubMed2006

Rational rats.

Explore the source record for details and available documents.

Animals↗

PubMed2006

Contingency knowledge is necessary for learned motivated behaviour in humans: relevance for addictive behaviour.

AIMS: Many forms of human conditioned behaviour depend upon explicit knowledge of the predictive contingency between stimuli, responses and the reinforcer. However, it remains uncertain whether the conditioning of three key behaviours in drug addiction-selective attention, instrumental drug-seeking behaviour and emotional state--are dependent upon contingency knowledge. To test this possibility, we employed an avoidance procedure to generate rapidly these three forms of conditioned behaviour without incurring the methodological problems of drug conditioning. DESIGN: In two experiments, participants (16 students) were trained on a schedule in which one stimulus (S +) predicted the occurrence of a startling noise, which could be cancelled by performing an instrumental avoidance response. MEASUREMENTS: The allocation of attention to the S + and the rate and probability of the avoidance response in the presence of S + were measured. Following training, participants were tested for their knowledge of the stimulus-noise contingencies arranged in the study and rated the emotional qualities of the stimuli. FINDINGS: Both experiments showed that S + gained control of selective attention, instrumental avoidance behaviour and subjective anxiety, but only in participants who reported explicit knowledge of the Pavlovian contingency between the S + and the startling noise. CONCLUSIONS: The implication of the present findings is that the control of selective attention, instrumental drug-seeking behaviour and emotional state by drug-paired stimuli is mediated by cognitive knowledge of the predictive contingency between the stimulus and the drug.

Adult↗

PubMed2005

The interaction between response effects during the acquisition of response priming.

In three experiments we investigated the role of associative learning in the acquisition of response priming by effect stimuli, by examining their interaction during response-effect learning. Having replicated the ability of visual effect stimuli to prime their associated responses, we paired a response with a compound consisting of visual and auditory effects before assessing the ability of the auditory effect stimulus to prime the response. This priming was reduced if the visual stimulus had been pre-trained as an effect of the response. By contrast, priming by the visual effect stimulus was potentiated when the auditory effect had been pre-trained. We interpret these interactions in terms of contemporary associative learning theory derived from studies of conditioning.

Adult↗

PubMed2005

Food caching by western scrub-jays (Aphelocoma californica) is sensitive to the conditions at recovery.

Western scrub-jays (Aphelocoma californica) cached perishable and nonperishable food items, which they could recover after both short and long retention intervals. When perishable items were always degraded at recovery, jays decreased the number of perishable items cached and increased their caching of nonperishable items, relative to a control group whose caches were always fresh at recovery. Jays reduced the number of nonperishable items cached, however, when highly preferred food items were degraded only after the long retention intervals. The findings are discussed in terms of the role of retrospective and prospective processes in the control of caching.

Animals↗

PubMed2005

Simulations of a modified SOP model applied to retrospective revaluation of human causal learning.

Dickinson and Burke (1996) proposed a modified version of Wagner's (1981) SOP associative theory to explain retrospective revaluation of human causal judgments. In this modified SOP (MSOP), excitatory learning occurs when cue and outcome representations are either both directly activated or both associatively activated. By contrast, inhibitory learning occurs when one representation is directly activated while the other is associatively activated. Finite node simulations of MSOP yielded simple acquisition, overshadowing, blocking, and inhibitory learning under forward contingencies. Importantly, retrospective revaluation was predicted in the form of unovershadowing and backward inhibitory learning. However, MSOP did not yield backward blocking. These predictions are evaluated against the relevant empirical evidence and contrasted with the predictions of other associative theories that have been applied to retrospective revaluation of human causal and predictive learning.

Forecasting↗

PubMed2004

Conditioned suppression and freezing as measures of aversive Pavlovian conditioning: effects of discrete amygdala lesions and overtraining.

Freezing and suppression are measures of conditioned fear that correlate in unlesioned animals. Both the basolateral (BLA) and central (CeN) nuclei of the amygdala are required for conditioned freezing, though there can be recovery with overtraining. The neuroanatomical substrates of conditioned suppression are less clear, with evidence both for a specific requirement of the CeN and for disruption by BLA lesions. The present study investigated the impact of selective excitotoxic lesions of the BLA and CeN upon the acquisition and expression of conditioned fear, measured by freezing and both on-baseline and off-baseline conditioned suppression in the same rats. BLA and CeN lesions both abolished all measures of conditioned fear after 9 trials of fear conditioning. However, when conditioning was extended to 33 trials, whereas rats with combined lesions of both the BLA and CeN continued to show no conditioned fear responses, there was a pattern of recovery observed after selective lesions. There was a partial recovery of freezing with both lesions, and full recovery of conditioned suppression, except for off-baseline suppression in CeN lesioned rats. These results indicate that with few conditioning trials, both the BLA and CeN are required in a serial manner for conditioned fear responses, but that overtraining can mitigate such impairments, likely involving parallel pathways in and through the amygdala.

Amygdala↗

PubMed2004

Prediction error during retrospective revaluation of causal associations in humans: fMRI evidence in favor of an associative model of learning.

Associative learning theory assumes that prediction error is a driving force in learning. A competing view, probabilistic contrast (PC) theory, is that learning and prediction error are unrelated. We tested a learning phenomenon that has proved troublesome for associative theory--retrospective revaluation--to evaluate these two models. We previously showed that activation in right lateral prefrontal cortex (PFC) provides a reliable signature for the presence of prediction error. Thus, if the associative view is correct, retrospective revaluation should be accompanied by right lateral PFC activation. PC theory would be supported by the absence of this activation. Right PFC and ventral striatal activation occurred during retrospective revaluation, supporting the associative account. Activations appeared to reflect the degree of revaluation, predicting later brain responses to revalued cues. Our results support a modified associative account of retrospective revaluation and demonstrate the potential of functional neuroimaging as a tool for evaluating competing learning models.

Adult↗

PubMed2004

Explicit knowledge of stimulus-outcome contingencies and stimulus control of selective attention and instrumental action in human smoking behaviour.

RATIONALE: External stimuli (S+) that reliably signal that addictive drugs are available command the focus of selective attention and control instrumental action that procures the drug. According to incentive salience theory, as the contingency between the S+ and the drug is learned the magnitude of attentional orienting towards the S+ increases. By contrast, alternative theories propose that processing of the S+ becomes more efficient with training such that the measured attentional orienting response elicited by the S+ decreases. OBJECTIVES: The aim of the present study was to prompt half of participants to acquire explicit knowledge of the stimulus-reinforcer contingencies arranged in training, to examine the impact of this manipulation on the magnitude of attentional orienting towards the S+. METHODS: Smokers (n=32) completed an instrumental discrimination training procedure in which a set of stimuli were established as differential predictors that an instrumental response would yield tobacco-smoke reinforcement. During training, attention for the stimuli and performance of the instrumental tobacco-seeking response were measured in parallel. One group (n=16) was prompted to develop explicit knowledge of the discriminative contingencies in training whereas another group (n=16) underwent discrimination training without prompting. RESULTS: The prompted group reported accurate knowledge of the contingencies and showed no attentional orienting response towards the S+. By contrast, the unprompted group reported inaccurate knowledge of the contingencies and showed an attentional orienting response towards the S+. The S+ appeared to control the instrumental tobacco-seeking response in both groups equally. CONCLUSIONS: The results suggest that attention for drug paired S+ is associated with the process of learning about the relationship between those cues and the drug.

Attention↗

PubMed2004

Conditioned activity and instrumental reinforcement following long-term oral consumption of cocaine by rats.

Food-reinforced conditioned activity and instrumental responding were measured in rats after 50 weeks of continuous access to a cocaine-saccharin solution in their home cages. The elevation of conditioned activity produced by acute access to the cocaine-saccharin solution in the home cage during testing was abolished by long-term preexposure to the cocaine solution, an effect that was reversed by systemic administration of cocaine immediately prior to testing. By contrast, chronic cocaine preexposure enhanced instrumental responding for both cocaine-sucrose and pure sucrose solutions. These results support the idea that long-term cocaine exposure enhances subsequent reinforcement.

Animals↗

PubMed2003

Coding of predicted reward omission by dopamine neurons in a conditioned inhibition paradigm.

Animals learn not only about stimuli that predict reward but also about those that signal the omission of an expected reward. We used a conditioned inhibition paradigm derived from animal learning theory to train a discrimination between a visual stimulus that predicted reward (conditioned excitor) and a second stimulus that predicted the omission of reward (conditioned inhibitor). Performing the discrimination required attention to both the conditioned excitor and the inhibitor; however, dopamine neurons showed very different responses to the two classes of stimuli. Conditioned inhibitors elicited considerable depressions in 48 of 69 neurons (median of 35% below baseline) and minor activations in 29 of 69 neurons (69% above baseline), whereas reward-predicting excitors induced pure activations in all 69 neurons tested (242% above baseline), thereby demonstrating that the neurons discriminated between conditioned stimuli predicting reward versus nonreward. The discriminative responses to stimuli with differential reward-predicting but common attentional functions indicate differential neural coding of reward prediction and attention. The neuronal responses appear to reflect reward prediction errors, thus suggesting an extension of the correspondence between learning theory and activity of single dopamine neurons to the prediction of nonreward.

Animals↗

PubMed2003

Concurrent disjoint and reciprocal classification by Cebus apella in seriation tasks: evidence for hierarchical organization.

We report the results of a 4-year-long study of capuchin monkeys ( Cebus apella ) on concurrent three-way classification and linear size seriation tasks using explicit ordering procedures, requiring subjects to select icons displayed on touch screens rather than manipulate and sort actual objects into groups. The results indicate that C. apella is competent to classify nine items concurrently, first into three disjoint classes where class exemplars are identical to one another, then into three reciprocal classes which share common exemplar (size) features. In the final phase we compare the relative efficiency of executive control under conditions where both hierarchical and/or linear organization can be utilized. Whilst this shows a superiority of categorical based size seriation for a nine item test set suggesting an adaptive advantage for hierarchical over linear organization, Cebus nevertheless achieved high levels of principled linear size seriation with sequence lengths not normally achieved by children below the age of six years.

Animals↗

PubMed2003

Discriminative stimuli that control instrumental tobacco-seeking by human smokers also command selective attention.

RATIONALE: Incentive salience theory states that acquired bias in selective attention for stimuli associated with tobacco-smoke reinforcement controls the selective performance of tobacco-seeking and tobacco-taking behaviour. OBJECTIVES: To support this theory, we assessed whether a stimulus that had acquired control of a tobacco-seeking response in a discrimination procedure would command the focus of visual attention in a subsequent test phase. METHODS: Smokers received discrimination training in which an instrumental key-press response was followed by tobacco-smoke reinforcement when one visual discriminative stimulus (S+) was present, but not when another stimulus (S-) was present. The skin conductance response to the S+ and S- assessed whether Pavlovian conditioning to the S+ had taken place. In a subsequent test phase, the S+ and S- were presented in the dot-probe task and the allocation of the focus of visual attention to these stimuli was measured. RESULTS: Participants learned to perform the instrumental tobacco-seeking response selectively in the presence of the S+ relative to the S-, and showed a greater skin conductance response to the S+ than the S-. In the subsequent test phase, participants allocated the focus of visual attention to the S+ in preference to the S-. Correlation analysis revealed that the visual attentional bias for the S+ was positively associated with the number of times the S+ had been paired with tobacco-smoke in training, the skin conductance response to the S+ and with subjective craving to smoke. Furthermore, increased exposure to tobacco-smoke in the natural environment was associated with reduced discrimination learning. CONCLUSIONS: These data demonstrate that discriminative stimuli that signal that tobacco-smoke reinforcement is available acquire the capacity to command selective attentional and elicit instrumental tobacco-seeking behaviour.

Adult↗

PubMed2003

The effect of lesions of the basolateral amygdala on instrumental conditioning.

In three experiments, we assessed the effect of lesions of the amygdala basolateral complex (BLA) on instrumental conditioning in rats. In experiment 1, the lesion had no effect on the acquisition of either lever pressing or chain pulling in food-deprived rats whether these actions earned food pellets or a maltodextrin solution. The lesion did attenuate, however, the impact of outcome devaluation, induced by sensory-specific satiety, on instrumental performance both when assessed in extinction and when reward was delivered contingent on instrumental performance. In experiment 2, evidence was found to suggest that the lesioned rats differed from shams in their ability to encode the specific action-outcome contingencies to which they were exposed during training: lesioned rats failed to adjust their performance appropriately when the action-outcome contingency was degraded. These effects were not caused by an inability of BLA lesioned rats to discriminate the two instrumental actions; these rats were similar to shams in their acquisition of a heterogeneous instrumental chain involving lever pressing and chain pulling (experiment 3). In experiment 4, however, lesions of the BLA were found to produce a deficit in the ability of rats to use the specific properties of the instrumental outcomes used in the previous experiments to discriminate rewarded from unrewarded actions in a free operant discrimination situation. Together these results suggest that in instrumental conditioning, the BLA mediates outcome encoding, specifically relating the sensory features of nutritive commodities to the emotional consequences induced by their consumption.

Amygdala↗