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Biomedical subjects

A Dickinson

Publications and source records attributed to A Dickinson.

At least 19 recordsLinked to original sources
PubMed2007

Stimulus-outcome interactions during instrumental discrimination learning by rats and humans.

The associative structure mediating goal-directed action was investigated using congruent and incongruent conditional discriminations. The stimulus was the same as the outcome in each component of the congruent discriminations, whereas the stimulus of one component of the incongruent discriminations was the same as the outcome of the other component. Humans, but not rats, learned the congruent discrimination more rapidly than the incongruent discrimination, a difference that the authors attribute to the fact that outcome-response associations caused response conflict in the incongruent discrimination. Moreover, responding was resistant to outcome devaluation following incongruent, but not congruent, training, suggesting that both humans and rats adopted a stimulus-response strategy to resolve the incongruent discrimination.

Adult↗
PubMed2003

Early onset familial Alzheimer's disease: Mutation frequency in 31 families.

BACKGROUND: Three causative genes have been identified for autosomal dominant AD. OBJECTIVE: To determine the proportion of patients with early onset AD with a positive family history accounted for by mutations in these genes. METHODS: A mutational analysis of the amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) genes was performed in 31 probands with probable or definite AD from UK families with an age at onset (AAO) <61 years. RESULTS: The mean AAO was 46.9 years (median 45 years; range 33 to 60 years). The majority of patients (23 of 31; 74%) fulfilled recognized criteria for autosomal dominant inheritance. In 17 (55%) probands the authors identified eight novel PSEN1 sequence variants and eight recognized pathogenic mutations. In 4 (13%) probands the authors identified one novel APP sequence variant (H677R) and two recognized mutations. Thus in this series 21 of 31 (68%) probands were associated with a sequence variant in APP or PSEN1. Nine of the 11 (82%) probands with neuropathologically confirmed AD who additionally fulfilled recognized criteria for autosomal dominant inheritance were associated with a sequence variant in APP or PSEN1. The 10 patients in whom the authors were unable to identify a mutation in APP, PSEN1, or PSEN2 were older than the probands with sequence variants (55.4 vs 44.7 years: p = 0.001). CONCLUSIONS: Sequence variants in APP and PSEN1 accounted for the majority of neuropathologically confirmed autosomal dominant early onset AD; no mutations in PSEN2 were detected. There may be a further genetic factor involved in the etiology of autosomal dominant early onset AD.

Adult↗
PubMed2003

Attentional orienting towards smoking-related stimuli.

According to incentive salience theory, conditioned stimuli (CS+) associated with drug reinforcement acquire the capacity to elicit a conditioned attentional orienting response, which controls drug-seeking and drug-taking behaviour. We sought evidence for this proposal by measuring visual attentional orienting towards smoking pictures presented briefly in the periphery of the visual field, versus control pictures likewise presented, in smokers versus non-smokers. In each trial, smokers and non-smokers responded manually to a dot probe stimulus that appeared in a location previously occupied by either a smoking picture or a control picture. Attentional bias scores were calculated by subtracting the median reaction time (RT) in the former condition from the median RT in the latter condition. In two experiments, light-smokers (smokers of fewer than 20 cigarettes/day) produced a mean bias score that was significantly greater than that of heavy-smokers (smokers of 20 or more cigarettes/day) and non-smokers. In addition, when smokers from the two experiments were pooled, a significant quadratic relationship was found between cigarettes/day and the attentional bias for the smoking stimuli. These findings are consistent with incentive salience theories and dual-process theories of addiction.

Adolescent↗
PubMed2002

Effects of cytotoxic nucleus accumbens lesions on instrumental conditioning in rats.

In two experiments the involvement of the nucleus accumbens in instrumental conditioning was investigated using rats as subjects. In experiment 1, extensive bilateral cytotoxic lesions of the nucleus accumbens mildly suppressed instrumental responding reinforced with food, but had no detectable effect on the sensitivity of the rats' performance either to outcome devaluation or to degradation of the instrumental contingency. In experiment 2, restricted accumbens lesions reliably attenuated the excitatory effect of systemically administered d-amphetamine on lever pressing for a conditioned reinforcer, and completely abolished Pavlovian-instrumental transfer. Taken together these results give a picture of the involvement of the rat nucleus accumbens in instrumental conditioning. They support the widely held theory that the nucleus accumbens mediates the excitatory effects of appetitively conditioned Pavlovian signals on instrumental performance and refute the hypothesis that the nucleus accumbens is part of the neural circuitry by which incentive value is attached to the representations of instrumental outcomes.

Animals↗
PubMed2001

Elements of episodic-like memory in animals.

A number of psychologists have suggested that episodic memory is a uniquely human phenomenon and, until recently, there was little evidence that animals could recall a unique past experience and respond appropriately. Experiments on food-caching memory in scrub jays question this assumption. On the basis of a single caching episode, scrub jays can remember when and where they cached a variety of foods that differ in the rate at which they degrade, in a way that is inexplicable by relative familiarity. They can update their memory of the contents of a cache depending on whether or not they have emptied the cache site, and can also remember where another bird has hidden caches, suggesting that they encode rich representations of the caching event. They make temporal generalizations about when perishable items should degrade and also remember the relative time since caching when the same food is cached in distinct sites at different times. These results show that jays form integrated memories for the location, content and time of caching. This memory capability fulfils Tulving's behavioural criteria for episodic memory and is thus termed 'episodic-like'. We suggest that several features of episodic memory may not be unique to humans.

Animals↗
PubMed2001

Two-octapeptide repeat deletion of prion protein associated with rapidly progressive dementia.

Insertions of integral numbers of an octapeptide repeat in the prion protein gene are pathogenic mutations associated with inherited prion diseases. Conversely, deletions of a single octapeptide repeat are found as normal polymorphisms in many populations and do not predispose individuals to prion disease. The authors report a two-octapeptide repeat deletion in an elderly woman with a rapidly progressive dementia consistent with Creutzfeldt-Jakob disease. This mutation was absent from more than 3,000 individuals and may be causally related to prion disease and represent a novel disease mechanism.

Aged↗
PubMed2001

Dopamine responses comply with basic assumptions of formal learning theory.

According to contemporary learning theories, the discrepancy, or error, between the actual and predicted reward determines whether learning occurs when a stimulus is paired with a reward. The role of prediction errors is directly demonstrated by the observation that learning is blocked when the stimulus is paired with a fully predicted reward. By using this blocking procedure, we show that the responses of dopamine neurons to conditioned stimuli was governed differentially by the occurrence of reward prediction errors rather than stimulus-reward associations alone, as was the learning of behavioural reactions. Both behavioural and neuronal learning occurred predominantly when dopamine neurons registered a reward prediction error at the time of the reward. Our data indicate that the use of analytical tests derived from formal behavioural learning theory provides a powerful approach for studying the role of single neurons in learning.

Animals↗
PubMed2001

Moms and guilt.

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Adult↗
PubMed2001

The single life.

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Anecdotes as Topic↗
PubMed2001

The luvox debate.

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Adolescent↗
PubMed2001

Autopsy-confirmed familial early-onset Alzheimer disease caused by the l153V presenilin 1 mutation.

BACKGROUND: Three affected individuals are described from a small English kindred with early-onset autosomal dominant familial Alzheimer disease (FAD) caused by a leucine-to-valine change at codon 153 (L153V) of the presenilin 1 (PSEN1) gene. METHODS: Clinical information on the pedigree was collected directly from family members and from hospital records. Samples of DNA were screened by means of direct sequencing of all coding exons of PSEN1. One patient underwent neuropathological examination. RESULTS: Mean age at onset of symptoms was 35.3 years (95% confidence interval [CI], 34.6-36.0 years); at death, 44.0 years (95% CI, 39.1-48.9 years). Mean duration of illness was 8.3 years (95% CI, 4.7-11.9 years). Myoclonus was a late feature in 1 patient; seizures were not reported in any subjects. Spastic paraparesis and extrapyramidal signs were absent. The neuropsychometric profile of 1 patient showed relatively preserved naming skills in the setting of global cognitive deficits. Results of neuropathological examination demonstrated the signature lesions of Alzheimer disease and the presence of occasional cortical Lewy bodies. CONCLUSIONS: The PSEN1 L153V mutation lies in the main mutation cluster of PSEN1 in the second transmembrane domain. It causes early-onset FAD with clinical features similar to those of other reported FAD pedigrees.

Adult↗
PubMed2001

The neuropsychological basis of addictive behaviour.

The argument advanced in this review is that drug addiction can be understood in terms of normal learning and memory systems of the brain which, through the actions of chronically self-administered drugs, are pathologically subverted, thereby leading to the establishment of compulsive drug-seeking habits, strengthened by the motivational impact of drug-associated stimuli and occurring at the expense of other sources of reinforcement. We review data from our studies that have utilized procedures which reveal the various influences of pavlovian stimuli on goal-directed behaviour, namely discriminated approach, pavlovian-to-instrumental transfer and conditioned reinforcement, in order to demonstrate their overlapping and also unique neural bases. These fundamental studies are also reviewed in the context of the neural and psychological mechanisms underlying drug-seeking behaviour that is under the control of drug-associated environmental stimuli. The ways in which such drug-seeking behaviour becomes compulsive and habitual, as well as the propensity for relapse to drug-seeking even after long periods of relapse, are discussed in terms of the aberrant learning set in train by the effects of self-administered drugs on plastic processes in limbic cortical-ventral striatal systems.

Animals↗