Reward enhancement by psychomotor stimulant drugs [proceedings].
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Animals↗
Biomedical subjects
T W Robbins
Publications and source records attributed to T W Robbins.
Tryptophan depletion in normal volunteers produces selective impairments in learning and memory.
The amino-acid L-tryptophan is essential in the synthesis of brain serotonin, and its depletion can lead to a widespread reduction in central serotonergic activity. A placebo-controlled cross-over within-subjects design (n = 12) examined the effects of tryptophan depletion on human cognitive performance. A low-tryptophan (low-TRP) drink successfully reduced the levels of plasma and total free tryptophan. Computerized tests of memory, learning and executive function revealed selective and non-sedative impairments on cognitive performance following the active drink. Specifically, low-TRP impaired learning as seen in tests of visual discrimination and paired associates. Furthermore, low-TRP lengthened thinking times during the Tower of London planning task, but only in subjects already familiar with the task, suggesting a retrieval deficit. No evidence was found for an effect of the low-TRP drink on measures sensitive to frontal lobe dysfunction, supporting instead a specific role for the serotonergic system in the processes of memory and learning not directly implicated in frontal lobe function.
Adult↗
Are the effects of psychomotor stimulant drugs on hyperactive children really paradoxical?
The improved "attention" exhibited by hyperactive children treated with amphetamine-like compounds is postulated to be related to a normal action of these drugs in producing stereotyped behavior. Such activity can be conceptualised as an increased "focusing" of attention, which would be expected to aid performance in tasks involving sustained concentration of attention, but impair performance on tasks involving reversals in cognitive strategy. These behavioural actions of the drugs can be linked to the functioning of central dopaminergic mechanisms.
Amphetamines↗
CANTAB battery: proposed utility in neurotoxicology.
The CANTAB battery was developed for the assessment of cognitive deficits in humans with neurodegenerative diseases or brain damage. It consists of a series of interrelated computerized tests of memory, attention, and executive function, administered via a touch sensitive screen. It allows a decomposition of complex tasks commonly used in clinical assessment into their cognitive components and enables the extrapolation of findings from the animal literature. Tests include versions of the Wisconsin Card-Sorting Test and the Tower and London and also the Delayed Matching-to-Sample test, widely used in monkeys for visual recognition memory. The tests are constructed in such a way that they may be given to animals (monkeys) with minimal change. The nonverbal nature of the CANTAB tests makes them largely language independent and culture free. CANTAB has been standardized on a large, predominantly elderly, population and validated in neurosurgical patients as well as in patients with basal ganglia disorders, Alzheimer's disease, depression, and schizophrenia. In addition, CANTAB has been used to evaluate: a) the therapeutic effects of dopaminergic and cholinergic medication in neurodegenerative disease; b) cognition in 5-11-year-old normal, learning-disabled, and autistic children; c) deficits in patients with HIV infection; and d) early, asymptomatic Huntington's disease. The latter illustrate its usefulness in early identification of progressive disorders. It is suggested that the battery should have particular utility across a wide range of age and intelligence in longitudinal assessment after exposure to toxicants, and allow meaningful comparison with experimental studies of toxic effects in other species.
Animals↗
Limbic-striatal interactions in reward-related processes.
Stimuli with formerly motivationally neutral properties gain incentive properties from their predictive association with primary reinforcement, and are termed conditioned reinforcers. Infusions of the indirect dopamine (DA) agonist d-amphetamine into the ventral striatum selectively enhanced responding for a light that was positively correlated with water. These selective stimulatory effects were blocked by 6-OHDA lesions of the ventral, but not dorsal striatum, and resembled those produced by DA itself when infused into the ventral striatum. However, the choice of the lever producing the conditioned reinforcer was not affected by ventral striatal DA depletion. This choice was, however, attenuated by excitotoxic lesions of the basolateral nucleus of the amygdala, suggesting an interaction between this structure and DA-dependent processes of the ventral striatum in the processes by which reward-related stimuli come to affect action. Parallel findings were obtained using a second order schedule of sexual reinforcement. Other observations indicated that the amygdala lesion did not impair the discriminative property of the reward-related stimuli, or affect primary motivation. Experiments using explicit conditional visuo-spatial discrimination tasks suggest that similar discriminative properties are preserved following DA depletion from the ventral, but not the dorsal, striatum. These results possibly represent a dissociation between stimulus-response (or habit) and stimulus-reward associative mechanisms, modulated respectively by the dorsal and ventral striatum.
Animals↗
Depletion of unilateral striatal dopamine impairs initiation of contralateral actions and not sensory attention.
Although Parkinson's disease has traditionally been considered as a motor disorder, there has been much recent interest in the nature and the neural substrates of parkinsonian dementia and cognitive dysfunction. These disabilities, which can induce visuospatial impairment and visual 'neglect', may also have a bearing on the controversy about the normal functions of the nigrostriatal dopamine (DA) projection and the basal ganglia. The observations that neurones in both substantia nigra and striatum respond to sensory events in terms of neuronal firing or DA release, also suggest a role for striatum in sensorimotor integration. An important behavioural correlate of this integration is the 'sensorimotor neglect' syndrome in animals with unilateral lesions of the nigrostriatal projection who fail to orient to contralateral sensory events. However, this neglect may arise not from contralateral sensory inattention, but from an inability to express this sensory selection via motor output. We present here two lines of evidence that unilateral striatal DA depletion in the rat does not affect sensory attention to visual signals of reward, but rather impairs the initiation (though not the completion) of contralateral motor acts. These results not only help to clarify the function of the nigrostriatal DA projection, but also show that depletion in this system is linked specifically to a process of response initiation, which may be the fundamental impairment in Parkinson's disease.
Animals↗
The cerebral cortex of the rat and visual attentional function: dissociable effects of mediofrontal, cingulate, anterior dorsolateral, and parietal cortex lesions on a five-choice serial reaction time task.
Dissociable effects of bilateral excitotoxic lesions of different regions of the rat neocortex, including medial prefrontal and anterior cingulate cortices, were investigated in a five-choice serial reaction time task that provides several indices of the accuracy and speed of attentional function. Whereas medial prefrontal cortical lesions impaired performance of the task as revealed by a reduction in choice accuracy, an increase in the latency to respond correctly to the visual target and enhanced perseverative responding, lesions of the anterior cingulate cortex specifically increased premature responding. By contrast, lateral frontal cortical lesions did not significantly disrupt baseline performance of the task, but rather increased the latency to respond correctly to the visual target during various behavioral manipulations, for example, when the length of the intertrial interval was varied unpredictably and during interpolation of distracting bursts of white noise. Lesions of the parietal cortex failed to disrupt any aspect of task performance investigated. These behavioral effects in the five-choice task were compared with the effect of these same lesions on acquisition and retention of a one-trial passive avoidance task. The main finding from this paradigm was that lesions of the lateral frontal cortex produced a significant disruption to the retention of passive avoidance, which stands in marked contrast to the successful retention observed by animals of the other lesion groups. In addition, this pattern of results reveals that the 'disinhibitory' effect of cingulate cortex lesions are relatively specific to the five-choice attentional task. Finally, the results of the present study are compared with the findings of previous experiments using the five-choice task, which have examined the effect of selective manipulations of the ascending noradrenergic, cholinergic, dopaminergic, and serotonergic projections. In particular, the deficits in attentional function observed following cholinergic lesions of the nucleus basalis magnocellularis appear to be attributable to cholinergic denervation of the medial frontal cortex. These results are discussed in terms of the role of parallel distributed neural systems within the neocortex that mediate continuous attentional performance in the rat.
Acoustic Stimulation↗
Early detection and differential diagnosis of Alzheimer's disease and depression with neuropsychological tasks.
The development of novel treatments for Alzheimer's disease (AD), aimed at ameliorating symptoms and modifying disease processes, increases the need for early diagnosis. Neuropsychological deficits such as poor episodic memory are a consistent feature of early-in-the-course AD, but they overlap with the cognitive impairments in other disorders such as depression, making differential diagnosis difficult. Computerised and traditional tests of memory, attention and executive function were given to four subject groups: mild AD (n = 26); questionable dementia (QD; n = 43); major depression (n = 37) and healthy controls (n = 39). A visuo-spatial associative learning test accurately distinguished AD from depressed/control subjects and revealed an apparent sub-group of QD patients who performed like AD patients. QD patients' performance correlated with the degree of subsequent global cognitive decline. Elements of contextual and cued recall may account for the task's sensitivity and specificity for AD.
Aged↗
Cambridge Neuropsychological Test Automated Battery (CANTAB): a factor analytic study of a large sample of normal elderly volunteers.
The CANTAB battery was administered to a large group (n = 787) of elderly volunteers in the age range from 55 to 80 years. This battery, which is based on tests used to identify the neural substrates of learning and memory in non-human primates, has now been extensively used in the assessment of various forms of dementia and also validated on patients with neurosurgical lesions of the frontal and temporal lobes. The tests employed were pattern and spatial recognition, simultaneous and delayed matching to sample, learning of visuospatial paired associates, a matching to sample, reaction time task and a test of spatial working memory. The sample was banded into different IQ bands based on performance on 5 standard tests of intelligence. The MMSE was also administered to exclude cases of possible dementia (n = 16) in the normal sample. In general, performance declined with age and IQ, but these factors did not interact. A factor analysis (with varimax rotation) identified 4 factors with eigenvalues greater than 1, which accounted for over 60% of the variance. Factor 1 was equated with general learning and memory ability and loaded significantly with the Intelligence scores; factor 2 was related to speed of responding and loaded most heavily with Age. Comparisons were also made of performance on CANTAB of those subjects with dementing scores on the MMSE and the lowest 5th percentile of the population sample. The results are discussed in terms of the utility of the CANTAB battery for the assessment of dementia and of the implications for theories of changes in cognitive function during normal aging.
Aged↗