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J T Coull

Publications and source records attributed to J T Coull.

26 records · Page 2Linked to original sources
PubMed1995

Differential effects of clonidine, haloperidol, diazepam and tryptophan depletion on focused attention and attentional search.

As the catecholamines have long been implicated in attentional processes, the present investigation compared the effects of the mixed alpha 1/alpha 2 adrenoceptor agonist clonidine (CLO), the benzodiazepine diazepam (DZP), the D1/D2 antagonist haloperidol (HAL) and a low-tryptophan drink (Lo-TRP) on performance of tests of selective attention with distractors in four groups of young, healthy volunteers. Using a placebo-controlled, cross-over design, selective and dissociable effects on performance were found with each pharmacological manipulation. Specifically, CLO acted to broaden the focus of attention, HAL generally slowed reaction times during attentional search, and DZP and Lo-TRP produced differential effects on stimulus-response compatibility during attentional search. Furthermore, these results underline the usefulness of employing a single test with several neurochemical manipulations, allowing for a comprehensive analysis of the neurochemical basis of attention.

Adult↗
PubMed1995

Contrasting effects of clonidine and diazepam on tests of working memory and planning.

The alpha 2 adrenoceptor has recently been implicated in working memory (WM), a function dependent on the integrity of the prefrontal cortex. Using a double-blind, placebo-controlled design, the present investigation examines the effects of two doses (1.5 micrograms/kg and 2.5 micrograms/kg) of the mixed alpha 1/alpha 2 adrenoceptor agonist clonidine (CLO) on performance of various computerised tests of WM and planning in healthy, young volunteers. These are compared to the effects produced by two doses (5 mg and 10 mg) of diazepam (DZP) on largely the same set of neuropsychological tests in a comparable set of subjects. Administration of CLO resulted in impulsivity of responding in a planning task, as well as differential dose-dependent effects on two analogous tests of spatial and visual WM. The nature of these effects were suggestive of mnemonic, rather than executive, dysfunction. Conversely, DZP produced specific deficits on tests of spatial WM and planning very similar to those seen following lesions to the frontal lobes. Therefore, these two sedative drugs produce doubly dissociable, dose-dependent effects on different aspects of cognitive function.

Adult↗
PubMed1995

Clonidine and diazepam have differential effects on tests of attention and learning.

The noradrenergic system has repeatedly been implicated in the mediation of attentional processes. Using a double-blind, placebo-controlled design, the present investigation examines the effects of two doses (1.5 micrograms/kg and 2.5 micrograms/kg) of the alpha 2 adrenoceptor agonist clonidine (CLO) on performance of various computerised tests of attention and learning in healthy, young volunteers. These are compared to the effects produced by two doses (5 mg and 10 mg) of diazepam (DZP) on largely the same set of neuropsychological tests in a comparable set of subjects. Both doses of CLO were found to impair performance of the RVIP test of sustained attention, while the higher dose alone improved visuo-spatial learning. Conversely, the higher dose of DZP produced profound deficits on visuo-spatial learning, and impaired attentional set-shifting. This study suggests a role for the alpha 2 adrenoceptor in selective attention, and for the benzodiazepine receptor in specific cognitive processes mediated by discrete cortical regions.

Adult↗
PubMed1994

Pharmacological manipulations of the alpha 2-noradrenergic system. Effects on cognition.

Electrophysiological and neurosurgical lesion studies with experimental animals have implicated the ascending dorsal noradrenergic bundle of the locus coeruleus system in cognitive process such as memory, learning and selective attention. However, it has also been suggested that noradrenaline (norepinephrine) is crucial in certain cognitive functions associated with the frontal lobes, particularly the prevention of distractibility by irrelevant stimuli. The alpha 2-receptors of the prefrontal cortex appear to be of particular importance in this respect. Studies with humans and experimental primates provide substantial support for this view. The aged primate brain is prone to degeneration of the locus coeruleus, as well as profound catecholamine depletion in the prefrontal cortex, and so is ideal for psychopharmacological investigation of the role of noradrenaline in frontal lobe function. Elderly monkeys show deficits in performance of the delayed response task, which can be reversed directly by both the mixed alpha 1/alpha 2-agonist clonidine, the more specific alpha 2-agonist guanfacine and also, indirectly, by the alpha 2-antagonist yohimbine. It is suggested that these results can be explained by an attenuation of the distracting properties of irrelevant stimuli following stimulation of noradrenergic activity. Conversely, distractibility is magnified whenever noradrenergic activity is reduced. This is supported by similar findings in psychopharmacological studies of healthy humans. The exception to this is when the locus coeruleus is likely to be firing, e.g. in times of stress or when novel stimuli are encountered. Clonidine attenuates locus coeruleus firing on such occasions, and so counteracts any beneficial (or deleterious) effects of stress on task performance. alpha 2-Adrenoceptor agents have little therapeutic value in patients with dementia of the Alzheimer's type. However, they may have some clinical use in patients who have a cognitive symptomatology similar to that of patients who have received neurosurgical excisions to the frontal lobes, e.g. deficits in working memory, executive function or focused attention, with relative sparing of episodic short term memory. Patients with Korsakoff's disease, attention deficit disorder or schizophrenia may benefit from treatment with alpha 2-agents. In particular, idazoxan has putative therapeutic effects in patients with a neurodegenerative disorder, namely dementia of frontal type.

Aging↗
PubMed1993

Tetrahydroaminoacridine (THA) in Alzheimer's disease: an assessment of attentional and mnemonic function using CANTAB.

A placebo-controlled cross-over trial (n = 89) investigated the use of a chronic dose of the cholinesterase inhibitor THA, as a treatment for dementia of the Alzheimer type (DAT). Effects on both subjective clinical rating scales and objective computerised tests were assessed. In regard to the former, analysis of the three main clinical outcome measures showed statistically significant effects of the drug on the Mini-Mental State Examination (MMSE) and the Abbreviated Mental Test Score (AMTS), but not on the Activities of Daily Living scale (ADL). Using the objective computerised CANTAB tests, sensitive to specific aspects of memory and attention, evidence was found for improvements in attentional function rather than memory, in patients with mild to moderate DAT. Although these improvements were significant, they were small and restricted to certain tests of attentional function. Nevertheless, they add to the growing body of evidence that the cholinergic system is involved in the control of attentional processes; and are substantiated by the findings of a second study examining the effects of an acute dose of nicotine on attentional and mnemonic performance in patients with DAT. This study found significant improvements in cognitive performance in patients receiving nicotine, in objective tests of attention but not of short-term memory. These data will clearly provide important comparative data for future investigations of putative cognitive enhancing drugs in DAT sufferers.

Activities of Daily Living↗
PubMed1990

Military surgery.

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Education, Medical, Graduate↗
PubMedDate not supplied

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↗