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The effects of scopolamine upon control of attention and memory in humans

Dunne, Michael P. (1990) The effects of scopolamine upon control of attention and memory in humans. PhD thesis, Murdoch University.

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Research into the effects of scopolamine hydrobromide, a post­synaptic cholinergic receptor blocking drug, upon cognition in humans has been conducted for at least two decades. In that time, a distinct pattern of effects has emerged. Within a dose range of 0.3 to 1.2 mg (oral), scopolamine has been found to impair the acquisition of new information in verbal and spatial learning tasks, to reduce stimulus sensitivity in tests of vigilance and to impair selective attention. Generally it is thought that information retrieval, both of newly learned and autobiographical material, is unaffected by this drug.

A primary reason for research interest in scopolamine is that the effects have been found to resemble the pattern of impairment found in advanced age, and particularly in Alzheimer's Disease (AD). This is often referred to as the 'Scopolamine model of dementia'. Coupled with the observation of extensive damage to CNS cholinergic neurons in AD, the hypothesis has emerged that acetylcholine activity influences many important cognitive processes.

Recent theoretical analyses of cognitive loss in AD have proposed that there is a selective impairment to effortful (i.e. active, conscious) processes, whereas the more automatic (i.e. reflexive, unconscious) aspects of cognition remain intact. If the scopolamine model is to remain valid in this perspective, then it should be possible to show that, in normal humans, the effects of the drug are specific to effortful cognitive control processes. This thesis describes six experiments designed to test this prediction.

It is presented in three parts. In Part I, two experiments examined the effects of O. 6mg and O. 9mg oral scopolamine upon the control of attention to targets in visual space. Results confirmed the prediction that the ability to detect stimuli in high probability locations on a VDU is impaired, while detection of stimuli in low probability locations is enhanced. It was argued that the drug broadened the attentional focus, and that this is due to a general reduction in cognitive control.

In Part II, two studies sought to find evidence that the drug impairs the active selection of information from semantic memory. Here, subjects were not provided with material to learn, but rather were asked to sustain the retrieval of items from natural semantic categories for extended periods (8 to 12 min). In the second study of this pair, subjects were also constrained as to the type of retrieval strategy they could use. Results failed to confirm the prediction. The drug had no main or interactive effects on active control over semantic memory retrieval.

In Part III, two studies tested the prediction that scopolamine would selectively impair the more difficult, controlled aspects of encoding and retrieval following presentation of verbal material (i.e. an episodic memory task) in two sensory modalities (auditory and visual). Subjects were required to recall lists of words, and to actively group their recall on the basis of the items' sensory modality. The first study found that the drug impaired recall, but not recognition, and did not have an effect on more automatic phenomena such as word priming effects and the recall advantage for auditory material. In addition, there was some evidence from statistical interactions that the drug impaired subjects' ability to actively cluster the presented material on the basis of input modality.

The second experiment examined effects of scopolamine upon list learning and modality clustering when subjects were given five attempts to recall the same i terns. This experiment introduced two levels of task difficulty, by varying the extent to which item input modality was consistent across learning trials. Pilot testing (non-drug) revealed that list learning and clustering ability were significantly impaired in the variable, as compared to consistent, modality condition. In the full experiment, scopolamine impaired total recall but not recognition. The drug did not directly effect subjects' ability to group items on the basis of modality, and the size of the drug effect on immediate recall was similar for both the easy (i.e. consistent modality) and difficult (i.e. variable modality) learning trials. There were some interactions between drug and task variables which indicated a weak effect upon attention

Taken together, these six experiments show the following pattern. Control over visual attention is impaired by scopolamine, and this agrees with some previous research. However, this reduction in cognitive control appears to be specific, rather than general, since the attempts to find an effect of the drug on active control of retrieval from semantic memory and the conscious organisation of material in episodic memory were unsuccessful.

In theoretical terms, this series of experiments does not support the view that anticholinergic drug effects are specific to effortful processing. It was argued that the pattern of drug effects observed here is not simply due to low potency of a O. 9mg oral dose. Numerous previous experiments have observed subtle effects of scopolamine 0.9mg oral (and lower doses) on various measures of cognitive function. It was concluded that a low to moderate dose of oral scopolamine does have selective effects on different cognitive processes, but that this selectivity is not related to the amount of cognitive effort involved in the tasks.

This work has identified some important limits to the scopolamine model of dementia, and extended research with this drug into several domains of human memory not previously examined. The implications for future research are discussed.

Item Type: Thesis (PhD)
Murdoch Affiliation: School of Social Sciences
Supervisor(s): Hartley, Laurence
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