Abstract
The cholinergic neurotransmitter system is critically linked to cognitive functions including attention. The current studies were designed to evaluate the effect of a cholinergic agonist and an antagonist on performance during a selective visual attention task where the inherent salience of attended/unattended stimuli was modulated. Two randomized, placebo-controlled, crossover studies were performed, one (n=9) with the anticholinesterase physostigmine (1.0 mg/h), and the other (n=30) with the anticholinergic scopolamine (0.4 mc/kg). During the task, two double-exposure pictures of faces and houses were presented side by side. Subjects were cued to attend to either the face or the house component of the stimuli, and were instructed to perform a matching task with the two exemplars from the attended category. The cue changed every 4–7 trials to instruct subjects to shift attention from one stimulus component to the other. During placebo in both studies, reaction time (RT) associated with the first trial following a cued shift in attention was longer than RT associated with later trials (p<0.05); RT also was significantly longer when attending to houses than to faces (p<0.05). Physostigmine decreased RT relative to placebo preferentially during trials greater than one (p<0.05), with no change during trial one; and decreased RT preferentially during the attention to houses condition (p<0.05) vs attention to faces. Scopolamine increased RT relative to placebo selectively during trials greater than one (p<0.05), and preferentially increased RT during the attention to faces condition (p<0.05). The results suggest that enhancement or impairment of cholinergic activity preferentially influences the maintenance of selective attention (ie trials greater than 1). Moreover, effects of cholinergic manipulation depend on the selective attention condition (ie faces vs houses), which may suggest that cholinergic activity interacts with stimulus salience. The findings are discussed within the context of the role of acetylcholine both in stimulus processing and stimulus salience, and in establishing attention biases through top-down and bottom-up mechanisms of attention.
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Acknowledgements
We thank Harvey Iwamoto for preparation of the selective attention task; Joanna Szczepanik, Jane Lange, Alice Liu, and Ashish Khanna for providing technical support, and the 5SW Day Hospital staff for nursing support.
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Dr Furey and Dr Drevets have submitted a patent application for the use of scopolamine as an antidepressant and antianxiety agent in mood and anxiety disorders. The patent currently is pending. No other potential conflict of interest exists for any of the authors.
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Furey, M., Pietrini, P., Haxby, J. et al. Selective Effects of Cholinergic Modulation on Task Performance during Selective Attention. Neuropsychopharmacol 33, 913–923 (2008). https://doi.org/10.1038/sj.npp.1301461
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DOI: https://doi.org/10.1038/sj.npp.1301461
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