Selective Effects of Cholinergic Modulation on Task Performance during Selective Attention

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 ¼ 9) with the anticholinesterase physostigmine (1.0 mg/h), and the other (n ¼ 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 (po0.05); RT also was significantly longer when attending to houses than to faces (po0.05). Physostigmine decreased RT relative to placebo preferentially during trials greater than one (po0.05), with no change during trial one; and decreased RT preferentially during the attention to houses condition (po0.05) vs attention to faces. Scopolamine increased RT relative to placebo selectively during trials greater than one (po0.05), and preferentially increased RT during the attention to faces condition (po0.05). 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.

Cortical cholinergic signaling controls the detection of cues

“…However, in addition to results from our electrochemical recordings studies (18,19), a considerable literature on the effects of pharmacological manipulations of the cholinergic system on attentional performance in animals and humans (27)(28)(29) is consistent with the present attribution of a cholinergic mechanism underlying the effects of optogenetic stimulation on cue detection processes (as defined in the introduction).…”

Parkinson's disease, visual hallucinations and apomorphine: A review of the available evidence

“…PD patients with VH were found to have impaired attention and higher cortical visuoperception, due to prefrontal cortex and parietooccipital cortex dysfunction respectively on functional imaging [16][17][18][19], and higher Lewy body density and alpha-synuclein aggregation was found in prefrontal, temporal and visuoperceptive areas in patients with coexistent PD and VH than age matched controls without VH [20][21][22][23].…”

“…Low cholinergic activity following the use of anticholinergic drugs impairs attention [17,18] and visual processing [19], and can sometimes induce delirium with VH, even in individuals without clinical evidence of PD (Han et al, 2001) [20]. In contrast, use of cholinesterase inhibitors improves attention, thalamic function and visual processing in a dose-dependent manner [17,[21][22][23].…”

“…In top-down processing, an interpretation of the visual information is generated based on perceptual expectations and prior knowledge. Visual information from the inferior temporal cortex is dealt with in the lateral prefrontal cortex via the uncinate fascicle [15], and via cortico-thalamo-cortical loops [16][17][18]. The mediodorsal and reticular thalamic nuclei are essential in gating and filtering relevant visual information [19,20].…”

Recent developments of functional magnetic resonance imaging research for drug development in Alzheimer's disease

“…The modulation due to AD -related drug mechanisms have also been investigated by using anticholinesterase physotigmine on healthy subject populations during tasks of working memory, emotion processing, visual attention and found that cholinesterase inhibitors may through modulation of activation in visual areas (increased) and frontal areas (decreased) lead to enhancement of stimulus processing and selectivity improve cognitive performance (Furey et al 2000;Bentley et al 2003;Bentley et al 2004;Furey et al 2008). In addition, similar approach has been utilized in studies comparing healthy subjects with AD patients during a visual attentional task where activation pattern was investigated during placebo and physotigmine-induced modulation of the activation (Bentley et al 2008).…”