The cholinergic system has long been implicated in cognitive functions. Here, I will present a body of work evaluating the impact of cholinergic modulation on brain function during a working memory (WM) task in young healthy individuals. Using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), we will review systematic changes in brain response to WM following cholinergic enhancement using the anti-cholinesterase physostigmine. Using PET, we show that during cholinergic enhancement, performance on a face WM task improved while the WM-critical prefrontal cortical region reduced the response magnitude. No such changes were seen in those participants receiving a placebo. The only brain region showing an increase in response was the medial occipital areas. Together, these changes suggested that enhanced processing in visual regions produced an enhanced visual percept of the stimuli, making the task easier and reducing the need to recruit the prefrontal cortex. Subsequently, a study was designed to utilise the improved temporal resolution of fMRI to compare responses in visual processing areas to task-relevant and task-irrelevant stimuli under placebo and cholinergic enhancement. We found that, together with an improvement in task performance, visual processing areas showed increased responses selectively to task-relevant stimuli, with a reduced response to task-irrelevant stimuli. Together, these results suggest that increasing cholinergic activity enhances representations of task-relevant stimuli through signal-to-noise mechanisms and that this improved representation reduces the need to recruit the prefrontal cortex.
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