Abstract
The neurotransmitter acetylcholine (ACh) regulates many aspects of cognition, including attention and memory. Previous research in animal models has shown that plasticity in sensory systems often depends on the behavioral relevance of a stimulus and/or task. However, experimentally increasing ACh release in the cortex can result in experience-dependent plasticity, even in the absence of behavioral relevance. In humans, the pharmacological enhancement of ACh transmission by administration of the cholinesterase inhibitor donepezil during performance of a perceptual task increases the magnitude of perceptual learning (PL) and its specificity to physical parameters of the stimuli used for training. Behavioral effects of PL have previously been shown to persist for many months. In the present study, we tested whether enhancement of PL by donepezil is also long-lasting. Healthy human subjects were trained on a motion direction discrimination task during cholinergic enhancement, and follow-up testing was performed 5–15 months after the end of training and without additional drug administration. Increases in performance associated with training under donepezil were evident in follow-up retesting, indicating that cholinergic enhancement has beneficial long-term effects on PL. These findings suggest that cholinergic enhancement of training procedures used to treat clinical disorders should improve long-term outcomes of these procedures.
Highlights
Perceptual learning (PL) is the improvement of performance on a perceptual task with training
In a previous study (Rokem and Silver, 2010), we demonstrated that enhancement of cholinergic transmission by the cholinesterase inhibitor donepezil increased the magnitude and specificity of visual PL of motion direction discrimination (MDD; Figure 1A) in healthy humans
We found that the beneficial effects of pharmacological cholinergic enhancement on PL are long-lasting
Summary
Perceptual learning (PL) is the improvement of performance on a perceptual task with training. When participants practice a motion direction discrimination (MDD) task (Figure 1A) for a particular direction of motion and in a particular location in the visual field, the resulting improvement in performance does not fully generalize to other directions of motion or to other visual field locations (Ball and Sekuler, 1982, 1987) Another hallmark of PL is the persistence of learning for extended periods of time. In rodents, pairing of electrical stimulation of the basal forebrain and auditory stimulation with a tone at a particular frequency resulted in reorganization of the primary auditory cortical map such that the size of the auditory cortical region that responded to the previously paired tone increased (Kilgard and Merzenich, 1998) Both of these findings suggest that synchronous ACh signaling and stimulus presentation modified the receptive fields of neurons in a stimulus-specific manner. We tested whether the effects of donepezil on PL were maintained several months after the end of drug administration and training
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