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. 2013 May 29:7:66.
doi: 10.3389/fncom.2013.00066. eCollection 2013.

The benefits of cholinergic enhancement during perceptual learning are long-lasting

Ariel Rokem  1 , Michael A Silver
Affiliations

The benefits of cholinergic enhancement during perceptual learning are long-lasting

Ariel Rokem et al. Front Comput Neurosci. .

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.

Keywords: acetylcholine; donepezil; neural plasticity; perceptual learning; vision.

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Figures

Figure 1
Figure 1
Motion direction discrimination (MDD) task. (A) In each trial, participants viewed two sequentially-presented fields of dots that were moving in either the same or different directions. MDD thresholds were measured by applying a psychophysical staircase (Watson and Pelli, 1983) to the angular difference in directions between the two motion stimuli (α). (B) During each course of PL, participants practiced the MDD task for one location (quadrant pair 1 or 2) and one direction of motion.
Figure 2
Figure 2
Motion direction discrimination thresholds. Thresholds for each combination of location and direction of motion were assessed at three different time points: before any training (dark green), one day after the completion of the second course of training (light green), and 5–15 months after training (yellow). Thresholds were separately averaged across subjects for the location that was trained under donepezil (left) or under placebo (right). In each location, the trained direction is defined as zero degrees, and all other directions are rotated accordingly. Thresholds decreased following training (light green < dark green), and there is no evidence of decay in the benefits of training in follow-up testing (light green similar to yellow).
Figure 3
Figure 3
Long-term retention of the benefits of training. For each subject, percent learning was computed for each training condition (donepezil, placebo, and the mean of location/direction combinations that were not trained under either), relative to the initial pre-training measurement for that direction/location combination. Error bars are standard errors of the mean within each condition.
Figure 4
Figure 4
Individual subject data. Individual participants' data are presented as a function of the time interval between the initial course of training and follow-up measurements. (A) Percent learning for each subject in the donepezil-trained condition (filled red circles) and placebo-trained condition (filled blue circles). The two percent learning scores for each subject are connected with a dashed line. For participants in the “donepezil first” group, the dashed line is red. For the “donepezil second” subjects, the dashed line is blue. There was no indication of decay of learning following the cessation of training. (B) Within-subject differences between the donepezil-trained and the placebo-trained conditions. Percent learning was greater for the donepezil-trained condition than the placebo-trained condition in 7 out of 8 participants.
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