Abstract
The neurotransmitter acetylcholine (ACh) has previously been shown to play a critical role in cognitive processes such as attention and learning. In this study, we examined the role of ACh in perceptual learning (PL) of a motion direction discrimination task in human subjects. We conducted a double-blind, placebo-controlled, crossover study, in which each participant trained twice on the task, once while cholinergic neurotransmission was pharmacologically enhanced by the cholinesterase inhibitor donepezil and once while ingesting a placebo. Relative to placebo, donepezil increased the improvement in direction discrimination performance due to PL. Furthermore, PL under the influence of donepezil was more specific for the direction of motion that was discriminated during training and for the visual field locations in which training occurred. In order to study the neural mechanisms underlying these effects, we measured fMRI responses to either trained or untrained directions of motion before and after training, in both placebo and drug conditions. Spatial specificity was assessed by comparing pre- and post-training fMRI responses in portions of retinotopic cortex representing the spatial locations of trained and untrained stimuli. Direction specificity was assessed with fMRI adaptation (fMRI-A), a procedure based on the fact that when presented with a pair of stimuli in succession, neurons will typically respond more weakly to the second stimulus if they also responded to the first stimulus. Consequently, two consecutively presented stimuli will generate a smaller response if they excite overlapping populations of neurons. In each block, an adapting direction (trained or untrained) was presented, and in each trial an additional probe stimulus, which differed from the adapting direction by some angular offset, was shown. The dependence of the response amplitude on this angular offset allowed the generation of adaptation ‘direction tuning curves’ for motion-sensitive areas in visual cortex.
This work was supported by NIH grant R21-EY17926 (MAS), the Hellman Family Faculty Fund (MAS), and National Research Service Award F31-AG032209 (AR).