UC Berkeley

Acetylcholine is a neuromodulator implicated in cognitive processes such as attention and memory, as well as the regulation of sensory cortical plasticity. In animal models, acetylcholine boosts the amplitude of visually evoked cortical responses, especially to behaviorally pertinent stimuli. Perceptual learning is a well-studied manifestation of sensory cortical plasticity, and can be induced and subtly probed in humans with minimal invasiveness. Previous studies of the effects of pharmacological cholinergic enhancement on perceptual learning in humans have yielded mixed results across different tasks. In this dissertation, I present two experiments that combine behavioral pharmacology and repeated psychophysical training in healthy human subjects to assess the effects of increased cholinergic neurotransmission on a broadly used and thoroughly studied measure of visual perceptual learning: the texture discrimination task.

In Chapter 2, I describe a study of the effects of transient cholinergic enhancement (a single drug dose administered at training’s onset) on perceptual learning induced by a brief course of texture discrimination task training. The results indicate that transient cholinergic enhancement neither increased nor decreased the extent or location selectivity of texture discrimination learning, and are consistent with several competing interpretations. One possibility is that the plasticity mechanisms mediating improved texture discrimination performance are impervious to cholinergic modulation. Conversely, it is also possible that cholinergic effects on texture discrimination learning would have emerged had our drug administration and/or training procedures been more substantial and/or prolonged.

I address this second possibility directly in the experiment detailed in Chapter 3. This study assesses the effects of sustained cholinergic enhancement (multiple drug doses administered throughout training) on perceptual learning during a course of texture discrimination training over several days. The results demonstrate that sustained cholinergic enhancement significantly increased the magnitude, but neither the location nor background orientation specificity, of texture discrimination learning compared to placebo. These results shed light on the interpretation of the findings discussed in Chapter 2, and demonstrate that the processes underlying improved performance on the texture discrimination task are indeed susceptible to cholinergic modulation. While sustained cholinergic enhancement significantly boosted texture discrimination learning’s magnitude, it also tended to reduce the background orientation specificity of this learning. This suggests that selective facilitation of plasticity for the neuronal population representing task-relevant stimuli is unlikely to be the primary biological mechanism through which cholinergic enhancement bolsters texture discrimination learning. Other possibilities consistent with the results include cholinergic effects on visual responsiveness, attention, and memory consolidation.