Recent studies have indicated that training-induced cortical plasticity may offer promising opportunities for the remediation of several different neurological conditions, such as stroke-induced movement disorders, dystonia, and dyslexia. However, extremely intensive training has been required, and has yielded results that, although promising, fall far short of a full cure. For this reason, there has been much interest in attempts to enhance cortical plasticity, including the use of noradrenergic drugs such as amphetamine in stroke-rehabilitation, and disinhibition of motor cortex in healthy subjects using ischemic nerve block. The study proposed here will investigate a novel approach, exploiting a newly available opportunity to apply plasticity-enhancing results from the animal literature to studies in humans. Experiments in animals have shown that cortical plasticity can be greatly enhanced by increasing the levels of the neurotransmitter acetylcholine (ACh). New drugs, known as cholinesterase inhibitors, that safely and effectively increase ACh levels in humans have recently been developed and FDA-approved. The specific drug that we propose to use is galantharnine hydrobromide (trade name Reminyl). The effect of the drug on cortical plasticity will be assessed using both visual psychophysics and fMR1. The psychophysical measure will be the rate at which the subjects learn to more accurately perform a simple visual perceptual learning task: learning to discriminate the orientation of a grating. The hypothesis to be tested is that learning of the visual task that takes place under the influence of the drug will proceed more quickly than learning that is paired with a placebo. Functional MRI will be used to assess the effect of the drug on cortical plasticity, by comparing the pre-training versus post-training brain activation changes that are caused by learning the visual task while on the drug against those caused by learning the task on placebo. If the novel method of enhancing plasticity that is proposed here should turn out to be successful, then there could be a wide range of potential clinical and practical applications.
