BehavioralSystemsCognitive Focusing Effect of Acetylcholine on Neuroplasticity in the Human.pdf

14442 • The Journal of Neuroscience, December 26, 2007 • 27(52):14442–14447 Behavioral/Systems/Cognitive Focusing Effect of Acetylcholine on Neuroplasticity in the Human Motor Cortex 1 1 2 1 1 Min-Fang Kuo, Jan Grosch, Felipe Fregni, Walter Paulus, and Michael A. Nitsche 1 2 Department of Clinical Neurophysiology, Georg-August-University Go¨ttingen, 37075 Go¨ttingen, Germany, and Harvard Center for Noninvasive Brain Stimulation, Boston, Massachusetts 02215 Cholinergic neuromodulation is pivotal for arousal, attention, and cognitive processes. Loss or dysregulation of cholinergic inputs leads to cognitive impairments like those manifested in Alzheimer’s disease. Such dysfunction can be at least partially restored by an increase of acetylcholine (ACh). In animal studies, ACh selectively facilitates long-term excitability changes induced by feed-forward afferent input. Consequently, it has been hypothesized that ACh enhances the signal-to-noise ratio of input processing. However, the neurophys- iological foundation for its ability to enhance cognition in humans is not well documented. In this study we explore the effects of rivastigmine, a cholinesterase inhibitor, on global and synapse-specific forms of cortical plasticity induced by transcranial direct current stimulation (tDCS) and paired associative stimulation (PAS) on 10–12 healthy subjects, respectively. Rivastigmine essentially blocked the induction of the global excitability enhancement elicited by anodal tDCS and revealed a tendency to first reduce and then stabilize cathodal tDCS-induced inhibitory aftereffects. However, ACh enhanced the synapse-specific excitability enhancement produced by facilitatory PAS and consolidated the inhibitory PAS-induced ex