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The Journal of Neuroscience, December 26, 2007, 27(52):14442-14447; doi:10.1523/JNEUROSCI.4104-07.2007

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Behavioral/Systems/Cognitive
Focusing Effect of Acetylcholine on Neuroplasticity in the Human Motor Cortex

Min-Fang Kuo,¹ Jan Grosch,¹ Felipe Fregni,² Walter Paulus,¹ and Michael A. Nitsche¹

¹Department of Clinical Neurophysiology, Georg-August-University Göttingen, 37075 Göttingen, Germany, and ²Harvard Center for Noninvasive Brain Stimulation, Boston, Massachusetts 02215

Correspondence should be addressed to Michael A. Nitsche, Department of Clinical Neurophysiology, Georg-August-University Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen, Germany. Email: mnitsch1{at}gwdg.de

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 neurophysiological 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 excitability diminution. These findings are in line with a cholinergic focusing effect that optimizes the detection of relevant signals during information processing in humans.

Key words: neuroplasticity; acetylcholine; transcranial direct current stimulation; paired associative stimulation; motor cortex; human

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Received May 17, 2007; revised Oct. 18, 2007; accepted Nov. 1, 2007.

Correspondence should be addressed to Michael A. Nitsche, Department of Clinical Neurophysiology, Georg-August-University Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen, Germany. Email: mnitsch1{at}gwdg.de

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