Focusing Effect of Acetylcholine on Neuroplasticity in the Human Motor Cortex

Abstract

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.

Transcranial Electrical Stimulation: Methodology and Applications

“…Fourth, interhemispheric inhibition must be accounted for, especially in motor cortex stimulation, where any motor effect on one side of the body will be followed by the opposite effect on the other side of the body (Vines et al, 2006). Fifth, when experimenting with patient groups, medication must be carefully considered, because it has been shown that different substances may significantly alter the effects of tDCS (Kuo et al, 2007;Kuo et al, 2008;Nitsche et al, 2003;Nitsche et al, 2004;Terney et al, 2008).…”

“…The authors concluded that immediate effects of tDCS are due to modulation of sodium and calcium channels, whereas lasting after effects of tDCS are due to N-methyl-Daspartate-receptor-dependent neuroplasticity (Nitsche et al, 2003). Similarly, rivastigmine, an acetylcholine agonist, is shown to block any tDCS induced excitatory or inhibitory effects on MEPs after 13-min=1-mA anodal or cathodal stimulation of the primary motor cortex (Kuo, Grosch, Fregni, Paulus, & Nitsche, 2007).…”

Transcranial Direct Current Stimulation (tDCS): Modulation of Executive Function in Health and Disease

“…Pharmacological and magnetic resonance spectroscopy studies have established the role of tDCS in regulating different neurotransmitter systems including glutamate [26], GABA [27], dopamine [28], serotonin [29], and acetylcholine [30]. The neuroplastic after-effects of anodal and cathodal modulation have been linked to N-methyl-D-aspartate (NMDA) receptor-dependent plasticity [31•] and can be pharmacologically suppressed by the sodium channel blocker carbamazepine, the calcium channel blocker flunarizine [26], the NMDA receptor antagonist dextromethorphan (DMO) [32], and the β-blocker propranolol [33].…”

Unraveling Acetylcholine Impact on Human Cortical Plasticity

“…Recent studies have investigated the possibility of boosting PAS-and TDCSinduced plasticity using drugs, including those that act on cholinergic transmission (Kuo et al, 2007;Thirugnanasambandam et al, 2011;Grundey et al, 2012). Acetylcholine (ACh) may play an important role in attention, learning, and memory by modulating cortical LTP and LTD (Laviolette and van der Kooy, 2004;Changeux, 2010).…”

“…Acetylcholine (ACh) may play an important role in attention, learning, and memory by modulating cortical LTP and LTD (Laviolette and van der Kooy, 2004;Changeux, 2010). After enhancing global cholinergic transmission with rivastigmine, a cholinesterase inhibitor, Kuo et al (2007) found that anodal TDCS failed to increase MEPs, whereas PAS 25 elicited long-term MEP enhancement. More recently, Thirugnanasambandam et al (2011) examined the specific contribution of the nicotinic ACh receptor (AChR) to PAS-and TDCSinduced plasticity in nonsmokers.…”