Modification of motor cortical excitability by an acetylcholinesterase inhibitor

Acetylcholine powerfully modulates the excitability of neocortical neurones and networks. This study applied focal transcranial magnetic stimulation (TMS) to eight healthy subjects to test the effects of a single oral dose of 40 mg tacrine, an acetylcholinesterase inhibitor, on motor cortical excitability. It was found that tacrine decreased short-interval intracortical inhibition, and increased intracortical facilitation and short-interval intracortical facilitation. Motor thresholds, motor evoked potential amplitude, cortical silent period (CSP) duration, and measures of spinal and neuromuscular excitability remained unchanged. The effects peaked at 2–6 h and fully reversed after 24 h. All effects can be explained by a reduction of motor cortical GABAergic inhibitory neurotransmission via activation of presynaptic muscarinic M2 receptors, but other more complex mechanisms may also have contributed and are discussed. The findings predict that acetylcholine has the potential to promote plasticity and learning in human motor cortex.