Muscarinic receptor blockade has differential effects on the excitability of intracortical circuits in the human motor cortex

Abstract

The aim of the present study was to investigate whether muscarinic receptor blockade with scopolamine modifies the excitability of specific cortical networks of the human motor cortex as tested with transcranial magnetic stimulation. The effects of scopolamine on the excitability of human motor cortex were investigated in four healthy subjects using transcranial magnetic stimulation before and after an intravenous dose of scopolamine (0.006 mg/kg). We measured the threshold for motor responses, amplitude of motor responses, the duration of the cortical silent period, intracortical inhibition and facilitation, and short-latency inhibition produced by somatosensory input from the hand. In addition, we evaluated the amplitude of motor responses evoked by electrical anodal stimulation, since these responses originate from direct activation of corticospinal axons in the white matter and are not sensitive to changes in cortical excitability. Scopolamine decreased the threshold to magnetic stimuli and increased the amplitude of motor responses evoked by magnetic stimulation. In contrast, motor responses evoked by electrical stimulation were unaffected by administration of scopolamine. Scopolamine also led to a highly significant reduction in the amount of short-latency inhibition produced by somatosensory input from the hand. In contrast, short-latency intracortical inhibition and facilitation were not modified by scopolamine. The differential effect of scopolamine on motor responses evoked by magnetic and electrical stimulation of the motor cortex and the selective effect on somatosensory inhibition demonstrate that muscarinic blockade modifies the excitability of specific cortical networks in the human motor cortex.

Cortical Hypoexcitability in Chronic Smokers? A Transcranial Magnetic Stimulation Study

“…This would explain the SAI increase and MEP amplitude reduction, which is the opposite finding of the work by Di Lazzaro et al (2000) with blocking muscarinic receptors. Nicotinic, but not muscarinic receptors could also activate an alternative, non-GABAergic pathway that could explain the CSP prolongation.…”

Dissociated effects of diazepam and lorazepam on short‐latency afferent inhibition

“…Animal experiments showed consistently that diazepam and other benzodiazepines decrease ACh release at various subcortical and cortical sites (Petkov et al 1983;Imperato et al 1993). The anticholinergic drug scopolamine reduces SAI (Di Lazzaro et al 2000a). Thus, it may be speculated that both diazepam and lorazepam similarly decrease SAI through suppression of ACh release, but diazepam more than compensates for this by increasing neurotransmission through the GABA A receptor subtype that mediates inhibition in the SAI circuit, whereas lorazepam has not sufficient affinity for this receptor to reverse the decrease of SAI produced by its anticholinergic effect.…”

“…This effect, named short-latency afferent inhibition (SAI) of the motor cortex, is produced by interactions within the cerebral cortex (Tokimura et al 2000). Since this inhibitory phenomenon is reduced or abolished by the muscarinic antagonist scopolamine (Di Lazzaro et al 2000a), we suggested that it might be a non-invasive way of testing cholinergic activity in the SAI pathway. More recently, we showed (Di Lazzaro et al 2005) that also the benzodiazepine lorazepam results in a suppression of SAI, concomitantly with an increase in a different intracortical inhibitory phenomenon, the so-called short-latency intracortical inhibition (SICI) (Kujirai et al 1993).…”

Corticospinal excitability in patients with anoxic, traumatic, and non-traumatic diffuse brain injury

“…In humans, muscarinic antagonist (i.e. scopolamine and atropine) was shown to enhance motor cortex excitability in normal subjects [55,56]. Some benzodiazepines can reduce SAI [57], which might suggest GABAA circuits to be involved in SAI modulation.…”