  Animal models indicate that motor behaviour is shaped by monoamine
neurotransmitters released diffusely throughout the brain and spinal cord. We
present strong evidence that human motor pathways are equally affected by
neuromodulation through noradrenergic and serotonergic projections arising from
the brainstem. To do so, we have identified and collated human experiments
examining the off-label effects of well-characterised serotonergic and
noradrenergic drugs on lab-based electrophysiology measures of
corticospinal-motoneuronal excitability. Specifically, we focus on the effects
that serotonin and noradrenaline associated drugs have on muscle responses to
magnetic or electrical stimulation of the motor cortex and peripheral nerves,
and other closely related tests of motoneuron excitability, to best segment
drug effects to a supraspinal or spinal locus. We find that serotonin enhancing
drugs tend to reduce the excitability of the human motor cortex, but that
augmented noradrenergic transmission increases motor cortical excitability by
enhancing measures of intracortical facilitation and reducing inhibition. Both
monoamines tend to enhance the excitability of human motoneurons. Overall, this
work details the importance of neuromodulators for the output of human motor
pathways and suggests that commonly prescribed monoaminergic drugs have
off-label motor control uses outside of their typical psychiatric/neurological
indications.
