Mechanisms influencing stimulus-response properties of the human corticospinal system

Clin Neurophysiol. 2001 May;112(5):931-7. doi: 10.1016/s1388-2457(01)00523-5.


Background: Stimulus-response (S-R) properties of the corticospinal system in humans depend on the interactions that take place at different sites along the corticospinal pathway. The mechanisms influencing stimulus-response curves elicited by transcranial magnetic stimulation (TMS) and their operation site along the human neuraxis are poorly understood. In this study, we investigated the effects of CNS-active drugs with distinct mechanisms of action on S-R curves. Effects of each of these drugs on S-R curves would point to the involvement of specific mechanisms. Additionally, relative sensitivity of S-R curves compared with other measures of corticospinal excitability was studied.

Methods: We studied the effects of lorazepam, which is a positive allosteric modulator of GABA(A) receptors; lamotrigine, an inhibitor of voltage-gated Na(+) and Ca(2+) channels; and D-amphetamine, an indirect agonist of the dopaminergic-adrenergic system on S-R curves, motor thresholds (MT), and intracortical inhibition (ICI) and facilitation (ICF) with a double-pulse technique. Maximum peripheral M responses and F waves were investigated as measures of the total alpha-motoneuron pool and its excitability.

Results: F and M waves were unaffected by either the drugs or placebo. S-R curves were significantly depressed by lorazepam and lamotrigine without changes in ICI and ICF. Both S-R curves and ICF were enhanced by D-amphetamine. MT increased only with lamotrigine.

Conclusions: S-R curves were influenced by changes in the GABAergic and monoaminergic system and Na(+) and Ca(2+) channel properties. Our results indicate that, out of different parameters of motor system excitability, S-R curves were the most sensitive.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Brain / drug effects
  • Brain / physiology*
  • Calcium Channel Blockers / pharmacology
  • Dextroamphetamine / pharmacology*
  • Dopamine Agonists / pharmacology
  • Electric Stimulation
  • Electromyography
  • Evoked Potentials, Motor / drug effects
  • Evoked Potentials, Motor / physiology*
  • Female
  • GABA Modulators / pharmacology
  • Humans
  • Lamotrigine
  • Lorazepam / pharmacology*
  • Magnetics
  • Male
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / innervation
  • Muscle, Skeletal / physiology
  • Pyramidal Tracts / drug effects
  • Pyramidal Tracts / physiology*
  • Triazines / pharmacology*
  • Ulnar Nerve / drug effects
  • Ulnar Nerve / physiology*


  • Calcium Channel Blockers
  • Dopamine Agonists
  • GABA Modulators
  • Triazines
  • Lorazepam
  • Dextroamphetamine
  • Lamotrigine