Mechanisms influencing stimulus-response properties of the human corticospinal system

• Published in: Clinical neurophysiology Vol. 112; no. 5; pp. 931 - 937
• Main Authors: Boroojerdi, B, Battaglia, F, Muellbacher, W, Cohen, L.G
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Shannon Elsevier Ireland Ltd 01-05-2001; Elsevier Science
• Subjects: Adult; Biological and medical sciences; 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; Excitability; Female; Fundamental and applied biological sciences. Psychology; GABA Modulators - pharmacology; Humans; Lorazepam - pharmacology; Magnetics; Male; Motor control and motor pathways. Reflexes. Control centers of vegetative functions. Vestibular system and equilibration; Motor system; Muscle, Skeletal - drug effects; Muscle, Skeletal - innervation; Muscle, Skeletal - physiology; Pyramidal Tracts - drug effects; Pyramidal Tracts - physiology; Stimulus-response curve; Transcranial magnetic stimulation; Triazines - pharmacology; Ulnar Nerve - drug effects; Ulnar Nerve - physiology; Vertebrates: nervous system and sense organs; Excitability; Stimulus-response curve; Transcranial magnetic stimulation; Motor system; Facilitation; Human; Dopamine; Calcium; Central nervous system; Electrophysiology; Corticospinal bundle; Ionic channel; Sodium; Pyramidal motor pathway; Magnetic stimulus; GABA; Norepinephrine; Motor evoked potential; Inhibition; Gabaergic receptor A; Neurotransmission
• ISSN: 1388-2457; 1872-8952
• 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
α-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.