Mechanisms influencing stimulus-response properties of the human corticospinal system.
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.
Boroojerdi
B
B
Human Cortical Physiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. boroojeb@ninds.nih.gov
Battaglia
F
F
Muellbacher
W
W
Cohen
L G
LG
D000328:Adult; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003913:Dextroamphetamine / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D004558:Electric Stimulation; D004576:Electromyography; D019054:Evoked Potentials, Motor / Q000187:drug effects / Q000502:physiology*; D005260:Female; D018757:GABA Modulators / Q000494:pharmacology; D006801:Humans; D000077213:Lamotrigine; D008140:Lorazepam / Q000494:pharmacology*; D008280:Magnetics; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D011712:Pyramidal Tracts / Q000187:drug effects / Q000502:physiology*; D014227:Triazines / Q000494:pharmacology*; D014459:Ulnar Nerve / Q000187:drug effects / Q000502:physiology*
D002121:Calcium Channel Blockers; D018491:Dopamine Agonists; D018757:GABA Modulators; D014227:Triazines; D008140:Lorazepam; D003913:Dextroamphetamine; D000077213:Lamotrigine