Pharmaco-transcranial magnetic stimulation studies of motor excitability

Application of a single dose of a central nervous system (CNS) active drug with a defined single mode of action has been proven useful to explore and characterize the pharmacophysiological properties of transcranial magnetic stimulation (TMS) measures of motor cortical and corticospinal excitability in humans. With this pharmaco-TMS approach, it was demonstrated that different TMS measures reflect axon excitability (motor threshold), or inhibitory (cortical silent period, short-interval intracortical inhibition, long-interval intracortical inhibition, short-latency afferent inhibition) or excitatory synaptic excitability (motor evoked potential amplitude, intracortical facilitation, short-interval intracortical facilitation) of distinct neuronal elements in the CNS. Pharmaco-TMS has opened an exciting window into human cortical physiology. The array of pharmacophysiologically well defined TMS measures is now used by neurologists, psychiatrists, and clinical neurophysiologists for diagnosis or treatment monitoring in neuropsychiatric disease. This chapter reviews systematically the TMS measures of motor cortical and corticospinal excitability from the perspective of pharmacophysiological characterization. For example, it is demonstrated that blockers of voltage-gated sodium channels specifically increase motor threshold but do not alter other TMS measures of excitability, whereas positive modulators at γ-butyric acid (GABA) type A receptors, such as benzodiazepines, enhance short-interval intracortical inhibition and depress motor evoked potential amplitude but have no effect on motor threshold.