Biological effects of non-invasive brain stimulation

By incorporating the known physiology of the spinal cord epidural activity evoked by single-pulse, paired-pulse, and repetitive transcranial magnetic stimulation (TMS) with the anatomical and computational characteristics of the canonical model of the cerebral cortex circuit, and composed of layer II and III and layer V excitatory pyramidal cells, inhibitory interneurons, corticocortical and thalamocortical inputs, the characteristics and nature of the corticospinal activity evoked by TMS including its regular and rhythmic nature, the dose dependence, and pharmacological modulation of the discharge might be explained elegantly. TMS inducing strong depolarization of the superficial excitatory cells of the circuit may lead to the recruitment of fully synchronized clusters of excitatory neurons, including layer V pyramidal tract neurons (PTNs), and inhibitory neurons producing a high-frequency (~670Hz) repetitive discharge of the corticospinal axons. The role of the inhibitory circuits is crucial to entrain the firing of the excitatory networks to produce a high-frequency discharge. The integrative properties of the circuit might also provide a good framework for interpretation of the changes in corticospinal activity produced by paired and repetitive TMS. The changes can be produced presynaptically to PTN cells or at the level of these cells, depending mainly on the intensity of magnetic stimuli.