Figure 1

Cortical circuits activated by motor cortex simulation. Panel a. Left: Post stimulus time histograms of individual axon responses after motor cortex (M1) intracortical stimulation in monkeys (modified from⁶). The peaks of the histograms reveal different patterns of discharge: 1. high-frequency (≈660 Hz) repetitive discharge with a D-wave (i.e. the earliest response originating from the direct activation of corticospinal axons) followed by several I-waves (i.e. longer latency responses originating from indirect activation of corticospinal cells through trans-synaptic inputs); 2. high-frequency repetitive discharge with only I-waves; 3. lower frequency discharge at ≈330 Hz (see the insert); 4. more temporally-dispersed responses. Right: Corticospinal volleys recorded at epidural level after different forms of magnetic stimulation in two human subjects. Monophasic lateromedial (LM) TMS evokes a high-frequency (≈660 Hz) repetitive discharge with a D-wave followed by several I-waves, monophasic posterior-to-anterior (PA) TMS preferentially evokes only I-waves, biphasic TMS evokes a lower frequency activity (≈330 Hz, see the insert for subject 2), monophasic anterior-to-posterior (AP) TMS evokes both lower frequency and temporally dispersed responses. Panel b. Diagrammatic representation of possible sites of activation of corticospinal neurons (CSNs) using different TMS techniques on M1. Two pyramidal tract neurons are represented. Monophasic PA TMS preferentially activates CSNs trans-synaptically evoking high-frequency I-waves; biphasic PA-AP TMS and monophasic AP TMS preferentially activate trans-synaptically different CSNs, evoking lower frequency I-waves and temporally dispersed volleys; TMS with a circular coil centred over the vertex preferentially activates CSNs at the level of the axon hillock; monophasic LM TMS preferentially activate the corticospinal axons at some distance from the cell body.