Figure 1.

Model of ccPAS and STDP. (Left) ccPAS can be delivered by stimulating two cortical areas, A and B, that are axonally connected (here, left and right M1, coronal slice with MRI tractography) with bifocal TMS. To induce STDP in area B, areas A and B are stimulated at slightly different times (“asynchrony”). Note that the axons are long-range, which results in an axonal conduction delay from area A to B (here, 9 milliseconds) that must be considered when selecting the asynchrony. (Right) During ccPAS, to induce STDP in the target synapse in area B, TMS pulses are delivered at three different asynchronies on separate days. The target synapse is shown with the presynaptic component (axon terminal) for a neuron originating in area A and the postsynaptic component (dendrite) for a neuron in area B; the black arrowheads indicate the direction of effective connectivity being considered in the main experiment analysis, and the red color indicates which side of the synapse is activated first. When the asynchrony is slightly longer than the conduction delay (top), presynaptic activations occur before presynaptic, leading to strengthening of the target synapse, which results in increased effective connectivity A → B. If the asynchrony equals the conduction delay (middle), both sides of the synapse are activated simultaneously, and there is no STDP. When the asynchrony is shorter than the conduction delay (bottom), synaptic efficacy at the target synapse decreases, which results in weaker effective connectivity A → B. Note that the transcallosal connections between A and B are reciprocal; here, we only illustrate the direction from A → B. Supplementary Data Figure S1 shows the pre- to postsynaptic timings in area A for the opposite B → A direction for the same ccPAS protocol (control experiment for directionality). LTD, long-term depression; LTP, long-term potentiation. [Color figure can be viewed at www.neuromodulationjournal.org]