Why should phase-amplitude CFC, and theta/HG CFC in particular, show any relation to learning and memory? One clue comes from the literature focused on the induction of long-term synaptic potentiation (LTP). Several distinct protocols for inducing LTP are used by experimentalists, but one of the most effective uses a high-frequency (~100 Hz) burst of 6–7 stimulations, with bursts repeated at a slower (~3–5 Hz) interburst interval [76, 77]. This pattern corresponds to a high gamma burst recurring at theta rates – exactly what is produced by strong theta/HG phase-amplitude CFC. Furthermore, shifting the timing of such a burst relative to the phase of the ongoing endogenous theta rhythm can depotentiate previously-established LTP or induce long-term depression (LTD) [78, 79]. That is, artificial LTP/LTD induction protocols may be tapping into a naturally occurring process whereby synaptic strength is regulated by theta/HG CFC. Support for this hypothesis also comes from the observation that theta-burst transcranial magnetic stimulation (TMS) at the scalp is the most effective protocol for potentiating the motor cortical evoked potential [80]. These results, combined with the fact that CFC
