Evidence for high-fidelity timing-dependent synaptic plasticity of human motor cortex.

Area of Science:

• Neuroscience
• Motor Control
• Synaptic Plasticity

Background:

• Single transcranial magnetic stimulation (TMS) pulses evoke indirect (I)-waves in corticospinal neurons via transynaptic input.
• Repeated stimulus pairs at specific inter-pulse intervals (IPIs) can induce long-term potentiation (LTP)-like increases in excitability.
• I-wave TMS (ITMS) at a 1.5 ms IPI has shown similarities to timing-dependent plasticity models.

Purpose of the Study:

• To investigate if TMS doublets timed *not* to coincide with I-wave firing induce long-term depression (LTD)-like effects.
• To explore the temporal resolution of plasticity mechanisms in the human motor cortex.

Main Methods:

• A crossover study in 10 subjects using TMS doublets with 1.5 ms IPI (ITMS(1.5)) and 2 ms IPI (ITMS(2)).
• Measurement of motor-evoked potential (MEP) amplitude, resting motor threshold (RMT), and short-interval cortical inhibition (SICI) from the first dorsal interosseous (FDI) muscle.
• Comparison of excitability changes following ITMS(1.5) versus ITMS(2).

Main Results:

• ITMS(1.5) significantly increased corticomotor excitability (~60%) for 15 minutes.
• ITMS(2) significantly reduced MEP amplitude (~35%) for 15 minutes, suggesting LTD-like effects.
• Neither RMT nor SICI changed significantly, indicating plasticity at the synaptic level rather than altered membrane excitability or inhibition.

Conclusions:

• Human motor cortex exhibits timing-dependent synaptic plasticity with a temporal resolution in the hundreds of microseconds.
• Precisely timed TMS can induce bidirectional plasticity (LTP/LTD) by targeting I-wave interactions.
• These findings advance our understanding of neuroplasticity and potential therapeutic applications of TMS.