Human cortical slices reveal pulse-number-dependent synaptic plasticity during theta-burst magnetic stimulation

Abstract

Theta-burst transcranial magnetic stimulation is widely used to modulate human brain activity in clinical and experimental settings, yet how clinically relevant stimulation protocols engage synaptic plasticity in human cortical circuits remains poorly understood. Here, we combined controlled magnetic stimulation of viable adult human cortical slices with single-cell electrophysiology to determine whether pulse number constrains synaptic plasticity during intermittent theta-burst stimulation (iTBS). As a functional reference, 10 Hz repetitive magnetic stimulation delivered with 900 pulses robustly potentiated excitatory synaptic transmission in human cortical pyramidal neurons. Similarly, iTBS900 significantly potentiated AMPA receptor-mediated miniature excitatory postsynaptic currents. In contrast, the clinically established 600-pulse iTBS protocol failed to reliably induce detectable synaptic plasticity under otherwise identical stimulation conditions. Paired within-patient experiments confirmed distinct synaptic responses to iTBS600 and iTBS900 in the same human cortical tissue preparations. Together, these findings identify pulse number as an important determinant of theta-burst magnetic stimulation-induced synaptic plasticity in human cortical microcircuits and highlight stimulation dose as a relevant parameter for the design and refinement of therapeutic stimulation protocols.