Dependence of cortical neuronal strength-duration properties on TMS pulse shape

•The TMS pulse shape and selection of pulse widths influences the properties of the cortical strength-duration curve.•Larger hyperpolarizing TMS pulse trailing phase increases motor thresholds resulting in longer cortical strength-duration time constant and smaller rheobase.•Modulation of transient sodium channels by the trailing hyperpolarising phase is likely to mediate the effects of TMS pulse shape on cortical strength-duration curve properties. The aim of present study was to explore the effects of different combinations of transcranial magnetic stimulation (TMS) pulse width and pulse shape on cortical strength-duration time constant (SDTC) and rheobase measurements. Resting motor thresholds (RMT) at pulse widths (PW) of 30, 45, 60, 90 and 120 µs and M−ratios of 0.2, 0.1 and 0.025 were determined using figure-of-eight coil with initial posterior-to-anterior induced current. The M−ratio indicates the relative phases of the induced current with lower values signifying a more unidirectional stimulus. Strength-duration time constant (SDTC) and rheobase were estimated for each M−ratio and various PW combinations. Simulations of biophysically realistic cortical neuron models assessed underlying neuronal populations and physiological mechanisms mediating pulse shape effects on strength-duration properties. The M−ratio exerted significant effect on SDTC (F(2,44) = 4.386, P = 0.021), which was longer for M−ratio of 0.2 (243.4 ± 61.2 µs) compared to 0.025 (186.7 ± 52.5 µs, P = 0.034). Rheobase was significantly smaller when assessed with M−ratio 0.2 compared to 0.025 (P = 0.026). SDTC and rheobase values were most consistent with pulse width sets of 30/45/60/90/120 µs, 30/60/90/120 µs, and 30/60/120 µs. Simulation studies indicated that isolated pyramidal neurons in layers 2/3, 5, and large basket-cells in layer 4 exhibited SDTCs comparable to experimental results. Further, simulation studies indicated that reducing transient Na+ channel conductance increased SDTC with larger increases for higher M−ratios. Cortical strength-duration curve properties vary with pulse shape, and the modulating effect of the hyperpolarising pulse phase on cortical axonal transient Na+ conductances could account for these changes, although a shift in the recruited neuronal populations may contribute as well. The dependence of the cortical strength-duration curve properties on the TMS pulse shape and pulse width selection underscores the need for consistent measurement methods across