Randomising stimulus intensity improves the variability and reliability of the assessment of corticospinal excitability

•Input/output curves from the right first dorsal interosseous muscle in blocked, random-blocked or inter-trial randomisation modes are highly correlated.•An inter-trial randomisation protocol resulted in less variability than blocks of increasing intensity or randomised blocks.•Reliability, as assessed through stimulations on successive days in a sub-cohort of participants, was highest for the inter-trial randomisation protocol. Advances in the control of transcranial magnetic stimulation (TMS) have enabled greater randomisation of stimulus intensity. It is unclear if such randomisation improves assessments of corticospinal excitability. We recorded the amplitude of TMS-induced motor evoked potentials (MEPs) from the first dorsal interosseous muscle of eleven participants, during three TMS protocols: blocks of increasing intensity (IB), randomised blocks (RB) and inter-stimulus randomisation (IR). Stimulus intensities from 90 to 140% of active motor threshold described corticospinal input-output (I/O) properties. The experiment was repeated in five participants. Although MEP amplitudes did not differ between IB, RB and IR stimulation protocols, variability was lowest in the IR protocol, compared to IB and RB protocols. Reliability was highest in the IR protocol, compared to IB and IR protocols. Randomising TMS intensity between each trial produces less variable and more reliable estimates of corticospinal excitability than previously used blocked protocols and produces the same I/O measures. Inter-trial randomization of TMS intensities appears to be the most reliable method for constructing I/O curves at multiple time points and decreases the variability of responses.