Sensitivity to Instruction Strategies in Motor Learning Is Predicted by Anterior–Posterior TMS Motor Thresholds

<b>Background:</b> The impact of exogenous explicit knowledge on early motor learning is highly variable and may be influenced by excitability within the procedural sensorimotor network. Recent transcranial magnetic stimulation (TMS) studies suggest that variability in interneuron recruitment by anterior-posterior (AP) currents is linked to differences in functional connectivity between premotor and motor regions. <b>Objectives:</b> This study used controllable pulse parameter TMS (cTMS) to assess how AP-sensitive interneuron excitability interacts with explicit knowledge to influence motor learning. <b>Methods</b>: Seventy-two participants were grouped as AP-positive (n = 36) and AP-negative groups (n = 36) based on whether an AP threshold could be obtained before reaching maximal stimulator output. A narrow (30 µs) stimulus was employed to target the longest latency corticospinal inputs selectively. Participants then practiced a continuous visuomotor tracking task and completed a delayed retention test. Half of each group received explicit knowledge of a repeated sequence embedded between random sequences. Random sequence tracking performance assessed general sensorimotor efficiency; repeated sequence performance assessed sequence-specific learning. <b>Results</b>: Both AP₃₀-positive participants, with and without explicit knowledge, and the AP₃₀-negative without explicit knowledge demonstrated similar improvements in sensorimotor efficiency driven by offline consolidation. However, AP₃₀-negative participants given explicit instruction exhibited significantly reduced improvement in sensorimotor efficiency, primarily due to impaired offline consolidation. <b>Conclusions</b>: These findings suggest that individuals with low excitability in long-latency AP-sensitive inputs may be more vulnerable to interference from explicit instruction. The current results highlight the importance of accounting for individual differences in interneuron excitability when developing instructional strategies for motor learning.