A Distal–Proximal Gradient of Hebbian Plasticity in the Human Arm

Corticospinal–motoneuronal connections are more prominent in distal than proximal upper-limb muscles, but whether this anatomical specialization influences the capacity for activity-dependent plasticity remains unknown. Here, we tested whether Hebbian stimulation targeting corticospinal–motoneuronal connections, induces muscle-specific plasticity in proximal and distal arm muscles in healthy humans. We applied a spike-timing-dependent stimulation protocol comprising 180 paired stimuli, with transcranial magnetic stimulation timed to evoke corticospinal volleys 1–2 ms before motoneurons were antidromically activated by electrical stimulation of the brachial plexus for the biceps brachii or the ulnar nerve for the first dorsal interosseous (FDI). Corticospinal excitability was assessed by measuring motor-evoked potentials (MEPs) before and 30 min after stimulation. Hebbian stimulation increased MEP amplitudes in both muscles, but facilitation was greater in the FDI than in the biceps. Because resting motor threshold was higher for the biceps than for the FDI, in a control experiment we matched stimulation intensities between muscles. Under these conditions, Hebbian stimulation continued producing greater facilitation in the FDI than in the biceps, indicating that the difference was not attributable to stimulation intensity. Moreover, changes in MEP amplitude were associated with maximal MEP size in the FDI but not in the biceps, whereas no muscle-specific association was observed with peripheral responses (M-max), supporting a stronger relationship between corticospinal drive and Hebbian plasticity in the distal than in the proximal arm muscle. Together, these findings identify a distal-to-proximal gradient in Hebbian plasticity across arm muscles, which may contribute to optimizing targeted neuromodulation approaches for upper-limb rehabilitation.