The long-latency stretch reflex (LLSR) in human elbow muscles probably depends on multiple pathways; one possible contributor is the reticulospinal tract. Here we attempted to induce plastic changes in the LLSR by pairing noninvasive stimuli that are known to activate reticulospinal pathways, at timings predicted to cause spike timing-dependent plasticity in the brainstem. In healthy human subjects, reflex responses in flexor muscles were recorded following extension perturbations at the elbow. Subjects were then fitted with a portable device that delivered auditory click stimuli through an earpiece, and electrical stimuli around motor threshold to the biceps muscle via surface electrodes. We tested the following four paradigms: biceps stimulus 10 ms before click (Bi-10ms-C); click 25 ms before biceps (C-25ms-Bi); click alone (C only); and biceps alone (Bi only). The average stimulus rate was 0.67 Hz. Subjects left the laboratory wearing the device and performed normal daily activities. Approximately 7 h later, they returned, and stretch reflexes were remeasured. The LLSR was significantly enhanced in the biceps muscle (on average by 49%) after the Bi-10ms-C paradigm, but was suppressed for C-25ms-Bi (by 31%); it was unchanged for Bi only and C only. No paradigm induced LLSR changes in the unstimulated brachioradialis muscle. Although we cannot exclude contributions from spinal or cortical pathways, our results are consistent with spike timing-dependent plasticity in reticulospinal circuits, specific to the stimulated muscle. This is the first demonstration that the LLSR can be modified via paired-pulse methods, and may open up new possibilities in motor systems neuroscience and rehabilitation.

Key points Pairing stimulation of a finger flexor or extensor muscle at the motor point with transcranial magnetic stimulation (TMS) of the motor cortex generated plastic changes in motor output. Increases in output were greater in intrinsic hand muscles than in the finger flexor. No changes occurred in the finger extensor. This gradient was seen irrespective of which muscle was stimulated paired with transcranial magnetic stimulation. Intermittent theta‐burst stimulation also produced increases in output, although these were similar across muscles. We suggest that intrinsic hand and flexor muscles have a higher potential to show plasticity than extensors, although only when plasticity is induced by sensory input. This may relate to differences seen in recovery of function in these muscles after injury, such as post‐stroke. Abstract The ability of the motor system to show plastic change underlies skill learning and also permits recovery after injury. One puzzling observation is that, after stroke, upper limb flexor muscles show good recovery but extensors remain weak, with this being a major contributor to residual disability. We hypothesized that there might be differences in potential for plasticity across hand and forearm muscles. In the present study, we investigated this using two protocols based on transcranial magnetic brain stimulation (TMS) in healthy human subjects. Baseline TMS responses were recorded from two intrinsic hand muscles: flexor digitorum superficialis (FDS) and extensor digitorum communis (EDC). In the first study, paired associative stimulation (PAS) was delivered by pairing motor point stimulation of FDS or EDC with TMS. Responses were then remeasured. Increases were greatest in the hand muscles, smaller in FDS and non‐significant in EDC, irrespective of whether stimulation of FDS or EDC was used. In the second study, intermittent theta‐burst rapid rate TMS was applied instead of PAS. In this case, all muscles showed similar increases in TMS responses. We conclude that the potential to show plastic changes in motor cortical output has the gradient: hand muscles > flexors > extensors. However, this was only seen in a protocol that requires integration of sensory input (PAS) and not when plasticity was induced purely by cortical stimulation (rapid rate TMS). This observation may relate to why functional recovery tends to favour flexor and hand muscles over extensors.

Key points Delivering transcranial magnetic brain stimulation over the motor cortex during motor imagination leads to enhanced motor output, which is selective for the muscles primarily involved in the imagined movement. This novel protocol may be useful to enhance function after damage to the motor system, such as after stroke. Abstract Several paired stimulation paradigms are known to induce plasticity in the motor cortex, reflected by changes in the motor evoked potential (MEP) following the paired stimulation. Motor imagery (MI) is capable of activating the motor system and affecting cortical excitability. We hypothesized that it might be possible to use MI in conjunction with transcranial magnetic stimulation (TMS) to induce plasticity in the human motor system. TMS was delivered to the motor cortex of healthy human subjects, and baseline MEPs recorded from forearm flexor, forearm extensor and intrinsic hand muscles. Subjects were then asked to imagine either wrist flexion or extension movements during TMS delivery (n = 90 trials). Immediately after this intervention, MEP measurement was repeated. Control protocols tested the impact of imagination or TMS alone. Flexion imagination with TMS increased MEPs in flexors and an intrinsic hand muscle. Extensor imagination with TMS increased MEPs in extensor muscles only. The control paradigms did not produce significant changes. We conclude that delivering TMS during MI is capable of inducing plastic changes in the motor system. This new protocol may find utility to enhance functional rehabilitation after brain injury.