Spike Timing-Dependent Plasticity in the Long-Latency Stretch Reflex Following Paired Stimulation from a Wearable Electronic Device.

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. SIGNIFICANCE STATEMENT: This report is the first demonstration that the long-latency stretch reflex can be modified by repeated, precisely timed pairing of stimuli known to activate brainstem pathways. Furthermore, pairing was achieved with a portable electronic device capable of delivering many more stimulus repetitions than conventional laboratory studies. Our findings open up new possibilities for basic research into these underinvestigated pathways, which are important for motor control in healthy individuals. They may also lead to paradigms capable of enhancing rehabilitation in patients recovering from damage, such as after stroke or spinal cord injury.