Title: Pre-synaptic modulation of afferent feedback in the macaque spinal cord does not modulate with cycles of peripheral oscillations around 10 Hz Running title: Lack of rapid modulation in pre-synaptic inhibition Authors:

CC-BY-NC-ND 4.0 International license peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was not. KEY POINTS  Presynaptic inhibition of afferent feedback is known to modulate during voluntary movements  Spinal interneuron circuits have previously been demonstrated to modulate activity with the phase of ~10 Hz physiological tremor, in a manner which promotes cancellation of oscillations and hence tremor reduction  In this study, we investigated whether afferent pre-synaptic inhibition could also modulate on the faster timescale of tremor oscillations  Although we found evidence for task-dependent modulation of pre-synaptic inhibition (a timescale of around 1 s), there was no evidence for modulation with the phase of tremor (timescale around 100 ms)  The results suggest that pre-synaptic inhibition modulates afferent feedback gain dependent on overall motor state, rather than in response to moment-by-moment fluctuations in output (116 words). CC-BY-NC-ND 4.0 International license peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was not. ABSTRACT Spinal interneurons are partially phase-locked to physiological tremor around 10Hz. The phase of spinal activity is approximately opposite to descending drive to motoneurons, leading to partial phase cancellation and tremor reduction. Pre-synaptic inhibition of afferent feedback has been demonstrated to increase during voluntary movements, but it is not known whether it tracks more rapid fluctuations in output such as during tremor. In this study, we recorded dorsal root potentials (DRPs) from the C8 and T1 roots in two macaque monkeys following intra-spinal micro-stimulation (1-3Hz, 30-100µA), whilst the animals performed an index finger flexion task which elicited substantial peripheral oscillations around 10Hz. Forty one responses were identified with latency <5ms; these were narrow (mean width 0.59 ms), and likely resulted from antidromic activation of afferents following stimulation near terminals. Significant modulation during task performance occurred in 16/41 responses, reflecting terminal excitability changes generated by pre-synaptic inhibition (Wall's excitability test). Stimuli falling during large-amplitude 8-12Hz oscillations in finger acceleration were extracted, and sub-averages of DRPs constructed for stimuli delivered at different oscillation phases. Although some apparent phase-dependent modulation was seen, this was not above the level expected by chance fluctuation. We conclude that although pre-synaptic inhibition modulates over the timescale of a voluntary movement (around one second), it does not follow more rapid changes in motor output. This suggests that pre-synaptic inhibition is not part of the spinal systems for …