Altered regulation of Ia afferent input during voluntary contraction in humans with spinal cord injury
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Evaluation Summary:
This paper will be of interest to basic and clinical neurophysiologists who are focused on understanding neural mechanisms that influence recovery following spinal cord injury (SCI). The work compares the afferent regulation of motor output to soleus muscle in controls and individuals with SCI. The results indicate differences between groups such that there is less facilitation in the SCI group during muscle contraction.
(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #3 agreed to share their name with the authors.)
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Abstract
Sensory input converging on the spinal cord contributes to the control of movement. Although sensory pathways reorganize following spinal cord injury (SCI), the extent to which sensory input from Ia afferents is regulated during voluntary contraction after the injury remains largely unknown. To address this question, the soleus H-reflex and conditioning of the H-reflex by stimulating homonymous [depression of the soleus H-reflex evoked by common peroneal nerve (CPN) stimulation, D1 inhibition] and heteronymous (d), [monosynaptic Ia facilitation of the soleus H-reflex evoked by femoral nerve stimulation (FN facilitation)] nerves were tested at rest, and during tonic voluntary contraction in humans with and without chronic incomplete SCI. The soleus H-reflex size increased in both groups during voluntary contraction compared with rest, but to a lesser extent in SCI participants. Compared with rest, the D1 inhibition decreased during voluntary contraction in controls but it was still present in SCI participants. Further, the FN facilitation increased in controls but remained unchanged in SCI participants during voluntary contraction compared with rest. Changes in the D1 inhibition and FN facilitation were correlated with changes in the H-reflex during voluntary contraction, suggesting an association between outcomes. These findings provide the first demonstration that the regulation of Ia afferent input from homonymous and heteronymous nerves is altered during voluntary contraction in humans with SCI, resulting in lesser facilitatory effect on motor neurons.
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Author Response
Reviewer #2 (Public Review):
The authors clearly show that the regulation of Ia afferent input is altered during voluntary movements in individuals with chronic, incomplete spinal cord injury. This is informative as afferent stimulation (epidural or transcutaneous) is a principal research strategy to enable voluntary movement in individuals with chronic spinal cord injury. A subset of enrolled individuals was tested with adjusted stimulus intensities to match intact individuals' responses at rest; however, the criteria for the selection of this group of subjects were not described.
We clarified that the subgroup of subjects tested with adjusted stimulus intensities was the group of individuals that was able to return for this additional testing. This information was added to the manuscript.
The correlation graphs …
Author Response
Reviewer #2 (Public Review):
The authors clearly show that the regulation of Ia afferent input is altered during voluntary movements in individuals with chronic, incomplete spinal cord injury. This is informative as afferent stimulation (epidural or transcutaneous) is a principal research strategy to enable voluntary movement in individuals with chronic spinal cord injury. A subset of enrolled individuals was tested with adjusted stimulus intensities to match intact individuals' responses at rest; however, the criteria for the selection of this group of subjects were not described.
We clarified that the subgroup of subjects tested with adjusted stimulus intensities was the group of individuals that was able to return for this additional testing. This information was added to the manuscript.
The correlation graphs clearly show two disparate population responses, so it is not clear that there is a strong correlation between inhibition or facilitation of the H-reflex independent of spinal cord injury. As the adjusted stimulus responses showed the function of the circuit in injured individuals, why were those measures not used in the correlation analysis?
The reviewer raises a good point. Please see our response to point #5 from reviewer #1. We did not observed a correlation between changes in H-reflex size and the D1 inhibition and FN facilitation in the adjusted responses. This could be related, at least in part, to the smaller number of participants tested in the adjusted condition. This information was added to the manuscript.
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Evaluation Summary:
This paper will be of interest to basic and clinical neurophysiologists who are focused on understanding neural mechanisms that influence recovery following spinal cord injury (SCI). The work compares the afferent regulation of motor output to soleus muscle in controls and individuals with SCI. The results indicate differences between groups such that there is less facilitation in the SCI group during muscle contraction.
(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #3 agreed to share their name with the authors.)
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Reviewer #1 (Public Review):
The authors sought to define how inputs from type Ia sensory fibers change after spinal cord injury (SCI). The model used to answer this question involved measuring the H-reflex of participants with SCI or able-bodied controls at rest or during a voluntary contraction at 30% of maximal EMG activity. These studies were done with/without stimulation of either the common peroneal nerve (D1 inhibition) or femoral nerve just prior to measuring H-reflexes. Participants with SCI were motor-incomplete with AIS C or D injuries. Participants taking anti-spasticity medications were asked to discontinue these prior to evaluation. Some strengths of the study were the number of participants in the SCI group, the effort to ensure that differences between SCI and controls as far as baseline physiological parameters did not …
Reviewer #1 (Public Review):
The authors sought to define how inputs from type Ia sensory fibers change after spinal cord injury (SCI). The model used to answer this question involved measuring the H-reflex of participants with SCI or able-bodied controls at rest or during a voluntary contraction at 30% of maximal EMG activity. These studies were done with/without stimulation of either the common peroneal nerve (D1 inhibition) or femoral nerve just prior to measuring H-reflexes. Participants with SCI were motor-incomplete with AIS C or D injuries. Participants taking anti-spasticity medications were asked to discontinue these prior to evaluation. Some strengths of the study were the number of participants in the SCI group, the effort to ensure that differences between SCI and controls as far as baseline physiological parameters did not explain the differences in effects of Ia fibers, and the inclusion of a control group. The results showed that in persons with SCI, D1 inhibition of the H-reflex was decreased by voluntary soleus muscle contraction in controls but not persons with SCI whereas femoral nerve stimulation increased the H-reflex during voluntary contraction in controls but not persons with SCI. The results thus elucidate changes in the effects of proprioceptive signals activated by muscle stretch on motor neuron activity in persons with motor-incomplete SCI that depend on whether the proprioceptive input comes from the extensor muscle being contracted or another extensor muscle from the same limb. The large, open question posed by these studies is why there is discordance in results observed with the femoral nerve and common perineal nerve conditioning paradigms when examining H-reflexes during submaximal soleus contraction.
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Reviewer #2 (Public Review):
The authors clearly show that the regulation of Ia afferent input is altered during voluntary movements in individuals with chronic, incomplete spinal cord injury. This is informative as afferent stimulation (epidural or transcutaneous) is a principal research strategy to enable voluntary movement in individuals with chronic spinal cord injury. A subset of enrolled individuals was tested with adjusted stimulus intensities to match intact individuals' responses at rest; however, the criteria for the selection of this group of subjects were not described.
The correlation graphs clearly show two disparate population responses, so it is not clear that there is a strong correlation between inhibition or facilitation of the H-reflex independent of spinal cord injury. As the adjusted stimulus responses showed the …
Reviewer #2 (Public Review):
The authors clearly show that the regulation of Ia afferent input is altered during voluntary movements in individuals with chronic, incomplete spinal cord injury. This is informative as afferent stimulation (epidural or transcutaneous) is a principal research strategy to enable voluntary movement in individuals with chronic spinal cord injury. A subset of enrolled individuals was tested with adjusted stimulus intensities to match intact individuals' responses at rest; however, the criteria for the selection of this group of subjects were not described.
The correlation graphs clearly show two disparate population responses, so it is not clear that there is a strong correlation between inhibition or facilitation of the H-reflex independent of spinal cord injury. As the adjusted stimulus responses showed the function of the circuit in injured individuals, why were those measures not used in the correlation analysis?
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Reviewer #3 (Public Review):
The authors were investigating the influence of Ia afferent fibers on the excitability of motor neurons innervating soleus using two different methodologies. One method involves conditioning the common peroneal nerve in advance of the tibial nerve stimulation which is shown to suppress the H-reflex via presynaptic inhibition. The other method involves conditioning the femoral nerve following stimulation of the tibial nerve that acts to facilitate the H-reflex. Two groups were compared; individuals with spinal cord injury and uninjured controls. Two conditions were compared; muscle at rest and muscle contracting at 30% MVC. Both groups showed reduced H-reflex during common peroneal conditioning during a contraction but the SCI group showed less of this reduction. For the femoral conditioning, only the control …
Reviewer #3 (Public Review):
The authors were investigating the influence of Ia afferent fibers on the excitability of motor neurons innervating soleus using two different methodologies. One method involves conditioning the common peroneal nerve in advance of the tibial nerve stimulation which is shown to suppress the H-reflex via presynaptic inhibition. The other method involves conditioning the femoral nerve following stimulation of the tibial nerve that acts to facilitate the H-reflex. Two groups were compared; individuals with spinal cord injury and uninjured controls. Two conditions were compared; muscle at rest and muscle contracting at 30% MVC. Both groups showed reduced H-reflex during common peroneal conditioning during a contraction but the SCI group showed less of this reduction. For the femoral conditioning, only the control group showed facilitation during a contraction while both groups showed facilitation at rest. The data indicate that individuals with SCI have reduced facilitation of motor output during voluntary contraction.
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