Neuromuscular Stimulation as an Intervention Tool for Recovery from Upper Limb Paresis after Stroke and the Neural Basis
Round 1
Reviewer 1 Report
This is a well-written review paper. It extensively investigated the role of functional neuromuscular stimulation in the upper extremity recovery process. I would like to recommend the publication. But, it can still be further improved by adding more works, like the works of Professor FE Zajac, Professor N Hogen, Professor DP Popovic, Professor Ronald Triolo, Professor William Durfee, etc. I can provide some references to you:
Popovic, Dejan B., Mirjana B. Popovic, and Thomas Sinkjær. "Neurorehabilitation of upper extremities in humans with sensory‐motor impairment." Neuromodulation: Technology at the Neural Interface 5.1 (2002): 54-66.
Daly, Janis J., et al. "Response to upper-limb robotics and functional neuromuscular stimulation following stroke." Journal of rehabilitation research & development 42.6 (2005).
Triolo, Ronald, et al. "Challenges to clinical deployment of upper limb neuroprostheses." Journal of rehabilitation research and development 33 (1996): 111-122.
Smith, Brian T., et al. "Reliability of percutaneous intramuscular electrodes for upper extremity functional neuromuscular stimulation in adolescents with C5 tetraplegia." Archives of physical medicine and rehabilitation 75.9 (1994): 939-945.
Durfee, W. K. "[140] Evaluation of command channels for upper limb neural prostheses." Journal of Rehabilitation Research and Development 28.1 (1991): 116-117
Author Response
Comments from Reviewer 1:
Comment:
But, it can still be further improved by adding more works, like the works of Professor FE Zajac, Professor N Hogen, Professor DP Popovic, Professor Ronald Triolo, Professor William Durfee, etc. I can provide some references to you:
1.Popovic, Dejan B., Mirjana B. Popovic, and Thomas Sinkjær. "[1] of upper extremities in humans with sensory‐motor impairment." Neuromodulation: Technology at the Neural Interface 5.1 (2002): 54-66.
- Daly, Janis J., et al. "Response to upper-limb robotics and functional neuromuscular stimulation following stroke." Journal of rehabilitation research & development42.6 (2005).
Triolo, Ronald, et al. "Challenges to clinical deployment of upper limb neuroprostheses." Journal of rehabilitation research and development 33 (1996): 111-122. tetraplegia
Smith, Brian T., et al. "Reliability of percutaneous intramuscular electrodes for upper extremity functional neuromuscular stimulation in adolescents with C5 tetraplegia." Archives of physical medicine and rehabilitation 75.9 (1994): 939-945. tetraplegia
Durfee, W. K. "[140] Evaluation of command channels for upper limb neural prostheses." Journal of Rehabilitation Research and Development 28.1 (1991): 116-117
Our reply:
Thank you for your valuable advice.
We added 2 references (1, 2) to introduction section (Line 42).
Other papers were not added, because they focused on improvement of tetraplegia using functional electrical stimulation. Our current interest of this review is in improvement of upper limb paresis due to stroke using NMES.
Author Response File: 
Author Response.pdf
Reviewer 2 Report
This is a very interesting and important article. However, I have some suggestions which may improve the quality of this paper.
Since this is a review paper, it is suggested that the authors should cite their own, definitely important work, not as "we" throughout the manuscript.
More figures should be included. For example a figure about NMES would be helpful. Furthermore, the chapter about the underlying mechanisms should be expanded. Neuroimaging studies (PET, fMRI) are important and an image showing the effects of NMES on the brain would be great.
Minor: Are there any sex differences in this kind of studies? Please address in the review.
Line 34-40 More references are needed.
Reword last sentence in line 61.
Author Response
Comments from Reviewer 2:
This is a very interesting and important article. However, I have some suggestions which may improve the quality of this paper.
Comment 1:
Since this is a review paper, it is suggested that the authors should cite their own, definitely important work, not as "we" throughout the manuscript.
Reply to comment 1
Thank you for your suggestion. We agreed with you and changed as following:
Line 166: We changed our recent study into raw data from Obayashi et al.
Line 233: changed into A recent report.
Line 277: we changed We into A study by Obayashi et al.,
Line 301: change into A recent study
Comment 2:
More figures should be included. For example a figure about NMES would be helpful. Furthermore, the chapter about the underlying mechanisms should be expanded. Neuroimaging studies (PET, fMRI) are important and an image showing the effects of NMES on the brain would be great.
Reply to comment 2:
Thank you for your valuable advice. Explanatory figures were added as Figure 7.
Comment 3:
Minor: Are there any sex differences in this kind of studies? Please address in the review.
Our reply:
Thank you for your important comment. We added discussion as following (Line 338-351):
As you know, some reports have pointed out gender difference in functional outcome after a stroke [50] as well as the influence of gender on functional reorganization after a stroke [51]. The former suggested that females had worse functional recovery than males. Furthermore, gender difference in functional outcome was significantly modified by stroke severity, with the differences being prominent for mild and moderate but not for severe strokes. The latter study estimated gender differences in brain excitability in acute phase of stroke, demonstrating gender differences in functional asymmetry of inter-hemispheric excitability in an opposite manner. Therefore, it is plausible that the beneficial effect of NMES or other neuromodulations, such as rTMS and t-DCS, on motor recovery might be influenced by gender difference. However, to the best of our knowledge, there has been no study to focus on gender difference in terms of benefits from neuromodulation. Further studies will be awaited.
Comment 4:
Line 34-40 More references are needed.
Our reply:
We added 6 more references there.
Comment 5:
Reword last sentence in line 61.
Our reply:
We deleted last sentence.
Reviewer 3 Report
Line 44 stroke duration and stroke severity are not considered to be “stimulation parameters” while the remaining items listed would be stimulation parameters. Rephase or remove stoke duration and stroke severity from this sentence.
Line 60 should “values” be replaced by “stimulation parameters” not sure what “values” of NMES is meant to convey
Line 78 exclusion criteria includes 6) peripheral nerve stimulation, 7) sensory stimulation. This needs to be clarified. NMES does stimulate peripheral nerves and would it not be considered a form of sensory stimulation as well? Define better what is more specifically meant by exclusion items 6 & 7, what types of sensory stimulation etc.
Table columns need to be widened and/or width of vertical lines decreased as often the first letter of the text is covered by the dividing vertical line. It looks as if there is some room remaining to expand the overall width of each Table, or in many cases the text in each box can be shifted to the right 1-2 spaces as there is adequate room available in many of the table boxes.
Line 109 & 220 the term “stroke durations” should be rephrased as you are really meaning “time after stroke” or “time poststroke” or “time since stroke”. A stroke is a physiological event and the words “stroke duration” implies more about how long the actual stoke event actually lasted.
Line 111 “PR” was defined in the abstract, but I recommend defining it the first time used in the manuscript body as well.
Figures 2 Define FMA in the legend as you did for Figure 3, and put “PR” after Progress rates in the legend of Figure 4.
Also, in the legend it needs to mentioned whether the error bars are standard deviation or standard error. Standard Deviation is preferred, but either way it needs to be defined in each figure legend. Also, significant differences should be denoted by an “*” in all figures.
Figures 4 & 6 Please remove the word “Figure 4” and “Figure 6” as the legend identifies the figures and removal will make Figs 4& 6 consistent with the other figures.
Below are some minor English/Grammar corrections.
Line 43 & 288 Replace precisely with Specifically or More specifically
Line 55 Possibly such an endeavor may give…
Line 65 toward overcoming motor disability
Line 168-169 Remove the dash after Figure 6a and Figure 6b,c,d
Line 184 These factors are only the tip of the iceberg.
Line 191 replace slower pace with “smaller gains” also later in sentence “there exists”
Line 196 replace as regarding with”With regards” also later in this sentence “there may also be optimal time windows”
Line 200 replace expected with anticipated
Line 232 “our”
Line 270 “Which mode to select”
Line 328 “the most benefits before reaching a plateau”
Line 337 “reorganization of the damaged
Line 348 Seventeen
Line 388 “ to provide stronger”
Line 391 “rPMS is different”
Line 392 “benefits would endure.”
Line 396 replace challenge with knowledge
Line 402 replace would with will be required
Author Response
Comments from reviewer 3
Comment1:
Line 44 stroke duration and stroke severity are not considered to be “stimulation parameters” while the remaining items listed would be stimulation parameters. Rephase or remove stoke duration and stroke severity from this sentence.
Our reply:
I agree to your comment. So, we changed the sentence as following:
heterogeneous stimulation parameters, such as target muscles, doses or durations of treatment, and outcome measures and different conditions such as stroke duration, stroke severity. (Line 17-19, line 43-46)
Comment 2:
Line 60 should “values” be replaced by “stimulation parameters” not sure what “values” of NMES is meant to convey
Our reply:
We changed value into usefulness. (Line 61)
Comment 3:
Line 78 exclusion criteria includes 6) peripheral nerve stimulation, 7) sensory stimulation. This needs to be clarified. NMES does stimulate peripheral nerves and would it not be considered a form of sensory stimulation as well? Define better what is more specifically meant by exclusion items 6 & 7, what types of sensory stimulation etc.
Our reply:
We think that NMES transcutaneously stimulate mainly motor points of target muscles at the level above the motor threshold, but not peripheral nerve (for example, invasive (implanted, percutaneous) stimulation, PNS at the level above the sensory threshold but bellow the motor threshold) nor sensory stimulation (for example, somatosensory stimulation, priming, mobilization and tactile stimulation, proprioceptive stimulation, transcutaneous vagus nerve stimulation, cervical spine afferent stimulation). We added in method section (Line 77-84)
Comment 4:
Table columns need to be widened and/or width of vertical lines decreased as often the first letter of the text is covered by the dividing vertical line. It looks as if there is some room remaining to expand the overall width of each Table, or in many cases the text in each box can be shifted to the right 1-2 spaces as there is adequate room available in many of the table boxes.
Our reply:
Thank you for your valuable advice. We changed into widened columns of Table 1.
Comment 5:
Line 109 & 220 the term “stroke durations” should be rephrased as you are really meaning “time after stroke” or “time poststroke” or “time since stroke”. A stroke is a physiological event and the words “stroke duration” implies more about how long the actual stoke event actually lasted.
Our reply:
We agree with you. We changed stroke duration into “time since stroke”. (Lines 111, 112, and 223)
Comment 6:
Line 111 “PR” was defined in the abstract, but I recommend defining it the first time used in the manuscript body as well.
Our reply:
We described the definition of PR in the introduction section. (Line 44-45)
Comment 7:
Figures 2 Define FMA in the legend as you did for Figure 3, and put “PR” after Progress rates in the legend of Figure 4.
Our reply: We changed it.
Comment 8:
Also, in the legend it needs to mentioned whether the error bars are standard deviation or standard error. Standard Deviation is preferred, but either way it needs to be defined in each figure legend. Also, significant differences should be denoted by an “*” in all figures.
Our reply:
The error bars express standard errors. Significant differences were denoted by * in figures 3 and 4.
Comment 9:
Figures 4 & 6 Please remove the word “Figure 4” and “Figure 6” as the legend identifies the figures and removal will make Figs 4& 6 consistent with the other figures.
Our reply:
We removed it.
Comment 10:
Below are some minor English/Grammar corrections.
Line 43 & 288 Replace precisely with Specifically or More specifically
Line 55 Possibly such an endeavor may give…
Line 65 toward overcoming motor disability
Line 168-169 Remove the dash after Figure 6a and Figure 6b,c,d
Line 184 These factors are only the tip of the iceberg.
Line 191 replace slower pace with “smaller gains” also later in sentence “there exists”
Line 196 replace as regarding with”With regards” also later in this sentence “there may also be optimal time windows”
Line 200 replace expected with anticipated
Line 232 “our”
Line 270 “Which mode to select”
Line 328 “the most benefits before reaching a plateau”
Line 337 “reorganization of the damaged
Line 348 Seventeen
Line 388 “ to provide stronger”
Line 391 “rPMS is different”
Line 392 “benefits would endure.”
Line 396 replace challenge with knowledge
Line 402 replace would with will be required
Our reply:
Thank you for your kind corrections. We are willing to change it all. In addition, further English editing has been done by a native English -speaker again.
