Changes in Electroencephalography by Modulation of Interferential Current Stimulation

Round 1

Reviewer 1 Report

Extensive amount of work and improvements have been made! Now I am sure that this work meets criteria given the journal-level papers.

Author Response

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Reviewer 2 Report

The authors provided a careful revision of the manuscript with more graphs and extended bibliography.  Therefore, I consider that the manuscript has been upgraded to be published in Applied Science.

Author Response

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Reviewer 3 Report

I do not have any further comments.

Author Response

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Reviewer 4 Report

I thank the authors for their responses. However, after a second reading, I still think that whatever the authors interpret as significant (even if, according to them, only in practical, rather than statistical terms) is only driven by a baseline difference, and no conclusions can be drawn whatsoever. Further, the authors' attempt to better visualise the data by the bar graphs was not successful, as a plot with this many bars bears no relevant use. I suggest the authors replicate their study first, carefully controlling for baseline differences. In its current state, the data do not provide the smallest clue to answer the research question.

Author Response

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This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.

Round 1

Reviewer 1 Report

• Careful inspection of the results reported in the tables makes me think that the significant group effect in the beta waves is only driven by a baseline difference between the 3 groups (lower values for HF-LI group already pre-test). I think the results would only be interesting in the case of an interaction of group and period because that would potentially quantify comparable baseline levels but differential levels post-test. Now, it is impossible to say whether IFC effectively modulates anything or not, as the baseline differences obstruct any conclusions.
• The quality of the figures is really low, particularly since the dimensions are off.
• I think the results reported in the tables would be more comprehensible in a graph. Also, what is the reasoning for splitting the analyses by electrodes? Averaging across electrodes, with electrode as a factor, may massively declutter the results.
• I think many claims in the discussion do not follow from the results:
  • “This indicated that appropriate electrical stimulation can activate the frontal lobe and that brainwave activation induced by an LF-HI stimulus may effectively enhance cognitive function.” See my first comment. Assuming cognitive function improvement based on the current results seems a bit of a stretch. Also, isn’t the premise how motor functions may be modulated?
  • “The results of this study indicate that in all three groups, the various intensities and frequencies stimulated different areas of the brain and provided various levels of brainwave activation.” What do the authors base this claim on? In my reading, this refers to Gamma waves, but the only effect they found was a group difference for Beta waves?

“However, brain mapping identified activation of theta waves after the intervention, depending on the stimulation parameters.” I assume the authors are referring to Figure 4 here. However, this is just a different representation of the (non-significant) results reported in Table 3, so I don’t think their claim is warranted.

Reviewer 2 Report

This paper tests the effect of IFC stimulation on the human brain under various conditions, namely HF-LI, LF-HI, and HF-HI. It finds significant brainwave changes in the beta band, but no changes in the theta and gamma bands. The paper is clearly written. It can be published as is. I have no further comments.

Reviewer 3 Report

The authors provide a deep and thought-out analysis of three different type of electrical stimulation that can affect brainwave activation. However, clear differences are only found on ɣ-waves. The data is presented in tables which are difficult to look, I believe that making use of graphics will facilitate the understanding of the paper for the readers. Also, it would be nice to present a more detailed discussion regarding the differences observed on the different stimulations.  

Reviewer 4 Report

Very interesting paper of an exellent qaulity. It was a pleasure to read it. I would only expand a little bit literature background as I did not see any up-to date citations (from 2019 onwards).

Reviewer 5 Report

The manuscript “Changes in Brainwave Modulation by Interferential Current Stimulation” by Cho and Kim studied changes in 8-channel EEG of healthy adults in response to three levels of interferential current stimulation. Results showed significant increase in relative beta power observed in frontal and central electrodes. There is some existing research about interferential current (IFC) stimulation investigating, for example, the effect of altered IFC on nerve excitation, but not investigating the change of brainwaves in terms of power spectra of different frequency bands. In this sense, the current study presented in the manuscript show valuable results, there are several major flaws that make the manuscript and the authors’ goals hard to follow logically.

1. Though there have not been many studies on IFC stimulation effects on EEG, there have been several that reported effects of electrical stimulation (TENS and others) in EEG. It would be helpful and more holistic if the authors include these studies in the introduction as a review of using EEG as a quantitative measure of stimulation.
2. Pain was briefly mentioned several times in the manuscript. However, it is unclear whether pain is actually relevant to this study. This study analyzed EEG response to IFC in healthy subjects and did not report whether the stimulation applied around the thoracic spines elicit any innocuous or noxious sensations. Therefore, the authors’ statement in lines 271-272 “the changes in brain waves in this study confirm that painful stimuli can later the EEG signal in various ways” seem to be too bold of a move, as the experiment itself did not involve pain.
3. Though there is value in quantitatively characterizing EEG responses to IFC stimulation, the authors did not clearly explain the goals of the experiment. Why only beta, gamma and theta bands were selected for analysis?
4. Overall, the results section only has one paragraph of text. It is not very clear what exactly the EEG effects are in response to the three types of stimulation. The presentation of results could also be improved. For example, results from tables 2 to 4 can be better presented if a graphical approach (barplots) is used rather than listing all the numbers out.
5. The authors made the conclusion: “confirmed that electrical stimulation significantly affects brainwave activation, and the psychological stability of the patient during rehabilitation, which could not be previously quantified” However, the study only showed some statistically significant difference in EEG before and after IFC stimulation and did not include any patient studies nor experiments or measures that indicated “psychological stability”. It is worrisome that the authors claimed, based on current results, that e-stim affects the psychological stabilities of patients during rehabilitation. Furthermore, the patient population and the type of rehabilitation are not specified either.­­
6. Related to the previous comment, in the Introduction section (line 22-25) “This study provides a foundation for future applications in selectively treating patients based on their unique characteristics and changes. These results could be utilized in patient rehabilitation by controlling feedback at a proper stimulation level depending on the patient’s condition.” It might be better to provide a brief description on what unique characteristics and changes are. Otherwise this sentence seems not containing much information to me.
7. The Discussion section seems to be extensive, but the relevancy between studies cited and results from the current study is unclear. Overall, based on the use of IFC stimulation, the authors could make a better case for using EEG as a measure of stimulation response in future patient treatment. Examples include:
   1. Line 206-211: It is unclear whether this section was a general statement of IFC or specifically pertaining to the current study.
   2. Line 233-234: this sentence seems irrelevant. How does increased cerebral blood flow relate to the context of this manuscript? More in detail, how was these patients' "enhancement of cognitive function" achieved?
   3. Line 235-236: The reference cited here studied alpha wave. But in the Results section, the authors did not present any results in the alpha band. The notion of “appropriate electrical stimulation can activate the frontal lobe and that brainwave activation induced by an LF-HI stimulus may effectively enhance cognitive function” was not fully supported or explained in this manuscript. Why LF-HI stimulus in particular? In which frequency band?
   4. Line 246: What did the study by Sekimoto et al. (published 2000) do that led them to show no laterality in EEG? Sekimoto’s study seems to be a sleep study and the main results are in delta wave, a frequency band not presented by the authors. In addition, the abstract from Sekimoto et al. indicated that they only observed no laterality “in parietal, occipital anterotemporal, and postero-temporal regions.” How does this affect the authors making the connection between Sekimoto’s study and this current study?
   5. Line 258-263: How is this overview of theta wave related to the current study?
   6. Line 273-276 “Nevertheless, the EEG data failed to identify significant changes in the alpha and beta bands in the HF-HI stimulus group. A previous study inferred that HF-HI electrical stimulation leads to the secretion of endogenous opioids within the central nervous system that result in downward pain control [39].” There seems to be a logical gap between these two sentences. The way to compose and express the idea can be improved.
   7. Line 278-280 How did the authors reach this statement?
8. Line 284-285 What does “brainwave activation needs to be measured at each brainwave band” mean? In general, each EEG frequency band was extracted using band pass filters with the raw EEG data. Future direction on age groups – it seems that the study presented in this manuscript recruited young adults in early twenties (if second content row of Table 1 is age). Age of participant, thus, does not introduce much variability to this current study.

 

Methodology:

1. In the abstract and introduction, the authors mentioned “brain signals from the motor cortex”. Why specifically measuring from the motor cortex?
2. This study calculated power of each frequency band. Why is power spectral density used as a metric? What are its benefit over evoked potential, a method that is widely used in studying brain response to stimulation?
3. The experimental paradigm was not clearly explained in the manuscript. In lines 118-119, the authors mentioned 10 epochs of data with each 30-second-long. However, in line 148, it seems like the recorded data length is 180 s. This doesn’t seem to follow 10 epochs and 30 s each. How were each epoch determined?
4. What were the stimulation waveform and pulse width? How were stimulation parameters determined (lines 160-161)?
5. Table 1: What does each row mean? What do F and p stand for, and how were they calculated?
6. Analytical method:
   1. Line 143: How were “artifacts removed”? Was it through existing algorithm such as automatic artifact removal or independent component analysis?
   2. Line 177: The authors mentioned Mauchly’s sphericity test in the Results section, but this method was not explained in the Methods section.

 

Vague description and unclear logic:

1. line 67-69 “However, electrical current conductivity is evenly applied to all tissues. Therefore, the actual acquired brainwave response patterns to maximum electrical stimulation are reportedly various and irregular [9].” It is hard for me to understand the underlying knowledge/logic between the first and the second sentence and the causal relationship between them. Further explanation will be better.
2. Line 287-289 “Moreover, careful preparation of subjects is required to ensure that the results are reliable, as psychogenic causes have a considerable impact on cerebral blood flow velocity, which is related to changes in the autonomic nervous system [41]” I did not understand what “careful preparation of subjects” really meant and what kind of preparation is required to ensure the results are reliable. The reliability is not defined either.

 

The manuscript has a few places that need editorial and grammatical changes. Some examples are included below:

1. Page 1:
   1. Line 33 “neural membranes” should be “neuronal membranes”
   2. Line 35 “which affect” should be “which affects”
2. Page 3:
   1. Line 108: 256 Hz/channels/s. Hertz is defined as cycles per second. What does “s” stand for in this sampling frequency? If it stands for seconds, the “s” should be deleted.
   2. Line 109-110: “0.6-Hz low frequency pass filter, 46-Hz high frequency pass filter, and 60-Hz notch filter”. Articles are needed here.
3. Tables 2-4: hard to follow. Might work better if presented as barplots.
4. Page 11:
   1. Figure 4: the color bars are not lined with the mapped activity figure. Labels of columns of Figure 4 and Figure 5 are “Pre” “Post” “Post 30” without explanations in captions and not consistent with previous notations in Table 2-4 as “Pre-test” “Post-test” “Post-30”.
5. Page 12:
   1. Line 242 “…may be cause by external stimulation” -> “caused”
   2. Line 269: “When pain control electrical …” -> “pain-controlled”?