Transcranial Photobiomodulation for Executive Function in Bipolar Disorder (TPEB): Study Protocol

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

A.        The proficiency in the English language in this study is fine.

B.        The title effectively captures the scope of the study.

C.        Abstract: The abstract is well written. However, it is unclear what are treatments 1 and 2 to 5. That part is a little bit confusing.

D.        Introduction: The introduction is adequately written. It would be nice to mention what BDP1 and 2 are (line 38).

It would be beneficial to mention somewhere earlier in the text who and what will be the sham group.

„Its safety was demonstrated in 1,410 acute stroke 107 patients [57,58]“. - Is there a newer reference (newer data)?

“...with evidence for cognitive benefits in both healthy individuals and patients with neuropsychiatric conditions”. Are there any adverse effects associated with this type of treatment?

Could you please change 1500 ms to seconds?

Overall, this paper is written appropriately, it is well-structured, technically sound, and interesting to read. Due to the attractiveness of the subject, it is likely to attract a wide readership, therefore, the paper can be considered for publication after correction.

 

 

 

Author Response

Comment 1: Abstract: The abstract is well written. However, it is unclear what treatments 1 and 2 to 5 are. That part is a little bit confusing. 
Response 1: Thank you for your observation. We have revised the abstract to clearly specify what treatments 1, 2, 3, 4, and 5 are. 

Comment 2: Introduction: The introduction is adequately written. It would be nice to mention what BDP1 and 2 are (line 38). 
Response 2: We have revised the introduction to include a brief explanation of the main differences between BDP1 and BDP2 on lines 40 and 41.  
 
Comment 3: It would be beneficial to mention somewhere earlier in the text who and what will be the sham group. 
Response 3: We have updated the text to clearly define the sham group. This information is now included to provide clarity on the study design. Additionally, we have updated Figure 4 to reflect these changes. 
 
Comment 5: “Its safety was demonstrated in 1,410 acute stroke 107 patients [57, 58].” – Is there a newer reference (newer data)? 
Response 5: We have conducted a literature review and identified newer references. The manuscript has been updated to include these and other relevant references. 
 
Comment 6: “…with evidence for cognitive benefits in both healthy individuals and patients with neuropsychiatric conditions.” Are there any adverse effects associated with this type of treatment? 
Response 6: We have added a few sentences discussing the potential adverse effects associated with the treatment (lines 112-115).  
 
Comment 7: Could you please change 1500 ms to seconds? 
Response 7: Thank you for this suggestion. We agree that a scale in seconds is easier to conceptualize. Concurrently, because computerized behavioral tasks are customarily described in more granular scales, we decided to describe the procedure using milliseconds. For this reason, we prefer to keep that statement on that same scale. 
 
Comment 8: Overall, this paper is written appropriately, it is well-structured, technically sound, and interesting to read. Due to the attractiveness of the subject, it is likely to attract a wide readership, therefore, the paper can be considered for publication after correction. 
Response 8: We are grateful for your positive evaluation of our paper. We believe the revisions made in response to your comments have strengthened the manuscript. 

Reviewer 2 Report

Comments and Suggestions for Authors

The TPEB study aims to provide valuable insights into the potential of t-PBM 28 as a therapeutic intervention to enhance executive function in BD. Through their approach authors demonstrate that t-PBM has the potential to reduce impulsivity, in addition improve decision-making as well as alleviate manic symptoms. They discuss how when/if successful t-PBM could offer a non invasive and potentially a more effective treatment option for addressing the cognitive symptoms in BD patients.  The study delivers meaningful findings although with some limitations which authors already stated in the discussions section. Overall I find the work interesting and support publication.

Comments on the Quality of English Language

No comments

Author Response

Comment 1:  The TPEB study aims to provide valuable insights into the potential of t-PBM 28 as a therapeutic intervention to enhance executive function in BD. Through their approach, authors demonstrate that t-PBM has the potential to reduce impulsivity, in addition to improving decision-making as well as alleviating manic symptoms. They discuss how, when/if successful, t-PBM could offer a non-invasive and potentially more effective treatment option for addressing the cognitive symptoms in BD patients. The study delivers meaningful findings, although with some limitations which authors already stated in the discussions section. Overall, I find the work interesting and support publication. 
Response 1: Thank you for taking the time to review our manuscript. We are happy that you are interested in our work and want to support it. We are glad that we clearly acknowledge and address the limitations of this study and are optimistic that our research can lead to more effective, non-invasive treatment of cognitive symptoms in patients. Thank you for your generous comments. 

Reviewer 3 Report

Comments and Suggestions for Authors

This study explores the effectiveness of transcranially applied red and near infrared light on individuals with bipolar disorder. There is a real need for the development for a non-pharamacological, non-invasive treatment for this set of conditions, so the study is most timely. The study is most comprehensive and systematic, testing a range of both clinical and biological measures. The authors already have some very promising preliminary results. In general, it is a most worthwhile exploration, worthy of publication. I look forward with great anticipation to the results. My comments/suggestions are minor.

. I like the comparison of single vs repeated applications over prefrontal cortex, but the time period of treatment was not very clear. Perhaps I missed it, but how many times over what real period of time will the individuals be exposed to the treatment? This could be made more front and centre. In my experience, the light needs to be applied consistently over an extended period for it to be effective. 

Author Response

Comment 1: This study explores the effectiveness of transcranially applied red and near-infrared light on individuals with bipolar disorder. There is a real need for the development of a non-pharmacological, non-invasive treatment for this set of conditions, so the study is most timely. The study is most comprehensive and systematic, testing a range of both clinical and biological measures. The authors already have some very promising preliminary results. In general, it is a most worthwhile exploration, worthy of publication. I look forward with great anticipation to the results. My comments/suggestions are minor. 
Response 1: Thank you for your positive feedback and recognition of the importance and timeliness of our study. We appreciate your support for its publication. 
 
Comment 2: I like the comparison of single vs repeated applications over the prefrontal cortex, but the time period of treatment was not very clear. Perhaps I missed it, but how many times over what real period of time will the individuals be exposed to the treatment? This could be made more front and center. In my experience, the light needs to be applied consistently over an extended period for it to be effective. 
Response 2: Thank you for highlighting this point. We have revised the manuscript to clearly specify the time period and frequency of the treatment applications. Additionally, we have updated Figure 4 to reflect these changes.