Point-to-Point Response to Reviewers' Comments对审查员意见的点对点回应

Dear Editor and Reviewers,亲爱的编辑和审稿人

We would like to express our sincere gratitude for your thoughtful and constructive feedback on our manuscript titled "Perturbational Complexity Index in Assessing Responsiveness to rTMS Treatment in Patients with Disorders of Consciousness: A Cross-Over Randomized Controlled Trial Study." We appreciate the time and effort you have invested in reviewing our work and providing valuable suggestions for improvement. We have carefully considered each comment and have made the necessary revisions to the manuscript. Below, we provide a point-by-point response to the reviewers' comments, detailing the changes made in the revised manuscript.您对我们题为"Perturbational Complexity Index in Assessing Responsiveness to rTMS Treatment in Patients with Disorders of Consciousness：我们感谢您花费时间和精力审查我们的工作，并提出宝贵的改进建议。我们认真考虑了每一条意见，并对手稿进行了必要的修改。下面，我们将逐点回应审稿人的意见，并详细介绍修订稿中的改动。

Reviewer 4:审查员 4：

Comment:
All my comments and questions were addressed by the authors.我的所有意见和问题都得到了作者的回复。

Response:
Thank you for your positive feedback. We are pleased that our revisions and explanations were satisfactory. We appreciate your support and have made additional minor improvements to the manuscript to enhance its clarity and precision.感谢您的积极反馈。我们很高兴我们的修改和解释令人满意。我们感谢您的支持，并对稿件做了一些小的改进，以提高其清晰度和准确性。

Reviewer 2:审查员 2：

Comment 1:
The authors addressed all my concerns.作者解决了我所有的担忧。

Response:
Thank you for your continued support and positive evaluation of our manuscript. We are glad that our previous revisions have addressed your concerns.感谢您一直以来对我们稿件的支持和积极评价。我们很高兴之前的修订解决了您的问题。

Reviewer 5:审查员 5：

Comment 1:
Thank you for these explanations. It seems thresholds for rTMS in DOC can differ from what I was used to.感谢您的解释。看来经颅磁刺激在 DOC 中的阈值可能与我以前习惯的不同。

Response:
We appreciate your understanding regarding the thresholds for rTMS in patients with disorders of consciousness (DoC). As noted, rTMS protocols can vary depending on the specific clinical population and study design. We have included a brief explanation in the Discussion section to highlight these differences and provide context for readers who may be more familiar with alternative protocols.我们感谢您对意识障碍 (DoC) 患者经颅磁刺激阈值的理解。如前所述，经颅磁刺激方案会因特定的临床人群和研究设计而有所不同。我们在 "讨论 "部分进行了简要说明，以强调这些差异，并为更熟悉其他方案的读者提供背景资料。

Comment 2:
I understand that the authors did not have individual brain scans of the patients, and while PCI can be successfully used with the template brain, I know that this could be challenging in the clinical population. I would like to note that PCI is usually used with all channels, while PCIst can be successfully implemented with a reduced number of channels (Comolatti et al., 2018). I am glad the authors would like to explore GFP and potentially PCIst with fewer channels in their further studies.据我所知，作者并没有患者的个人脑部扫描结果，虽然 PCI 可以成功用于模板脑，但我知道这在临床人群中可能具有挑战性。我想指出的是，PCI 通常使用所有通道，而 PCIst 可以在减少通道数量的情况下成功实现（Comolatti 等人，2018 年）。我很高兴作者希望在进一步研究中探索 GFP 以及可能使用较少通道的 PCIst。

Response:
Thank you for this important observation. We agree that while PCI is typically calculated using data from all channels, PCIst is indeed more flexible and can be implemented with fewer channels, which may be advantageous in certain clinical settings. We have added a discussion of this point in the revised manuscript, acknowledging the potential benefits of exploring GFP and PCIst with a reduced number of channels in future studies.感谢您提出这一重要意见。我们同意，虽然 PCI 通常使用所有通道的数据进行计算，但 PCIst 确实更加灵活，可以使用较少的通道来实现，这在某些临床环境中可能是有利的。我们在修改后的手稿中增加了对这一点的讨论，承认在未来的研究中使用更少的通道探索 GFP 和 PCIst 的潜在优势。

Reviewer 1:审查员 1：

Comment:
I am forced to confirm my basic methodological critique for this study: the perturbational complexity index (the main outcome measure of this study) is extremely sensitive to small displacement of the coil throughout the stimulation session. The only way to avoid or minimize this problem is the use of a neuronavigation system, which is not the case in this study. So, results were, and remain, not interpretable.我不得不确认我对这项研究在方法论上的基本批评：扰动复杂性指数（本研究的主要结果测量指标）对整个刺激过程中线圈的微小位移极为敏感。避免或尽量减少这一问题的唯一方法是使用神经导航系统，而本研究并没有使用该系统。因此，研究结果过去和现在都无法解释。

Response:
We sincerely appreciate your continued engagement with our manuscript. We acknowledge that the absence of a neuronavigation system is a limitation of our study. However, we would like to reiterate that we have taken significant measures to ensure the consistency and accuracy of coil placement throughout the stimulation sessions. Specifically, we used the 10-20 international EEG system with F3 electrodes to localize the L-DLPFC, a method that has been considered both effective and feasible for clinical applications. Additionally, a physical therapist was present during all sessions to monitor and adjust the coil placement as necessary.我们衷心感谢您对我们手稿的持续关注。我们承认，没有神经导航系统是我们研究的一个局限。但是，我们想重申，我们已经采取了重要措施来确保整个刺激过程中线圈放置的一致性和准确性。具体来说，我们使用了带有 F3 电极的 10-20 国际脑电图系统来定位 L-DLPFC ，这种方法被认为在临床应用中既有效又可行。此外，在所有治疗过程中都有一名理疗师在场，以监控并在必要时调整线圈的位置。

Furthermore, while we understand your concerns regarding the interpretability of the results, we believe that our findings still contribute valuable insights into the application of rTMS in patients with DoC. The limitations associated with coil placement were clearly acknowledged in the manuscript, and we plan to incorporate a neuronavigation system in future studies to address this issue more effectively.此外，虽然我们理解您对结果可解释性的担忧，但我们相信我们的研究结果仍能为经颅磁刺激在 DoC 患者中的应用提供有价值的见解。手稿中明确承认了线圈放置的局限性，我们计划在今后的研究中采用神经导航系统，以更有效地解决这一问题。

Conclusion:

We would like to extend our heartfelt thanks once again to the reviewers and the editor for their insightful feedback. We believe that the revisions have significantly improved the quality of our manuscript. We look forward to your final decision and are hopeful that our manuscript will now meet the standards required for publication in the Journal of NeuroEngineering and Rehabilitation.我们再次衷心感谢审稿人和编辑提出的宝贵意见。我们相信，经过修改，我们的稿件质量有了显著提高。我们期待着您的最终决定，并希望我们的稿件现在能达到在《神经工程与康复杂志》上发表的标准。

Thank you for your continued support.感谢您一如既往的支持。

Sincerely,此致敬礼
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