Daily high-frequency transcranial random noise stimulation (hf-tRNS) for sleep disturbances and cognitive dysfunction in patients with mild vascular cognitive impairments: A study protocol for a pilot randomized controlled trial

Yuqi Gong; Jing Li; Yuk Shan Yuen; Natalie Shu Yang; Zeyan Li; Wai Kwong Tang; Hanna Lu

doi:10.1371/journal.pone.0309233

Peer Review History

Original SubmissionApril 12, 2024
11 Jun 2024 Decision Letter - Hantong Hu, Editor PONE-D-24-08334Daily high-frequency transcranial random noise stimulation (hf-tRNS) for sleep disturbances and cognitive dysfunction in patients with mild vascular cognitive impairments: a study protocol for a pilot randomized controlled trialPLOS ONE Dear Dr. Lu, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. ============================== ACADEMIC EDITOR: Please clearly specify the anticipated start date of this study in the main text of the manuscript, the specific registration date on ClinicalTrials.gov, and the current latest stage of the research. ============================== Please submit your revised manuscript by Jul 26 2024 11:59PM. 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Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions? The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field. Reviewer #1: Yes Reviewer #2: Yes ******** 2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses? The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory. Reviewer #1: Yes Reviewer #2: Yes ****** 3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable? Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible. Reviewer #1: Yes Reviewer #2: Yes ****** 4. Have the authors described where all data underlying the findings will be made available when the study is complete? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: No ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes ****** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics. You may also provide optional suggestions and comments to authors that they might find helpful in planning their study. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: 1. Please explain clearly what HF and LF describes and its relevance to the Autonomic Nervous System. In the 1960s Dr Paul Nogier of GLEM ( Lyon) described and demonstrated how oscillations and corrections were necessary for wellbeing whilst teaching the central mechanisms of auricular medicine. 2. One needs to elaborate further the correlations between the lack of night sleep ( insomnia etc) and chronic inflammation and the negative outcomes on health and wellbeing. It is not the lack of sleep that is the main issue- it is the resultant chronic inflammatory response which is the major concern to the brain and body. 3.The left parietal lobe is described as the important region for measuring the changes. Why only the left parietal lobe? There is no comment on changes possible at the SCN - home of sleep regulation / Alzheimers D / Parkinsons D. Were these regions explored? Could there be a dysregulation of the functional connectivity between LPL and SCN which contributes to the sleep and cognitive changes? Reviewer #2: Its an interesting study to look at different modalities for potentially boosting cognitive function. However, MOCA is a rather low sensitivity instrument to assess for change compared to a more comprehensive neuropsychological test battery. Also, please provide details of stimulation parameters in the sham group and how you have tested to assess whether it produces enough local irritation to serve as an effective sham. ****** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: Yes: IM QUAH-SMITH Reviewer #2: No ******** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0309233.r001
Revision 1
5 Jul 2024 Author Response Reviewer #1: Dr. Im Quah-smith Comment 1. Please explain clearly what HF and LF describes and its relevance to the Autonomic Nervous System. In the 1960s Dr Paul Nogier of GLEM (Lyon) described and demonstrated how oscillations and corrections were necessary for wellbeing whilst teaching the central mechanisms of auricular medicine. Response 1. Thank you for your question regarding the description and relevance of HF (high-frequency) and LF (low-frequency) stimulation and their connection to the autonomic nervous system (ANS). We appreciate your interest in this topic and the opportunity to provide clarification. HF or LF in our paper refer to specific frequency ranges used in transcranial random noise stimulation (tRNS). Conventionally, LF-tRNS is administered within the range of 0.1 Hz to 100 Hz, while HF-tRNS is delivered within the range of 101 Hz to 640 Hz (Terney, 2008). In our paper, the specific frequency range used for HF-tRNS is between 101 Hz and 640 Hz. We have updated the details of high-frequency stimulation on page 11 line 280-285. Indeed, the effects of transcranial random noise stimulation (tRNS) on regulating the autonomic nervous system (ANS) are still relatively limited in research, and there is insufficient evidence to support its direct impact on the ANS. Most studies related to tRNS primarily focus on its effects on brain function and neuroplasticity. However, the pioneered studies of Dr. Paul Nogier may lead to another critical modality of neuromodulation, named transcutaneous vagus nerve stimulation (tVNS). The electrical impulses delivered by tVNS device could activate specific vagal pathways, triggering a cascade of physiological responses. One of the primary effects of tVNS is the modulation of neurotransmitters, such as norepinephrine, which play vital roles in the regulation of autonomic nervous system. Although we could not include tVNS in current pilot clinical trial, this topic is a definitely valuable idea that is worthy to explore in our next trial. Reference Terney D, Chaieb L, Moliadze V, Antal A, Paulus W. Increasing human brain excitability by transcranial high-frequency random noise stimulation. Journal of Neuroscience. 2008;28(52):14147–14155. Comment 2. One needs to elaborate further the correlations between the lack of night sleep (insomnia etc) and chronic inflammation and the negative outcomes on health and wellbeing. It is not the lack of sleep that is the main issue- it is the resultant chronic inflammatory response which is the major concern to the brain and body. Response 2. Thank you for your insightful comment regarding the interconnections between insomnia, chronic inflammation, and their adverse implications for health and well-being. We appreciate your emphasis on the significance of chronic inflammation as a substantial concern impacting the brain and overall bodily functions. Based on your comment, we have done a brief literature review. Indeed, sleep plays a pivotal role in modulating cytokine levels and leading to inflammatory response. Sleep deprivation has been shown to activate inflammatory pathways and trigger the release of cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) (Besedovsky et al., 2012). Moreover, recent research has demonstrated that salivary biomarkers exhibit higher reliability, with increased intra-class correlation coefficient (ICC) for inflammatory markers compared to oxidative stress markers (Nam, 2019). However, the findings regarding IL-6, IL-1β, and TNF-alpha in saliva are diverse, with a study have reported elevated secretion of various inflammatory markers, including C-reactive protein, IL-6, and TNF-alpha, in relation to reduced or disrupted sleep (Rico-Rosillo, 2018). Some studies reporting an increase in IL-6 but a decrease in IL-1β and TNF-alpha (Zhang, 2020), while others found an increase in both TNF-alpha and IL-1β (Pinto, 2016). Some studies observed no significant association between TNF-alpha and IL-1β levels and sleep quality (Reinhardt, 2019), while another study reported an increase in IL-1β levels (LaVoy, 2020). Despite the intricacies surrounding these findings, chronic inflammatory responses have been linked to various health conditions, including cardiovascular disease, metabolic disorders, neurodegenerative diseases, mood disorders, and impaired cognitive function (Irwin, 2019; Prather et al., 2017). Given the complexity of these relationships, it is crucial to consider the role of chronic inflammatory in sleep disturbances and continue conducting research in this field to further comprehend the intricate association between sleep quality and salivary cytokines. Therefore, we have updated this part in the discussion and future directions highlighting the intricate correlations between sleep deprivation, chronic inflammation, and their profound impact on health and well-being on page 2, line 26 - 44. Meanwhile, for enhancing the assessment of night sleep, we employed the proxy of sleep efficiency for measuring individual’s night sleep quality and duration using the formula as: Duration of night sleep/Hours in bed * 100%. References Besedovsky L, Lange T, Born J. Sleep and immune function. Pflügers Archiv-European Journal of Physiology. 2012;463(1):121–137. Nam Y, Kim YY, Chang JY, Kho HS. Salivary biomarkers of inflammation and oxidative stress in healthy adults. Archives of Oral Biology. 2019;97:215–222. Rico-Rosillo MG, Vega-Robledo GB. Sleep and immune system. Revista Alergia Mexico. 2018;65(2):160–170. Zhang L, Zhang R, Shen Y, Qiao S, Hui Z, Chen J. Shimian granules improve sleep, mood and performance of shift nurses in association changes in melatonin and cytokine biomarkers: a randomized, double-blind, placebo-controlled pilot study. Chronobiology international. 2020;37(4):592–605. Pinto AR, Da Silva NC, Pinato L. Analyses of melatonin, cytokines, and sleep in chronic renal failure. Sleep and Breathing. 2016;20:339–344. Reinhardt ́EL, Fernandes PACM, Markus RP, Fischer FM. Night work effects on salivary cytokines TNF, IL-1β and IL-6. Chronobiology international. 2019;36(1):11–26. LaVoy EC, Palmer CA, So C, Alfano CA. Bidirectional relationships between sleep and biomarkers of stress and immunity in youth. International Journal of Psychophysiology. 2020;158:331–339. Irwin MR. Sleep and inflammation: partners in sickness and in health. Nature Reviews Immunology. 2019;19(11):702–715. Prather AA, Gurfein B, Moran P, Daubenmier J, Acree M, Bacchetti P, et al. Tired telomeres: poor global sleep quality, perceived stress, and telomere length in immune cell subsets in obese men and women. Brain, behavior, and immunity. 2015;47:155–162. Comment 3. The left parietal lobe is described as the important region for measuring the changes. Why only the left parietal lobe? There is no comment on changes possible at the SCN - home of sleep regulation / Alzheimers D / Parkinsons D. Were these regions explored? Could there be a dysregulation of the functional connectivity between LPL and SCN which contributes to the sleep and cognitive changes? Response 3. Thank you for your valuable comment on why we selected left parietal lobe and whether we explored other regions like the suprachiasmatic nucleus (SCN) in sleep regulation. As you highlighted, we acknowledge the crucial role of the SCN in circadian rhythms and sleep regulation and explain the rationale of selecting left parietal lobe as treatment target on page 10. The SCN, as the master circadian clock, interacts with various brain regions to regulate sleep-wake cycles. Emerging evidence suggests that the SCN and default mode network (DMN) show synchrony in regulating the arousal state of the brain system (Kaufmann, 2006). Furthermore, abnormal functional connectivity between SCN and DMN may be an underlying pathophysiological mechanism of sleep-wake disorders (Kyeong et al., 2017). Since SCN is located in the deep structures of the brain, transcranial current stimulation is unable to deliver the stimulation to deep structures. Focusing on the DMN, the brain regions involved in DMN include: medial prefrontal cortex, posterior cingulate cortex and inferior parietal lobule (IPL). Among the three brain regions, prefrontal cortex and posterior cingulate cortex are located at the medial surface of brain, which is unable to stimulate through weak current stimulation. IPL is located on the outer surface of the brain, which makes it a good candidate for the stimulation target. Besides, previous studies have showed that the LPL is involved in various cognitive processes that are often disrupted in neurodegenerative diseases, making it a focal point for our investigation of cognitive changes (Buckner et al., 2008). Thus, we updated this part in the rationale of selecting IPL as treatment target on Page 10 Line 260 - 272. We appreciate your insightful comment and recognize the importance of exploring the functional connectivity between the LPL and the SCN. We will consider incorporating these aspects into our future studies to gain a more comprehensive understanding of the complex relationship between brain regions involved in sleep regulation, cognitive changes, and neurodegenerative diseases. Addressing these connections could provide valuable insights into potential therapeutic targets for improving cognitive and sleep-related outcomes in affected patients. Reference Kaufmann C, Wehrle R, Wetter T, Holsboer F, Auer D, Pollmächer T, et al. Brain activation and hypothalamic functional connectivity during human non-rapid eye movement sleep: an EEG/fMRI study. Brain. 2006;129(3):655–667. Kyeong S, Choi SH, Shin JE, Lee WS, Yang KH, Chung TS, et al. Functional connectivity of the circadian clock and neural substrates of sleep-wake disturbance in delirium. Psychiatry Research: Neuroimaging. 2017;264:10–12. Buckner RL, Andrews-Hanna JR, Schacter DL. The brain’s default network: anatomy, function, and relevance to disease. Annals of the New York Academy of Sciences. 2008;1124(1):1–38. Reviewer #2: Comment 1. It’s an interesting study to look at different modalities for potentially boosting cognitive function. However, MOCA is a rather low sensitivity instrument to assess for change compared to a more comprehensive neuropsychological test battery. Response 1. Thank you for your feedback on our study. We appreciate your interest and valuable input regarding the assessment of cognitive function. We have carefully considered your comments and would like to address your concerns. We understand that you have raised a point about the sensitivity of the Montreal Cognitive Assessment (MoCA) in assessing change compared to a more comprehensive neuropsychological test battery. We agree that a broader range of assessments can provide a more thorough evaluation of cognitive function. In our study, we have incorporated multiple cognitive tests to complement the MoCA and enhance the validity of our findings on page 12 line 310 - 336. To assess subjective sleep quality, we utilized the Pittsburgh Sleep Quality Index (PSQI), a self-report questionnaire consisting of 19 items. The PSQI provides a measure of global subjective sleep quality, and we employed the validated Chinese version of the PSQI. For attentional function, we employed the Attention Network Test (ANT), which measures complex attention. The ANT paradigm, implemented using E-Prime 3.0 software, includes different cues and flankers to evaluate attentional networks. To assess executive function, we utilized the Category Verbal Fluency Test (CVFT). Participants were instructed to generate as many words as possible within a 60-second timeframe for specific categories, such as animals, fruits, and vegetables. The total number of correct words generated across the three categories served as a measure of executive function. In addition to these cognitive assessments, we included objective measures to evaluate circadian rhythms and global cognition. Actigraphic records were used to quantify the sleep-wake cycle and estimate objective sleep efficiency. This objective measurement provides information on sleep quality and the sleep-wake cycle, allowing for the assessment of circadian rhythms in the participants. Comment 2. Also, please provide details of stimulation parameters in the sham group and how you have tested to assess whether it produces enough local irritation to serve as an effective sham. Response 2. Thank you for your question regarding the stimulation parameters in the sham group and the assessment of local irritation to ensure its effectiveness as a sham condition. We appreciate the opportunity to provide additional details on this aspect of our study. In the sham group, the stimulation modality employed was sham transcranial current stimulation (tCS). The duration of the sham stimulation was limited to 30 seconds, and the electrode placement was identical to that of the active stimulation groups. This ensured that the participants in the sham group experienced the same electrode positioning and initial sensations as the active stimulation groups. To assess the effectiveness of the sham stimulation in producing enough local irritation, we aimed to replicate the temporary skin sensation by keeping the electrodes in place for an additional 20 minutes following the 30-second sham stimulation. So that we can ensure that participants in the sham group experienced a similar tingling sensation as the active stimulation groups. This approach allowed us to maintain blinding and provide an effective control condition for comparison with the active stimulation groups. We acknowledge that providing a more specific assessment or measure to evaluate local irritation would have strengthened our study. In future study, we will consider incorporating additional information on any specific assessments conducted to evaluate the effectiveness of the sham stimulation in producing local irritation. https://doi.org/10.1371/journal.pone.0309233.r002
24 Jul 2024 Decision Letter - Hantong Hu, Editor PONE-D-24-08334R1Daily high-frequency transcranial random noise stimulation (hf-tRNS) for sleep disturbances and cognitive dysfunction in patients with mild vascular cognitive impairments: a study protocol for a pilot randomized controlled trialPLOS ONE Dear Dr. Lu, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please submit your revised manuscript by Sep 07 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. 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Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses? The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory. Reviewer #2: Yes ****** 3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable? Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible. Reviewer #2: Yes ****** 4. Have the authors described where all data underlying the findings will be made available when the study is complete? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #2: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #2: Yes ****** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics. You may also provide optional suggestions and comments to authors that they might find helpful in planning their study. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #2: Please clarify "skin physiological test" under sham method. For sham group, consider having a low amplitude stimulation for longer in sham group as the skin sensation is caused by current as well as the application of electrodes. Have you considered the inaccuracy of actigraphy in assessing sleep and how you will address in data interpretation. You can consider including sleep diary. Sleep diaries are also not accurate, but having redundancy in sleep assessment could be helpful. It will also provide information about subjective improvement or worsening from the patient's perspective. ****** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #2: No ******** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0309233.r003
Revision 2
5 Aug 2024 Author Response Thank you for your thoughtful and constructive comments on our manuscript. We appreciate your insights and the opportunity to clarify and improve our study. Regarding the "skin physiological test" mentioned in the sham method, we apologize for the lack of clarity. This test is a preliminary assessment designed to ensure that the application of electrodes and any potential low-level electrical stimulation do not induce unintended physiological changes in the skin. Specifically, we monitor skin temperature and any signs of irritation or discomfort at the electrode sites before and after the sham stimulation. The primary goal is to confirm the integrity of the skin and ensure that the sham method does not produce any physiological effects that could confound the study results. We also appreciate your suggestion to consider low amplitude stimulation for the sham group. Incorporating a low amplitude stimulation for a longer duration can better mimic the sensation of active stimulation without delivering therapeutic current levels. This modification will enhance the effectiveness of participant blinding and ensure the integrity of the sham condition. Given that we have completed the training of experimental setting, we will definitely implement this sham condition in our future clinical trials to maintain consistency. Additionally, we acknowledge the limitations of actigraphy in accurately assessing sleep patterns and appreciate your suggestion to address this issue. Currently, we use the Philips Actiwatch2, which provides key metrics such as Bedtime, Get Up Time, Time in Bed (hours), Total Sleep Time (hours), Onset Latency (minutes), Sleep Efficiency (percent), and Wake After Sleep Onset (WASO, minutes). These daily sleep statistics allow for the derivation of additional parameters to further evaluate circadian rhythms and sleep quality. The above contents have been updated on Page 13, Paragraph 2. The Philips Actiwatch monitoring system has been validated for reliable sleep record-keeping (Sadeh, 2011; Roomkham, 2019; Menghini, 2024). Although the PSQI scale can cover the period participants wore the Actiwatch, we recognize the value of including a sleep diary to complement actigraphy data. Combining actigraphy with self-reported sleep data will provide a more comprehensive view of the participants' sleep patterns. This approach will help mitigate the inaccuracies inherent in each method and improve the reliability of our sleep assessment. We agree that using a sleep diary alongside actigraphy in this study can enhance the assessment of sleep quality. However, if we add sleep diary into treatment outcomes, then there will be too many outcome measures in a pilot study. Of course, we will use sleep diary in the full-size clinical trial. This will allow us to capture subjective improvements or worsening in sleep from the patients' perspective, which is essential for understanding the broader impact of our intervention. We believe these modifications will address your concerns and enhance the rigor and reliability of our study. Thank you once again for your valuable feedback References: Roomkham S, Hittle M, Cheung J, Lovell D, Mignot E, Perrin D. Sleep monitoring with the Apple Watch: Comparison to a clinically validated actigraph. F1000Research. 2019;8:754. Menghini L, Balducci C, de Zambotti M. Is it Time to Include Wearable Sleep Trackers in the Applied Psychologists’ Toolbox? The Spanish Journal of Psychology. 2024;27:e8. Sadeh A. The role and validity of actigraphy in sleep medicine: an update. Sleep Medicine Reviews. 2011;15(4):259-267. https://doi.org/10.1371/journal.pone.0309233.r004
8 Aug 2024 Decision Letter - Hantong Hu, Editor Daily high-frequency transcranial random noise stimulation (hf-tRNS) for sleep disturbances and cognitive dysfunction in patients with mild vascular cognitive impairments: a study protocol for a pilot randomized controlled trial PONE-D-24-08334R2 Dear Dr. Lu, We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Hantong Hu Academic Editor PLOS ONE Additional Editor Comments (optional): Thank you to the authors for the careful revisions during the two rounds. I believe this manuscript now meets the publication standards and recommend it for publication. Reviewers' comments: https://doi.org/10.1371/journal.pone.0309233.r005
Formally Accepted
15 Aug 2024 Acceptance Letter - Hantong Hu, Editor PONE-D-24-08334R2 PLOS ONE Dear Dr. Lu, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks to review your paper and let you know the next and final steps. Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. If we can help with anything else, please email us at customercare@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Hantong Hu Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0309233.r006

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