PONE-D-20-19305

Diurnal variation of motor activity in adult ADHD patients analyzed with methods from graph theory

PLOS ONE

Dear Dr. Ole Bernt Fasmer,

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Pan Lin

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Partly

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). 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: No

Reviewer #2: No

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4. 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

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: This paper focuses on the diurnal variation of motor activity in normal, ADHD and clinic not ADHD people, as well as their comparisons. Authors used a portable actigraphy to record the motor series and tried to character motor feature of ADHD by adopting 12 measures. They reported that in normal people, the evening activity show higher variability and less complexity than morning activity, but it is not observed in ADHD. They also considered the effects of age, gender, cyclothymic temperament on the results. In my opinion, using a portable actigraphy to study motor function has a promising future in clinical diagnosis, exploring neural basis and so on, and authors also obtained some interesting results. But before the publication, there are many problems need to be addressed.

1. Can authors declare the difference between this paper and Ref.17?

2. It is really hard for me to understand how a graph is built from a single motor series

3. Discussion needs to be majorly revised. Many descriptions are actually results (e.g., lines 452-456, 464-468). And many sentences are meaningless (e.g., lines 448, 461-463). Most importantly, many measures can characterize the diurnal difference, but their meanings for patients are not clear explained. For example, in lines 425-426, the description on RMSSD is actually a definition, not its meaning for ADHD. I suggest authors pay more effort to dig deeper meaning of this paper.

4. I notice that many results are not provided in a table (e.g., lines 393-398) and just written in main text. I suggest that a summarize on results in a table is more clear for readers.

5. In graph theory, many measures are given, but the degree, path, acyclic and spanning subgraph are not used in later analysis. If true, please delete them.

6. CT is cyclothymic temperament? Please identify the abbreviation while using it first time.

7. Line 323, 39 should be 39 patients or something.

8. The grammatical tense is not consistent, e.g., lines338 uses ‘was’, line 342 uses ‘is’, pleases unite them through the paper.

9. Line 344, what does the (1.34) mean.

10. After tables, *p=0.05 should be p<0.05.

11. Line 385, p=0.05 is not significant, pleases revise the description

12. Lines 397-398, I didn’t found the results corresponding to the description.

13. Line 404, I know that 8/12 indicates only 8 measures are significant, but it is really a strange description, can we just use 8?

14. Line 483, authors should present the current results and then compare them to previous.

15. Line 500, is it a replicated description ‘differently put; reduced amplitude….. Reduced….’

16. In conclusion, I suggest authors don’t use newly, because it is hard to identify what is really new.

17. Finally, can author explain to me why we have a higher variability and lower complexity in the evening, does it relate to our brain in some aspects?

Reviewer #2: Based on previous studies, the authors tested the assumption that diurnal variation of motor activity of ADHD patients is less than normal controls. With measures from variability, complexity and graph theory aspects, they conducted analysis of wrist-worn actigraphs time-series from ADHD patients, normal controls and clinical controls with mood and anxiety disorders. Their results suggested most of the measures being different between morning and evening in normal controls are not significantly different in both ADHD patients and non-ADHD clinical controls, but “bridge” is significantly different in ADHD and not different in non-ADHD. These results largely support their assumptions about reduced diurnal variation in ADHD. In addition, the exception of changes in bridge may suggest specificity about the diurnal regulation of motor activity in ADHD patients, when comparing with other mental disorders showing diurnal regulation disorders.

However, I have several concerns regarding to the results that should be clarified by authors.

Major 1: During the construction of similarity graph, the similar was detected by max(ux,uv)/min(ux,uv)<1.2. The authors explained this definition with analogy to the tolerance in sample entropy. However, unlike sample entropy where the tolerance range is a fix value (0.2*std), this definition will lead to a flexible range depending on the amplitude of the denominator. In other word, smaller signal value in the bottom will have narrower tolerance range and harder to “be similar” to others. The authors should explain why they use this criteria and what will be the consequence in the following computation of graph measures.

Minor 1: For readability, I suggest the authors to give a schematic illustration for the construction of similarity graph on time-series. In addition, authors can show example of actigraphs time-series. In addition, different kinds of activity jumps detected by graph measures, degree, bridge, and k-clique detect should be given to guide understanding.

Minor 2: The discussion about diurnal fluctuations and weak circadian rhythms, etc are too far away from the topic and the presented evidences, given the fact that the authors cannot explain what is told by the bridge changes.

Minor 3: Not clear why in healthy controls the evening registrations showed higher variability and lower complexity compared to morning registrations. In principle sample entropy is associated with measures of variability. The authors can recheck.

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Reviewer #1: No

Reviewer #2: No

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Diurnal variation of motor activity in adult ADHD patients analyzed with methods from graph theory

PONE-D-20-19305R1

Dear Dr. Fasmer,

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.

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Kind regards,

Pan Lin

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). 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

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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. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: I recommend the publication because the authors have addressed all my comments. But I still have two minor requests:

1. There is no any label in figures. 1 and 2. In figure 1, three actigraph recordings are for ADHD, normal and control ADHD? please clearly state it. In figure 2, it is more clear if showing the value of max (xu , xv) / min (xu , xv).

2. In method, please first show the construction of Similarity graph and then show the Graph theory.

Reviewer #2: (No Response)

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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: No

Reviewer #2: No