PONE-D-24-24703Executive Functioning is Associated to Everyday Interference of Pain in Patients with Chronic PainPLOS ONE

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Reviewers' comments:

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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: No

Reviewer #2: Partly

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

Reviewer #1: Yes

Reviewer #2: N/A

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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: Yes

Reviewer #2: Yes

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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: In the present study, the authors investigated the relationship of chronic pain and executive functions. They report that lower scores in test of executive functioning were related to pain interference and a reduced life control. Pain characteristics (duration, intensity, spreading) were not related with measures of executive functioning. Additionally, they found an association with depression and pain self-management. They conclude that the assessment of executive functioning may help in the rehabilitation of patients with chronic pain.

The authors performed a rigorous data collection and report their Methods and Result in a comprehensive, straightforward matter. However, the Introduction of the manuscript would benefit from a more detailed elaboration of the research background to be able to follow the authors’ line of thought and the development of their research question. Unfortunately, the authors only report correlational evidence which is unable to support the strong conclusions they draw from their study. Nonetheless, the evidence the authors gathered is of interest for researchers and clinicians. Therefore, I suggest the authors to revise the manuscript to tune down their interpretations and stress more clearly the weaknesses of correlational findings. My detailed suggestions/comments on Major and Minor points of criticism are outlined below.

----Major----

Abstract

- The authors state that “lower performance on tests of executive functioning was related to a higher degree of pain interference and a lower degree of life control due to pain” (ll. 29-30) – can it be concluded from the data that the lower degree of life control was due to the pain? Could it also be that patients that, for some reason, have lower control over their lives experience chronic pain more severely (e.g., due to generally reduced life satisfaction)?

Introduction

-The authors rapidly jump to the association between chronic pain and cognition. While this is straightforward, I would suggest to start with a more basic introduction of chronic pain, e.g. that it is not (necessarily) based on any physical problems and has no biological value. For readers who do not know this it might be confusing to jump to the cognitive side of the problem so rapidly.

-Several aspects in the introduction need more explaining. For example, the authors mention the “cognitive resources theory” (l. 66) and the “neuromodulator/neuroplasticity theory” (l. 67) but do not present any further information about these theories. It would be important to know more details about these theories to be able to follow the authors’ line of thought on why the current study is necessary to understand the relationship between chronic pain and executive functions.

-Why is this study framed as an “exploratory study” (l. 73)? The authors present relevant literature that justifies the investigation of chronic pain and cognitive functions quite well.

-Related to the previous comment, the authors should formulate their hypotheses more clearly at the end of the introduction.

Materials and Methods

-Did the authors exclude participants who reported a history of drug abuse? Aside from “medical treatment” (l. 103) this could also affect both cognitive functions as well as pain processing.

-Why did the authors decide to use “raw scores” (l. 176) for the analyses instead of standardized scores?

-Why did the authors not use “gender” or “sex” as a covariate in their analyses? It is widely known that gender/sex influences pain perception.

-The authors should elaborate on why they included measures of kinesiophobia (l. 123)

-In the introduction, the authors rightly criticize that the relationship between chronic pain and executive functions has been addressed using correlational evidence. However, they also report merely correlational evidence themselves. Therefore, I am unsure about the merit of this work, especially as a standalone manuscript. Certainly, the authors conducted a rigorous study, but the work presented here would rather be a side note on e.g. data on “neuroinflammatory markers and functional and structural brain imaging” (l.99 -100) they refer to, but do not report here.

-Did the authors correct for multiple comparisons? This would be appropriate when performing multiple correlations.

Discussion

-The authors make strong interpretations based on their correlational analyses and combine them with very broad speculations based on other findings reported in literature. These conclusions the authors draw are not justified based on their study, especially since the lack of an experimental manipulation does not allow for any interpretations of causality.

----Minor----

Abstract

-what does “everyday interference of pain” (l. 27) refer to? Is this how much pain interferes with the everyday life of the participants?

- The sentence “Depression was also associated with self management of pain, indicating that patients with lower executive functioning in combination with depression may need special attention in the rehabilitation of patients with chronic pain” (ll. 34-36) seems a bit odd; I suggest shortening to “Depression was also associated with self management of pain, indicating that patients with lower executive functioning in combination with depression may need special attention during rehabilitation”

Materials and Methods

-The authors state that “Both male and female participants were included” (l. 97) – did they specifically exclude people with other gender identities?

-Why were not all patients included in the linear regression analyses? Additionally, why was the sample size lower for the TAMPA Scale of Kinesiophobia regression?

Discussion

-Sudden change of font color on page 20

-In their conclusion, the authors write “Affected executive functions seem to be common in patients with chronic pain. Pain characteristics such as pain intensity, pain duration, and pain spreading do not seem to be associated with executive functioning.” These statements seem like direct contradictions of each other, which is a bit confusing. I suggest rephrasing.

Reviewer #2: The reviewer enjoyed reading the article in general. Some general suggestions from the reviewer might enhance the reading experience, such as, clearer sentence structure and consistent referencing style.

The introduction section gave a brief picture about the relationship between executive function and pain. It also provided a brief background of the current study, but would appreciate it if the authors could extend on the theoretical assumptions of the study with explicitly stated hypotheses of the directions of impacts. In addition, the authors might need to rephrase on ref number 17 about availability of interference and experimental studies over correlational studies.

In the methodology parts, the reviewer would suggest to the authors that repeating exclusion criteria, upper age limit, and the demographic variables from ref number 20 would assist the readers to follow the argument. Statistical features of the psychometrics and external validity of both of the scales and the neuropsychological tests would also be necessary to equip readers with an enhanced understanding of the measures. Restructuring the paragraphs under "instruments and procedures" into two separate sections would also be helpful in smoothening the understanding of the methodology parts.

The reviewer would also like to suggest the inclusion of reference between lines 192-194 so that readers can better understand the established relationship between the mentioned variables with pain and executive functions (possibly they might have been discussed in the introduction). Moreover, there may be a necessity to state explicitly on the multicollinearity of the HADS subscales with previous evidence and with the current dataset so that the authors might have an option to either choose to include only one subscale or to compute them into a single measurement with better support from the evidence. Lastly the authors are suggested to take into consideration of statistical tests, e.g., the Kolmogorov-Smirnov test, instead of visual inspection of the Gaussian distribution.

Regarding the results and discussion of the paper, the reviewers would like to suggest that the conversion between raw scores and scaled scores may be difficult for readers to follow and may require some elaboration of those data, together with the effect size of the statistics to report the magnitude of the associations. It was also observed that the direction of CWIT may be different from the other measures, which further brings up the question if the authors would consider putting all dependent variables in a single model consisting of all the executive functions measures with examination of multicollinearity included. The same suggestion lies also between exploration of associations between executive functions and pain characteristics.

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Reviewer #1: Yes: Sophie Siestrup

Reviewer #2: No

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Executive Functioning is Associated to Everyday Interference of Pain in Patients with Chronic Pain

PONE-D-24-24703R1

Dear Dr. Berginström,

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.

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Vincenzo De Luca

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

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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

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

Reviewer #1: Yes

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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

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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

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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 congratulate Dr Berginström and his colleagues on doing a great job on the revision. All of my points were addressed adequately and convincingly. Only a minor suggestion: Concerning their reply that they “did not want to make type-II-errors and missing out on reporting possibly interesting results” I feel like they could even include a statement like this in the limitations sections to make it very transparent to the readers why they decided against corrections.

Respectfully

Sophie Siestrup

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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.

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Reviewer #1: Yes: Sophie Siestrup

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