PONE-D-19-25834

The relationship between executive functions and fluid intelligence in Multiple Sclerosis

PLOS ONE

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PLOS ONE

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2. We noticed you have some minor occurrence of overlapping text with the following previous publication(s), which needs to be addressed:

https://www.frontiersin.org/articles/10.3389/fnbeh.2014.00046/full

https://www.sciencedirect.com/science/article/pii/S0165178116315116?via%3Dihub

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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: Partly

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?

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Reviewer #1: No

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: Summary:

The authors of this study aimed to examine the role of fluid intelligence (g) in executive dysfunction in patients with multiple sclerosis by using several classical and non-traditional tests of executive functioning, as well as MRI. This is an interesting topic, as executive dysfunction is common in MS, and its underlying mechanisms require further investigation. However, the manuscript has a number of issues that detract from its interesting findings.

Overall Comments:

-Overall, more care is needed in explaining the authors’ reasoning (see below). The Introduction and Discussion sections need particular improvement, including an improved discussion of the prior MS literature and how it relates specifically to this study’s scope.

-The manuscript would benefit from proofreading for typos, clarity/word usage, and grammar/punctuation. There are also some inaccurate statements and conclusions which should be addressed.

Introduction:

-The Introduction should include a more detailed explanation of concepts specifically related to this study and how they relate to MS, particularly Spearman’s g, executive functioning (e.g., what is meant by “classical executive functions tests”), multitasking, and theory of mind. What are the authors’ specific reasons for studying this topic in MS, as opposed to the other populations that are cited? How does the MD system relate to MS specifically? Why were these particular tests chosen for the study (executive functioning, multitasking, theory of mind), and have other studies found these tests to be impaired in MS? What is the reasoning behind the predictions in the authors’ hypothesis?

-Lines 45-48: Please add citation(s).

-Lines 51-54: The characterization of cognitive deficits associated with MS should be improved. MS cognitive impairments don’t “mainly include deficits in visuospatial perception and executive functions,” and this is not stated by Chiaravalloti & Deluca (2008). Rather, they cite difficulties with “complex attention, efficiency of information processing, executive functioning, processing speed, and long-term memory.”

Methods:

-Line 83: Please add a citation for the Poser and McDonald criteria that were used.

-Line 98-99: Who examined the patients and controls for comorbidities?

-Fluid intelligence (g): Is Matrix Reasoning a commonly used measure of g? If so, please cite other studies that do so. Is there a reason WAIS-III was used rather than a more updated version of the WAIS?

-WCST: Why was the Nelson’s modified version used? As the participant’s first sorting choice becomes the first correct feature, and participants are told that the rules have changed, it seems that this test is less challenging than the traditional version.

-Hotel task: It’s questionable whether this is truly a multitasking activity, as tasks were completed one at a time; rather, this seems like more a test of task-switching, goal-monitoring, and memory for intended actions. Manly (2002) referred to this as a task of “ability to monitor the time, switch between the tasks and keep track of their intentions.” Also, was there a limit on how many times the participants could consult the clock? Please also specify which version of the Hotel task was used (i.e., Manly versus Torralva).

-Faux pas: Is this the same version of the test used by Stone (1998)? Were any modifications made, such as providing the written version of the story? Did the written version of the story remain in front of the participant when they were asked questions about it?

-Were all tests administered in Spanish? If so, were all participants fluent in Spanish? Why are some executive functioning test data unavailable for some patients? How many patients completed the Faux Pas task? Did all control participants complete all executive functioning tests?

-MRI acquisition: Please explain why just a subset of patients and controls underwent MRI scanning. Was this subset matched for age, gender, and education? Why weren’t analyses performed with the other cognitive tests?

Results:

-A significant statistical difference between the two groups does not necessarily imply clinical impairment (e.g., lines 211, 214).

-Line 213: The between-group p-value for Verbal Fluency is different in the text (p=.041) than in Table 2 (p=.005); please check this.

-Line 221: What were the correlations and p-values with classical/non-classical tests and g for the MS and control groups (ie, not combined groups)? Please explain why data from patients and controls were combined for the correlations with g.

-Figure 1: Would be helpful to also include scatterplots for the non-classical tests (Hotel task and Faux Pas)

-Matrix reasoning is referred to as “g” in the initial Results section, while the other tests are referred to by their test names. It would be preferable to use the name “Matrix reasoning” rather than “g” (as is done in the Grey-matter Analysis results section), as the Matrix reasoning test is a stand-in estimate for the concept of g, rather than being g itself.

-Lines 230-231: Be careful in stating that frontal deficits were “entirely” explained by fluid intelligence – this is likely an overstatement.

-Depression is mentioned in the Introduction, and the Methods section states that depression was measured with the BDI. However, depression was not included in analyses in the Results section.

-Grey-matter analysis: This section seems incomplete and could benefit from a more detailed/clear explanation of the results. For example, please explain why patient and control data was combined in some analyses. Also, the text states that the somatosensorial mask had a significant correlation in the combined group, but this correlation does not seem to be indicated as significant in Table 3 (Lines 250-251).

Discussion:

-Be careful not to overstate or overgeneralize the conclusions. For example, “We found that MS patients show clear deficits in all classical executive tests” (Only three tests were used in this study, not “all” available executive tests. This does not imply that all MS patients have executive dysfunction, merely that there was a difference at the group level in this patient sample. Also, significant group differences do not necessarily imply clinical impairment.) Another example is the statement that “Most imaging studies regarding MS are exploratory” – this is inaccurate. The authors also state that “Cognitive deficits were entirely explained by a loss in fluid intelligence (no clinical deficit remained)”; this overstates the results and does not make sense clinically.

-As discussed above, the Hotel task does not appear to be a test of multitasking. As such, be careful about making conclusions regarding multitasking in this study.

-Why do the authors think between-group differences were non-significant for the Hotel task? Have other authors found difficulties with similar tasks in MS?

-Starting at line 283: The authors state that they aimed to search for a link between MS cognitive deficits and the MD system. However, it seems these analyses were only performed for Matrix Reasoning and Faux Pas tests; also, the results weren’t significant for the MS group (this finding is not specifically stated in the Discussion). It therefore seems a bit misleading to cite the results of the control group alone and together with the patient group, as these don’t relate to the MS findings per se.

-Lines 296-298 (“Nevertheless… social cognition test”): This statement is unclear.

-Line 303 (“support a parcellation of cognitive functions based on the role of fluid intelligence”): This statement is unclear as well; please clarify.

-Line 306: Multitasking was not included in the covariate analyses.

-The conclusions of the last paragraph seem to be overstated based on the scope and results of the study. As Matrix reasoning can also be interpreted as a test of nonabstract reasoning, reduced performance on this test may not necessarily imply a “general cognitive loss” that explains deficits on classical executive tests.

-A discussion of study limitations is largely missing; only one limitation is mentioned at the end of the manuscript. Similarly, future directions for the research should be explained further.

Reviewer #2: This manuscript provides an interesting insight into the relationship between fluid intelligence and performance on a variety of executive function tasks. Controlling for g in the MS-HC comparisons helped illustrate their main point and the additional analysis of fatigue was also appreciated as a useful comparison.

Introduction: The introduction is mostly focused on cognition at large and only 1-2 sentences are dedicated to introducing your background work, relating g to executive function tasks. This is merely a recommendation, however I would suggest cutting back some of the opening text on cognition at large so that there is more space to provide readers more immediately relevant background.

Analysis/Results:

- Page 10 & 11. Regarding the correlations between g and other tests. Here you provide "average within-group correlations", yet in the MRI section, you instead provide correlations which reflect the correlation in either MS, HCs, or both. Please be consistent. It would probably be best to do the same here and provide all 3 correlations for these test values with g. Please also provide p-values for these correlations in Table 2.

- Page 11: The statement "This suggests that, for classical executive tasks, frontal deficits were entirely explained by fluid intelligence" is not fully supported by the results. The results of the ANCOVA at least suggest that g and the executive function tasks have overlapping variance. That said, we can not conclude the frontal deficits are ENTIRELY explained by g. I would suggest pulling back on this conclusion and perhaps moving the interpretation to the discussion section.

- Page 13: Table 3 results show that g correlates with MD, DMN, and somatosensory network GM volume. Please add a star to the p-value for the somatosensory, as this indicates statistical significance (P<0.02). Also, these results show that correlation with g is not unique to the MD and DMN, since the correlation appears for somatosensory network as well. To make the intended point, the author should see if these correlations with g remain after controlling for whole brain gray matter volume. That way, if the significance of the local correlations remain, the authors will know that this correlation is locally specific. The authors may just be picking up on the expected correlation between gray matter volume at large and cognition at large rather than for their intended hypothesized correlation between g and volume of MD system specifically. As an aside, perhaps change "raw matrix" in Table 3 to "g" so is consistent with rest of manuscript.

Discussion:

- page 15. On the bottom, the authors again assert that the cognitive deficits are ENTIRELY explained by g. This is not supported by the ANCOVA results. Please provide a more conservative interpretation of these results.

- Page 16. The authors say "we propose that deficits in classical executive tasks might be explained by damage to the distributed frontoparietal MD system". As they stand, the results don't provide support for this conclusion uniquely. From the results presented, one could also conclude that DMN and somatosensory are equally related.

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Reviewer #1: No

Reviewer #2: No

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The relationship between executive functions and fluid intelligence in Multiple Sclerosis

PONE-D-19-25834R1

Dear Dr. Roca,

We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.

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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: (No Response)

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

Reviewer #1: (No Response)

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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: (No Response)

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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: (No Response)

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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: (No Response)

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Reviewer #1: No