PONE-D-24-30533Prestimulus functional connectivity reflects attention orientation in a prospective memory task: a magnetoencephalographic (MEG) studyPLOS ONE

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Additional Editor Comments:

Please provide details of the data acquisition parameters. For Freesurfer, please explain details of the preprocessing.

For the whole manuscript, please be consistent about within- and between-network or inter/intra.

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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: No

Reviewer #2: Yes

Reviewer #3: Yes

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

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: 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: Yes

Reviewer #2: Yes

Reviewer #3: 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

Reviewer #3: 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: Review comments:

This study investigates prestimulus functional connectivity (FC) related to attention orientation in a prospective memory (PM) task using MEG. The authors differentiated the FC patterns between the monitoring and maintenance PM tasks during the prestimulus period. They observed increased inter-network FC of the dorsal attention network in the alpha band for the monitoring-load task, and increased FC of the ventral attention network with the frontoparietal and default mode networks for the maintenance-load task. These results demonstrate that different networks are engaged in PM depending on the specific features of the task.

While I find this manuscript interesting, I have serious concerns about the analysis and the results. I hope the authors can address and clarify some of the ambiguities present in the current manuscript.

1. The authors introduce three models/theories: the preparatory attention and memory theory, the multiprocess framework, and the attention to the delayed intention model. These theories offer different interpretations of the mechanisms underlying PM. It would be helpful if the authors could clarify whether the FC data from the current study supports any of these theoretical accounts. Providing an integrated view that links the neural data with these theoretical frameworks could strengthen the manuscript, as the relationship between the cognitive theories and neural data is currently unclear.

2. While I agree that MEG offers excellent temporal resolution compared to fMRI, I feel that this advantage could be better shown in the study. Could the authors provide more detailed temporal analyses of FC during the prestimulus interval? This could highlight the unique temporal dynamics captured by MEG.

3. The task description is somewhat unclear. To help readers better understand the experimental design and procedure, it would be beneficial if the authors provided visual illustrations, including timing and trial examples, in a figure.

4. Behavioural results are also crucial for understanding how the prestimulus neural data relates to task performance. Could the authors include these results in the manuscript?

5. It is unclear which brain hemisphere's data were analysed for the FC analysis. Clarifying this would help readers understand the lateralization of the observed effects.

6. I have some questions regarding the FC analysis method. Could the authors clarify whether they extracted and normalized the correlation values before averaging and comparing the IntraNC and InterNC values among the conditions? It is important to ensure that any averaging of correlation values is done following proper normalization, as correlation is not a linear measure and cannot be simply averaged without introducing statistical inaccuracies.

7. Following up on the previous comment, could the authors elaborate on the statistical analysis conducted based on raw or normalized power values in Figure 7 (or on p.22)? I am uncertain whether statistical tests can be appropriately conducted on raw power spectra. A more detailed explanation would enhance the clarity of the results.

8. Could the authors specify the scale used in Figures 3 through 6? This would aid in the interpretation of the data presented.

Reviewer #2: This study investigates the neural bases of prospective memory (PM) from a network connectivity perspective, using MEG data to assess functional connectivity (FC) across different brain networks under varying PM task demands. Specifically, the authors analyze two PM conditions—monitoring-load and maintenance-load—that emphasize either attentional monitoring or memory maintenance. By focusing on the prestimulus phase, the study identifies distinct connectivity patterns: increased inter-network FC of the Dorsal Attention Network (DAN) in the alpha band in the monitoring-load condition, and heightened connectivity of the Ventral Attention Network (VAN) with the FrontoParietal Control and Default Mode Networks (FPCN and DMN) in the maintenance-load condition. These findings suggest that top-down and bottom-up mechanisms are differentially engaged depending on PM task requirements.

While the study addresses an important and innovative approach to understanding PM processes through functional connectivity, several points require clarification and further elaboration to strengthen the manuscript.

Introduction

Page 3: Although original, the anecdote about Amedeo Modigliani’s paintings does not seem entirely appropriate for introducing the concept of prospective memory (PM) in a scientific context. I suggest reserving this example for a more popular science publication and omitting it from the scientific paper, as it may detract from the formality and focus of the study.

Page 4, line 82: In the retrieval phase, it should be noted that the associated intention must not only be correctly retrieved but also executed. Including an example to explain each phase would improve clarity.

Page 5: When discussing The Multiprocess Framework, it’s important to address focal and non-focal cues and provide clear explanations, particularly since focality and salience are features manipulated in this experiment.

Page 5: “However, opposite patterns of activation have been observed in the medial and lateral aPFC and between the ventral and dorsal portions of the FPN during specific PM phases or in relation to PM task features.” This needs a brief explanation of how task features impact activation in these regions. Include a review of previous studies that have examined the role of the number of intentions, salience, and focality in PM, focusing on studies that explore these aspects at a neural level.

Page 8. I recommend including a section titled "In the Present Study" to improve the flow and clarity of the text. In the hypotheses, clearly state the expected behavioral outcomes as well.

Materials and Methods

Page 10. Data Acquisition: Please specify any inclusion or exclusion criteria for participant recruitment and indicate whether participants received any form of compensation. Additionally, clarify how the sample size was determined. Conducting a power analysis to estimate the expected effect size would further support the adequacy of the chosen sample size.

Page 10. For MRI data, provide additional imaging parameters such as voxel size, repetition time, and echo time.

Page 10-11. Task procedure: It is essential to clarify certain aspects of the experimental setup to improve transparency and reproducibility. What were the specific timings and intervals for each trial and block, including the presentation duration of task stimuli, inter-trial intervals, number of PM and ongoing trials per block, and any breaks between blocks? What mode and device were used to present stimuli, and what software was employed for stimulus delivery and response recording? Additionally, how were responses collected, and was response latency recorded? In the Maintenance-load block participants were instructed to maintain three different intentions in memory—what specifically were these intentions? Finally, did participants receive any practice or familiarization trials to ensure understanding of the tasks before starting the experimental blocks?

Page 12.” …considering only the ongoing trials with a correct response.” Please provide the average number of ongoing trials included per participant and block.

Page 12. Mention if any power analysis was conducted in the different analyses to ensure sufficient sensitivity for the paired t-tests, particularly given the multiple comparisons and FDR correction.

Page 13-14. Please 1) include specific hypotheses regarding the IntraNC and InterNC comparisons within the hypotheses section of the experiment, and 2) explain how these processes of segregation and integration relate to PM processes within each of the networks of interest. This addition will clarify the expected outcomes and their connection to PM mechanisms across different networks.

Results

Page 17. What about the behavioral results? Please include them to confirm that the typical effects of a PM task are observed. Additionally, conducting a correlation analysis between behavioral outcomes and neuroimaging data could help interpret how functional connectivity influences performance in a prospective memory task. This would provide a more comprehensive understanding of the relationship between brain connectivity and behavioral execution in PM contexts.

Page 17. Include a brief discussion on the functional significance of these findings within each subsection, even if further elaborated in the discussion. This will provide readers with immediate insight into the relevance of the observed changes in the context of PM tasks.

Page 22. Specify in the hypotheses section whether increases in alpha or theta power were expected in certain networks across conditions, based on prior literature or theoretical models of PM.

Discussion

Page 23. How can you ensure that the prestimulus phase is not influenced by performance in the immediately preceding trial? Could there be differences in this phase resulting from a correct or incorrect response in the preceding ongoing trial? How might this be controlled?

Page 23. The PM cues in the different conditions (maintenance vs.monitoring) differ in focality and salience. While salience refers to the ease or difficulty with which a PM cue is perceptually detected, focality pertains to the similarity in processing between the PM cue stimulus and the stimulus in ongoing trials. Although both characteristics relate to detection and monitoring processes in PM, could each affect functional connectivity of these processes differently? Additionally, how might the results change if only focality were manipulated, given its direct connection to different retrieval mechanisms within the Multiprocess Framework?

Page 26. "In contrast, in the Maintenance-load condition, the processes underlying intention retrieval occurred only after the detection of the PM cue, to retrieve the correct intention among multiple ones related to that cue"— I agree with this interpretation. To support this claim, is it possible to perform these post-stimulus analyses with the data you have?

Study Limitations and Future Perspectives

Page 28. There seems to be a potential contradiction here. In page 12, you mention segmenting the signal into epochs from 1.5 seconds before to 1.5 seconds after stimulus presentation, which would suggest that post-stimulus connectivity analysis is possible. However, in the limitations section, you note that post-stimulus analysis is not feasible due to participants' rapid responses (as early as 400 ms). Could you clarify this point? Specifically, is it possible to conduct any preliminary post-stimulus analysis within the available 1.5-second epoch, even if limited?

Reviewer #3: In this paper, authors investigated the effects of external (monitoring condition) and internal (maintenance condition) attention to detect a Prospective Memory cue on functional connectivity using MEG data. The neurosphysiological data demonstrated that the monitoring-load condition with respect to the baseline condition was characterized by increased inter-network FC of the DAN and that the maintenance-load condition (with respect to the baseline condition) was characterized by increased inter-network connectivity between the VAN and the FPN and the DMN. Both the modulations are observed in the alpha band. In addition, the authors hypothesized specific modulations in the theta band that however failed to reach significance after the correction of multiple comparisons for probable methodological concerns (i.e. the length of the prestimulus time window). The aim of the work is clear and well written.

Comments:

I understand why the authors focus the analysis on the networks involved in PM processing (i.e. DAN, DMN and VAN) and on the FPCN. However I believe that showing functional connectivity also within and between the other Yeo networks (not employed in this study) could strengthen the specificity of the results. If the authors believe that this whole-brain analysis would worsen the clarity of the text, they could add findings in supplementary materials.

In addition, I think that it would be very interesting to evaluate the directionality of these interactions in the frequency domain, for example using the directed transfer function that has been used on MEG data at the source level (e.g. using the Atlantis Processing Toolbox: atlantis.psychologia.uj.edu.pl, Spadone et al., 2021 Brain Connectivity). The authors could investigate this in future research and discuss the importance of examining directionality in communication.

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

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<p>Prestimulus functional connectivity reflects attention orientation in a prospective memory task: a magnetoencephalographic (MEG) study

PONE-D-24-30533R1

Dear Dr. VICENTIN,

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,

Farzin Hajebrahimi, Ph.D

Academic Editor

PLOS ONE

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

Reviewer #3: 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

Reviewer #3: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: 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

Reviewer #2: Yes

Reviewer #3: 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

Reviewer #2: (No Response)

Reviewer #3: 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: It is unclear why the authors chose not to include a scale or unit for the colorbar in the figures, despite this being an important aspect for interpretation. In their response, they stated, “The scale on the left represents t-values derived from statistical comparisons.” Could the authors clarify if they are referring to the color squares on the left as representing t-values from the statistical comparisons? Including a clear and explicit scale/unit for the colorbar would greatly enhance the clarity and interpretability of the figures.

Reviewer #2: I agree with the changes made to the manuscript, as they effectively address the comments and questions raised in the previous review round. This article sheds light on a relatively unexplored area within prospective memory research, and I believe it will be of great value to the journal's readers and researchers in the field.

Reviewer #3: Thank you for addressing my concerns. The manuscript is technically sound, and data support the conclusions.

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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: Yes:  Cristina López-Rojas

Reviewer #3: No

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