-->PONE-D-25-64475-->-->Inter-brain functional connectivity: Are we measuring the right thing?-->-->PLOS One

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Additional Editor Comments:

Dear authors

Attached are the reviews of your manuscript. As you will notice, particularly in the feedback from Reviewer 1, there are several significant issues that need to be addressed or clarified before your manuscript can be considered for publication again. Please ensure that you address these points while preparing the revised version if you wish to resubmit your manuscript for consideration.

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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: Yes

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: 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 this ms. the authors describe a much needed and timely study, in which they have used simulations of MEG and EEG data to highlight the need of developing novel and robust connectivity measures for use in inter-/cross-brain analyses of interacting dyads. They start out by reviewing the state of the art, the growing numbers of hyperscanning studies and group studies by the type of connectivity metric used. The authors cogently argue that previous studies have not been able to comprehensively account for inter-individual frequency differences (both across and within individual brains), which explains the need for methodological developments to address this issue. In their simulations they used oscillatory signals with a fixed for one interaction partner and with varying frequency for the other person, while employing various measures of cross-brain functional connectivity in the alpha band. These analyses were repeated for variable SNRs. Results demonstrate that phase-based interbrain connectivity measures were highly sensitive to inter-individual peak frequency differences. In contrast to this, amplitude-envelope-based measures of inter-brain connectivity were more robust to such differences and provide a more reliable measure of amplitude coupling. SNR reductions decreased connectivity estimates for all measures. I only have minor comments and strongly support the publication of this well-written ms. that is likely to make strong contribution to the relevant literature.

-Would it not make sense to also use sets of oscillatory signals with varying frequency for both interaction partners? In recent years, the social interaction mismatch hypothesis as been formulated (e.g. Redcay & Schilbach 2019) and describes the idea that interpersonal similarity - at different levels of scientific assessment - could be related to communication success. Could the here described simulations be extended to address this?

-The authors note that their MEG/EEG signal simulations as continuous sinusoidal oscillations modulated by an identical aperiodic signal that is unlikely to occur in real life, but do not go into any detail how this could be changed or addressed in future research. I would find this quite helpful.

-In the discussion the authors suggest that connectivity metrics should take human physiology into account, but leave open how this could be done. Are thinking more in terms of brain physiology or would they also consider whole-body physiology, as for instance suggested by the growing field of brain-heart-introspection science?

-The authors also stress that cross-brain connectivity measures should be related to social behavior, but also do not touch upon recent developments towards observer-dependent measures of social interaction (e.g. Lahnakoski et al. 2020 and others) that might be helpful along the way.

Reviewer #2: This manuscript uses simulations to examine a well-known property of same-frequency phase-based synchrony metrics in the specific context of MEG/EEG hyperscanning: when two signals have different dominant (peak) frequencies, phase-based measures computed within a fixed band can rapidly lose apparent synchrony. In the presented simulations, PLV and coherence decrease as the peak frequency of participant 2 diverges from participant 1, while amplitude envelope correlation (AEC) remains relatively stable. The question is relevant to hyperscanning practice because inter-individual peak-frequency variability is common, and many studies still apply within-brain connectivity measures to across-brain data without explicit frequency alignment.

However, several aspects of the simulation design and the framing of conclusions make the paper’s claims broader than what is demonstrated. In particular, the simulations appear to favour AEC by construction (shared envelope modulator across participants) and do not establish “ground truth” coupling conditions needed to support strong claims about reliability or about the extent of misestimation in the literature. In addition, novelty and positioning relative to prior methodological discussions are unclear.

Major comments

1. The central effect demonstrated—that phase synchronization metrics at a given frequency degrade when the compared signals are at different frequencies—is a general property of same-frequency phase metrics, not something unique to inter-brain analyses. The manuscript frames the issue as a “critical limitation” of hyperscanning work, but the novelty is currently unclear unless the authors show what is specifically different (or more severe) in hyperscanning practice versus within-brain connectivity (e.g., typical cross-person mismatch distributions, developmental dyads, region-specific peak differences, time-varying peak frequency, etc.). As written, the work risks restating a general signal-processing property without sufficiently demonstrating new insight specific to hyperscanning.

2. Based on the Methods, P1 and P2 signals appear to be generated independently except for sharing an identical slow aperiodic modulator (the oscillation is “amplitude-modulated by an identical aperiodic 1/fχ signal”). This design choice is important: it makes amplitude envelopes correlated across participants by construction, which will favour AEC even when carrier frequencies differ. The Discussion acknowledges that the AEC scenario is idealized, but the main take-home message still implies AEC is broadly “more reliable.”

To support claims about “reliable connectivity estimates,” the simulations should include explicit ground-truth conditions that separate:

• true inter-brain phase coupling (present vs absent),

• true inter-brain amplitude coupling (present vs absent),

• common-driver scenarios (shared exogenous modulation), and

• correlated noise across participants versus independent noise.

Without these controls, the current AEC result is not an informative benchmark for real hyperscanning datasets, where stimulus-locked co-modulation and shared environmental noise are common confounds.

3. Only PLV and “coherence” are used as phase-based measures. Hyperscanning papers commonly use phase-lag metrics aimed at mitigating spurious zero-lag coupling and mixing artefacts (e.g., imaginary coherence, wPLI). Even if these metrics are still sensitive to frequency mismatch, readers will expect them to be considered or clearly explained as out of scope. At minimum, the authors should either (a) include representative phase-lag metrics to show that mismatch sensitivity generalises, or (b) explicitly restrict the scope to frequency-mismatch effects and avoid general claims about “phase-based metrics” in hyperscanning.

Similarly, AEC is often computed with additional steps (e.g., orthogonalization) in EEG/MEG connectivity work to reduce leakage-driven correlations. Because the manuscript raises signal mixing as relevant (especially for EEG), the choice of AEC implementation and its implications should be discussed and/or tested.

4. Band definition and common alignment strategies are not tested

The simulation computes connectivity in a fixed alpha band (7–13 Hz) while P1 is fixed at 10 Hz and P2 varies 6–14 Hz. Many analysis pipelines instead use individual alpha frequency (IAF)-centred bands or compute connectivity at subject-specific peaks. If the practical recommendation is that researchers should not assume identical peak structure across brains, the paper would be more actionable if it tested at least one standard mitigation strategy (e.g., IAF±2 Hz per person, or connectivity computed at each participant’s own peak with an explicit cross-person mapping). As presented, the simulations quantify the expected failure mode of fixed-band, same-frequency phase metrics under mismatch—but do not show how much standard practices mitigate the issue.

5. Claims about the literature are stronger than the evidence provided

The manuscript suggests that many hyperscanning studies “may have misestimated” inter-brain interdependencies due to unaccounted frequency differences. This is plausible, but currently speculative. The paper does not provide evidence about typical mismatch magnitudes in real hyperscanning datasets, nor does it quantify how often common pipelines would produce meaningful underestimation or false negatives. A more defensible statement, based on the simulations shown, would be: phase-based measures computed within a fixed band can strongly underestimate coupling when peak frequencies differ; therefore, studies assuming aligned peaks without testing alignment risk underestimating inter-brain coupling and producing inconsistent results across samples.

Minor comments

1. Define “accuracy,” “reliability,” and “robustness” quantitatively. These terms are used somewhat interchangeably.

2. Tone in the final paragraph

The phrase about “tempering enthusiasm” is rhetorically strong. It would read as more scientifically grounded if tied directly to the demonstrated limitations (frequency mismatch + metric choice + confounds), rather than as a general statement about “simplified indices.”

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Reviewer #1: Yes: Leonhard Schilbach

Reviewer #2: No

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Inter-brain functional connectivity: Are we measuring the right thing?

PONE-D-25-64475R1

Dear Dr. Avendano-Diaz,

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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Kind regards,

Kiyoshi Nakahara, PhD

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: (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

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