PONE-D-24-02974Loneliness and the persistence of fear: Perceived social isolation reduces evaluative fear extinctionPLOS ONE

Dear Dr. Eisenberger,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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The manuscript has elicited positive feedback from both reviewers, who have acknowledged the commendable execution of the study and the articulation of the paper. Nonetheless, both reviewers have highlighted significant concerns regarding the manuscript's positioning within the extensive body of literature on loneliness and fear conditioning. A particular point of contention is the methodological approach adopted in the study, notably the preference for subjective reports over objective measures such as skin conductance response. This methodological choice has been identified as a potential weakness by one reviewer, a critique that finds some justification within the traditional animal literature context. However, it is also pertinent to note that recent discussions within the field have begun to challenge the validity of fear conditioning as a reliable measure of fear. The reliance on subjective reports for assessing both loneliness and fear conditioning/extinction introduces complex issues that merit careful consideration. We strongly encourage the authors to address these critical points, alongside the detailed feedback provided by the reviewers, to enhance the manuscript's contribution to the field.

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Additional Editor Comments :

Editorial Feedback

The manuscript has elicited positive feedback from both reviewers, who have acknowledged the commendable execution of the study and the articulation of the paper. Nonetheless, both reviewers have highlighted significant concerns regarding the manuscript's positioning within the extensive body of literature on loneliness and fear conditioning. A particular point of contention is the methodological approach adopted in the study, notably the preference for subjective reports over objective measures such as skin conductance response. This methodological choice has been identified as a potential weakness by one reviewer, a critique that finds some justification within the traditional animal literature context. However, it is also pertinent to note that recent discussions within the field have begun to challenge the validity of fear conditioning as a reliable measure of fear. The reliance on subjective reports for assessing both loneliness and fear conditioning/extinction introduces complex issues that merit careful consideration. We strongly encourage the authors to address these critical points, alongside the detailed feedback provided by the reviewers, to enhance the manuscript's contribution to the field.

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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: Yes

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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: 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: This manuscript presents a large-scale study of the effects of loneliness on the extinction of evaluative fear learning. The authors extend with this work their previous findings with classical fear conditioning. The topic of the manuscript is of interest and importance to better understand how loneliness may have an impact on fear extinction processes and therefore also clinical fear exposure. The methods are sound and the manuscript is well written.

I just have a few minor points that I would like to see implemented:

- Abstract: Please add more information about the methods used. Given the large sample size used, it would also be good to see the final n used for the extinction analysis already here.

- Throughout the manuscript there are frequent references to manuscripts in preparation or submitted. I am not sure what Plos One's policy is on this, but I would prefer to see a reference to a pre-registration or preprint so that the reader can actually read the source of the reference. For example, in the Methods "(see: L. Lazar, EAH (author), & 181 NIE (author), in prep))

- Methods: "(...) protocols designed to examine the effects of a prosocial behavior intervention on feelings of well-being" There is no indication that the study was pre-registered. Was this analysis or the larger study pre-registered somewhere? If so, please provide a reference.

- It’s not clear what is used as the “9 target neutral images”. Are these also images from the IAPS with the same neutral content as the secondary neutral images used for the evaluative conditioning? Please clarify this in the methods.

- l.364, l.393 The justification of the results should be in the Discussion section only.

Reviewer #2: This paper studied the fear learning and extinction in high and low loneliness participants. And the authors found that the patterns of the extinction of the evaluative fear associations were different between the high and low individuals. This manuscript presents a compelling and well-executed study that significantly contributes to the field of social bonds on fear learning. The authors demonstrate a thorough understanding of the research topic and employ a rigorous methodology to investigate their research questions. Overall, the manuscript is well-written, engaging, and likely to generate interest among readers. However, there are still some questions in the manuscript. The details are as follows:

Major questions

1. In the Introduction, the authors mentioned the negative influence of perception of being socially isolated on mental health outcomes and they also mentioned that no study have invested the associations between loneliness and fear learning. The definition between perception of social isolation and social exclusion are very similar. According to previous study (Cacioppo&Cacioppo, 2016), Social exclusion has been defined broadly as “the experience of being kept apart from others physically or emotionally， Therefore, perception of social isolation, ostracism, and romantic rejection fall under the broad rubric of social exclusion”. Thus, Dou et al.(2020) have already investigated that the influences of social exclusion on fear learning in humans and found the participants after social exclusion inhibited fear conditioning compared with those after social inclusion. Surprisingly, I found the authors introduced lots of animal’s studies, rather than mentioned this closely related paper in humans in the introduction section.

2. In the introduction and discussion sections, the authors used a large amount sentence to interpret that the anxiety may play an important role in relation between loneliness and fear extinction. However, the author did not report any anxiety score for each participant. As the authors mentioned, the individuals with anxiety disorders showed a dysfunction patterns during the classical conditioning and extinction(Lissek et al., 2005; Duits et al., 2015). Whether the high loneliness groups showed higher anxiety scores compared to the low loneliness groups? Thus, whether the different patterns of extinction in high/low loneliness were also due to the differences of anxiety scores?

3. Similarly, the lots of previous studies(Cacioppo et al., 2006; Erzen & Çikrikci, 2018; Matthews et al., 2016; Singh & Misra, 2009) have already reported loneliness showed a close relationship with depression, even in different ages, such as youth, adult, and elderly. Moreover, previous research have reported individuals with depression showed dysfunction in affective processing, especially the reward learning(Admon & Pizzagalli, 2015). During this study, whether the depression showed a significant difference between the high and low loneliness group? And what role did the depression play between the loneliness and reward learning and extinction?

4. In the previous fear learning and extinction paradigm, compared to subjective ratings, some physiological responses to conditioned stimulus(CS) (such as skin conductance responses, SCR) were more widely used((Lonsdorf et al., 2017). Thus, the dependent variables in this manuscript were only the subjective ratings, which might influence accuracy of the results of the acquisition and extinction. I think this is a limitation in this manuscript.

5. Similarly, the habitation stage was also common adopted in the conditioning studies, which could reduce the extra variable evoked by the stimuli. However, the authors did not adopt the habitation stage in this study.

6. Although the influence of the different interventions (including prosocial behavior intervention, self-kindness internation, and control) are calculated, the influence of on the extinction might also mixed in the experiment, which might be better to add in the limitation section.

7. Although the authors set the cut-off for the loneliness or not, I am still curious about the correlation between UCLA scores and the ratings in both of the acquisition and extinction throughout the whole samples.

Minor questions

1. The figure of the procedure was not clear enough. What were the details in the acquisition section? Whether the CS and US presented on the screen at the same time or not?

2. In figures of acquisition and extinction, the error bar were missing, which could be added to improve the quality of the figures.

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Reviewer #1: No

Reviewer #2: Yes: Haoran Dou

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Loneliness and the persistence of fear: Perceived social isolation reduces evaluative fear extinction

PONE-D-24-02974R1

Dear Dr. Eisenberger,

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,

Rei Akaishi

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

The revisions submitted by the authors have been both thorough and meticulous. The manuscript now satisfactorily addresses all the concerns raised during the initial review. The authors have diligently incorporated the suggested changes, enhancing both clarity and coherence throughout the document. Moreover, the revisions reflect a deep and comprehensive understanding of the subject matter, as demonstrated by the nuanced responses to all inquiries. Overall, the careful and detailed nature of these revisions has significantly improved the manuscript, making it ready for publication.

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: (No Response)

Reviewer #2: Yes

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

Reviewer #1: (No Response)

Reviewer #2: 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: (No Response)

Reviewer #2: 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: (No Response)

Reviewer #2: 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: (No Response)

Reviewer #2: The revisions made by the authors have been thorough and detailed. The manuscript now adequately addresses all the queries raised during the initial review process. The author has diligently incorporated the suggested changes, providing clarity and coherence throughout the document. Additionally, the revisions demonstrate a comprehensive understanding of the subject matter, as evidenced by the nuanced responses to all inquiries. Overall, the meticulous nature of the revisions ensures that the manuscript is now significantly improved and ready for further consideration.

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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: Haoran Dou

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