PONE-D-19-23160

Repeated noninvasive stimulation of the ventromedial prefrontal cortex reveals cumulative amplification of pleasant compared to unpleasant scene processing: a single subject pilot study

PLOS ONE

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Academic Editor

PLOS ONE

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Reviewers' comments:

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Comments to the Author

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Reviewer #1: Yes

Reviewer #2: Partly

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

Reviewer #1: I Don't Know

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

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Reviewer #1: This manuscript examined a single-subject pilot study of repeated noninvasive stimulation on the ventromedial prefrontal cortex, suggesting a cumulative effect of repeated tDCS on the valence processing of emotional stimuli.

The abstract summarized the primary outcomes of the study and is logical. The introduction contains three paragraphs, and the first paragraph illustrated the vital role of vmPFC on emotion processing and the different activity pattern of pleasant and unpleasant stimuli. The second paragraph demonstrated the single tDCS effect on vmPFC. It revealed an increased neuronal activation of pleasant stimuli after excitatory tDCS and vice versa after inhibitory tDCS. It then pointed out the inconsistent outcomes of consecutive tDCS stimulation and the rationale of conducting the new tDCS paradigm. The third paragraph showed the hypothesizes of the research.

For the method, authors clearly described tDCS paradigm and MEG procedure. However, it seems a bit unclear about the passive viewing procedure. I am a bit confused whether the passive viewing task uses the same pictures in each tDCS sessions, or different pictures in each session? How the valence of pictures balanced? Besides, the study design without a sham tDCS group, how to prevent the placebo effect of the subject, especially under the non-blind condition?

The result is answered the three hypothesizes, and the three figures also well displayed the outcomes.

In the discussion part, the authors explained the relationship between three occurred cluster and tDCS stimulation, pointing out the possible changes of the neuroplasticity. Author also depicted potential limitations, especially the non-blind condition.

Reviewer #2: Comments to the Corresponding Author

The manuscript focuses on the cumulative emotional modulation of tDCS. The theme is worth studying and the manuscript makes good reading. However, there are several issues of concern that need to be addressed:

1) One big problem is the reliability and repeatability of the result. All findings were from a case, lacking of control condition that limits the interpretation and conclusions about the clinical significance of the results. The interpretation of the results is speculative, as mentioned in the limitations, these might be explained by inter-individual differences, and need to be tested in a representative sample.

2) The introduction seems to be too short and too vague. The authors need to provide a more comprehensive theoretical and empirical literature review of the associations between emotional modulation and repeated tDCS to highlight the importance of repeated tDCS in emotional processing research.

3) The interval between sessions of inhibitory stimulation and sessions of excitatory stimulation seems too long (one month), why?

4) How long did each stimulus present? How long is the interval between stimuli? More details are needed to describe the viewing task in Procedure.

5) Could you give further elaboration of results? It may be more readable and clearer to combine the analysis and result part.

6) In the discussion, author mentioned “While such implicit effects might potentially explain the non-cumulative effects across sessions it is unlikely to explain the cumulation of effects”, can you give a clearer explanation?

7) The authors admit the limitation of the study in that non-blinding design may cause additional influence such as attention. What ways do the authors consider can be used to examine or control this influence? Also, in the further study, single-blind or double-blind design might be more proper.

In sum, I had upon carefully reading this paper, though the research topic is of interest to many researchers in emotional modulation as well as in brain stimulation, but it needs much improvement.

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Reviewer #1: No

Reviewer #2: No

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Repeated noninvasive stimulation of the ventromedial prefrontal cortex reveals cumulative amplification of pleasant compared to unpleasant scene processing: a single subject pilot study

PONE-D-19-23160R1

Dear Dr. Junghoefer,

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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With kind regards,

Tifei Yuan

Academic Editor

PLOS ONE

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