Anxiety makes time pass quicker: neural correlates

  1. I Sarigiannidis
  2. K Kieslich
  3. C Grillon
  4. M Ernst
  5. JP Roiser
  6. OJ Robinson

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Abstract

Anxiety can be an adaptive process that promotes harm avoidance. It is accompanied by shifts in cognitive processing, but the precise nature of these changes and the neural mechanisms that underlie them are not fully understood. One theory is that anxiety impairs concurrent (non-harm related) cognitive processing by commandeering finite neurocognitive resources. For example, we have previously shown that anxiety reliably ‘speeds up time’, promoting temporal underestimation, possibly due to loss of temporal information. Whether this is due anxiety ‘overloading’ neurocognitive processing of time is unknown. We therefore set out to understand the neural correlates of this effect, examining whether anxiety and time processing overlap, particularly in regions of the cingulate cortex. Across two studies (an exploratory Study 1, N=13, followed by a pre-registered Study 2, N=29) we combined a well-established anxiety manipulation (threat of shock) with a temporal bisection task while participants were scanned using functional magnetic resonance imaging. Consistent with our previous work, time was perceived to pass more quickly under induced anxiety. Anxiety induction led to widespread activation in cingulate cortex, while the perception of longer intervals was associated with more circumscribed activation in a mid-cingulate area. Importantly, conjunction analysis identified convergence between anxiety and time processing in the insula and mid-cingulate cortex. These results provide tentative support for the hypothesis that anxiety impacts cognitive processing by overloading already-in-use neural resources. In particular, overloading mid-cingulate cortex capacity may drive emotion-related changes in temporal perception, consistent with the hypothesised role of this region in mediating cognitive affective and behavioural responses to anxiety.

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  1. eLife

    ###Reviewer #3

    Introduction:

    1. For those not familiar with personality/trait constructs, harm avoidance should be defined.

    2. The authors unnecessarily make a distinction between emotion and cold cognition, or emotion and non-emotional perception. I don't think this distinction needs to be made and furthermore, the separation of emotion and cognition is a little antiquated in what we know about holistic processing of the brain.

    3. There is no mention of the amygdala or bed nucleus of the stria-terminalis in discussions of anxiety and especially in anticipation. Nor is there any mention of anticipatory or arousal components of anxiety.

    4. There are two competing points brought up in the introduction, regarding the pre-SMA: 1) that the pSMA is involved in time tracking and 2) that the pSMA is involved in threat related shock. This appears to be problematic due to the proposed hypotheses. Perhaps, the authors could adjust the hypotheses to illustrate why only time perception is a main effect hypothesis and time and anxiety are an interaction hypothesis.

    5. Hypothesis 5 is unclear, I assume the brain (neural changes) are being correlated with time estimation (behavioral index?), but it is unclear.

    Methods:

    1. Nim-Stim images need to be described in more detail in the methods and not just in the figure caption.

    2. The experimental methods specifics needs to be more clear regarding the differences in stimulus duration. This is an important distinction between the two studies and not enough details are given. It should be clearly worded and not left up to the reader to try and interpret the table.

    3. Why did the number of shocks differ between participants? That seems like a confound for the neural interpretation. The authors need to explain.

    4. There is no mention of fMRI screening for Study 1.

    5. Why a power calculation for Study 2, but not 1?

    6. The methods section is written such that the amount of explanation between the two studies needs to be resolved. They are quite different, i.e., how many total shocks in Study 1? There are inconsistencies throughout.

    7. Why are different analysis methods used to examine behavioral effects? ANOVA vs. paired sample t test? Details like this need to be explained throughout the manuscript if the authors are trying to compare two data sets.

    8. It isn't clear or mentioned that Study 1 was a pilot study for Study 2 until the neuroimaging analysis section. This needs to be explained and more detail should be included much earlier in the manuscript.

    9. For information: Siemens Skyra and Prisma scanners have built in dummy scans at the beginning of sequences to allow for equilibration.

    10. The neuroimaging methods require much more detail, i.e., SPM version used, etc., etc.

    11. ROIs description needs more detail, i.e., a 10mm sphere. 10mm what? Radius, circumference? That's a huge ROI for subcortical regions.

  2. eLife

    ###Reviewer #2

    The manuscript "Anxiety makes time pass quicker: neural correlates" outlines an interesting and potentially important set of experiments aimed at replicating a previously reported effect of distorted time perception while under threat of electric shock while adding fMRI measurement of brain activity during the task. The manuscript has multiple strengths, in my opinion, including the use of a cleverly designed paradigm coupled with sophisticated neuroimaging methods, pre-registered predictions and analysis plan, and a potentially informative mechanistic focus. The study is also well grounded in the literature and the manuscript well written. I have some concerns, however, with the current version of the manuscript. These concerns mostly center on the strength of evidence afforded by the current design and the interpretability of the design and results. I outline these concerns, point by point below.

    1. The choice to pre-register the predictions and analysis plan is laudable. For clarity, I believe the authors should indicate, up front, what aspects of the study were pre-registered rather than simply saying that it is pre-registered.

    2. There are potentially important differences between the study pre-registration and the reported hypotheses and analysis. Sticking rigidly to the pre-registration is certainly not necessary to benefit from a pre-registration but I believe all potentially substantive deviations from the pre-registration should be identified and explained in the manuscript for transparency. For example, the specific brain regions mentioned in Prediction 2 are not consistent between the manuscript and pre-registration.

    3. In the pre-registration, I didn't see Prediction 4 (interaction of time-related and anxiety-related neural processing) but this may be attributable to inconsistent wording between the pre-registration and manuscript.

    4. The pre-registration discusses planned hypotheses and analysis involving functional connectivity but I do not see this mentioned in the manuscript.

    5. Some description of why faces (versus anything else) were used as stimuli is needed for readers to understand the task.

    6. Related to point 6 above, it is reported that the durations of stimuli were randomized but I did not see a description of randomization of the face stimuli themselves. This is needed (if I didn't just miss it).

    7. The authors indicated that the study was powered to detect the effect of threat on (I assume) behavior. I would guess that this is one of the largest effects that could be tested for in this study. In fact, the study appears underpowered to detect anything but very large effects. This could explain why many effects tested were not found (especially the interactions). I believe this should be explicitly acknowledged as a limitation for readers to be able to appropriately evaluate the strength of evidence for the claims made.

    8. Given the short ITIs in the task, perhaps the effects attributed to anxiety caused by threat of shock are in actuality effects due to continued processing of the previous aversive shock. I know the authors said they regressed out the effect of shock from the brain measures but it is unclear how one would regress out the effects of processing of previous shocks. Perhaps this potential confound has been addressed in previous reports of this task but I think some brief attention to the issue here would help readers to evaluate the results.

    9. Given the fact that shocks always occurred during the ITI and never during the cue, readers may be left wondering if the participants were indeed anxious versus, e.g., distracted, during the temporal decision task since they technically are not even yet at risk of receiving a shock at that moment of the task. Some clarification of this point would be helpful.

    10. Related to and overlapping with some of the points above, I request that the authors add a statement to the paper confirming whether, for the experiment, they have reported all measures, conditions and data exclusions and how they determined their sample sizes. The authors should, of course, add any additional text to ensure the statement is accurate. This is the standard reviewer disclosure request endorsed by the Center for Open Science [see http://osf.io/hadz3 ]. I include it, where appropriate, in every review.

  3. eLife

    ###Reviewer #1

    This manuscript reports a pair of studies investigating the neural correlates of the temporal underestimation that has been shown to accompany anxiety in previous studies. Hypotheses were pre-registered, including increased activation in the anterior cingulate during threat and that "threat-related bold signal changes will correlate with the threat related behavioural changes". The current work found threat-related activity in the anterior cingulate gyrus, and that greater mid-cingulate activity for longer estimates of stimulus duration, with a trend toward overlap between these contrasts, which was subthreshold after correcting for multiple comparisons. In addition, activity associated with state anxiety and temporal estimation overlapped in the insula and putamen. The authors interpret these findings as consistent with the overloading hypothesis that vigilance during state anxiety and duration perception rely on overlapping areas, resulting in inaccurate duration perception during anxiety. However, these results should be interpreted with caution given that, as the authors note, there was no interaction between threat and perceived duration, and no correlation "between the underestimation of time during threat and either insula or midcingulate activation in the interaction contrast". Given the relatively small sample size, these null findings may have been the result of low power. Nevertheless, the current study will likely serve as a useful starting point for future work on this topic.

    Below are my comments on the manuscript:

    1. In the pre-registration, hypothesis 2 refers to the ACC and frontopolar areas, while in the manuscript I am not seeing the frontopolar areas. I know this region is particularly susceptible to dropout, so it is possible you were unable to adequately test this hypothesis – if so, this should be stated in the manuscript. In addition, the manuscript lists right IFG in the hypotheses, but I am not seeing results reported for this region.

    2. It would be good to explain why you chose to use 10 mm spheres centered on your ROIs, rather than using all voxels that met the p>.05 threshold in the clusters identified in Study 1.

    Minor comments:

    The abstract starts off talking about how anxiety can be adaptive, however, unless I missed something, they don't explicitly tie this thought into temporal underestimation. From the perspective of someone who is naive to literature on temporal underestimation, it seems that causing temporal underestimation would be maladaptive, if it causes one to underestimate how long you've been worrying about something. I would suggest either making the relationship between these ideas more explicit in the text, or either removing this first sentence or moving it to a less prominent spot.

    If there was a methodological reason for switching to a train of shocks (ex. an expectation that it would elicit more anxiety) in Study 2, it may be helpful for future researchers to state it. If it was simply a matter of equipment available at the second site, then no changes are needed.

  4. eLife

    ##Preprint Review

    This preprint was reviewed using eLife’s Preprint Review service, which provides public peer reviews of manuscripts posted on bioRxiv for the benefit of the authors, readers, potential readers, and others interested in our assessment of the work. This review applies only to version 1 of the manuscript.

    ###Summary:

    This manuscript reports a pair of studies investigating the neural correlates of the temporal underestimation that has been shown to accompany anxiety in previous studies. Hypotheses were pre-registered, including increased activation in the anterior cingulate during threat and that "threat-related bold signal changes will correlate with the threat related behavioural changes". The current work found threat-related activity in the anterior cingulate gyrus, and that greater mid-cingulate activity for longer estimates of stimulus duration, with a trend toward overlap between these contrasts, which was subthreshold after correcting for multiple comparisons. In addition, activity associated with state anxiety and temporal estimation overlapped in the insula and putamen. The authors interpret these findings as consistent with the overloading hypothesis that vigilance during state anxiety and duration perception rely on overlapping areas, resulting in inaccurate duration perception during anxiety.

    The reviewers and I identified several strong points:

    1. The current study may serve as a useful starting point for future work.

    2. Interesting set of experiments aimed at replicating a previously reported effect of distorted time perception while under threat of electric shock while adding fMRI measurement of brain activity during the task.

    3. Clever paradigm.

    4. Pre-registered predictions and analytic plan.

    5. Grounded in the literature.

    Yet, on balance, there was consensus that the study provides only an incremental advance, largely owing to limitations of the approach.

    Major/general concerns are:

    1. Insufficient power. E.g.

    -"The authors indicated that the study was powered to detect the effect of threat on (I assume) behavior. I would guess that this is one of the largest effects that could be tested for in this study. In fact, the study appears underpowered to detect anything but very large effects. This could explain why many effects tested were not found (especially the interactions). I believe this should be explicitly acknowledged as a limitation for readers to be able to appropriately evaluate the strength of evidence for the claims made."

    -"The results should be interpreted with caution given that, as the authors note, there was no interaction between threat and perceived duration, and no correlation "between the underestimation of time during threat and either insula or midcingulate activation in the interaction contrast". Given the relatively small sample size, these null findings may have been the result of low power."

    1. Writing style. The reviewers found the lack of attention to polishing the manuscript distracting, e.g. "The methods section appears to be written by two different authors with major inconsistencies in style and phrasing"

    2. Missing details. Crucial methodological details are lacking or inconsistent, making it difficult to fully evaluate the approach

  5. Version published to 10.1101/2020.07.11.198390 on bioRxiv