Edited by: Alexander J. Shackman, University of Maryland, USA
Reviewed by: Michael X. Cohen, University of Amsterdam, Netherlands; Alexander J. Shackman, University of Maryland, USA; Nathan Fox, University of Maryland, USA; James F. Cavanagh, Brown University, USA; Greg Hajcak, Stony Brook University, USA; Joseph M. Orr, University of Colorado at Boulder, USA
*Correspondence: Jason S. Moser, Department of Psychology, Michigan State University, Psychology Building, 110-B, East Lansing, MI 48823, USA e-mail:
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Research involving event-related brain potentials has revealed that anxiety is associated with enhanced error monitoring, as reflected in increased amplitude of the error-related negativity (ERN). The nature of the relationship between anxiety and error monitoring is unclear, however. Through meta-analysis and a critical review of the literature, we argue that anxious apprehension/worry is the dimension of anxiety most closely associated with error monitoring. Although, overall, anxiety demonstrated a robust, “small-to-medium” relationship with enhanced ERN (
Anxiety is a common human experience characterized by a variety of symptoms, including worrisome thoughts, physiologic arousal, and strategic avoidance behaviors (Barlow,
One especially active area of neuroscience research aimed at tackling this issue has focused on how anxiety is related to error monitoring. Error monitoring concerns the signaling and detection of errors in order to optimize behavior across a range of tasks and situations, and this monitoring function is therefore a fundamental component of behavioral regulation. A growing body of research indicates that anxiety is associated with enhanced amplitude of the error-related negativity (ERN) of the human event-related brain potential (ERP), suggesting that anxiety is associated with exaggerated error monitoring (Olvet and Hajcak,
Anxiety is not a monolithic construct, however. Researchers and laypersons alike use the term “anxiety” to refer to many different states and traits such as “stress,” “fear,” “worry,” among others (cf. Barlow,
The purpose of the current review is to expand on this argument in two important ways: (1) by conducting the first large-scale test of this hypothesis using meta-analysis, and (2) by providing a detailed conceptual framework that can be used to generate mechanistic hypotheses and guide future studies. Regarding the latter, we leverage four key findings about anxiety and cognitive control: (1) anxious apprehension/worry is significantly involved in cognitive abnormalities in anxiety; (2) anxious performance is characterized by processing inefficiency; (3) enhanced ERN in anxiety is observed without corresponding deficits in task performance; and (4) individuals with chronic anxiety exhibit enhanced transient “reactive” control but reduced preparatory “proactive” control. We used these findings to develop a new
The ERN is an ERP component that reaches maximal amplitude over frontocentral recording sites within 100 ms after response errors in simple reaction time tasks (See Figure
The confluence of cognitive and emotional processing within the dACC/MCC has contributed to disagreements among researchers regarding the functional significance of the ERN. To date, however, the two dominant models of the function significance of the ERN are the conflict monitoring (Yeung et al.,
Numerous studies have noted that individual differences in anxiety are associated with increased ERN amplitude (for reviews, see Olvet and Hajcak,
Despite evidence pointing to a specific association between anxious apprehension and enhanced ERN, very few empirical demonstrations of this specificity have been conducted. We aimed to address this gap by employing meta-analysis to provide a large-scale test of the hypothesis that anxious apprehension is the dimension of anxiety most closely associated with enhanced ERN.
Although our main focus for the meta-analysis is on the ERN, we also report findings related to the correct-response negativity (CRN). The CRN is a negative ERP component observed following correct responses that has similar topography, morphology, and perhaps functional significance to the ERN (See Figure
Published studies examining the ERN and anxiety were initially identified using the MEDLINE-PubMed and Google Scholar databases using the terms “anxiety,” “OCD,” “GAD,” “obsessive-compulsive,” “generalized anxiety,” “worry,” “action monitoring,” “performance monitoring,” “conflict monitoring,” “error-related negativity,” “Ne,” and “ERN.” Additional studies were identified from the reference sections of the articles obtained from the online searches and from contacting investigators for additional unpublished datasets. This initial search yielded a total of 75 studies and datasets.
Figure
Using our inclusion/exclusion criteria, a total of 37 studies were included in the present meta-analysis (see Table
Aarts and Pourtois, |
Volunteers | Go/NoGo | STAI-T | M |
Amodio et al., |
Volunteers | Go/NoGo | BIS | AA |
Beste et al., |
Volunteers | Go/NoGo flanker | ASI | M |
Boksem et al., |
Volunteers | Letter flanker | BIS | AA |
Carrasco et al., |
Pediatric OCD | Arrow flanker | K-SADS-PL | AA |
Carrasco et al., |
Pediatric OCD | Arrow flanker | K-SADS-PL | AA |
Carrasco et al., |
Pediatric anxiety | Arrow flanker | K-SADS-PL | AA |
Cavanagh and Allen, |
Volunteers | Letter flanker | BIS | AA |
Chang et al., |
Volunteers | Letter flanker | ASR | M |
Gehring et al., |
OCD | Color stroop | SCID | AA |
Gründler et al., |
Volunteers | Letter flanker | OCI-R | AA |
Hajcak et al., |
Pediatric OCD | Simon | Y-BOCS | AA |
Hanna et al., |
Pediatric OCD | Arrow flanker | K-SADS-PL | AA |
Inzlicht et al., |
Volunteers | Color stroop | BIS | AA |
Inzlicht et al., |
Volunteers | Color stroop | BFI-N | M |
Johannes et al., |
OCD | Go/NoGo | SCID | AA |
Kaczkurkin, |
Volunteers | Letter flanker | OCI-R | AA |
Ladouceuer et al., |
Pediatric anxiety | Arrow flanker | K-SADS-PL | M |
Larson and Clayson, |
Volunteers | Arrow flanker | STAI-T | M |
Larson et al., |
Volunteers | Color stroop | STAI-T | M |
Larson et al., |
Volunteers | Arrow flanker | STAI-T | M |
Luu et al., |
Volunteers | Letter flanker | PANAS | M |
Meyer et al., |
Pediatric anxiety | Arrow flanker | Parent-SCARED | M |
Moran et al., |
Volunteers | Letter flanker | PSWQ | AA |
Moran et al., |
Volunteers | Letter flanker | MASQ-AA | M |
Olvet and Hajcak, |
Volunteers | Letter flanker | DASS | M |
Olvet and Hajcak, |
Volunteers | Arrow flanker | BFI-N | M |
Rabinak et al., |
Veterans | Arrow flanker | SCID | M |
Riesel et al., |
OCD | Arrow flanker | SCID | AA |
Ruchsow et al., |
OCD | Go/NoGo flanker | SCID | AA |
Santesso et al., |
Pediatric OC | Letter flanker | CBCL-OC | AA |
Stern et al., |
OCD | Letter flanker | SCID | AA |
Tops and Boksem, |
Volunteers | Letter flanker | BIS | AA |
Weinberg et al., |
GAD | Arrow flanker | SCID | AA |
Weinberg et al., |
GAD | Arrow flanker | SCID | AA |
Xiao et al., |
GAD | Letter flanker | Chinese MINI | AA |
Xiao et al., |
OCD | Letter flanker | Chinese MINI | AA |
Δ
For the present analysis, we used the varying-coefficient model
Pearson's
We attempted to obtain data for all measures from all published studies and known unpublished datasets, but complete coverage was not possible in all cases. Thus, many of the following analyses were conducted with subsets of the total number of datasets.
The first set of analyses aimed to quantify the overall relationships between anxiety—broadly defined—and ERN, CRN, and ΔERN. Effect sizes were computed across studies using the reported associations between anxiety measures or groups and the ERN. Most studies reported on a single anxiety-related measure or group. In some other cases, investigators included more than one anxiety-related measure. In these cases, we chose the anxiety-related measure that was most consistently used across studies so as to maximize the potential for comparability across studies.
The focal analyses tested the hypothesis that anxious apprehension is the dimension of anxiety most closely associated with the ERN (as well as the CRN and ΔERN). To do this, we created two groups of studies based on their measures of anxiety. The first group was called the “anxious apprehension” group, which included studies of GAD and OCD diagnoses and symptoms as well as studies of the BIS. Our decision to include the BIS in the anxious apprehension group was based on four considerations: (1) three of the seven items (42%) making up the BIS measure used in ERN research include the word “worry” (Carver and White,
See Table
Overall |
− |
1757 | 32 | − |
||
Apprehension | − |
1077 | 20 | − |
– | – |
Mixed | − |
826 | 13 | − |
– | – |
Overall | −0.063 | 1264 | 20 | −0.129; 0.004 | 0.041 | −0.086; 0.168 |
Overall | − |
1437 | 26 | − |
||
Apprehension | − |
889 | 16 | − |
– | – |
Mixed | −0.058 | 694 | 11 | −0.150; 0.035 | – | – |
One concern is that nearly all studies conducted with patient samples were included in the anxious apprehension group thus potentially conflating the dimension of anxiety under study with patient status
All told, the results of the current meta-analysis indicate that anxiety, broadly defined, demonstrates a small to medium association with ERP indices of error monitoring. Most importantly, the findings are consistent with the hypothesis that an enhanced ERN is more strongly associated with the anxious apprehension dimension of anxiety as opposed to other anxiety-related constructs. Specifically, associations between anxious apprehension and ERN and ΔERN were more than three times as large as those with other forms of anxiety
First, the current meta-analysis included a relatively small number of studies. However, this is the first meta-analysis of its kind and the total number of studies (
Third and most importantly, the task of pin-pointing the association between type of anxiety and error monitoring has received limited attention in the literature. Most studies have taken a more global approach by focusing on individuals with symptoms of GAD or OCD, or by considering associations between relatively generic anxiety symptoms and error monitoring ERPs. We are aware of only two studies that have attempted to empirically isolate specific relationships between facets of anxiety and error monitoring: our recent study (Moser et al.,
We acknowledge that we took a conservative approach to classifying the content of specific measures and compared studies that used fairly clear measures of anxious apprehension—GAD and OCD-related measures—to all others. It is evident from the effect size estimates and figures that there is much more consistency of positive findings in the studies using more precise measures of anxious apprehension. Ideally, there would be more studies directly comparing ERN magnitudes across groups of participants created using targeted instruments of different anxiety constructs—e.g., anxious apprehension vs. anxious arousal. This is a challenge we hope future research will undertake, as it is not only important to the current topic but also to building a more biologically informed rubric for mental disorder classification (cf. Cuthbert and Insel,
In the next section, we use the results of this meta-analysis as a starting point for building a conceptual framework to explain why anxious apprehension/worry is the dimension of anxiety most closely associated with enhanced ERN. In short, we propose a
Our conceptual framework is an extension of existing affective-motivational models of the association between anxiety-related constructs and enhanced ERN (Luu and Tucker,
The present proposal builds on our earlier explanation for why anxious apprehension shows a particularly strong association with enhanced ERN (Moran et al.,
ACT increased specificity of the earlier work by proposing that anxiety is associated with a deficit in attentional control that results from an imbalance in activity between the frontal goal-directed attention system—concerned with goals and plans—and the parietal stimulus-driven attention system—concerned with salience and threat. Specifically, the ACT suggests that anxious individuals are characterized by enhanced activity of the stimulus-driven attention system and decreased functionality of the goal-driven system. Anxious individuals are therefore tuned to prioritize salient internal (e.g., worry) and external (e.g., angry face) sources of potential threat at the expense of affectively-neutral task-relevant stimuli. When no source of external threat or distraction is present (e.g., during performance of a standard conflict task) worry is distracting and likely to deplete goal-driven resources. Our initial formulation of the anxiety-ERN relationship (Moran et al.,
The notion that anxiety's influence on cognitive performance is primarily the result of the distracting effects of worry also appears as the cornerstone of work by Beilock and colleagues (Beilock and Carr,
As initially noted by Eysenck and Calvo (
How did they come to hypothesize the role of compensatory effort? First, Eysenck and colleagues showed that anxiety is often related to longer reaction times, but intact accuracy, across a range of reasoning, reading, attention, and working memory tasks (as reviewed by Eysenck and Calvo,
More recently, neuroimaging studies have provided additional support for the claim that enhanced processing resources (compensatory effort) help anxious individuals maintain typical levels of performance (for a review see Berggren and Derakshan,
In addition, a recent neuroimaging study showed that anxiety's deleterious effect on math performance was curtailed to the extent that high math anxious participants recruited frontal control brain regions (Lyons and Beilock,
Directly related to the ERN, processing inefficiency provides an explanation for a curious finding from Endrass et al. (
Consistent with PET/ACT and the above-reviewed studies, anxious individuals seem to demonstrate typical levels of performance in the standard conflict tasks used in ERN studies. Yet, they consistently show enhanced ERN. Indeed, only three individual studies of the 37 included in the present meta-analysis of the ERN reported a significant relationship between anxiety and error rate. A binomial test suggests that this is consistent with a 5% false positive rate (
To further evaluate this issue, we conducted an additional meta-analysis on error rate and reaction time for those studies reported on in our meta-analysis of the ERN. As we did with the ERN, we first conducted the meta-analysis across all studies for which we could calculate effect sizes. Then, we conducted moderation analysis by anxiety type. This analysis yielded no significant relationship between anxiety (across all studies) and error rate (
Thus, in line with the notion that anxiety is characterized by processing inefficiency, we suggest that enhanced ERN in anxiety may index a compensatory effort signal aimed at maintaining a standard level of performance (Moran et al.,
Braver (
According to Braver (
A recent study by Nash et al. (
We adopt the conflict monitoring theory of the ERN and its recent extensions (Yeung and Cohen,
Thus, our
Our compensatory error-monitoring hypothesis largely hinges on two ideas: (1) that the cognitive load of worry begins a cascade of processes that lead to enhanced ERN in anxious individuals, and (2) enhanced ERN in anxiety reflects a compensatory attention/effort response. In this section, we present data from our own lab that provides more direct support for these underlying assertions of our model.
If enhanced ERN in anxiety results from the cognitive load of worries on processing resources, it follows that experimentally induced cognitive load should also lead to enhanced ERN. Recent experimental data from our lab supports this notion that cognitive load—an affectively-neutral analog to distracting worries—enhances the ERN. In a study by Schroder et al. (
More directly, we conducted an experiment examining the effect of verbal working memory load (WML) on the ERN (Moran and Moser,
Of key interest was the prediction that ERN amplitude should be increased in conditions of increased WM load. The main effect of accuracy [
To test the prediction that individual differences in sensitivity to load should correlate with changes in ERN amplitude, we also correlated the ERN with a well-validated ERP index of WM-retention. In particular, we measured the left-anterior positive slow-wave potential (SWP) that shows greater magnitude on high- vs. low-WML trials (Ruchkin et al.,
Consistent with previous work, high WML memory sets elicited greater left-anterior positivity than low WML memory sets during the rehearsal period [
Regarding our assertion that enhanced ERN in anxiety reflects a compensatory attention/effort response, we present results from a novel analysis examining associations between anxious apprehension, ERN, and academic performance—as measured by grade-point average (GPA)—on a subsample of data from a larger dataset (Moran et al.,
We tested these predictions in 59 undergraduates (24 female,
Consistent with previous work (Hirsh and Inzlicht,
Together, these exploratory analyses provide further evidence that enhanced ERN among worriers functions as a compensatory control signal insomuch as worriers with a large ERN achieved the same GPA as non-worriers. In contrast, individuals with high worry and a low ERN, suggesting a lack of effortful compensatory control, tended to have significantly poorer academic achievement. Although preliminary, these findings are consistent with the Lyons and Beilock (
To this point, we have provided theoretical rationale and empirical evidence for our
The first, and perhaps most obvious, prediction for future research to test is that inducing worry should lead to an enhancement of the ERN. Borkovec and Inz (
Similarly, we predict that worries captured at ERN testing should relate to enhanced ERN and may mediate the association between trait worry and enhanced ERN. Specifically, on- and/or off-task worries could be measured following flanker performance and related to the ERN. If worries during task performance are responsible for co-opting goal-driven resources and causing compensatory deployment of reactive control resources, then such measures of worry should relate to enhanced ERN. The Cognitive Interference Questionnaire (CIQ; Sarason and Stoops,
Following from our formulations and the preliminary findings of Endrass et al. (
Treatment studies not only offer the chance to help improve anxious peoples' functioning but also to test theory-derived hypotheses. With respect to our view that the anxiety-ERN relationship reflects reductions in proactive control and compensatory increases in reactive control, one treatment possibility is to train anxious individuals to adopt more of a proactive control strategy. Proactive control training has been successfully implemented in individuals with schizophrenia, resulting in decreased symptoms and more proactive brain activity (Edwards et al.,
A particularly exciting feature of this last set of predictions concerning treatment effects on the ERN in anxious individuals is that it provides a context in which to interpret broader effects of anxiety treatment on the ERN. To date, one study in pediatric OCD patients showed that the ERN did not change with successful cognitive-behavioral treatment (CBT) of OCD (Hajcak et al.,
The current framework provides an important link between anxiety research and computational models of cognition. Thus, we suggest that future research in this area (and in other allied areas as well) apply computational modeling to test predictions about the associations between anxiety and error-monitoring ERPs and related performance measures. Yeung and Cohen (
This framework also provides the foundation for incorporating other conflict- and error-monitoring ERPs that have failed to be adequately addressed by researchers primarily interested in the anxiety-ERN relationship. Regarding the CRN, for example, the results of the current meta-analysis suggest that it is not reliably associated with anxiety, thus failing to support the notion of general overactive action monitoring in anxiety (e.g., Hajcak et al.,
The N2, a fronto-central negativity observed around 250–350 ms in the stimulus-locked ERP on correct trials, is a relevant action-monitoring ERP that is purported to reflect pre-response conflict elicited by the co-activation of correct and incorrect responses when stimuli are associated with both (e.g., incongruent flanker stimuli; Yeung et al.,
The major advance of our proposal is that it attempts to directly account for the relationship between anxiety and the ERN. Although there exist emotional-motivational accounts of the ERN and its within- and between-subjects variation (Pailing and Segalowitz,
Researchers have suggested that the ERN is an affective or emotional response to errors (Luu and Tucker,
A related conceptualization suggests that variation in the magnitude of the ERN reflects individual differences in defensive reactivity (Hajcak and Foti,
Although the affective response and defensive reactivity models provide plausible accounts of heightened ERN amplitude in anxiety, they only loosely address the fact that some forms of anxiety are more closely tied to enhanced ERN than others. Our conceptual framework, on the other hand, uses this distinction as foundational for specifying the relationship between anxiety and the ERN. There are also contradictory findings in the literature that point to additional weaknesses in current approaches to conceptualizing the connection between anxiety and the ERN.
With regard to the affective response interpretation, the cognitive vs. affective subdivision model of the ACC is not supported by extant research (Shackman et al.,
Regarding the defensive reactivity interpretation, evidence speaking directly to the assertion that “… anxious individuals who are characterized by increased ERNs may exhibit a greater defensive response to errors compared with non-anxious individuals” (Hajcak and Foti,
Our overarching goal in this paper has been to provide a foundation for future research addressing the relationship between anxiety and error processing, both quantitatively and conceptually. In particular, we provide estimates of the effect sizes concerning associations between dimensions of anxiety and error-monitoring ERPs elicited in standard conflict tasks. This meta-analytic result provides a more exact understanding of the previous literature and can serve to help researchers design better studies for the future with an eye toward statistical power and precision. We have also articulated a framework that focuses on what enhanced ERN reflects about cognitive dysfunction in anxiety. Our view is that enhanced ERN in anxiety indexes the impact of anxious apprehension—i.e., worry—on post-decisional response conflict by way of its negative influence on active goal maintenance mechanisms and a resulting compensatory increase in “as-needed” reactive control. Such a dynamic reflects what Berggren and Derakshan (
In sum, we hope this model and our initial ideas for future research represents just the beginning of a deeper understanding of what error- and conflict-related ERPs can tell us about the impact of anxiety on cognition. The promise of more formalized models of cognitive dysfunction in anxiety will be realized to the extent that they offer new insights into how better to identify and treat the world's most ubiquitous mental health problem.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
The authors would like to thank Michael Larson for contributing his unpublished ERN data for inclusion in the meta-analysis. The authors would also like to thank Christine Larson for providing the data for the associations between BIS and PSWQ and MASQ-AA. Finally, the authors would like to thank Greg Hajcak Proudfit, Alexandria Meyer, Gilles Pourtois, and Anna Weinberg for contributing data from their published work for inclusion in the meta-analysis.
Given that the varying-coefficient model—the basis for the analysis presented in the main text—has rarely been applied in the published literature, we also present results computed from a more common meta-analytic framework. As these studies were rather heterogeneous in their reported effect sizes, our second analysis was conducted within the context of a random effects model (Cumming,
The results of this analysis are presented in Table
Overall |
− |
− |
− |
8.95 | 0.003 |
Apprehension | − |
− |
− |
– | – |
Mixed | −0.110 | −0.224 | 0.007 | – | – |
Overall | − |
− |
− |
0.88 | 0.358 |
Overall | − |
− |
− |
13.05 | <0.001 |
Apprehension | − |
− |
− |
– | – |
Mixed | −0.043 | −0.142 | 0.056 | – | – |
1It is important to note that all of these studies examined the relationship between anxiety and the response-locked ERN, as previously defined. The negative going ERP component elicited after negative feedback (i.e., feedback-related negativity or FRN; Miltner et al.,
2See Appendix for converging findings using a random effects model.
3In a sample of over 500 undergraduates, PSWQ was more than three times as highly correlated with BIS (
4 We thank Editor Alex Shackman for pointing out this potential confound.
5With respect to the ΔERN, it is important to note that it includes variance accounted for by the ERN and it is therefore difficult to discern whether its association with anxiety is driven by variance attributable to the ERN itself. Multivariate analyses are necessary to address this issue in future studies.