Error-Specific Cognitive Control Alterations in Generalized Anxiety Disorder

doi:10.1016/j.bpsc.2017.01.004

Biological Psychiatry: Cognitive Neuroscience and Neuroimaging

Volume 2, Issue 5, July 2017, Pages 413-420

https://doi.org/10.1016/j.bpsc.2017.01.004 Get rights and content

Abstract

Background

Trait anxiety is reliably associated with enhanced neural responses following errors: meta-analyses have described how the electrophysiological response to errors known as error-related negativity (ERN) is increased in anxious individuals, particularly in relation to worry. ERN has been related to a broader class of control signals, particularly via a common theta band denominator, but it is unknown whether worry relates to these alternative medial frontal metrics. Moreover, it is unclear if increased ERN in anxiety relates to altered cognitive control.

Methods

We examined electroencephalogram activities in subjects with generalized anxiety disorder (GAD) (n = 39) and control subjects (n = 52) during an executive control task. We leveraged a previously defined theta band network to examine if an altered control signal in GAD underlies a differential implementation of cognitive control.

Results

GAD and control groups were reliably dissociated by error-related and conflict-related neural activity in both time and frequency (i.e., theta band) domains. Moreover, we demonstrated that ERN, error-related theta power, and the single trial correlation between theta and response time were unique predictors of GAD status. Overall, we were able to account for nearly a quarter of the group variance and successfully classify GAD from control participants with two-thirds accuracy.

Conclusions

Collectively, these findings suggest that multiple neural metrics of error processing may uniquely distinguish individuals with clinical anxiety from healthy individuals and that mechanisms of control also differ in GAD; finally, these error-related neural measures have the potential to be sensitive and specific biosignatures of anxiety.

Section snippets

Methods and Materials

The current study combined participants from two separate previously published studies that examined ERN in relation to GAD (9, 10). The current study focused on 39 participants with a diagnosis of GAD (but not comorbid depression) and 52 individuals with no current DSM-IV diagnosis (healthy control subjects). All diagnoses were made using DSM-IV (11). Self-reported symptoms of anxiety and depression were gathered from most participants using the Mood and Anxiety Symptom Questionnaire (MASQ) (12

Behavior

Analyses of behavioral data were performed separately from trial-count matching and selection procedures implemented for EEG analysis. Subjects with GAD and control subjects did not differ in the number of errors committed (GAD group, median errors = 29, interquartile range = 14; control group, median errors = 33, interquartile range = 26; t₈₆ = 1.22, p = .23) or RT for any trial type (ts < 1.6) (Figure 1). When quantifying post-error slowing as the RT difference between post-error and the

Discussion

In the current study, we demonstrated that both error-related and conflict-related ERPs (i.e., ERN and N2, respectively) differentiate subjects with GAD from control subjects; moreover, subjects with GAD were characterized by increased time-frequency representations of these effects (i.e., error-related and conflict-related theta, respectively). By leveraging multiple error-specific network activities, we accounted for 23% of the group variance and effectively classified patients with up to 66%

Acknowledgments and Disclosures

This work was supported by the National Institute of General Medical Sciences Grant No. 1P20GM109089-01A1 (to JFC), National Institute of Mental Health Grant No. 1UH2MH109168-01 (to JFC), and National Institute on Alcohol Abuse and Alcoholism Grant No. R21AA0023947-01A1 (to JFC).

The authors report no biomedical financial interests or potential conflicts of interest.

References (30)

M. Falkenstein et al.
Effects of crossmodal divided attention on late ERP components. II. Error processing in choice reaction tasks
Electroencephalogr Clin Neurophysiol
(1991)
J.F. Cavanagh et al.
Frontal theta as a mechanism for cognitive control
Trends Cogn Sci
(2014)
A. Weinberg et al.
Increased error-related brain activity in generalized anxiety disorder
Biol Psychol
(2010)
A. Delorme et al.
EEGLAB: An open source toolbox for analysis of single-trial EEG dynamics including independent component analysis
J Neurosci Methods
(2004)
V.R. Steele et al.
Neuroimaging measures of error-processing: Extracting reliable signals from event-related potentials and functional magnetic resonance imaging
Neuroimage
(2016)
J.F. Cavanagh et al.
Identification of canonical neural events during continuous gameplay of an 8-bit style video game
Neuroimage
(2016)
J. Yordanova et al.
Parallel systems of error processing in the brain
Neuroimage
(2004)
J.S. Moser et al.
On the relationship between anxiety and error monitoring: A meta-analysis and conceptual framework
Front Hum Neurosci
(2013)
G. Hajcak
What we’ve learned from mistakes: Insights from error-related brain activity
Curr Dir Psychol Sci
(2012)
W.J. Gehring et al.
A neural system for error-detection and compensation
Psychol Sci
(1993)

K.R. Ridderinkhof et al.

The role of the medial frontal cortex in cognitive control

Science

(2004)

G. Hajcak et al.

Errors are aversive: Defensive motivation and the error-related negativity

Psychol Sci

(2008)

J.F. Cavanagh et al.

Frontal midline theta reflects anxiety and cognitive control: meta-analytic evidence

J Physiol Paris

(2014)

A. Weinberg et al.

Increased error-related brain activity distinguishes generalized anxiety disorder with and without comorbid major depressive disorder

J Abnorm Psychol

(2012)

M.B. First et al.

Structured Clinical Interview for DSM-IV Axis I Disorders

Clinician Version (SCID-CV)

(1996)

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Archival ReportError-Specific Cognitive Control Alterations in Generalized Anxiety Disorder

Abstract

Background

Methods

Results

Conclusions

Section snippets

Methods and Materials

Behavior

Discussion

Acknowledgments and Disclosures

Electroencephalogr Clin Neurophysiol

Trends Cogn Sci

Biol Psychol

J Neurosci Methods

Neuroimage

Neuroimage

Neuroimage

On the relationship between anxiety and error monitoring: A meta-analysis and conceptual framework

Front Hum Neurosci

What we’ve learned from mistakes: Insights from error-related brain activity

Curr Dir Psychol Sci

A neural system for error-detection and compensation

Psychol Sci

The role of the medial frontal cortex in cognitive control

Science

Errors are aversive: Defensive motivation and the error-related negativity

Psychol Sci

Frontal midline theta reflects anxiety and cognitive control: meta-analytic evidence

J Physiol Paris

Increased error-related brain activity distinguishes generalized anxiety disorder with and without comorbid major depressive disorder

J Abnorm Psychol

Structured Clinical Interview for DSM-IV Axis I Disorders

Clinician Version (SCID-CV)

Archival Report
Error-Specific Cognitive Control Alterations in Generalized Anxiety Disorder