The DOI matches its Crossref record; 59 of the 60 references it cites were found in a registry or an index.
Failure of Anterior Cingulate Activation and Connectivity With the Amygdala During Implicit Regulation of Emotional Processing in Generalized Anxiety Disorder
Open accessAbstract
OBJECTIVE: Clinical data suggest that abnormalities in the regulation of emotional processing contribute to the pathophysiology of generalized anxiety disorder, yet these abnormalities remain poorly understood at the neurobiological level. The authors recently reported that in healthy volunteers the pregenual anterior cingulate regulates emotional conflict on a trial-by-trial basis by dampening activity in the amygdala. The authors also showed that this process is specific to the regulation of emotional, compared to nonemotional, conflict. Here the authors examined whether this form of noninstructed emotion regulation is perturbed in generalized anxiety disorder. METHOD: Seventeen patients with generalized anxiety disorder and 24 healthy comparison subjects underwent functional MRI while performing an emotional conflict task that involved categorizing facial affect while ignoring overlaid affect label words. Behavioral and neural measures were used to compare trial-by-trial changes in conflict regulation. RESULTS: Comparison subjects effectively regulated emotional conflict from trial to trial, even though they were unaware of having done so. By contrast, patients with generalized anxiety disorder were completely unable to regulate emotional conflict and failed to engage the pregenual anterior cingulate in ways that would dampen amygdalar activity. Moreover, performance and brain activation were correlated with symptoms and could be used to accurately classify the two groups. CONCLUSIONS: These data demonstrate that patients with generalized anxiety disorder show significant deficits in the noninstructed and spontaneous regulation of emotional processing. Conceptualization of anxiety as importantly involving abnormalities in emotion regulation, particularly a type occurring outside of awareness, may open up avenues for novel treatments, such as by targeting the medial prefrontal cortex.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“A functional perspective of worry has been supported in studies utilizing neurobiological11, psychophysiological12–14, behavioral15, and self-report16–17 measurement.”
From AN OPEN TRIAL OF EMOTION REGULATION THERAPY FOR GENERALIZED ANXIETY DISORDER AND COOCCURRING DEPRESSION: Research Article: An Open Trial of Emotion Regulation Therapy (2015) · cites this paper as [11]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“these individuals may respond poorly to this motivational conflict, demonstrating deficits in different systems of regulation30 encompassing attentional (e.g., attentional flexibility in processing both interoceptive and exteroceptive emotional stimuli31–33, 11) and more cognitive elaborative strategies (e.g., meta-cognitive awareness, cognitive reappraisal34, 35).”
From AN OPEN TRIAL OF EMOTION REGULATION THERAPY FOR GENERALIZED ANXIETY DISORDER AND COOCCURRING DEPRESSION: Research Article: An Open Trial of Emotion Regulation Therapy (2015) · cites this paper as [11]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Considerable evidence supports this functional view of worry at neurobiological (Etkin, Prater, Hoeft, Menon, & Schatzberg, 2010), psychophysiological (Oathes, Siegel, & Ray, 2011; Weinberg, Klein, & Hajcak, 2012), behavioral (Cooper, Miranda, & Mennin, 2013), and self-report”
From A Pilot Study of Emotion Regulation Therapy for Generalized Anxiety and Depression: Findings From a Diverse Sample of Young Adults. (2018) · cites this paper as Etkin et al., 2010
In the citing paper
“Rather than processing emotion information and utilizing its motivational value, individuals with distress disorders often fail to enhance or diminish emotional experiences in a manner appropriate to a particular environmental context.”
From Emotion Regulation Therapy: A Mechanism-Targeted Treatment for Disorders of Distress (2017) · cites this paper as Etkin et al., 2010
In the citing paper
“For example, GAD with and without MDD is characterized by a failure to spontaneously regulate emotional conflict by shifting attention in response to a motivationally salient emotional stimulus in conflict adaptation task (Etkin et al., 2010; Etkin and Schatzberg, 2011).”
From Emotion Regulation Therapy: A Mechanism-Targeted Treatment for Disorders of Distress (2017) · cites this paper as Etkin et al., 2010
In the citing paper
“Emotion regulation deficits commonly occur in GAD (Mennin et al., 2007; Etkin et al., 2010; Etkin and Schatzberg, 2011), and MDD (Johnstone et al., 2007).”
From Emotion Regulation Therapy: A Mechanism-Targeted Treatment for Disorders of Distress (2017) · cites this paper as Etkin et al., 2010
In the citing paper
“One promising preliminary finding is related to emotional conflict adaptation (Etkin et al., 2010; Etkin and Schatzberg, 2011) wherein clients were administered a conflict adaptation task and evidenced pre- to mid-treatment improvements in their ability to shift their attention in the face of emotional conflict (pre to mid d = 0.74) to levels comparable to healthy controls (Etkin et al., 2010).”
From Emotion Regulation Therapy: A Mechanism-Targeted Treatment for Disorders of Distress (2017) · cites this paper as Etkin et al., 2010
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
(1970) · Cited by 24,983
(1998) · The Journal of Clinical Psychiatry · Cited by 19,139
(1998) · PubMed · Cited by 10,216
Statistical parametric maps in functional imaging: A general linear approach
Friston, K. J., Holmes, A. P., Worsley, K. J., Poline, J. ‐., Frith, C. D., & Frackowiak, R. S. J. (1994) · Human Brain Mapping · doi:10.1002/hbm.460020402 · Cited by 9,688
Conflict monitoring and cognitive control
Botvinick, M. M., Braver, T. S., Barch, D. M., Carter, C. S., & Cohen, J. D. (2001) · Psychological Review · doi:10.1037/0033-295x.108.3.624 · Cited by 7,351
Development and validation of the Penn State Worry Questionnaire
Meyer, T. J., Miller, M. L., Metzger, R. L., & Borkovec, T. D. (1990) · Behaviour Research and Therapy · doi:10.1016/0005-7967(90)90135-6 · Cited by 5,099
Maldjian, J. A., Laurienti, P. J., Kraft, R., & Burdette, J. H. (2003) · NeuroImage · doi:10.1016/s1053-8119(03)00169-1 · Cited by 5,066
The cognitive control of emotion
OCHSNER, K., & GROSS, J. (2005) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2005.03.010 · Cited by 4,495
Ekman, P. (1976) · Medical Entomology and Zoology · Cited by 4,345
A new SPM toolbox for combining probabilistic cytoarchitectonic maps and functional imaging data
Eickhoff, S. B., Stephan, K. E., Mohlberg, H., Grefkes, C., Fink, G. R., Amunts, K., & Zilles, K. (2005) · NeuroImage · doi:10.1016/j.neuroimage.2004.12.034 · Cited by 4,033
Spatial registration and normalization of images
Friston, K. J., Ashburner, J., Frith, C., Poline, J.-B., Heather, J. D., & Frackowiak, R. S. J. (1995) · Human Brain Mapping · doi:10.1002/hbm.460030303 · Cited by 3,744
Conflict monitoring and anterior cingulate cortex: an update
Botvinick, M. M., Cohen, J. D., & Carter, C. S. (2004) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2004.10.003 · Cited by 3,623
Etkin, A., & Wager, T. D. (2007) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2007.07030504 · Cited by 3,391
Self-citationPsychophysiological and Modulatory Interactions in Neuroimaging
Friston, K. J., Buechel, C., Fink, G. R., Morris, J., Rolls, E., & Dolan, R. J. (1997) · NeuroImage · doi:10.1006/nimg.1997.0291 · Cited by 3,097
Anterior Cingulate Conflict Monitoring and Adjustments in Control
Kerns, J. G., Cohen, J. D., MacDonald, A. W., Cho, R. Y., Stenger, V. A., & Carter, C. S. (2004) · Science · doi:10.1126/science.1089910 · Cited by 2,891
Sheehan, D., Lecrubier, Y., Harnett Sheehan, K., Janavs, J., Weiller, E., Keskiner, A., Schinka, J., Knapp, E., Sheehan, M., & Dunbar, G. (1997) · European Psychiatry · doi:10.1016/s0924-9338(97)83297-x · Cited by 2,149
Conflict monitoring versus selection-for-action in anterior cingulate cortex
Botvinick, M., Nystrom, L. E., Fissell, K., Carter, C. S., & Cohen, J. D. (1999) · Nature · doi:10.1038/46035 · Cited by 2,044
Optimizing the use of information: Strategic control of activation of responses.
Gratton, G., COLES, M. G. H., & Donchin, E. (1992) · Journal of Experimental Psychology General · doi:10.1037//0096-3445.121.4.480 · Cited by 1,866
Phelps, E. A., Delgado, M. R., Nearing, K. I., & LeDoux, J. E. (2004) · Neuron · doi:10.1016/j.neuron.2004.08.042 · Cited by 1,753
Watson, D., Weber, K., Assenheimer, J. S., Clark, L. A., Strauss, M. E., & McCormick, R. A. (1995) · Journal of Abnormal Psychology · doi:10.1037/0021-843x.104.1.3 · Cited by 1,423
Phillips, M. L., Ladouceur, C. D., & Drevets, W. C. (2008) · Molecular Psychiatry · doi:10.1038/mp.2008.65 · Cited by 1,383
Etkin, A., Egner, T., Peraza, D. M., Kandel, E. R., & Hirsch, J. (2006) · Neuron · doi:10.1016/j.neuron.2006.07.029 · Cited by 1,360
Self-citationModulating emotional responses: effects of a neocortical network on the limbic system
Hariri, A. R., Bookheimer, S. Y., & Mazziotta, J. C. (2000) · NeuroReport · doi:10.1097/00001756-200001170-00009 · Cited by 1,277
Amunts, K., Kedo, O., Kindler, M., Pieperhoff, P., Mohlberg, H., Shah, N. J., Habel, U., Schneider, F., & Zilles, K. (2005) · Anatomy and Embryology · doi:10.1007/s00429-005-0025-5 · Cited by 1,264
Lieberman, M. D., Eisenberger, N. I., Crockett, M. J., Tom, S. M., Pfeifer, J. H., & Way, B. M. (2007) · Psychological Science · doi:10.1111/j.1467-9280.2007.01916.x · Cited by 1,150
Egner, T., & Hirsch, J. (2005) · Nature Neuroscience · doi:10.1038/nn1594 · Cited by 1,144
Watson, D., Clark, L. A., Weber, K., Assenheimer, J. S., Strauss, M. E., & McCormick, R. A. (1995) · Journal of Abnormal Psychology · doi:10.1037//0021-843x.104.1.15 · Cited by 1,042
Parsing executive processes: Strategic vs. evaluative functions of the anterior cingulate cortex
Carter, C. S., Macdonald, A. M., Botvinick, M., Ross, L. L., Stenger, V. A., Noll, D. C., & Cohen, J. D. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.4.1944 · Cited by 954
Preliminary evidence for an emotion dysregulation model of generalized anxiety disorder
Mennin, D. S., Heimberg, R. G., Turk, C. L., & Fresco, D. M. (2005) · Behaviour Research and Therapy · doi:10.1016/j.brat.2004.08.008 · Cited by 919
(2004) · Cited by 863
Conflict adaptation effects in the absence of executive control
Mayr, U., Awh, E., & Laurey, P. (2003) · Nature Neuroscience · doi:10.1038/nn1051 · Cited by 793
Neural circuitry underlying the regulation of conditioned fear and its relation to extinction
Delgado, M. R., Nearing, K. I., LeDoux, J. E., & Phelps, E. A. (2008) · Neuron · doi:10.1016/j.neuron.2008.06.029 · Cited by 716
Monk, C. S., Telzer, E. H., Mogg, K., Bradley, B. P., Mai, X., Louro, H. M. C., Chen, G., McClure-Tone, E. B., Ernst, M., & Pine, D. S. (2008) · Archives of General Psychiatry · doi:10.1001/archpsyc.65.5.568 · Cited by 682 · cited 1×
“Two studies of adolescents with generalized anxiety disorder support this prediction (7, 8), and two similar studies of adults do not (9, 10).”
ResultEtkin, A., Prater, K. E., Schatzberg, A. F., Menon, V., & Greicius, M. D. (2009) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2009.104 · Cited by 664
Self-citationConflict-induced behavioural adjustment: a clue to the executive functions of the prefrontal cortex
Mansouri, F. A., Tanaka, K., & Buckley, M. J. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2538 · Cited by 559
Delineating components of emotion and its dysregulation in anxiety and mood psychopathology
Mennin, D. S., Holaway, R. M., Fresco, D. M., Moore, M. T., & Heimberg, R. G. (2007) · Behavior Therapy · doi:10.1016/j.beth.2006.09.001 · Cited by 527
Dissociable Neural Systems Resolve Conflict from Emotional versus Nonemotional Distracters
Egner, T., Etkin, A., Gale, S. A., & Hirsch, J. (2007) · Cerebral Cortex · doi:10.1093/cercor/bhm179 · Cited by 521
Self-citationSteer, R. A., & Beck, A. T. (1997) · Cited by 501
Self‐navigated spiral fMRI: Interleaved versus single‐shot
Glover, G. H., & Lai, S. (1998) · Magnetic Resonance in Medicine · doi:10.1002/mrm.1910390305 · Cited by 476
The neural correlates and functional integration of cognitive control in a Stroop task
Egner, T., & Hirsch, J. (2004) · NeuroImage · doi:10.1016/j.neuroimage.2004.09.007 · Cited by 469
Monk, C. S., Nelson, E. E., McClure, E. B., Mogg, K., Bradley, B. P., Leibenluft, E., Blair, R. J. R., Chen, G., Charney, D. S., Ernst, M., et al. (2006) · American Journal of Psychiatry · doi:10.1176/ajp.2006.163.6.1091 · Cited by 458
Petrovic, P., Dietrich, T., Fransson, P., Andersson, J., Carlsson, K., & Ingvar, M. (2005) · Neuron · doi:10.1016/j.neuron.2005.05.023 · Cited by 437
Abnormal attention modulation of fear circuit function in pediatric generalized anxiety disorder
McClure, E. B., Monk, C. S., Nelson, E. E., Parrish, J. M., Adler, A., Blair, R. J. R., Fromm, S., Charney, D. S., Leibenluft, E., Ernst, M., et al. (2007) · Archives of General Psychiatry · doi:10.1001/archpsyc.64.1.97 · Cited by 431
From Fear to Safety and Back: Reversal of Fear in the Human Brain
Schiller, D., Levy, I., Niv, Y., LeDoux, J. E., & Phelps, E. A. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.2265-08.2008 · Cited by 429
A method for removal of global effects from fMRI time series
Macey, P. M., Macey, K. E., Kumar, R., & Harper, R. M. (2004) · NeuroImage · doi:10.1016/j.neuroimage.2003.12.042 · Cited by 407
Nitschke, J. B., Sarinopoulos, I., Oathes, D. J., Johnstone, T., Whalen, P. J., Davidson, R. J., & Kalin, N. H. (2009) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2008.07101682 · Cited by 375
Subjective rating of emotionally salient stimuli modulates neural activity
Taylor, S. F., Phan, K. L., Decker, L. R., & Liberzon, I. (2003) · NeuroImage · doi:10.1016/s1053-8119(02)00051-4 · Cited by 371
Phillips, M. L., Ladouceur, C. D., & Drevets, W. C. (2008) · Molecular Psychiatry · doi:10.1038/mp.2008.82 · Cited by 366
Blair, K., Shaywitz, J., Smith, B. W., Rhodes, R., Geraci, M., Jones, M., McCaffrey, D., Vythilingam, M., Finger, E., Mondillo, K., et al. (2008) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2008.07071060 · Cited by 282
Affective Flexibility: Evaluative Processing Goals Shape Amygdala Activity
Cunningham, W. A., Van Bavel, J. J., & Johnsen, I. R. (2008) · Psychological Science · doi:10.1111/j.1467-9280.2008.02061.x · Cited by 260
Functional neuroanatomy of anxiety: a neural circuit perspective
Etkin, A. (2009) · Current Topics in Behavioral Neurosciences · doi:10.1007/7854_2009_5 · Cited by 227
Self-citationWhalen, P. J., Johnstone, T., Somerville, L. H., Nitschke, J. B., Polis, S., Alexander, A. L., Davidson, R. J., & Kalin, N. H. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.08.019 · Cited by 217
Paulesu, E., Sambugaro, E., Torti, T., Danelli, L., Ferri, F., Scialfa, G., Sberna, M., Ruggiero, G. M., Bottini, G., & Sassaroli, S. (2009) · Psychological Medicine · doi:10.1017/s0033291709005649 · Cited by 204
Habel, U., Windischberger, C., Derntl, B., Robinson, S., Kryspin‐Exner, I., Gur, R. C., & Moser, E. (2007) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2007.01.023 · Cited by 203
Regularized higher‐order in vivo shimming
Kim, D., Elfar Adalsteinsson, A., Glover, G. H., & Spielman, D. M. (2002) · Magnetic Resonance in Medicine · doi:10.1002/mrm.10267 · Cited by 200
McLaughlin, K. A., Mennin, D. S., & Farach, F. J. (2006) · Behaviour Research and Therapy · doi:10.1016/j.brat.2006.12.004 · Cited by 167
Hoeft, F., Lightbody, A. A., Hazlett, H. C., Patnaik, S., Piven, J., & Reiss, A. L. (2008) · Archives of General Psychiatry · doi:10.1001/archpsyc.65.9.1087 · Cited by 96
Self-citationStarosta, A. J., & Brenner, L. A. (2017) · Springer eBooks · doi:10.1007/978-3-319-56782-2_1972-2 · Cited by 77
Worsley (1996) · doi:10.1002/(sici)1097-0193(1996)4:1
Research works printed but not linked: 6
- 1994, American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th ed (DSM-IV)
- Etkin A, Arch Gen Psychiatry
- 10.1037/0096-3445.121.4.480 · DOI
- Sheehan DV, 1998, J Clin Psychiatry, 59, 22
- Beck AT, 1996, Manual for Beck Depression Inventory II (BDI-II)
- 10.1037/0021-843X.104.1.15 · DOI
Cited by
Sorted by citations
Emotional processing in anterior cingulate and medial prefrontal cortex
Etkin, A., Egner, T., & Kalisch, R. (2011) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2010.11.004 · Cited by 3,059
Self-citationUncertainty and anticipation in anxiety: an integrated neurobiological and psychological perspective
Grupe, D. W., & Nitschke, J. B. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3524 · Cited by 2,007
The neural bases of emotion regulation
Etkin, A., Büchel, C., & Gross, J. J. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn4044 · Cited by 1,244
Self-citationExplicit and implicit emotion regulation: a dual-process framework.
Gyurak, A., Gross, J. J., & Etkin, A. (2011) · Cognition and Emotion · doi:10.1080/02699931.2010.544160 · Cited by 1,015
Self-citationEarly developmental emergence of human amygdala–prefrontal connectivity after maternal deprivation
Gee, D. G., Gabard-Durnam, L. J., Flannery, J., Goff, B., Humphreys, K. L., Telzer, E. H., Hare, T. A., Bookheimer, S. Y., & Tottenham, N. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1307893110 · Cited by 871
Metadata
- Authors
- Etkin, A., Prater, K. E., Hoeft, F., Menon, V., & Schatzberg, A. F.
- Affiliations
- Stanford Medicine (US)
- Corresponding author
- Etkin, Amit
- Venue
- American Journal of Psychiatry
- Published
- 2010-05-01
- Volume
- 167
- Issue
- 5
- Pages
- 545-554
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- PMC
- PMC4367202
- OpenAlex
- W2123350238
- Cited by
- 550
- References
- 60
- Citations by year
- 2026: 11 · 2025: 16 · 2024: 20 · 2023: 20 · 2022: 21 · 2021: 35 · 2020: 46 · 2019: 40 · 2018: 39 · 2017: 44 · 2016: 43 · 2015: 51 · 2014: 48 · 2013: 44 · 2012: 36
- FWCI
- 47.73
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS058899, R21NS058899)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD047520, R01HD047520, K23HD054720)
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Health Sciences › Medicine › Psychiatry and Mental health › Psychosomatic Disorders and Their Treatments
- Keywords
- generalized anxiety disorder, emotion regulation, implicit emotion regulation, pregenual anterior cingulate cortex, amygdala, emotional conflict, medial prefrontal cortex, functional connectivity, symptom classification
- MeSH terms
- Adaptation, Psychological, Adult, Amygdala, Anxiety Disorders, Conflict, Psychological, Emotions, Female, Gyrus Cinguli, Humans, Magnetic Resonance Imaging, Male, Neural Pathways, Psychiatric Status Rating Scales, Case-Control Studies
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
