Skip to main content
    • Aa
    • Aa
  • Get access
    Check if you have access via personal or institutional login
  • Cited by 28
  • Cited by
    This article has been cited by the following publications. This list is generated based on data provided by CrossRef.

    Bertocci, Michele A. Bebko, Genna Dwojak, Amanda Iyengar, Satish Ladouceur, Cecile D. Fournier, Jay C. Versace, Amelia Perlman, Susan B. Almeida, Jorge R.C. Travis, Michael J. Gill, Mary Kay Bonar, Lisa Schirda, Claudiu Diwadkar, Vaibhav A. Sunshine, Jeffrey L. Holland, Scott K. Kowatch, Robert A. Birmaher, Boris Axelson, David Horwitz, Sarah M. Frazier, Thomas Arnold, L. Eugene Fristad, Mary A. Youngstrom, Eric A. Findling, Robert L. and Phillips, Mary L. 2016. Longitudinal Relationships Among Activity in Attention Redirection Neural Circuitry and Symptom Severity in Youth. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging,

    Chen, Guangxiang Hu, Xinyu Li, Lei Huang, Xiaoqi Lui, Su Kuang, Weihong Ai, Hua Bi, Feng Gu, Zhongwei and Gong, Qiyong 2016. Disorganization of white matter architecture in major depressive disorder: a meta-analysis of diffusion tensor imaging with tract-based spatial statistics. Scientific Reports, Vol. 6, p. 21825.

    Goya-Maldonado, Roberto Brodmann, Katja Keil, Maria Trost, Sarah Dechent, Peter and Gruber, Oliver 2016. Differentiating unipolar and bipolar depression by alterations in large-scale brain networks. Human Brain Mapping, Vol. 37, Issue. 2, p. 808.

    He, Hao Yu, Qingbao Du, Yuhui Vergara, Victor Victor, Teresa A. Drevets, Wayne C. Savitz, Jonathan B. Jiang, Tianzi Sui, Jing and Calhoun, Vince D. 2016. Resting-state functional network connectivity in prefrontal regions differs between unmedicated patients with bipolar and major depressive disorders. Journal of Affective Disorders, Vol. 190, p. 483.

    Laidi, Charles and Houenou, Josselin 2016. Brain functional effects of psychopharmacological treatments in bipolar disorder. European Neuropsychopharmacology,

    Sharma, Anup Satterthwaite, Theodore D. Vandekar, Lillie Katchmar, Natalie Daldal, Aylin Ruparel, Kosha Elliott, Mark A. Baldassano, Claudia Thase, Michael E. Gur, Raquel E. Kable, Joseph W. and Wolf, Daniel H. 2016. Divergent relationship of depression severity to social reward responses among patients with bipolar versus unipolar depression. Psychiatry Research: Neuroimaging, Vol. 254, p. 18.

    Vogt, Brent A. 2016. Midcingulate cortex: Structure, connections, homologies, functions and diseases. Journal of Chemical Neuroanatomy, Vol. 74, p. 28.

    Wolf, Robert Christian Nolte, Henrike Maria Hirjak, Dusan Hofer, Stefan Seidl, Ulrich Depping, Malte Sebastian Stieltjes, Bram Maier-Hein, Klaus Sambataro, Fabio and Thomann, Philipp Arthur 2016. Structural network changes in patients with major depression and schizophrenia treated with electroconvulsive therapy. European Neuropsychopharmacology, Vol. 26, Issue. 9, p. 1465.

    Brooks, J. O. Vizueta, N. Penfold, C. Townsend, J. D. Bookheimer, S. Y. and Altshuler, L. L. 2015. Prefrontal hypoactivation during working memory in bipolar II depression. Psychological Medicine, Vol. 45, Issue. 08, p. 1731.

    Caseras, Xavier Murphy, Kevin Lawrence, Natalia S Fuentes-Claramonte, Paola Watts, Jessica Jones, Derek K and Phillips, Mary L 2015. Emotion regulation deficits in euthymic bipolar I versus bipolar II disorder: a functional and diffusion-tensor imaging study. Bipolar Disorders, Vol. 17, Issue. 5, p. 461.

    Kanske, P Schönfelder, S Forneck, J and Wessa, M 2015. Impaired regulation of emotion: neural correlates of reappraisal and distraction in bipolar disorder and unaffected relatives. Translational Psychiatry, Vol. 5, Issue. 1, p. e497.

    Ryan, Kelly A. Dawson, Erica L. Kassel, Michelle T. Weldon, Anne L. Marshall, David F. Meyers, Kortni K. Gabriel, Laura B. Vederman, Aaron C. Weisenbach, Sara L. McInnis, Melvin G. Zubieta, Jon-Kar and Langenecker, Scott A. 2015. Shared dimensions of performance and activation dysfunction in cognitive control in females with mood disorders. Brain, Vol. 138, Issue. 5, p. 1424.

    Wang, Xiu-Li Du, Ming-Ying Chen, Tao-Lin Chen, Zi-Qi Huang, Xiao-Qi Luo, Ya Zhao, You-Jin Kumar, Poornima and Gong, Qi-Yong 2015. Neural correlates during working memory processing in major depressive disorder. Progress in Neuro-Psychopharmacology and Biological Psychiatry, Vol. 56, p. 101.

    Whalley, H. C. Sussmann, J. E. Romaniuk, L. Stewart, T. Kielty, S. Lawrie, S. M. Hall, J. and McIntosh, A. M. 2015. Dysfunction of emotional brain systems in individuals at high risk of mood disorder with depression and predictive features prior to illness. Psychological Medicine, Vol. 45, Issue. 06, p. 1207.

    Brooks, John O. and Vizueta, Nathalie 2014. Diagnostic and clinical implications of functional neuroimaging in bipolar disorder. Journal of Psychiatric Research, Vol. 57, p. 12.

    Delle-Vigne, D. Wang, W. Kornreich, C. Verbanck, P. and Campanella, S. 2014. Emotional facial expression processing in depression: Data from behavioral and event-related potential studies. Neurophysiologie Clinique/Clinical Neurophysiology, Vol. 44, Issue. 2, p. 169.

    Grotegerd, Dominik Stuhrmann, Anja Kugel, Harald Schmidt, Simone Redlich, Ronny Zwanzger, Peter Rauch, Astrid Veronika Heindel, Walter Zwitserlood, Pienie Arolt, Volker Suslow, Thomas and Dannlowski, Udo 2014. Amygdala excitability to subliminally presented emotional faces distinguishes unipolar and bipolar depression: An fMRI and pattern classification study. Human Brain Mapping, Vol. 35, Issue. 7, p. 2995.

    Langenecker, Scott A. Jacobs, Rachel H. and Passarotti, Alessandra M. 2014. Current Neural and Behavioral Dimensional Constructs Across Mood Disorders. Current Behavioral Neuroscience Reports, Vol. 1, Issue. 3, p. 144.

    Müller, Veronika I. Cieslik, Edna C. Kellermann, Tanja S. and Eickhoff, Simon B. 2014. Crossmodal emotional integration in major depression. Social Cognitive and Affective Neuroscience, Vol. 9, Issue. 6, p. 839.

    Tavitian, Lucy R. Ladouceur, Cecile D. Nahas, Ziad Khater, Beatrice Brent, David A. and Maalouf, Fadi T. 2014. Neutral face distractors differentiate performance between depressed and healthy adolescents during an emotional working memory task. European Child & Adolescent Psychiatry, Vol. 23, Issue. 8, p. 659.


Abnormal anterior cingulate cortical activity during emotional n-back task performance distinguishes bipolar from unipolar depressed females

  • M. A. Bertocci (a1), G. M. Bebko (a1), B. C. Mullin (a1), S. A. Langenecker (a2), C. D. Ladouceur (a1), J. R. C. Almeida (a1) and M. L. Phillips (a1) (a3)
  • DOI:
  • Published online: 21 November 2011

Depression in the context of bipolar disorder (BDd) is often misdiagnosed as unipolar disorder depression (UDd) leading to poor clinical outcomes for many bipolar sufferers. We examined neural circuitry supporting emotion regulation in females with either BDd or UDd as a first stage toward identifying biomarkers that may differentiate BDd from UDd.


Fifty-seven females aged 18–45 years participated in this study: 23 with UDd, 18 with bipolar disorder type I depression (BDId) and 16 healthy females. During 3-T functional magnetic resonance imaging (fMRI), the participants performed an emotional face n-back (EFNBACK) task, that is an n-back task with high (2-back) and low (0-back) memory load conditions flanked by two positive, negative or neutral face distracters. This paradigm examines executive control with emotional distracters–emotion regulation.


High memory load with neutral face distracters elicited greater bilateral and left dorsal anterior midcingulate cortex (dAMCC) activity in UDd than in healthy and BDId females respectively, and greater bilateral putamen activity in both depressed groups versus healthy females. High memory load with happy face distracters elicited greater left putamen activity in UDd than in healthy females. Psychotropic medication was associated with greater putamen activity to these contrasts in UDd females.


During high memory load with neutral face distracters, elevated dAMCC activity in UDd suggests abnormal recruitment of attentional control circuitry to maintain task performance, whereas elevated putamen activity unrelated to psychotropic medication in BDId females may suggest an attentional bias toward ambiguous neutral face distracters. Differential patterns of functional abnormalities in neural circuitry supporting attentional control during emotion regulation, especially in the dAMCC, is a promising neuroimaging measure to distinguish UDd from BDId in females.

Corresponding author
*Address for correspondence: M. A. Bertocci, Ph.D., Western Psychiatric Institute and Clinic, Loeffler Building, room 205, 121 Meyran Avenue, Pittsburgh, PA 15213, USA. (Email:
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

JR Almeida , A Versace , S Hassel , DJ Kupfer , ML Phillips (2010). Elevated amygdala activity to sad facial expressions: a state marker of bipolar but not unipolar depression. Biological Psychiatry 67, 414421.

A Anand , Y Li , Y Wang , K Gardner , M Lowe (2007). Reciprocal effects of antidepressant treatment on activity and connectivity of the mood regulating circuit: an fMRI study. Journal of Neuropsychiatry Clinical Neuroscience 19, 274282.

M Annett (1970). A classification of hand preference by association analysis. British Journal of Psychology 61, 303321.

K Blair , O Spreen (1989). Predicting premorbid IQ: a revision of the National Adult Reading Test. Clinical Neuropsychologist 3, 129136.

G Bush , LM Shin (2006). The Multi-Source Interference Task: an fMRI task that reliably activates the cingulo-frontal-parietal cognitive/attention network. Nature Protocols 1, 308313.

C Chen , B Lenox , R Jacob , A Calder , V Lupson , R Bisbrown-Chippendale , J Suckling , E Bullmore (2006). Explicit and implicit facial affect recognition in manic and depressed states of bipolar disorder: a functional magnetic resonance imaging study. Biological Psychiatry 59, 3139.

T Deckersbach , S Rauch , U Buhlman , M Ostacher , J Beucke , A Nierenberg , G Sachs , DD Dougherty (2008). An fMRI investigation of working memory and sadness in females with bipolar disorder: a brief report. Bipolar Disorders 10, 928942.

WC Drevets (2003). Neuroimaging abnormalities in the amygdala in mood disorders. Annals of the New York Academy of Sciences 985, 420444.

R Elliott , JS Rubinsztein , BJ Sahakian , RJ Dolan (2002). The neural basis of mood-congruent processing biases in depression. Archives of General Psychiatry 59, 597604.

J Epstein , H Pan , JH Kocsis , Y Yang , T Butler , J Chusid , H Hochberg , J Murrough , E Strohmayer , E Stern , DA Silbersweig (2006). Lack of ventral striatal response to positive stimuli in depressed versus normal subjects. American Journal of Psychiatry 163, 17841790.

C Fales , D Barch , M Rundle , M Mintun , A Snyder , J Cohen , J Mathews , Y Sheline (2008). Altered emotional interference processing in affective and cognitive-control brain circuitry in major depression. Biological Psychiatry 63, 377384.

M Folstein , S Folstein , P McHugh (1975). ‘Mini-Mental State’. A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research 12, 189198.

CHY Fu , SCR Williams , AJ Cleare , MJ Brammer , ND Walsh , J Kim , CM Andrew , EM Pich , PM Williams , LJ Reed , MT Mitterschiffthaler , J Suckling , ET Bullmore (2004). Attenuation of the neural response to sad faces in major depression by antidepressant treatment: a prospective, event-related functional magnetic resonance imaging study. Archives of General Psychiatry 61, 877889.

S Grimm , J Beck , D Schuepbach , D Hell , P Boesinger , F Permpohl , l Niehaus , H Boeker , G Northoff (2008). Imbalance between left and right dorsolateral prefrontal cortex in major depression is linked to negative emotional judgment: an fMRI study in severe major depressive disorder. Biological Psychiatry 63, 369376.

SA Gruber , J Rogowska , DA Yurgelun-Todd (2004). Decreased activation of the anterior cingulate in bipolar patients: an fMRI study. Journal of Affective Disorders 82, 191201.

SN Haber , K-S Kim , P Mailly , R Calzavara (2006). Reward-related cortical inputs define a large striatal region in primates that interface with associative cortical connections, providing a substrate for incentive-based learning. Journal of Neuroscience 26, 83688376.

M Hamilton (1960). A rating scale for depression. Journal of Neurology, Neurosurgery, and Psychiatry 23, 5662.

RM Hirschfeld , L Lewis , LA Vornik (2003). Perceptions and impact of bipolar disorder: how far have we really come? Results of the National Depressive and Manic-Depressive Association 2000 survey of individuals with bipolar disorder. Journal of Clinical Psychiatry 64, 161174.

T Johnstone , C van Reekum , H Urry , N Kalin , R Davidson (2007). Failure to regulate: counterproductive recruitment of top-down prefrontal-subcortical circuitry in major depression. Journal of Neuroscience 27, 88778884.

K Koch , K Pauly , T Kellermann , NY Seiferth , M Reske , V Backes , T Stöcker , NJ Shah , K Amunts , T Kircher , F Schneider , U Habel (2007). Gender differences in the cognitive control of emotion: an fMRI study. Neuropsychologia 45, 27442754.

CD Ladouceur , JS Silk , RE Dahl , L Ostapenko , DM Kronhaus , ML Phillips (2009). Fearful faces influence attentional control processes in anxious youth and adults. Emotion 9, 855864.

S Langenecker , L Bieliauskas , L Rapport , J Zubieta , E Wilde , S Berent (2005). Face emotion perception and executive functioning deficitis in depression. Journal of Clinical and Experimental Neuropsychology 27, 320333.

SA Langenecker , S Kennedy , L Guidotti , E Briceno , L Own , T Hooven , E Young , H Akil , DC Noll , J Zubieta (2007). Frontal and limbic activation during inhibitory control predicts treatment response in major depressive disorder. Biological Psychiatry 62, 12721280.

SA Langenecker , E Saunders , A Kade , M Ransom , M McInnis (2010). Intermediate cognitive phenotypes in bipolar disorder. Journal of Affective Disorders 122, 285293.

NS Lawrence , AM Williams , S Surguladze , V Giampietro , MJ Brammer , C Andrew , S Frangou , C Ecker , ML Phillips (2004). Subcortical and ventral prefrontal cortical neural responses to facial expressions distinguish patients with bipolar disorder and major depression. Biological Psychiatry 55, 578587.

V Lorenzetti , NB Allen , A Fornito , M Yücel (2009). Structural brain abnormalities in major depressive disorder: a selective review of recent MRI studies. Journal of Affective Disorders 117, 117.

JA Maldjian , PJ Laurienti , RA Kraft , JH Burdette (2003). An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets. NeuroImage 19, 12331239.

G Malhi , J Lagopoulos , P Ward , V Kumari , P Mitchell , GB Parker , B Ivanovski , P Schdev (2004). Cognitive generation of affect in bipolar depression: an fMRI study. European Journal of Neuroscience 19, 741754.

K McRae , KN Ochsner , IB Mauss , JJD Gabrieli , JJ Gross (2008). Gender differences in emotion regulation: an fMRI study of cognitive reappraisal. Group Processes and Intergroup Relations 11, 143162.

KN Ochsner , JJ Gross (2005). The cognitive control of emotion. Trends in Cognitive Sciences 9, 242249.

MN Pavuluri , MM Oconnor , E Harral , JA Sweeney (2007). Affective neural circuitry during facial emotion processing in pediatric bipolar disorder. Biological Psychiatry 62, 158167.

M Phillips , C Ladouceur , W Drevets (2008). A neural model of voluntary and automatic emotion regulation: implications for understanding the pathophysiology and neurodevelopment of bipolar disorder. Molecular Psychiatry 13, 833857.

ML Phillips (2003). Understanding the neurobiology of emotion perception: implications for psychiatry. British Journal of Psychiatry 182, 190192.

ML Phillips , WC Drevets , SL Rauch , R Lane (2003). Neurobiology of emotion perception II: Implications for major psychiatric disorders. Biological Psychiatry 54, 515528.

BA Rich , DT Vinton , R Roberson-Nay , RE Hommer , LH Berghorst , EB McClure , SJ Fromm , DS Pine , E Leibenluft (2006). Limbic hyperactivation during processing of neutral facial expressions in children with bipolar disorder. Proceedings of the National Academy of Sciences USA 103, 89008905.

A Schienle , A Schäfer , R Stark , B Walter , D Vaitl (2005). Gender differences in the processing of disgust- and fear-inducing pictures: an fMRI study. Neuroreport 16, 277280.

GJ Siegle , SR Steinhauer , ME Thase , AV Stenger , CS Carter (2002). Can't shake that feeling: event-related fMRI assessment of sustained amygdala activity in response to emotional information in depressed individuals. Biological Psychiatry 51, 693707.

GJ Siegle , W Thompson , CS Carter , SR Steinhauer , ME Thase (2007). Increased amygdala and decreased dorsolateral prefrontal BOLD responses in unipolar depression: related and independent features. Biological Psychiatry 61, 198209.

SM Strakowski , CM Adler , MP DelBello (2002). Volumetric MRI studies of mood disorders: do they distinguish unipolar and bipolar disorder? Bipolar Disorders 4, 8088.

S Surguladze , MJ Brammer , P Keedwell , V Giampietro , AW Young , MJ Travis , SCR Williams , ML Phillips (2005). A differential pattern of neural response toward sad versus happy facial expressions in major depressive disorder. Biological Psychiatry 57, 201209.

SA Surguladze , MJ Brammer , AW Young , C Andrew , MJ Travis , SCR Williams , ML Phillips (2003). A preferential increase in the extrastriate response to signals of danger. NeuroImage 19, 13171328.

N Tottenhan , J Tanaka , A Leon , T McCarry , M Nurse , T Hare (2009). The NimStim set of facial expressions: judgments from untrained research participants. Psychiatry Research 168, 242249.

MM Weissman , RC Bland , GJ Canino , C Faravelli , S Greenwald , H-G Hwu , PR Joyce , EG Karam , C-K Lee , J Lellouch , J-P Lépine , SC Newman , M Rubio-Stipec , JE Wells , PJ Wickramaratne , H-U Wittchen , E-K Yeh (1996). Cross-national epidemiology of major depression and bipolar disorder. Journal of the American Medical Association 276, 293299.

AW Young , D Rowland , AJ Calder , NL Etcoff , A Seth , DI Perrett (1997). Facial expression megamix: tests of dimensional and category accounts of emotion recognition. Cognition 63, 271313.

R Young , J Biggs , V Ziegler , D Meyer (1978). A rating scale for mania: reliability, validity, and sensitivity. British Journal of Psychiatry 133, 429435.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Psychological Medicine
  • ISSN: 0033-2917
  • EISSN: 1469-8978
  • URL: /core/journals/psychological-medicine
Please enter your name
Please enter a valid email address
Who would you like to send this to? *


Type Description Title
Supplementary Materials

Bertocci Supplementary Materials
Bertocci Supplementary Materials

 Unknown (206 KB)
206 KB