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Abnormal prefrontal activity subserving attentional control of emotion in remitted depressed patients during a working memory task with emotional distracters

  • R. Kerestes (a1) (a2), C. D. Ladouceur (a3), S. Meda (a4), P. J. Nathan (a2) (a5), H. P. Blumberg (a1), K. Maloney (a1), B. Ruf (a1), A. Saricicek (a1), G. D. Pearlson (a1) (a4), Z. Bhagwagar (a1) (a6) and M. L. Phillips (a3) (a7)
  • DOI:
  • Published online: 07 July 2011

Patients with major depressive disorder (MDD) show deficits in processing of facial emotions that persist beyond recovery and cessation of treatment. Abnormalities in neural areas supporting attentional control and emotion processing in remitted depressed (rMDD) patients suggests that there may be enduring, trait-like abnormalities in key neural circuits at the interface of cognition and emotion, but this issue has not been studied systematically.


Nineteen euthymic, medication-free rMDD patients (mean age 33.6 years; mean duration of illness 34 months) and 20 age- and gender-matched healthy controls (HC; mean age 35.8 years) performed the Emotional Face N-Back (EFNBACK) task, a working memory task with emotional distracter stimuli. We used blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to measure neural activity in the dorsolateral (DLPFC) and ventrolateral prefrontal cortex (VLPFC), orbitofrontal cortex (OFC), ventral striatum and amygdala, using a region of interest (ROI) approach in SPM2.


rMDD patients exhibited significantly greater activity relative to HC in the left DLPFC [Brodmann area (BA) 9/46] in response to negative emotional distracters during high working memory load. By contrast, rMDD patients exhibited significantly lower activity in the right DLPFC and left VLPFC compared to HC in response to positive emotional distracters during high working memory load. These effects occurred during accurate task performance.


Remitted depressed patients may continue to exhibit attentional biases toward negative emotional information, reflected by greater recruitment of prefrontal regions implicated in attentional control in the context of negative emotional information.

Corresponding author
*Address for correspondence: Miss R. Kerestes, School of Psychology and Psychiatry, Monash University Clayton Campus, Wellington Road, Clayton, Melbourne Victoria, Australia. (
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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.

JR Almeida , A Versace , A Mechelli , S Hassel , K Quevedo , DJ Kupfer , ML Phillips (2009). Abnormal amygdala-prefrontal effective connectivity to happy faces differentiates bipolar from major depression. Biological Psychiatry 66, 451459.

A Anticevic , G Repovs , DM Barch (2010). Resisting emotional interference: brain regions facilitating working memory performance during negative distraction. Cognitive, Affective and Behavioral Neuroscience 10, 159173.

DM Barch , YI Sheline , JG Csernansky , AZ Snyder (2003). Working memory and prefrontal cortex dysfunction: specificity to schizophrenia compared with major depression. Biological Psychiatry 53, 376384.

Z Bhagwagar , PJ Cowen , GM Goodwin , CJ Harmer (2004). Normalization of enhanced fear recognition by acute SSRI treatment in subjects with a previous history of depression. American Journal of Psychiatry 161, 166168.

KS Blair , BW Smith , DG Mitchell , J Morton , M Vythilingam , L Pessoa , D Fridberg , A Zametkin , D Sturman , EE Nelson , WC Drevets , DS Pine , A Martin , RJ Blair (2007). Modulation of emotion by cognition and cognition by emotion. NeuroImage 35, 430440.

A Carvajal-Rodriguez , J de Una-Alvarez , E Rolan-Alvarez (2009). A new multitest correction (SGoF) that increases its statistical power when increasing the number of tests. BMC Bioinformatics 10, 209.

L Clark , A Sarna , GM Goodwin (2005). Impairment of executive function but not memory in first-degree relatives of patients with bipolar I disorder and in euthymic patients with unipolar depression. American Journal of Psychiatry 162, 19801982.

JD Cohen , SD Forman , TS Braver , BJ Casey (1994). Activation of the prefrontal cortex in a non-spatial working memory task with functional MRI. Human Brain Mapping 1, 293304.

HR Cremers , LR Demenescu , A Aleman , R Renken , MJ van Tol , NJ van der Wee , DJ Veltman , K Roelofs (2009). Neuroticism modulates amygdala-prefrontal connectivity in response to negative emotional facial expressions. NeuroImage 49, 963970.

RJ Davidson (1992). Anterior cerebral asymmetry and the nature of emotion. Brain and Cognition 20, 125151.

F Dolcos , P Kragel , L Wang , G McCarthy (2006). Role of the inferior frontal cortex in coping with distracting emotions. Neuroreport 17, 15911594.

F Dolcos , G McCarthy (2006). Brain systems mediating cognitive interference by emotional distraction. Journal of Neuroscience 26, 20722079.

R Elliott , SC Baker , RD Rogers , DA O'Leary , ES Paykel , CD Frith , RJ Dolan , BJ Sahakian (1997). Prefrontal dysfunction in depressed patients performing a complex planning task: a study using positron emission tomography. Psychological Medicine 27, 931942.

R Elliott , R Zahn , JF Deakin , IM Anderson (2010). Affective cognition and its disruption in mood disorders. Neuropsychopharmacology 36, 153182.

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.

S Erk , A Kleczar , H Walter (2007). Valence-specific regulation effects in a working memory task with emotional context. NeuroImage 37, 623632.

CL Fales , DM Barch , MM Rundle , MA Mintun , J Mathews , AZ Snyder , YI Sheline (2009). Antidepressant treatment normalizes hypoactivity in dorsolateral prefrontal cortex during emotional interference processing in major depression. Journal of Affective Disorders 112, 206211.

CL Fales , DM Barch , MM Rundle , MA Mintun , AZ Snyder , JD Cohen , J Mathews , YI Sheline (2008). Altered emotional interference processing in affective and cognitive-control brain circuitry in major depression. Biological Psychiatry 63, 377384.

MB First (2002). The DSM series and experience with DSM-IV. Psychopathology 35, 6771.

PB Fitzgerald , A Srithiran , J Benitez , ZZ Daskalakis , TJ Oxley , J Kulkarni , GF Egan (2008). An fMRI study of prefrontal brain activation during multiple tasks in patients with major depressive disorder. Human Brain Mapping 29, 490501.

SD Forman , JD Cohen , M Fitzgerald , WF Eddy , MA Mintun , DC Noll (1995). Improved assessment of significant activation in functional magnetic resonance imaging (fMRI): use of a cluster-size threshold. Magnetic Resonance in Medicine 33, 636647.

L Freire , A Roche , JF Mangin (2002). What is the best similarity measure for motion correction in fMRI time series? IEEE Transactions on Medical Imaging 21, 470484.

CH Fu , SC 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.

IH Gotlib , E Krasnoperova , DN Yue , J Joormann (2004). Attentional biases for negative interpersonal stimuli in clinical depression. Journal of Abnormal Psychology 113, 121135.

E Grober , M Sliwinski (1991). Development and validation of a model for estimating premorbid verbal intelligence in the elderly. Journal of Clinical and Experimental Neuropsychology 13, 933949.

RC Gur , RJ Erwin , RE Gur , AS Zwil , C Heimberg , HC Kraemer (1992). Facial emotion discrimination: II. Behavioral findings in depression. Psychiatry Research 42, 241251.

RC Gur , BE Skolnick , RE Gur (1994). Effects of emotional discrimination tasks on cerebral blood flow: regional activation and its relation to performance. Brain and Cognition 25, 271286.

WW Hale 3rd (1998). Judgment of facial expressions and depression persistence. Psychiatry Research 80, 265274.

PO Harvey , P Fossati , JB Pochon , R Levy , G Lebastard , S Lehericy , JF Allilaire , B Dubois (2005). Cognitive control and brain resources in major depression: an fMRI study using the n-back task. NeuroImage 26, 860869.

K Hugdahl , BR Rund , A Lund , A Asbjornsen , J Egeland , L Ersland , NI Landro , A Roness , KI Stordal , K Sundet , T Thomsen (2004). Brain activation measured with fMRI during a mental arithmetic task in schizophrenia and major depression. American Journal of Psychiatry 161, 286293.

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

J Joormann , IH Gotlib (2007). Selective attention to emotional faces following recovery from depression. Journal of Abnormal Psychology 116, 8085.

RE Jorge , RG Robinson , SV Arndt , SE Starkstein , AW Forrester , F Geisler (1993). Depression following traumatic brain injury: a 1 year longitudinal study. Journal of Affective Disorders 27, 233243.

S Kaiser , J Unger , M Kiefer , J Markela , C Mundt , M Weisbrod (2003). Executive control deficit in depression: event-related potentials in a Go/Nogo task. Psychiatry Research: Neuroimaging 122, 169184.

MA Kim , E Tura , SG Potkin , JH Fallon , DS Manoach , VD Calhoun , JA Turner (2010). Working memory circuitry in schizophrenia shows widespread cortical inefficiency and compensation. Schizophrenia Research 117, 4251.

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.

BT Lee , JH Seok , BC Lee , SW Cho , BJ Yoon , KU Lee , JH Chae , IG Choi , BJ Ham (2008). Neural correlates of affective processing in response to sad and angry facial stimuli in patients with major depressive disorder. Progress in Neuro-Psychopharmacology and Biological Psychiatry 32, 778785.

JM Leppanen , M Milders , JS Bell , E Terriere , JK Hietanen (2004). Depression biases the recognition of emotionally neutral faces. Psychiatry Research 128, 123133.

SM Levens , IH Gotlib (2010). Updating positive and negative stimuli in working memory in depression. Journal of Experimental Psychology: General 139, 654664.

K Matsuo , DC Glahn , MA Peluso , JP Hatch , ES Monkul , P Najt , M Sanches , F Zamarripa , J Li , JL Lancaster , PT Fox , JH Gao , JC Soares (2007). Prefrontal hyperactivation during working memory task in untreated individuals with major depressive disorder. Molecular Psychiatry 12, 158166.

A Neumeister , WC Drevets , I Belfer , DA Luckenbaugh , S Henry , O Bonne , P Herscovitch , D Goldman , DS Charney (2006). Effects of a alpha 2C-adrenoreceptor gene polymorphism on neural responses to facial expressions in depression. Neuropsychopharmacology 31, 17501756.

G Okada , Y Okamoto , S Morinobu , S Yamawaki , N Yokota (2003). Attenuated left prefrontal activation during a verbal fluency task in patients with depression. Neuropsychobiology 47, 2126.

Y Paelecke-Habermann , J Pohl , B Leplow (2005). Attention and executive functions in remitted major depression patients. Journal of Affective Disorders 89, 125135.

S Paradiso , GJ Lamberty , MJ Garvey , RG Robinson (1997). Cognitive impairment in the euthymic phase of chronic unipolar depression. Journal of Nervous and Mental Disease 185, 748754.

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

ML Phillips , CD Ladouceur , WC 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.

M Preiss , H Kucerova , J Lukavsky , H Stepankova , P Sos , R Kawaciukova (2009). Cognitive deficits in the euthymic phase of unipolar depression. Psychiatry Research 169, 235239.

S Schoning , P Zwitserlood , A Engelien , A Behnken , H Kugel , H Schiffbauer , K Lipina , C Pachur , A Kersting , U Dannlowski , BT Baune , P Zwanzger , T Reker , W Heindel , V Arolt , C Konrad (2009). Working-memory fMRI reveals cingulate hyperactivation in euthymic major depression. Human Brain Mapping 30, 27462756.

YI Sheline , DM Barch , JM Donnelly , JM Ollinger , AZ Snyder , MA Mintun (2001). Increased amygdala response to masked emotional faces in depressed subjects resolves with antidepressant treatment: an fMRI study. Biological Psychiatry 50, 651658.

GJ Siegle , SR Steinhauer , ME Thase , VA 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.

LH Somerville , H Kim , T Johnstone , AL Alexander , PJ Whalen (2004). Human amygdala responses during presentation of happy and neutral faces: correlations with state anxiety. Biological Psychiatry 55, 897903.

S Surguladze , MJ Brammer , P Keedwell , V Giampietro , AW Young , MJ Travis , SC 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 , AW Young , C Senior , G Brebion , MJ Travis , ML Phillips (2004). Recognition accuracy and response bias to happy and sad facial expressions in patients with major depression. Neuropsychology 18, 212218.

JA Sweeney , JA Kmiec , DJ Kupfer (2000). Neuropsychologic impairments in bipolar and unipolar mood disorders on the CANTAB neurocognitive battery. Biological Psychiatry 48, 674684.

JV Taylor Tavares , L Clark , DM Cannon , K Erickson , WC Drevets , BJ Sahakian (2007). Distinct profiles of neurocognitive function in unmedicated unipolar depression and bipolar II depression. Biological Psychiatry 62, 917924.

N Tottenham , JW Tanaka , AC Leon , T McCarry , M Nurse , TA Hare , DJ Marcus , A Westerlund , BJ Casey , C Nelson (2009). The NimStim set of facial expressions: judgments from untrained research participants. Psychiatry Research 168, 242249.

TA Victor , ML Furey , SJ Fromm , A Ohman , WC Drevets (2010). Relationship between amygdala responses to masked faces and mood state and treatment in major depressive disorder. Archives of General Psychiatry 67, 11281138.

L Wang , KS LaBar , M Smoski , MZ Rosenthal , F Dolcos , TR Lynch , RR Krishnan , G McCarthy (2008). Prefrontal mechanisms for executive control over emotional distraction are altered in major depression. Psychiatry Research: Neuroimaging 163, 143155.

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