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Explicit and Implicit Facial Affect Recognition in Manic and Depressed States of Bipolar Disorder: A Functional Magnetic Resonance Imaging Study

      Background

      The pathophysiology of abnormal mood states–mania and depression–in patients with bipolar disorder remains unclear. Facial affect processing paradigms are an effective way of studying behavioral and functional magnetic resonance imaging (fMRI) correlates of affective disorders.

      Methods

      We used a factorial design to measure the neural correlates of tasks, tapping explicit and implicit recognition of sad, fearful, and happy facial expressions using event-related fMRI paradigms in three groups of participants: eight bipolar depressed patients, eight bipolar manic patients, and eight control subjects.

      Results

      Depressed and manic patients exhibited overactivated responses to fearful faces, as well as to mood-incongruent facial expressions, with the depressed group exhibiting overactivity in fronto-striato-thalamic systems in response to happy faces and the manic group exhibiting overactivity in the fusiform gyrus in response to sad faces. For manic patients, task type also affected the neural response to sad faces, with the corticolimbic regions showing overactivation for implicit processing and underactivation for explicit processing.

      Conclusions

      Depressed and manic patients exhibited abnormal neural responses to sad, fearful, and happy facial expressions. Additionally, the attentional level of sad facial affect processing has important consequences for abnormalities of amygdala and cingulate activation in manic patients.

      Key Words

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      References

        • Adolphs R.
        Neural systems for recognizing emotion.
        Curr Opin Neurobiol. 2002; 12: 169-177
        • Adolphs R.
        • Tranel D.
        • Hamann S.
        • Young A.W.
        • Calder A.J.
        • Phelps E.A.
        • et al.
        Recognition of facial emotion in nine individuals with bilateral amygdala damage.
        Neuropsychologia. 1999; 37: 1111-1117
        • Alexander G.E.
        • DeLong M.R.
        • Strick P.L.
        Parallel organization of functionally segregated circuits linking basal ganglia and cortex.
        Annu Rev Neurosci. 1986; 9: 357-381
        • Al Mousawi A.H.
        • Evans N.
        • Ebmeier K.P.
        • Roeda D.
        • Chaloner F.
        • Ashcroft G.W.
        Limbic dysfunction in schizophrenia and mania. A study using 18F-labelled fluorodeoxyglucose and positron emission tomography.
        Br J Psychiatry. 1996; 169: 509-516
        • American Psychiatric Association
        Diagnostic and Statistical Manual of Mental Disorders. 4th ed. American Psychiatric Association, Washington, DC1994
        • Bearden C.E.
        • Hoffman K.M.
        • Cannon T.D.
        The neuropsychology and neuroanatomy of bipolar affective disorder.
        Bipolar Disord. 2001; 3: 106-150
        • Beck A.T.
        • Rush A.J.
        • Shaw B.F.
        • Emery G.
        Cognitive Therapy of Depression. Guilford, New York1979
        • Berns G.S.
        • Nemeroff C.B.
        The neurobiology of bipolar disorder.
        Am J Med Genet C Semin Med Genet. 2003; 123: 76-84
        • Blair R.J.
        • Morris J.S.
        • Frith C.D.
        • Perrett D.I.
        • Dolan R.J.
        Dissociable neural responses to facial expressions of sadness and anger.
        Brain. 1999; 122: 883-893
        • Blumberg H.P.
        • Leung H.C.
        • Skudlarski P.
        • Lacadie C.M.
        • Fredericks C.A.
        • Harris B.C.
        • et al.
        A functional magnetic resonance imaging study of bipolar disorder.
        Arch Gen Psychiatry. 2003; 60: 601-609
        • Blumberg H.P.
        • Martin A.
        • Kaufman J.
        • Leung H.C.
        • Skudlarski P.
        • Lacadie C.
        • et al.
        Frontostriatal abnormalities in adolescents with bipolar disorder.
        Am J Psychiatry. 2003; 160: 1345-1347
        • Blumberg H.P.
        • Stern E.
        • Martinez D.
        • Ricketts S.
        • de Asis J.
        • White T.
        • et al.
        Increased anterior cingulate and caudate activity in bipolar mania.
        Biol Psychiatry. 2000; 48: 1045-1052
        • Blumberg H.P.
        • Stern E.
        • Ricketts S.
        • Martinez D.
        • de Asis J.
        • White T.
        • et al.
        Rostral and orbital prefrontal cortex dysfunction in the manic state of bipolar disorder.
        Am J Psychiatry. 1999; 156: 1986-1988
        • Bradley M.M.
        • Codispoti M.
        • Sabatinelli D.
        • Lang P.J.
        Emotion and motivation II.
        Emotion. 2001; 1: 300-319
        • Calder A.J.
        • Rowland D.
        • Young A.W.
        • Nimmo-Smith I.
        • Keane J.
        • Perrett D.I.
        Caricaturing facial expressions.
        Cognition. 2000; 76: 105-146
        • Caligiuri M.P.
        • Brown G.G.
        • Meloy M.J.
        • Eberson S.C.
        • Kindermann S.S.
        • Frank L.R.
        • et al.
        An fMRI study of affective state and medication on cortical and subcortical brain regions during motor performance in bipolar disorder.
        Psychiatry Res. 2003; 123: 171-182
        • Carter C.S.
        • Braver T.S.
        • Barch D.M.
        • Botvinick M.M.
        • Noll D.
        • Cohen J.D.
        Anterior cingulate cortex, error detection, and the online monitoring of performance.
        Science. 1998; 280: 747-749
        • Chang K.
        • Adleman N.E.
        • Dienes K.
        • Simeonova D.I.
        • Menon V.
        • Reiss A.
        Anomalous prefrontal-subcortical activation in familial pediatric bipolar disorder.
        Arch Gen Psychiatry. 2004; 61: 781-792
        • Critchley H.
        • Daly E.
        • Phillips M.
        • Brammer M.
        • Bullmore E.
        • Williams S.
        • et al.
        Explicit and implicit neural mechanisms for processing of social information from facial expressions.
        Hum Brain Mapp. 2000; 9: 93-105
        • Cummings J.L.
        • Mendez M.F.
        Secondary mania with focal cerebrovascular lesions.
        Am J Psychiatry. 1984; 141: 1084-1087
        • Damasio A.R.
        • Grabowski T.J.
        • Bechara A.
        • Damasio H.
        • Ponto L.L.
        • Parvizi J.
        • et al.
        Subcortical and cortical brain activity during the feeling of self-generated emotions.
        Nat Neurosci. 2000; 3: 1049-1056
        • Davidson R.J.
        • Irwin W.
        • Anderle M.J.
        • Kalin N.H.
        The neural substrates of affective processing in depressed patients treated with venlafaxine.
        Am J Psychiatry. 2003; 160: 64-75
        • Davidson R.J.
        • Lewis D.A.
        • Alloy L.B.
        • Amaral D.G.
        • Bush G.
        • Cohen J.D.
        • et al.
        Neural and behavioral substrates of mood and mood regulation.
        Biol Psychiatry. 2002; 52: 478-502
        • Drevets W.C.
        Neuroimaging and neuropathological studies of depression.
        Curr Opin Neurobiol. 2001; 11: 240-249
        • Drevets W.C.
        • Price J.L.
        • Simpson Jr, J.R.
        • Todd R.D.
        • Reich T.
        • Vannier M.
        • et al.
        Subgenual prefrontal cortex abnormalities in mood disorders.
        Nature. 1997; 386: 824-827
        • Elliott R.
        • Ogilvie A.
        • Rubinsztein J.S.
        • Calderon G.
        • Dolan R.J.
        • Sahakian B.J.
        Abnormal ventral frontal response during performance of an affective go/no go task in patients with mania.
        Biol Psychiatry. 2004; 55: 1163-1170
        • Elliott R.
        • Rubinsztein J.S.
        • Sahakian B.J.
        • Dolan R.J.
        The neural basis of mood-congruent processing biases in depression.
        Arch Gen Psychiatry. 2002; 59: 597-604
        • Fu C.H.Y.
        • Williams S.C.R.
        • Cleare A.J.
        • Brammer M.J.
        • Walsh N.D.
        • Kim J.
        • et al.
        Attenuation of the neural response to sad faces in major depression by antidepressant treatment.
        Arch Gen Psychiatry. 2004; 61: 877-889
        • Goodwin G.M.
        • Cavanagh J.T.
        • Glabus M.F.
        • Kehoe R.F.
        • O’Carroll R.E.
        • Ebmeier K.P.
        Uptake of 99mTc-exametazime shown by single photon emission computed tomography before and after lithium withdrawal in bipolar patients.
        Br J Psychiatry. 1997; 170: 426-430
        • Gorno-Tempini M.L.
        • Pradelli S.
        • Serafini M.
        • Pagnoni G.
        • Baraldi P.
        • Porro C.
        • et al.
        Explicit and incidental facial expression processing.
        Neuroimage. 2001; 14: 465-473
        • Gur R.C.
        • Erwin R.J.
        • Gur R.E.
        • Zwil A.S.
        • Heimberg C.
        • Kraemer H.C.
        Facial emotion discrimination: II. Behavioral findings in depression.
        Psychiatry Res. 1992; 42: 241-251
        • Hale III, W.W.
        Judgment of facial expressions and depression persistence.
        Psychiatry Res. 1998; 80: 265-274
        • Hamann S.
        • Canli T.
        Individual differences in emotion processing.
        Curr Opin Neurobiol. 2004; 14: 233-238
        • Hamilton M.
        A rating scale for depression.
        J Neurol Neurosurg Psychiatry. 1960; 23: 56-62
        • Hariri A.R.
        • Mattay V.S.
        • Tessitore A.
        • Fera F.
        • Weinberger D.R.
        Neocortical modulation of the amygdala response to fearful stimuli.
        Biol Psychiatry. 2003; 53: 494-501
        • Harrison P.J.
        The neuropathology of primary mood disorder.
        Brain. 2002; 125: 1428-1449
        • Haxby J.V.
        • Hoffman E.A.
        • Gobbini M.I.
        The distributed human neural system for face perception.
        Trends Cogn Sci. 2000; 4: 223-233
        • Kerns J.G.
        • Cohen J.D.
        • MacDonald III, A.W.
        • Cho R.Y.
        • Stenger V.A.
        • Carter C.S.
        Anterior cingulate conflict monitoring and adjustments in control.
        Science. 2004; 303: 1023-1026
        • Lane R.D.
        • Reiman E.M.
        • Ahern G.L.
        • Schwartz G.E.
        • Davidson R.J.
        Neuroanatomical correlates of happiness, sadness, and disgust.
        Am J Psychiatry. 1997; 154: 926-933
        • Lane R.D.
        • Reiman E.M.
        • Bradley M.M.
        • Lang P.J.
        • Ahern G.L.
        • Davidson R.J.
        • et al.
        Neuroanatomical correlates of pleasant and unpleasant emotion.
        Neuropsychologia. 1997; 35: 1437-1444
        • Lawrence N.S.
        • Williams A.M.
        • Surguladze S.
        • Giampietro V.
        • Brammer M.J.
        • Andrew C.
        • et al.
        Subcortical and ventral prefrontal cortical neural responses to facial expressions distinguish patients with bipolar disorder and major depression.
        Biol Psychiatry. 2004; 55: 578-587
        • Lennox B.R.
        • Jacob R.
        • Calder A.J.
        • Lupson V.
        • Bullmore E.
        Behavioural and neurocognitive responses to sad facial affect are attenuated in patients with mania.
        Psychol Med. 2004; 34: 795-802
        • Loeber R.T.
        • Gruber S.A.
        • Cohen B.M.
        • Renshaw P.F.
        • Sherwood A.R.
        • Yurgelun-Todd D.A.
        Cerebellar blood volume in bipolar patients correlates with medication.
        Biol Psychiatry. 2002; 51: 370-376
        • Lyon H.M.
        • Startup M.
        • Bentall R.P.
        Social cognition and the manic defense.
        J Abnorm Psychol. 1999; 108: 273-282
        • Malhi G.S.
        • Lagopoulos J.
        • Ward P.B.
        • Kumari V.
        • Mitchell P.B.
        • Parker G.B.
        • et al.
        Cognitive generation of affect in bipolar depression.
        Eur J Neurosci. 2004; 19: 741-754
        • Manji H.K.
        • Moore G.J.
        • Chen G.
        Clinical and preclinical evidence for the neurotrophic effects of mood stabilizers.
        Biol Psychiatry. 2000; 48: 740-754
        • Mayberg H.S.
        • Liotti M.
        • Brannan S.K.
        • McGinnis S.
        • Mahurin R.K.
        • Jerabek P.A.
        • et al.
        Reciprocal limbic-cortical function and negative mood.
        Am J Psychiatry. 1999; 156: 675-682
        • McClure E.B.
        • Monk C.S.
        • Nelson E.E.
        • Zarahn E.
        • Leibenluft E.
        • Bilder R.M.
        • et al.
        A developmental examination of gender differences in brain engagement during evaluation of threat.
        Biol Psychiatry. 2004; 55: 1047-1055
        • Mitterschiffthaler M.T.
        • Kumari V.
        • Malhi G.S.
        • Brown R.G.
        • Giampietro V.P.
        • Brammer M.J.
        • et al.
        Neural response to pleasant stimuli in anhedonia.
        Neuroreport. 2003; 14: 177-182
        • Morris J.S.
        • Friston K.J.
        • Buchel C.
        • Frith C.D.
        • Young A.W.
        • Calder A.J.
        • et al.
        A neuromodulatory role for the human amygdala in processing emotional facial expressions.
        Brain. 1998; 121: 47-57
        • Morris J.S.
        • Ohman A.
        • Dolan R.J.
        Conscious and unconscious emotional learning in the human amygdala.
        Nature. 1998; 393: 467-470
        • Morris J.S.
        • Ohman A.
        • Dolan R.J.
        A subcortical pathway to the right amygdala mediating “unseen” fear.
        Proc Natl Acad Sci U S A. 1999; 96: 1680-1685
        • Murphy F.C.
        • Sahakian B.J.
        • Rubinsztein J.S.
        • Michael A.
        • Rogers R.D.
        • Robbins T.W.
        • et al.
        Emotional bias and inhibitory control processes in mania and depression.
        Psychol Med. 1999; 29: 1307-1321
        • O’Connell R.A.
        • Van Heertum R.L.
        • Luck D.
        • Yudd A.P.
        • Cueva J.E.
        • Billick S.B.
        • et al.
        Single-photon emission computed tomography of the brain in acute mania and schizophrenia.
        J Neuroimaging. 1995; 5: 101-104
        • Ongur D.
        • Price J.L.
        The organization of networks within the orbital and medial prefrontal cortex of rats, monkeys and humans.
        Cereb Cortex. 2000; 10: 206-219
        • Peterson B.S.
        • Leckman J.F.
        • Tucker D.
        • Scahill L.
        • Staib L.
        • Zhang H.
        • et al.
        Preliminary findings of antistreptococcal antibody titers and basal ganglia volumes in tic, obsessive-compulsive, and attention deficit/hyperactivity disorders.
        Arch Gen Psychiatry. 2000; 57: 364-372
        • Peterson B.S.
        • Skudlarski P.
        • Anderson A.W.
        • Zhang H.
        • Gatenby J.C.
        • Lacadie C.M.
        • et al.
        A functional magnetic resonance imaging study of tic suppression in Tourette syndrome.
        Arch Gen Psychiatry. 1998; 55: 326-333
        • Phillips M.L.
        • Drevets W.C.
        • Rauch S.L.
        • Lane R.
        Neurobiology of emotion perception I.
        Biol Psychiatry. 2003; 54: 504-514
        • Phillips M.L.
        • Drevets W.C.
        • Rauch S.L.
        • Lane R.
        Neurobiology of emotion perception II.
        Biol Psychiatry. 2003; 54: 515-528
        • Phillips M.L.
        • Young A.W.
        • Senior C.
        • Brammer M.
        • Andrew C.
        • Calder A.J.
        • et al.
        A specific neural substrate for perceiving facial expressions of disgust.
        Nature. 1997; 389: 495-498
        • Rauch S.L.
        • Whalen P.J.
        • Shin L.M.
        • McInerney S.C.
        • Macklin M.L.
        • Lasko N.B.
        • et al.
        Exaggerated amygdala response to masked facial stimuli in posttraumatic stress disorder.
        Biol Psychiatry. 2000; 47: 769-776
        • Rubinsztein J.S.
        • Fletcher P.C.
        • Rogers R.D.
        • Ho L.W.
        • Aigbirhio F.I.
        • Paykel E.S.
        • et al.
        Decision-making in mania.
        Brain. 2001; 124: 2550-2563
        • Sheline Y.I.
        Neuroimaging studies of mood disorder effects on the brain.
        Biol Psychiatry. 2003; 54: 338-352
        • Sheline Y.I.
        • Barch D.M.
        • Donnelly J.M.
        • Ollinger J.M.
        • Snyder A.Z.
        • Mintun M.A.
        Increased amygdala response to masked emotional faces in depressed subjects resolves with antidepressant treatment.
        Biol Psychiatry. 2001; 50: 651-658
        • Soares J.C.
        • Mann J.J.
        The functional neuroanatomy of mood disorders.
        J Psychiatr Res. 1997; 31: 393-432
        • Starkstein S.E.
        • Fedoroff P.
        • Berthier M.L.
        • Robinson R.G.
        Manic-depressive and pure manic states after brain lesions.
        Biol Psychiatry. 1991; 29: 149-158
        • Stoll A.L.
        • Renshaw P.F.
        • Yurgelun-Todd D.A.
        • Cohen B.M.
        Neuroimaging in bipolar disorder.
        Biol Psychiatry. 2000; 48: 505-517
        • Strakowski S.M.
        • Adler C.M.
        • Holland S.K.
        • Mills N.
        • DelBello M.P.
        A preliminary fMRI study of sustained attention in euthymic, unmedicated bipolar disorder.
        Neuropsychopharmacology. 2004; 29: 1734-1740
        • Suckling J.
        • Bullmore E.
        Permutation tests for factorially designed neuroimaging experiments.
        Hum Brain Mapp. 2004; 22: 193-205
        • Videbech P.
        PET measurements of brain glucose metabolism and blood flow in major depressive disorder.
        Acta Psychiatr Scand. 2000; 101: 11-20
        • Whalen P.J.
        • Rauch S.L.
        • Etcoff N.L.
        • McInerney S.C.
        • Lee M.B.
        • Jenike M.A.
        Masked presentations of emotional facial expressions modulate amygdala activity without explicit knowledge.
        J Neurosci. 1998; 18: 411-418
        • Wild B.
        • Erb M.
        • Bartels M.
        Are emotions contagious? Evoked emotions while viewing emotionally expressive faces: Quality, quantity, time course and gender differences.
        Psychiatry Res. 2001; 102: 109-124
        • Winston J.S.
        • O’Doherty J.
        • Dolan R.J.
        Common and distinct neural responses during direct and incidental processing of multiple facial emotions.
        Neuroimage. 2003; 20: 84-97
        • Wrase J.
        • Klein S.
        • Gruesser S.M.
        • Hermann D.
        • Flor H.
        • Mann K.
        • et al.
        Gender differences in the processing of standardized emotional visual stimuli in humans.
        Neurosci Lett. 2003; 348: 41-45
        • Young R.C.
        • Biggs J.T.
        • Ziegler V.E.
        • Meyer D.A.
        A rating scale for mania.
        Br J Psychiatry. 1978; 133: 429-435