Advertisement

Neuronal Coding of Implicit Emotion Categories in the Subcallosal Cortex in Patients with Depression

      Background

      The subcallosal cingulate and adjacent ventromedial prefrontal cortex (collectively referred to here as the subcallosal cortex or SCC) have been identified as key brain areas in emotional processing. The SCC’s role in affective valuation as well as severe mood and motivational disturbances, such as major depression, has been largely inferred from measures of neuronal population activity using functional neuroimaging. On the basis of imaging studies, it is unclear whether the SCC predominantly processes 1) negatively valenced affective content, 2) affective arousal, or 3) category-specific affective information.

      Methods

      To clarify these putative functional roles of the SCC, we measured single neuron activity in the SCC of 15 human subjects undergoing deep brain stimulation for depression while they viewed emotionally evocative images grouped into categories that varied in emotional valence (pleasantness) and arousal.

      Results

      We found that the majority of responsive neurons were modulated by specific emotion categories, rather than by valence or arousal alone. Moreover, although these emotion-category-specific neurons responded to both positive and negative emotion categories, a significant majority were selective for negatively valenced emotional content.

      Conclusions

      These findings reveal that single SCC neuron activity reflects the automatic valuational processing and implicit emotion categorization of visual stimuli. Furthermore, because of the predominance of neuronal signals in SCC conveying negative affective valuations and the increased activity in this region among depressed people, the effectiveness of depression therapies that alter SCC neuronal activity may relate to the down-regulation of a previously negative emotional processing bias.

      Key Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Haber S.N.
        • Knutson B.
        The reward circuit: Linking primate anatomy and human imaging.
        Neuropsychopharmacology. 2009; 35: 4-26
        • Murray E.A.
        • Wise S.P.
        • Drevets W.C.
        Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala.
        Biol Psychiatry. 2011; 69: e43-e54
        • Der-Avakian A.
        • Markou A.
        The neurobiology of anhedonia and other reward-related deficits.
        Trends Neurosci. 2012; 35: 68-77
        • Phan K.L.
        • Wager T.
        • Taylor S.F.
        • Liberzon I.
        Functional neuroanatomy of emotion: A meta-analysis of emotion activation studies in PET and fMRI.
        Neuroimage. 2002; 16: 331-348
        • Hornak J.
        • Bramham J.
        • Rolls E.T.
        • Morris R.G.
        • O’Doherty J.
        • Bullock P.R.
        • et al.
        Changes in emotion after circumscribed surgical lesions of the orbitofrontal and cingulate cortices.
        Brain. 2003; 126: 1691-1712
        • Price J.L.
        • Drevets W.C.
        Neural circuits underlying the pathophysiology of mood disorders.
        Trends Cogn Sci. 2012; 16: 61-71
        • Lindquist K.A.
        • Wager T.D.
        • Kober H.
        • Bliss-Moreau E.
        • Barrett L.F.
        The brain basis of emotion: A meta-analytic review.
        Behav Brain Sci. 2012; 35: 121-143
        • Davis K.D.
        • Taylor K.S.
        • Hutchison W.D.
        • Dostrovsky J.O.
        • McAndrews M.P.
        • Richter E.O.
        • et al.
        Human anterior cingulate cortex neurons encode cognitive and emotional demands.
        J Neurosci. 2005; 25: 8402-8406
        • Kawasaki H.
        • Adolphs R.
        • Kaufman O.
        • Damasio H.
        • Damasio A.R.
        • Granner M.
        • et al.
        Single-neuron responses to emotional visual stimuli recorded in human ventral prefrontal cortex.
        Nat Neurosci. 2001; 4: 15-16
        • Wallis J.D.
        Cross-species studies of orbitofrontal cortex and value-based decision-making.
        Nat Neurosci. 2012; 15: 13-19
        • Hunt L.T.
        • Kolling N.
        • Soltani A.
        • Woolrich M.W.
        • Rushworth M.F.S.
        • Behrens T.E.J.
        Mechanisms underlying cortical activity during value-guided choice.
        Nat Neurosci. 2012; 15: 470-476
        • Lebreton M.
        • Jorge S.
        • Michel V.
        • Thirion B.
        • Pessiglione M.
        An automatic valuation system in the human brain: evidence from functional neuroimaging.
        Neuron. 2009; 64: 431-439
        • Vogt B.A.
        Pain and emotion interactions in subregions of the cingulate gyrus.
        Nature Rev Neurosci. 2005; 6: 533-544
        • 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: Converging PET findings in depression and normal sadness.
        Am J Psychiatry. 1999; 156: 675-682
        • George M.S.M.
        • Ketter T.A.T.
        • Parekh P.I.P.
        • Horwitz B.B.
        • Herscovitch P.P.
        • Post R.M.R.
        Brain activity during transient sadness and happiness in healthy women.
        Am J Psychiatry. 1995; 152: 341-351
        • Gradin V.B.
        • Kumar P.
        • Waiter G.
        • Ahearn T.
        • Stickle C.
        • Milders M.
        • et al.
        Expected value and prediction error abnormalities in depression and schizophrenia.
        Brain. 2011; 134: 1751-1764
        • Taylor Tavares J.V.
        • Clark L.
        • Furey M.L.
        • Williams G.B.
        • Sahakian B.J.
        • Drevets W.C.
        Neural basis of abnormal response to negative feedback in unmedicated mood disorders.
        Neuroimage. 2008; 42: 1118-1126
        • Pizzagalli D.A.
        • Iosifescu D.
        • Hallett L.A.
        • Ratner K.G.
        • Fava M.
        Reduced hedonic capacity in major depressive disorder: Evidence from a probabilistic reward task.
        J Psychiatr Res. 2008; 43: 76-87
        • Henriques J.B.
        • Glowacki J.M.
        • Davidson R.J.
        Reward fails to alter response bias in depression.
        J Abnorm Psychol. 1994; 103: 460-466
        • 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
        • Murray L.A.
        • Whitehouse W.G.
        • Alloy L.B.
        Mood congruence and depressive deficits in memory: A forced-recall analysis.
        Memory. 1999; 7: 175-196
        • Amemori K.-i.
        • Graybiel A.M.
        Localized microstimulation of primate pregenual cingulate cortex induces negative decision-making.
        Nat Neurosci. 2012; 15: 776-785
        • Fu C.H.Y.
        • Williams S.C.R.
        • J C.A.
        • Brammer M.J.
        • Walsh N.D.
        • Kim J.
        • et al.
        Attenuation of the neural response to sad faces in major depression by antidepressant treatment: A prospective, event-related functional magnetic resonance imaging study.
        Arch Gen Psychiatry. 2004; 61: 877-889
        • Siegle G.J.
        • Steinhauer S.R.
        • Thase M.E.
        • Stenger V.A.
        • Carter C.S.
        Can’t shake that feeling: Event-related fMRI assessment of sustained amygdala activity in response to emotional information in depressed individuals.
        Biol Psychiatry. 2002; 51: 693-707
        • Surguladze S.
        • Brammer M.J.
        • Keedwell P.
        • Giampietro V.
        • Young A.W.
        • Travis M.J.
        • et al.
        A differential pattern of neural response toward sad versus happy facial expressions in major depressive disorder.
        Biol Psychiatry. 2005; 57: 201-209
        • Neumeister A.
        • Drevets W.C.
        • Belfer I.
        • Luckenbaugh D.A.
        • Henry S.
        • Bonne O.
        • et al.
        Effects of a [alpha]2C-adrenoreceptor gene polymorphism on neural responses to facial expressions in depression.
        Neuropsychopharmacology. 2006; 31: 1750-1756
        • Victor T.A.
        • Furey M.L.
        • Fromm S.J.
        • Öhman A.
        • Drevets W.C.
        Relationship between amygdala responses to masked faces and mood state and treatment in major depressive disorder.
        Arch Gen Psychiatry. 2010; 67: 1128-1138
        • Holtzheimer P.E.
        • Kelley M.E.
        • Gross R.E.
        • Filkowski M.M.
        • Garlow S.J.
        • Barrocas A.
        • et al.
        Subcallosal cingulate deep brain stimulation for treatment-resistant unipolar and bipolar depression.
        Arch Gen Psychiatry. 2012; 69: 150-158
        • Mayberg H.S.
        • Lozano A.M.
        • Voon V.
        • McNeely H.E.
        • Seminowicz D.
        • Hamani C.
        • et al.
        Deep brain stimulation for treatment-resistant depression.
        Neuron. 2005; 45: 651-660
        • Bylsma L.M.
        • Morris B.H.
        • Rottenberg J.
        A meta-analysis of emotional reactivity in major depressive disorder.
        Clin Psychol Rev. 2008; 28: 676-691
        • Kaping D.
        • Vinck M.
        • Hutchison R.M.
        • Everling S.
        • Womelsdorf T.
        Specific contributions of ventromedial, anterior cingulate, and lateral prefrontal cortex for attentional selection and stimulus valuation.
        PLoS Biol. 2011; 9: e1001224
        • Kawasaki H.
        • Adolphs R.
        • Oya H.
        • Kovach C.
        • Damasio H.
        • Kaufman O.
        • et al.
        Analysis of single-unit responses to emotional scenes in human ventromedial prefrontal cortex.
        J Cogn Neurosci. 2005; 17: 1509-1518
        • Lewis P.
        • Critchley H.
        • Rotshtein P.
        • Dolan R.
        Neural correlates of processing valence and arousal in affective words.
        Cereb Cortex. 2006; 17: 742-748
        • Hamilton M.
        A rating scale for depression.
        J Neurol Neurosurg Psychiatry. 1960; 23: 56-62
        • Lozano A.M.
        • Mayberg H.S.
        • Giacobbe P.
        • Hamani C.
        • Craddock R.C.
        • Kennedy S.H.
        Subcallosal cingulate gyrus deep brain stimulation for treatment-resistant depression.
        Biol Psychiatry. 2008; 64: 461-467
        • Levy R.
        • Lozano A.M.
        • Hutchison W.D.
        • Dostrovsky J.O.
        Dual microelectrode technique for deep brain stereotactic surgery in humans.
        Neurosurgery. 2007; 60: 277-284
        • Lang P.J.
        • Bradley M.M.
        • Cuthbert B.N.
        International Affective Picture System (IAPS): Technical Manual and Affective Ratings.
        University of Florida Press, Gainesville1997
        • Hamani C.
        • Mayberg H.
        • Snyder B.
        • Giacobbe P.
        • Kennedy S.
        • Lozano A.M.
        Deep brain stimulation of the subcallosal cingulate gyrus for depression: Anatomical location of active contacts in clinical responders and a suggested guideline for targeting.
        J Neurosurg. 2009; 111: 1209-1215
      1. Spike2 (2006): Spike 2. 6.01 ed. Cambridge, UK: Cambridge Electronic Design.

        • Kennedy S.H.
        • Evans K.R.
        • Krüger S.
        • Mayberg H.S.
        • Meyer J.H.
        • McCann S.
        • et al.
        Changes in regional brain glucose metabolism measured with positron emission tomography after paroxetine treatment of major depression.
        Am J Psychiatry. 2001; 158: 899-905
        • Kennedy S.H.
        • Konarski J.Z.
        • Segal Z.V.
        • Lau M.A.
        • Bieling P.J.
        • McIntyre R.S.
        • et al.
        Differences in brain glucose metabolism between responders to CBT and venlafaxine in a 16-week randomized controlled trial.
        Am J Psychiatry. 2007; 164: 778-788
        • Nobler M.S.
        • Oquendo M.A.
        • Kegeles L.S.
        • Malone K.M.
        • Campbell C.C.
        • Sackeim H.A.
        • et al.
        Decreased regional brain metabolism after ect.
        Am J Psychiatry. 2001; 158: 305-308
        • Lozano A.M.
        • Giacobbe P.
        • Hamani C.
        • Rizvi S.J.
        • Kennedy S.H.
        • Kolivakis T.T.
        • et al.
        A multicenter pilot study of subcallosal cingulate area deep brain stimulation for treatment-resistant depression.
        J Neurosurg. 2012; 116: 315-322
        • Ressler K.J.
        • Mayberg H.S.
        Targeting abnormal neural circuits in mood and anxiety disorders: From the laboratory to the clinic.
        Nat Neurosci. 2007; 10: 1116-1124