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Neural Mechanisms of Grief Regulation

  • Peter J. Freed
    Correspondence
    Address reprint requests to Peter J. Freed, M.D., Assistant Professor of Clinical Psychiatry, Columbia University, Division of Molecular Imaging and Neuropathology, 1051 Riverside Drive, Unit 42, New York, NY 10032
    Affiliations
    Division of Molecular Imaging and Neuropathology, Columbia University and New York State Psychiatric Institute, New York, New York
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  • Ted K. Yanagihara
    Affiliations
    Program for Imaging & Cognitive Science (PICS), Departments of Radiology, Psychology, and Neuroscience, Columbia University, New York, New York
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  • Joy Hirsch
    Affiliations
    Program for Imaging & Cognitive Science (PICS), Departments of Radiology, Psychology, and Neuroscience, Columbia University, New York, New York
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  • J. John Mann
    Affiliations
    Division of Molecular Imaging and Neuropathology, Columbia University and New York State Psychiatric Institute, New York, New York
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      Background

      The death of an attachment figure triggers intrusive thoughts of the deceased, sadness, and yearning for reunion. Recovery requires reduction of symptoms. We hypothesized that symptoms might correlate with a capacity to regulate attention toward reminders of the deceased, and activity in, and functional connectivity between, prefrontal regulatory regions and the amygdala.

      Methods

      Twenty recently bereaved subjects rated intrusive thoughts of the deceased versus a capacity to avoid thoughts (grief style). Reaction time was measured while subjects completed an Emotional Stroop (ES) task contrasting deceased-related with control words during functional magnetic resonance imaging (fMRI). Subjects subsequently visualized the death of the deceased and rated induced emotions.

      Results

      Subjects demonstrated attentional bias toward deceased-related words. Bias magnitude correlated with amygdala, insula, dorsolateral prefrontal cortex (DLPFC) activity. Amygdala activity predicted induced sadness intensity. A double dissociation between grief style and both prefrontal and amygdala subregion activity was found. Intrusiveness correlated with activation of ventral amygdala and rostral anterior cingulate (rACC); avoidance correlated with deactivation of dorsal amygdala and DLPFC. A double dissociation between regulatory region and task-dependent functional connectivity (FC) was found. High DLPFC-amygdala FC correlated with reduced attentional bias, while low rACC-amygdala FC predicted sadness intensity.

      Conclusions

      Results are consistent with a model in which activity in and functional connectivity between the amygdala and prefrontal regulatory regions indexes differences in mourners' regulation of attention and sadness during pangs of grief, and may be used to distinguish between clinically relevant differences in grief style.

      Key Words

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      References

        • Rosenblatt P.
        • Walsh R.
        • Jackson D.
        Grief and Mourning in Cross-Cultural Perspective.
        Human Relations Area File Press, New Haven, CT1976
        • Kagawa-Singer M.
        The cultural context of death rituals and mourning practices.
        Oncol Nurs Forum. 1998; 25: 1752-1756
        • Archer J.
        Grief from an evolutionary perspective.
        in: Stroeb M. Hansson R. Stroeb W. Schut H. Handbook of Bereavement Research: Consequences, Coping, and Care. American Psychological Association, Washington, DC2001
        • Maciejewski P.K.
        • Zhang B.
        • Block S.D.
        • Prigerson H.G.
        An empirical examination of the stage theory of grief.
        JAMA. 2007; 297: 716-723
        • Lichtenthal W.
        • Cruess D.
        • Prigerson H.
        A case for establishing complicated grief as a distinct mental disorder in DSM-V.
        Clin Psychol Rev. 2004; 24: 637-662
        • Forstmeier S.
        • Maercker A.
        Comparison of two diagnostic systems for complicated grief.
        J Affect Disord. 2007; 99: 203-211
        • Freed P.J.
        • Mann J.J.
        Sadness and loss: Toward a neurobiopsychosocial model.
        Am J Psychiatry. 2007; 164: 28-34
        • O'Connor M.F.
        • Wellisch D.K.
        • Stanton A.L.
        • Eisenberger N.I.
        • Irwin M.R.
        • Lieberman M.D.
        Craving love?.
        Neuroimage. 2008; 42: 969-972
        • O'Connor M.F.
        • Gündel H.
        • McRae K.
        • Lane R.D.
        Baseline vagal tone predicts BOLD response during elicitation of grief.
        Neuropsychopharmacology. 2007; 32: 2184-2189
        • Gundel H.
        • O'Connor M.
        • Littrell L.
        • Fort C.
        • Lane R.
        Functional neuroanatomy of grief: An fMRI study.
        Am J Psychiatry. 2003; 160: 1946-1953
        • Mikulincer M.
        • Doleve T.
        • Shaver P.
        Attachment-related strategies during thought-suppression: Ironic rebounds and vulnerable self-representations.
        J Pers Soc Psychol. 2004; 87: 940-956
        • Cox W.M.
        • Fadardi J.S.
        • Pothos E.M.
        The addiction-stroop test: Theoretical considerations and procedural recommendations.
        Psychol Bull. 2006; 132: 443-476
        • Franken I.
        Drug craving and addiction: Integrating psychological and neuropsychopharmacological approaches.
        Prog Neuropsychopharmacol Biol Psychiatry. 2003; 27: 563-579
        • Wang L.
        • McCarthy G.
        • Song A.W.
        • Labar K.S.
        Amygdala activation to sad pictures during high-field (4 tesla) functional magnetic resonance imaging.
        Emotion. 2005; 5: 12-22
        • Goldin P.R.
        • Hutcherson C.A.
        • Ochsner K.N.
        • Glover G.H.
        • Gabrieli J.D.
        • Gross J.J.
        The neural bases of amusement and sadness: A comparison of block contrast and subject-specific emotion intensity regression approaches.
        Neuroimage. 2005; 27: 26-36
        • Phelps E.A.
        Emotion and cognition: Insights from studies of the human amygdala.
        Annu Rev Psychol. 2006; 57: 27-53
        • Amaral D.G.
        The primate amygdala and the neurobiology of social behavior: Implicaitons for understanding social anxiety.
        Biol Psychiatry. 2002; 51: 11-17
        • Panksepp J.
        Loneliness and the social bond: The brain sources of sorrow and grief.
        in: Affective Neuroscience. Oxford University Press, New York1998: 261-279
        • Lemche E.
        • Giampietro V.P.
        • Surguladze S.A.
        • Amaro E.J.
        • Andrew C.M.
        • Williams S.C.
        • et al.
        Human attachment security is mediated by the amygdala: Evidence from combined fMRI and psychophysiological measures.
        Hum Brain Mapp. 2006; 27: 623-635
        • Domes G.
        • Heinrichs M.
        • Glascher J.
        • Buchel C.
        • Braus D.F.
        • Herpertz S.C.
        Oxytocin attenuates amygdala responses to emotional faces regardless of valence.
        Biol Psychiatry. 2007; 62: 1187-1190
        • Bauman M.D.
        • Lavenex P.
        • Mason W.A.
        • Capitanio J.P.
        • Amaral D.G.
        The development of mother-infant interactions after neonatal amygdala lesions in rhesus monkeys.
        J Neurosci. 2004; 24: 711-721
        • Etkin A.
        • Egner T.
        • Peraza D.M.
        • Kandel E.R.
        • Hirsch J.
        Resolving emotional conflict: A role for the rostral anterior cingulate cortex in modulating activity in the amygdala.
        Neuron. 2006; 51: 871-882
        • Hare T.A.
        • Tottenham N.
        • Galvan A.
        • Voss H.U.
        • Glover G.H.
        • Casey B.J.
        Biological substrates of emotional reactivity and regulation in adolescence during an emotional go-nogo task.
        Biol Psychiatry. 2008; 63: 927-934
        • Etkin A.
        • Klemenhagen K.C.
        • Dudman J.T.
        • Rogan M.T.
        • Hen R.
        • Kandel E.R.
        • Hirsch J.
        Individual differences in trait anxiety predict the response of the basolateral amygdala to unconsciously processed fearful faces.
        Neuron. 2004; 44: 1043-1055
        • Goldin P.R.
        • McRae K.
        • Ramel W.
        • Gross J.J.
        The neural bases of emotion regulation: Reappraisal and suppression of negative emotion.
        Biol Psychiatry. 2008; 63: 577-586
        • MacDonald A.
        • Cohen J.
        • Stenger V.
        • Carter C.
        Dissociating the role of the dorsolateral prefrontal and anterior cingulate cortex in cognitive control.
        Science. 2000; 288: 1835-1838
        • Fales C.L.
        • Barch D.M.
        • Rundle M.M.
        • Mintun M.A.
        • Snyder A.Z.
        • Cohen J.D.
        • et al.
        Altered emotional interference processing in affective and cognitive-control brain circuitry in major depression.
        Biol Psychiatry. 2008; 63: 377-384
        • Ghashghaei H.T.
        • Hilgetag C.C.
        • Barbas H.
        Sequence of information processing for emotions based on the anatomic dialogue between prefrontal cortex and amygdala.
        Neuroimage. 2007; 34: 905-923
        • Ridderinkhof K.R.
        • Ullsperger M.
        • Crone E.A.
        • Nieuwenhuis S.
        The role of the medial frontal cortex in cognitive control.
        Science. 2004; 306: 443-447
        • Liberzon I.
        • Sripada C.S.
        The functional neuroanatomy of PTSD: A critical review.
        Prog Brain Res. 2008; 167: 151-169
        • Archer J.
        • Winchester G.
        Bereavement following death of a pet.
        Br J Psychol. 1994; 85: 259-271
        • Adams C.L.
        • Bonnett B.N.
        • Meek A.H.
        Predictors of owner response to companion animal death in 177 clients from 14 practices in Ontario.
        J Am Vet Med Assoc. 2000; 217: 1303-1309
        • Wrobel T.
        • Dye A.
        Grieving pet death: Normative, gender, and attachment issues.
        Omega: The Journal of Death and Dying. 2003; 47: 385-393
        • Goldstein R.Z.
        • Tomasi D.
        • Rajaram S.
        • Cottone L.A.
        • Zhang L.
        • Maloney T.
        • et al.
        Role of the anterior cingulate and medial orbitofrontal cortex in processing drug cues in cocaine addiction.
        Neuroscience. 2007; 144: 1153-1159
        • Beck A.T.
        • Ward C.
        • Mendelson M.
        Beck Depression Inventory (BDI).
        Arch Gen Psychiatry. 1961; 4: 561-571
        • Faschingbauer T.
        • Zisook S.
        • Devaul R.
        The Texas Revised Inventory of Grief.
        in: Zisook S. Biopsychosocial Aspects of Bereavement. American Psychiatric Press, Washington, DC1987: 111-124
        • Weiss D.S.
        • Marmar C.
        The Impact of Event Scale–Revised.
        in: Wilson J. Keane T. Assessing Psychological Trauma and PTSD. Guildford, New York1997
        • Whalen P.
        • Bush G.
        • McNally R.
        • McInerney S.
        • Jenike M.A.
        • Rauch S.L.
        The emotional counting Stroop paradigm: A functional magnetic resonance imaging probe of the anterior cingulate affective division.
        Biol Psychiatry. 1998; 44: 1219-1228
        • Schneider W.
        • Eschman A.
        • Zuccolotto A.
        E-Prime User's Guide.
        Psychology Software Tools, Inc, Pittsburgh2002
        • Algom D.
        • Chajut E.
        • Lev S.
        A rational look at the emotional Stroop phenomenon: A generic slowdown, not a Stroop effect.
        J Exp Psychol Gen. 2004; 133: 323-338
        • Jenkinson M.
        • Bannister P.
        • Brady M.
        • Smith S.
        Improved optimization for the robust and accurate linear registration and motion correction of brain images.
        Neuroimage. 2002; 17: 825-841
        • Worsley K.J.
        • Marrett S.
        • Neelin P.
        • Vandal A.C.
        • Friston K.J.
        • Evans A.C.
        A unified statistical approach for determining significant signals in images of cerebral activation.
        Hum Brain Mapp. 1996; 4: 58-73
        • Fox P.T.
        • Laird A.R.
        • Fox S.P.
        • Fox P.M.
        • Uecker A.M.
        • Crank M.
        • et al.
        BrainMap taxonomy of experimental design: Description and evaluation.
        Hum Brain Mapp. 2005; 25: 185-198
        • Damoiseaux J.S.
        • Beckmann C.F.
        • Arigita E.J.
        • Barkhof F.
        • Scheltens P.
        • Stam C.J.
        • et al.
        Reduced resting-state brain activity in the “default network” in normal aging.
        Cereb Cortex. 2008; 18: 1856-1864
        • Sorg C.
        • Riedl V.
        • Mühlau M.
        • Calhoun V.D.
        • Eichele T.
        • Läer L.
        • et al.
        Selective changes of resting-state networks in individuals at risk for Alzheimer's disease.
        Proc Natl Acad Sci U S A. 2007; 104: 18760-18765
        • Rogers B.P.
        • Morgan V.L.
        • Newton A.T.
        • Gore J.C.
        Assessing functional connectivity in the human brain by fMRI.
        Magn Reson Imaging. 2007; 25: 1347-1357
        • Mikulincer M.
        • Gillath O.
        • Shaver P.
        Activation of the attachment system in adulthood: Threat-related primes increase the accessibility of mental representations of attachment figures.
        J Pers Soc Psychol. 2002; 83: 881-895
      1. Dalgleish T. Power M. Handbook of Cognition and Emotion. John Wiley & Sons, New York1999
        • Egner T.
        • Hirsch J.
        Cognitive control mechanisms resolve conflict through cortical amplification of task-relevant information.
        Nat Neurosci. 2005; 8: 1784-1790
        • Compton R.
        • Banich M.
        • Mohanty A.
        • Milham M.
        • Herrington J.
        • Miller G.
        • et al.
        Paying attention to emotion: An fMRI investigation of cognitive and emotional Stroop tasks.
        Cogn Affect Behav Neurosci. 2003; 3: 81-96
        • Robbins S.J.
        • Ehrman R.N.
        The role of attentional bias in substance abuse.
        Behav Cogn Neurosci Rev. 2004; 3: 243-260
        • Price J.L.
        Comparative aspects of amygdala connectivity.
        Ann N Y Acad Sci. 2003; 985: 50-58
        • Naqvi N.H.
        • Rudrauf D.
        • Damasio H.
        • Bechara A.
        Damage to the insula disrupts addiction to cigarette smoking.
        Science. 2007; 315: 531-534
        • Platek S.M.
        • Keenan J.P.
        • Gallup G.G.
        • Mohamed F.B.
        Where am I?.
        Brain Res Cogn Brain Res. 2004; 19: 114-122
        • Leslie K.R.
        • Johnson-Frey S.H.
        • Grafton S.T.
        Functional imaging of face and hand imitation: Towards a motor theory of empathy.
        Neuroimage. 2004; 21: 601-607
        • Buchheim A.
        • Erk S.
        • George C.
        • Kachele H.
        • Ruchsow M.
        • Spitzer M.
        • et al.
        Measuring attachment representation in an fMRI environment: A pilot study.
        Psychopathology. 2006; 39: 144-152
        • Obleser J.
        • Wise R.J.
        • Alex Dresner M.
        • Scott S.K.
        Functional integration across brain regions improves speech perception under adverse listening conditions.
        J Neurosci. 2007; 27: 2283-2289
        • Humphries C.
        • Binder J.R.
        • Medler D.A.
        • Liebenthal E.
        Time course of semantic processes during sentence comprehension: An fMRI study.
        Neuroimage. 2007; 36: 924-932
        • Raettig T.
        • Kotz S.A.
        Auditory processing of different types of pseudo-words: An event-related fMRI study.
        Neuroimage. 2008; 39: 1420-1428
        • Kuchinke L.
        • Jacobs A.M.
        • Grubich C.
        • Võ M.L.
        • Conrad M.
        • Herrmann M.
        Incidental effects of emotional valence in single word processing: An fMRI study.
        Neuroimage. 2005; 28: 1022-1032
        • Gennari S.P.
        • MacDonald M.C.
        • Postle B.R.
        • Seidenberg M.S.
        Context-dependent interpretation of words: Evidence for interactive neural processes.
        Neuroimage. 2007; 35: 1278-1286
        • Parkes C.M.
        Bereavement: Studies of grief in adult life.
        Penguin Books, London1998
        • Bonanno G.A.
        • Goorin L.
        • Coifman K.
        Sadness and grief.
        in: Lewis M. Haviland-Jones J.M. Barrett L. Handbook of Emotions. 3rd ed. Guilford Press, New York2008: 797-810
        • Siegle G.J.
        • Thompson W.
        • Carter C.S.
        • Steinhauer S.R.
        • Thase M.E.
        Increased amygdala and decreased dorsolateral prefrontal BOLD responses in unipolar depression: Related and independent features.
        Biol Psychiatry. 2007; 61: 198-209
        • Najib A.
        • Lorberbaum J.P.
        • Kose S.
        • Bohning D.E.
        • George M.S.
        Regional brain activity in women grieving a romantic relationship breakup.
        Am J Psychiatry. 2004; 161: 2245-2256
        • O'Connor M.F.
        • Gündel H.
        • McRae K.
        • Lane R.D.
        Baseline vagal tone predicts BOLD response during elicitation of grief.
        Neuropsychopharmacology. 2007; 32: 2184-2189