Neural Substrates of Increased Memory Sensitivity for Negative Stimuli in Major Depression

Published:February 18, 2008DOI:


      Although memory biases for negatively valenced stimuli have been reliably associated with depression and have been postulated to play a critical role in the maintenance of this disorder, the neural bases of these biases have received little attention. In this study, we tested a model of heightened memory sensitivity for negative information in depression in which neural mechanisms that normally facilitate memory for affective material are over-recruited during encoding of negative material in depression.


      We used functional magnetic resonance imaging to examine amygdala activity and functional connectivity with the hippocampus and caudate-putamen during successful encoding—as assessed by a recognition memory probe 1 week after scanning—of negative, neutral, and positive pictures by 14 depressed and 12 nondepressed individuals.


      Depressed individuals demonstrated greater memory sensitivity than nondepressed participants to negative but not to neutral or positive stimuli. The right amygdala was more active and showed greater functional connectivity with the hippocampus and caudate-putamen in depressed than in control participants during encoding of subsequently remembered negative but not neutral or positive stimuli. The degree of memory-related right amygdala responsivity in the depressed participants was significantly correlated with depressive severity.


      These findings support the formulation that, in remembering negative information better than nondepressed persons, depressed individuals over-recruit a neural network involved more generally in enhancing memory for affective stimuli and that the degree to which they over-recruit this system is related to the severity of clinical symptomatology.

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


        • Beck A.T.
        Cognitive Therapy and the Emotional Disorders.
        International Universities Press, New York1976
        • Bradley B.P.
        • Mogg K.
        • Williams R.
        Implicit and explicit memory for emotion-congruent information in clinical depression and anxiety.
        Behav Res Ther. 1995; 33: 755-770
        • Ridout N.
        • Astell A.J.
        • Reid I.C.
        • Glen T.
        • O'Carroll R.E.
        Memory bias for emotional facial expressions in major depression.
        Cogn Emot. 2003; 17: 101-122
        • Watkins P.C.
        • Mathews A.
        • Williamson D.A.
        • Fuller R.D.
        Mood-congruent memory in depression—emotional priming or elaboration.
        J Abnorm Psychol. 1992; 101: 581-586
        • Ingram R.E.
        Toward an information-processing analysis of depression.
        Cogn Ther Res. 1984; 8: 443-477
        • Teasdale J.D.
        Negative thinking in depression: Cause, effect, or reciprocal relationship?.
        Adv Behav Res Ther. 1983; 5: 3-25
        • Adolphs R.
        • Cahill L.
        • Schul R.
        • Babinsky R.
        Impaired declarative memory for emotional material following bilateral amygdala damage in humans.
        Learn Mem. 1997; 4: 291-300
        • Cahill L.
        • Babinsky R.
        • Markowitsch H.J.
        • McGaugh J.L.
        The amygdala and emotional memory.
        Nature. 1995; 377: 295-296
        • Canli T.
        • Zhao Z.
        • Desmond J.E.
        • Glover G.
        • Gabrieli J.D.E.
        fMRI identifies a network of structures correlated with retention of positive and negative emotional memory.
        Psychobiology. 1999; 27: 441-452
        • Canli T.
        • Zhao Z.
        • Brewer J.
        • Gabrieli J.D.E.
        • Cahill L.
        Event-related activation in the human amygdala associates with later memory for individual emotional experience.
        J Neurosci. 2000; 20: RC99
        • Steinvorth S.
        • Levine B.
        • Corkin S.
        Medial temporal lobe structures are needed to re-experience remote autobiographical memories: Evidence from HM and WR.
        Neuropsychologia. 2005; 43: 479-496
        • Packard M.G.
        • Cahill L.
        • McGaugh J.L.
        Amygdala modulation of hippocampal-dependent and caudate nucleus-dependent memory processes.
        Proc Natl Acad Sci U S A. 1994; 91: 8477-8481
        • Dolcos F.
        • LaBar K.S.
        • Cabeza R.
        Interaction between the amygdala and the medial temporal lobe memory system predicts better memory for emotional events.
        Neuron. 2004; 42: 855-863
        • Kensinger E.A.
        • Corkin S.
        Two routes to emotional memory: Distinct neural processes for valence and arousal.
        Proc Natl Acad Sci U S A. 2004; 101: 3310-3315
        • Packard M.G.
        • Teather L.A.
        Amygdala modulation of multiple memory systems: Hippocampus and caudate-putamen.
        Neurobiol Learn Mem. 1998; 69: 163-203
        • Atallah H.E.
        • Lopez-Paniagua D.
        • Rudy J.W.
        • O'Reilly R.C.
        Separate neural substrates for skill learning and performance in the ventral and dorsal striatum.
        Nat Neurosci. 2007; 10: 126-131
        • Alexander G.E.
        • Delong M.R.
        • Strick P.L.
        Parallel organization of functionally segregated circuits linking basal ganglia and cortex.
        Ann Rev Neurosci. 1986; 9: 357-381
        • Levy R.
        • Friedman H.R.
        • Davachi L.
        • Goldman-Rakic P.S.
        Differential activation of the caudate nucleus in primates performing spatial and nonspatial working memory tasks.
        J Neurosci. 1997; 17: 3870-3882
        • 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: A prospective, event-related functional magnetic resonance imaging study.
        Arch Gen Psychiatry. 2004; 61: 877-889
        • 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: An fMRI study.
        Biol Psychiatry. 2001; 50: 651-658
        • Siegle G.J.
        • Steinhauer S.R.
        • Thase M.E.
        • Stenger V.A.
        • Carter C.S.
        Can't shake that feeling: Assessment of sustained event-related fMRI 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
        • Roberson-Nay R.
        • McClure E.B.
        • Monk C.S.
        • Nelson E.E.
        • Guyer A.E.
        • Fromm S.J.
        • et al.
        Increased amygdala activity during successful memory encoding in adolescent major depressive disorder: An fMRI study.
        Biol Psychiatry. 2006; 60: 966-973
        • First M.B.
        • Spitzer R.L.
        • Gibbon M.
        • Williams J.B.W.
        The Structured Clinical Interview for DSM-III-R Personality-Disorders (SCID-I).
        J Person Disord. 1995; 9: 83-91
        • Beck A.T.
        • Rush A.J.
        • Shaw B.F.
        • Emery G.
        Cognitive Therapy of Depression.
        The Guilford Press, New York1979
        • Lang P.J.
        • Greenwald M.K.(
        International Affective Picture System Standardization Procedure and Results for Affective Judgments: Technical Reports 1A-1C.
        Center for Research in Psychophysiology, University of Florida, Gainesville, Florida1993
        • Glover G.H.
        • Law C.S.
        Spiral-in/out BOLD fMRI for increased SNR and reduced susceptibility artifacts.
        Magn Reson Med. 2001; 46: 515-522
        • Burt D.B.
        • Zembar M.J.
        • Niederehe G.
        Depression and memory impairment: A meta-analysis of the association, its pattern, and specificity.
        Psychol Bull. 1995; 117: 285-305
        • Talairach J.
        • Tournoux P.
        Co-Planar Stereotaxic Atlas of the Human Brain.
        Thieme, Stuttgart, Germany1988
        • Heekeren H.R.
        • Marrett S.
        • Bandettini P.A.
        • Ungerleider L.G.
        A general mechanism for perceptual decision-making in the human brain.
        Nature. 2004; 431: 859-862
        • Zimmerman D.W.
        Statistical significance levels of nonparametric tests biased by heterogeneous variances of treatment groups.
        J Gen Psychol. 2000; 127: 354-364
        • Posse S.
        • Fitzgerald D.
        • Gao K.X.
        • Habel U.
        • Rosenberg D.
        • Moore G.J.
        • Schneider F.
        Real-time fMRI of temporolimbic regions detects amygdala activation during single-trial self-induced sadness.
        Neuroimage. 2003; 18: 760-768