Encoding of emotional memories depends on amygdala and hippocampus and their interactions

Abstract

We have studied patients with variable degrees of left hippocampal and amygdala pathology who performed a verbal encoding task during functional magnetic resonance imaging (fMRI) to assess the impact of pathology on emotional-memory performance and encoding-evoked activity. The severity of left hippocampal pathology predicted memory performance for neutral and emotional items alike, whereas the severity of amygdala pathology predicted memory performance for emotional items alone. Encoding-related hippocampal activity for successfully remembered emotional items correlated with the degree of left amygdala pathology. Conversely, amygdala-evoked activity with respect to subsequently remembered emotional items correlated with the degree of left hippocampal pathology. Our data indicate a reciprocal dependence between amygdala and hippocampus during the encoding of emotional memories.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: Recognition accuracy for each response type in patients and normal controls.
Figure 2: Structure–behavior relationships.
Figure 3: Structure–function relationships.
Figure 5: Anatomical specificity of hippocampal effects.
Figure 4: Amygdala–hippocampal reciprocal dependence during successful encoding of emotional words.

References

  1. 1

    Gallagher, M. & Chiba, A.A. The amygdala and emotion. Curr. Opin. Neurobiol. 6, 221–227 (1996).

    CAS  Article  Google Scholar 

  2. 2

    Cahill, L. & McGaugh, J.L. Mechanisms of emotional arousal and lasting declarative memory. Trends Neurosci. 21, 294–299 (1998).

    CAS  Article  Google Scholar 

  3. 3

    Dolan, R.J. Emotion, cognition and behavior. Science 298, 1191–1194 (2002).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  4. 4

    Hamann, S.B., Ely, T.D., Grafton, S.T. & Kilts, C.D. Amygdala activity related to enhanced memory for pleasant and aversive stimuli. Nat. Neurosci. 2, 289–293 (1999).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  5. 5

    Phelps, E.A., LaBar, K.S. & Spencer, D.D. Memory for emotional words following unilateral temporal lobectomy. Brain Cogn. 35, 85–109 (1997).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  6. 6

    Adolphs, R., Cahill, L., Schul, R. & Babinsky, R. Impaired declarative memory for emotional material following bilateral amygdala damage in humans. Learn. Mem. 4, 291–300 (1997).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  7. 7

    Strange, B.A., Henson, R.N., Friston, K.J. & Dolan, R.J. Brain mechanisms for detecting perceptual, semantic, and emotional deviance. Neuroimage 12, 425–433 (2000).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  8. 8

    Cahill, L. et al. Amygdala activity at encoding correlated with long-term, free recall of emotional information. Proc. Natl. Acad. Sci. USA 93, 8016–8021 (1996).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  9. 9

    McGaugh, J.L., Cahill, L. & Roozendaal, B. Involvement of the amygdala in memory storage: interaction with other brain systems. Proc. Natl. Acad. Sci. USA 93, 13508–13514 (1996).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  10. 10

    Squire, L.R. & Zola-Morgan, S. The medial temporal lobe memory system. Science 253, 1380–1386 (1991).

    CAS  Article  Google Scholar 

  11. 11

    Frisk, V. & Milner, B. The role of the left hippocampal region in the acquisition and retention of story content. Neuropsychologia 28, 349–359 (1990).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  12. 12

    Smith, M.L. & Milner, B. The role of the right hippocampus in the recall of spatial location. Neuropsychologia 19, 781–793 (1981).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. 13

    Alkire, M.T., Haier, R.J., Fallon, J.H. & Cahill, L. Hippocampal, but not amygdala, activity at encoding correlates with long-term, free recall of nonemotional information. Proc. Natl. Acad. Sci. USA 95, 14506–14510 (1998).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  14. 14

    Duncan, J.S. Imaging and epilepsy. Brain 120, 376–389 (1997).

    Article  Google Scholar 

  15. 15

    Woermann, F.G. et al. Regional changes in hippocampal T2 relaxation and volume: a quantitative magnetic resonance imaging study of hippocampal sclerosis. J. Neurol. Neurosurg. Psychiatry 65, 656–664 (1998).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  16. 16

    Duncan, J.S., Bartlett, P. & Barker, G.J. Technique for measuring hippocampal T2 relaxation time. AJNR Am. J. Neuroradiol. 17, 1805–1810 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. 17

    Van Paesschen, W. et al. Quantitative hippocampal MRI and intractable temporal lobe epilepsy. Neurology 45, 2233–2240 (1995).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  18. 18

    Bartlett, P.A., Richardson, M.P. & Duncan, J.S. Measurement of amygdala T2 relaxation time in temporal lobe epilepsy. J. Neurol. Neurosurg. Psychiatry 73, 753–735 (2002).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  19. 19

    Hudson, L.P. et al. Amygdaloid sclerosis in temporal lobe epilepsy. Ann. Neurol. 33, 622–631 (1993).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  20. 20

    Helmstaedter, C. & Kurthen, M. Memory and epilepsy: characteristics, course, and influence of drugs and surgery. Curr. Opin. Neurol. 14, 211–216 (2001).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  21. 21

    Ashburner, J. & Friston, K.J. Voxel-based morphometry—the methods. Neuroimage 11, 805–821 (2000).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  22. 22

    Friston, K.J. et al. Event-related fMRI: characterizing differential responses. Neuroimage 7, 30–40 (1998).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. 23

    Craik, F.I.M. & Lockhart, R.S. Levels of processing: A framework for memory. J. Verbal Learn. Verbal Behav. 11, 671–684 (1972).

    Article  Google Scholar 

  24. 24

    Tulving, E. Memory and consciousness. Can. Psychol. 26, 1–12 (1985).

    Article  Google Scholar 

  25. 25

    Windmann, S. & Kutas, M. Electrophysiological correlates of emotion-induced recognition bias. J. Cogn. Neurosci. 13, 577–592 (2001).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  26. 26

    Richardson, M.P., Strange, B.A., Duncan, J.S. & Dolan, R.J. Preserved verbal memory function in left medial temporal pathology involves reorganisation of function to right medial temporal lobe. Neuroimage 20, S112–119 (2003).

    Article  PubMed  PubMed Central  Google Scholar 

  27. 27

    Van Paesschen, W. et al. Quantitative neuropathology and quantitative magnetic resonance imaging of the hippocampus in temporal lobe epilepsy. Ann. Neurol. 42, 756–766 (1997).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  28. 28

    Van Paesschen, W. et al. The spectrum of hippocampal sclerosis: a quantitative magnetic resonance imaging study. Ann. Neurol. 41, 41–51 (1997).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  29. 29

    Kalviainen, R. et al. MRI-based hippocampal volumetry and T2 relaxometry: correlation to verbal memory performance in newly diagnosed epilepsy patients with left-sided temporal lobe focus. Neurology 48, 286–287 (1997).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  30. 30

    Kilpatrick, C. et al. Degree of left hippocampal atrophy correlates with severity of neuropsychological deficits. Seizure 6, 213–218 (1997).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  31. 31

    Lencz, T. et al. Quantitative magnetic resonance imaging in temporal lobe epilepsy: relationship to neuropathology and neuropsychological function. Ann. Neurol. 31, 629–637 (1992).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  32. 32

    Briellmann, R.S., Kalnins, R.M., Berkovic, S.F. & Jackson, G.D. Hippocampal pathology in refractory temporal lobe epilepsy: T2-weighted signal change reflects dentate gliosis. Neurology 58, 265–271 (2002).

    Article  PubMed  PubMed Central  Google Scholar 

  33. 33

    Golby, A.J. et al. Memory lateralization in medial temporal lobe epilepsy assessed by functional MRI. Epilepsia 43, 855–863 (2002).

    Article  PubMed  PubMed Central  Google Scholar 

  34. 34

    Dupont, S. et al. Episodic memory in left temporal lobe epilepsy: a functional MRI study. Brain 123, 1722–1732 (2000).

    Article  PubMed  PubMed Central  Google Scholar 

  35. 35

    Bellgowan, P.S. et al. Side of seizure focus predicts left medial temporal lobe activation during verbal encoding. Neurology 51, 479–484 (1998).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  36. 36

    Richter-Levin, G. & Akirav, I. Amygdala-hippocampus dynamic interaction in relation to memory. Mol. Neurobiol. 22, 11–20 (2000).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  37. 37

    Pitkanen, A., Pikkarainen, M., Nurminen, N. & Ylinen, A. Reciprocal connections between the amygdala and the hippocampal formation, perirhinal cortex, and postrhinal cortex in rat. A review. Ann. NY Acad. Sci. 911, 369–391 (2000).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  38. 38

    van Groen, T . & Wyss, J.M. Extrinsic projections from area CA1 of the rat hippocampus: olfactory, cortical, subcortical, and bilateral hippocampal formation projections. J. Comp. Neurol. 302, 515–528 (1990).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  39. 39

    Canteras, N.S. & Swanson, L.W. Projections of the ventral subiculum to the amygdala, septum, and hypothalamus: a PHAL anterograde tract-tracing study in the rat. J. Comp. Neurol. 324, 180–194 (1992).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  40. 40

    Krettek, J.E. & Price, J.L. Projections from the amygdaloid complex and adjacent olfactory structures to the entorhinal cortex and to the subiculum in the rat and cat. J. Comp. Neurol. 172, 723–752 (1977).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  41. 41

    Maren, S. & Fanselow, M.S. Synaptic plasticity in the basolateral amygdala induced by hippocampal formation stimulation in vivo. J. Neurosci. 15, 7548–7564 (1995).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  42. 42

    Seidenbecher, T., Laxmi, T.R., Stork, O. & Pape, H.C. Amygdalar and hippocampal theta rhythm synchronization during fear memory retrieval. Science 301, 846–850 (2003).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  43. 43

    Friston, K.J. et al. Statistical parametric maps in functional imaging: A general linear approach. Hum. Brain. Map. 2, 189–210 (1995).

    Article  Google Scholar 

  44. 44

    Otten, L.J., Henson, R.N. & Rugg, M.D. Depth of processing effects on neural correlates of memory encoding: relationship between findings from across- and within-task comparisons. Brain 124, 399–412 (2001).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We would like to thank the clinicians of the Department of Clinical and Experimental Epilepsy (J. Duncan, L. Sander, M. Walker, H. Cock, S. Sisodiya and M. Koepp) for referring patients to the study and P. Bartlett, Chief Radiographer at the Chalfont Centre for Epilepsy, for providing the volume and T2 data. M.P.R. is funded by a fellowship of the Medical Research Council, UK. R.J.D. is supported by a Wellcome Trust Programme Grant.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Mark P Richardson.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Statistical parametric map (SPM) overlaid on sagittal and coronal sections of the average T1 image from all 16 patients studied. The highlighted voxels show a significant positive correlation between gray matter density and recognition accuracy for R responses to neutral items at P < 0.01 and a significant negative correlation between T2 signal and recognition accuracy for R responses to neutral items at P < 0.01. These are the only voxels in the entire brain to show both these effects. (JPG 16 kb)

Supplementary Note (PDF 9 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Richardson, M., Strange, B. & Dolan, R. Encoding of emotional memories depends on amygdala and hippocampus and their interactions. Nat Neurosci 7, 278–285 (2004). https://doi.org/10.1038/nn1190

Download citation

Further reading

Search

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing