Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

A disproportionate role for the fornix and mammillary bodies in recall versus recognition memory

Nature Neuroscience volume 11, pages 834–842 (2008)Cite this article

Abstract

Uncovering the functional relationship between temporal lobe amnesia and diencephalic amnesia depends on determining the role of the fornix, the major interlinking fiber tract. In this study relating fornix volume with memory, we made magnetic resonance imaging–based volume estimates of 13 brain structures in 38 individuals with surgically removed colloid cysts. Fornix status was assessed directly by overall volume and indirectly by mammillary body volume (which atrophies after fornix damage). Mammillary body volume significantly correlated with 13 out of 14 tests of episodic memory recall, but correlated poorly with recognition memory. Furthermore, as the volumes of the left fornix and the left mammillary bodies decreased, the difference between recall and recognition scores increased. No other structure was consistently associated with memory. These findings support models of diencephalic memory mechanisms that require hippocampal inputs for recall, but not for key elements of recognition.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Figure 1: The fornix and mammillary bodies in colloid cyst surgery patients.
Figure 2: Mammillary bodies and memory.
Figure 3: Scatter plots comparing the individual volumes (ICV normalized, × 1,000) for the mammillary bodies and hippocampus against the combined recall index and combined recognition index.

Similar content being viewed by others

References

  1. Garcia-Bengochea, F. & Friedman, W.A. Persistent memory loss following section of the anterior fornix in humans: a historical review. Surg. Neurol. 27, 361–364 (1987).

    Article  CAS  Google Scholar 

  2. Woolsey, R.M. & Nelson, J.S. Asymptomatic destruction of the fornix in man. Arch. Neurol. 32, 566–568 (1975).

    Article  CAS  Google Scholar 

  3. D'Esposito, M., Verfaellie, M., Alexander, M.P. & Katz, D.I. Amnesia following traumatic bilateral fornix transection. Neurology 45, 1546–1550 (1995).

    Article  CAS  Google Scholar 

  4. Park, S.A., Hahn, J.H., Kim, J.I., Na, D.L. & Huh, K. Memory deficits after bilateral anterior fornix infarction. Neurology 54, 1379–1382 (2000).

    Article  CAS  Google Scholar 

  5. Poreh, A., Winocur, G., Moscovitch, M., Backon, M., Goshen, E., Ram, Z. & Feldman, Z. Anterograde and retrograde amnesia in a person with bilateral fornix lesions following removal of a colloid cyst. Neuropsychologia 44, 2241–2248 (2006).

    Article  Google Scholar 

  6. Hodges, J.R. & Carpenter, K. Anterograde amnesia with fornix damage following removal of IIIrd ventricle colloid cyst. J. Neurol. Neurosurg. Psychiatry 54, 633–638 (1991).

    Article  CAS  Google Scholar 

  7. McMackin, D., Cockburn, J., Anslow, P. & Gaffan, D. Correlation of fornix damage with memory impairment in six cases of colloid cyst removal. Acta Neurochir. (Wien) 135, 12–18 (1995).

    Article  CAS  Google Scholar 

  8. Aggleton, J.P. et al. Differential cognitive effects of colloid cysts in the third ventricle that spare or compromise the fornix. Brain 123, 800–815 (2000).

    Article  Google Scholar 

  9. Aggleton, J.P. & Brown, M.W. Episodic memory, amnesia and the hippocampal anterior thalamic axis. Behav. Brain Sci. 22, 425–466 (1999).

    Article  CAS  Google Scholar 

  10. Squire, L.R., Stark, C.E.L. & Clark, R.E. The medial temporal lobe. Annu. Rev. Neurosci. 27, 279–306 (2004).

    Article  CAS  Google Scholar 

  11. Yonelinas, A.P. The nature of recollection and familiarity: a review of 30 years of research. J. Mem. Lang. 46, 441–517 (2002).

    Article  Google Scholar 

  12. Squire, L.R., Wixted, J.T. & Clark, R.E. Recognition memory and the medial temporal lobe: a new perspective. Nat. Rev. Neurosci. 8, 872–883 (2007).

    Article  CAS  Google Scholar 

  13. Mayes, A.R. & Montaldi, D. The value of neuroradiological approaches in the study of organic amnesia. in Case Studies in the Neuropsychology of Memory (Parkin, A.J.) (Erlbaum Taylor and Francis, Hove, UK, 1997).

    Google Scholar 

  14. Gaffan, E.A., Gaffan, D. & Hodges, J.R. Amnesia following damage to the left fornix and to other sites: a comparative study. Brain 114, 1297–1313 (1991).

    Article  Google Scholar 

  15. Kapur, N. et al. Mamillary body damage results in memory impairment, but not amnesia. Neurocase 4, 509–517 (1998).

    Article  Google Scholar 

  16. Hildebrandt, H., Muller, S., Bussmann-Mork, B., Goebel, S. & Eilers, N. Are some memory deficits unique to lesions of the mammillary bodies? J. Clin. Exp. Neuropsychol. 23, 490–501 (2001).

    Article  CAS  Google Scholar 

  17. Vann, S.D. & Aggleton, J.P. The mammillary bodies: two memory systems in one? Nat. Rev. Neurosci. 5, 35–44 (2004).

    Article  CAS  Google Scholar 

  18. Loftus, M., Knight, R.T. & Amaral, D.G. An analysis of atrophy in the medial mammillary nucleus following hippocampal and fornix lesions in humans and nonhuman primates. Exp. Neurol. 163, 180–190 (2000).

    Article  CAS  Google Scholar 

  19. Wechsler, D. Wechsler Adult Intelligence Test 3rd edn (The Psychological Corporation, San Antonio, Texas, 1997).

    Google Scholar 

  20. Wechsler, D. Wechsler Test of Adult Reading (The Psychological Corporation, New York, 2001).

    Google Scholar 

  21. Wechsler, D. Wechsler Memory Scale 3rd edn (The Psychological Corporation, San Antonio, Texas, 1997).

    Google Scholar 

  22. Denby, C. et al. MRI measurement of fornix pathology: evidence of extensive fornix damage following surgical removal of colloid cysts in the third ventricle. Neurosci. Imaging (in the press) (2008).

    Google Scholar 

  23. Baddeley, A., Emslie, H. & Nimmo-Smith, I. The Doors and People Test: A Test of Visual and Verbal Recall and Recognition (Thames Valley Test Company, Bury St Edmunds, UK, 1994).

    Google Scholar 

  24. Warrington, E.K. Recognition Memory Test (NFER-Nelson, Windsor, UK, 1984).

    Google Scholar 

  25. Aggleton, J.P. & Brown, M.W. Interleaving brain systems for episodic and recognition memory. Trends Cogn. Sci. 10, 455–463 (2006).

    Article  Google Scholar 

  26. Carlesimo, G.A. et al. Bilateral damage to the mammillo-thalamic tract impairs recollection, but not familiarity in the recognition process: a single case investigation. Neuropsychologia 45, 2467–2479 (2007).

    Article  CAS  Google Scholar 

  27. Poletti, C.E. & Creswell, G. Fornix system efferent projections in the squirrel monkey: an experimental degeneration study. J. Comp. Neurol. 175, 101–128 (1977).

    Article  CAS  Google Scholar 

  28. Aggleton, J.P., Vann, S.D. & Saunders, R.C. Projections from the hippocampal region to the mammillary bodies in macaque monkeys. Eur. J. Neurosci. 22, 2519–2530 (2005).

    Article  Google Scholar 

  29. Dusoir, H., Kapur, N., Brynes, D.P., McKinstry, S. & Hoare, R.D. The role of diencephalic pathology in human memory disorder. Brain 113, 1695–1706 (1990).

    Article  Google Scholar 

  30. Saunders, R.C. & Aggleton, J.P. Origin and topography of fibers contributing to the fornix in macaque monkeys. Hippocampus 17, 396–411 (2007).

    Article  Google Scholar 

  31. Kopelman, M.D. The Korsakoff syndrome. Br. J. Psychiatry 166, 154–173 (1995).

    Article  CAS  Google Scholar 

  32. Victor, M. The irrelevance of mammillary body lesions in the causation of the Korsakoff amnestic state. Int. J. Neurol. 21–22, 51–57 (1987).

    PubMed  Google Scholar 

  33. Harding, A., Halliday, G., Caine, D. & Kril, J. Degeneration of anterior thalamic nuclei differentiates alcoholics with amnesia. Brain 123, 141–154 (2000).

    Article  Google Scholar 

  34. Von Cramon, D.Y., Hebel, N. & Schuri, U. A contribution to the anatomical basis of thalamic amnesia. Brain 108, 993–1008 (1985).

    Article  Google Scholar 

  35. Van der Werf, Y.D. et al. Deficits of memory, executive functioning and attention following infarction in the thalamus: a study of 22 cases with localized lesions. Neuropsychologia 41, 1330–1344 (2003).

    Article  Google Scholar 

  36. Vann, S.D., Saunders, R.C. & Aggleton, J.P. Distinct, parallel pathways link the medial mammillary bodies to the anterior thalamus in macaque monkeys. Eur. J. Neurosci. 26, 1575–1586 (2007).

    Article  Google Scholar 

  37. Baxter, M.G. & Chiba, A.A. Cognitive functions of the basal forebrain. Curr. Opin. Neurobiol. 9, 178–183 (1999).

    Article  CAS  Google Scholar 

  38. Eichenbaum, H., Yonelinas, A.P. & Ranganath, C. The medial temporal lobe and recognition memory. Annu. Rev. Neurosci. 30, 123–152 (2007).

    Article  CAS  Google Scholar 

  39. Kopelman, M.D. et al. Recall and recognition memory in amnesia: patients with hippocampal, medial temporal, temporal lobe or frontal pathology. Neuropsychologia 45, 1232–1246 (2007).

    Article  Google Scholar 

  40. Manns, J.R. & Squire, L.R. Impaired recognition memory on the doors and people test after damage limited to the hippocampal region. Hippocampus 9, 495–499 (1999).

    Article  CAS  Google Scholar 

  41. Bowles, B. et al. Impaired familiarity with preserved recollection after anterior temporal-lobe resection that spares the hippocampus. Proc. Natl. Acad. Sci. USA 104, 16382–16387 (2007).

    Article  CAS  Google Scholar 

  42. Dunn, J.C. Remember-know: a matter of confidence. Psychol. Rev. 111, 524–542 (2004).

    Article  Google Scholar 

  43. Cruz-Orive, L.M. Systematic sampling in stereology. Bull. Int. Stat. Inst. 52, 451–468 (1993).

    Google Scholar 

  44. García-Fiñana, M., Cruz-Orive, L.M., MacKay, C.E., Pakkenberg, B. & Roberts, N. Comparison of MR imaging against physical sectioning to estimate the volume of human cerebral compartments. Neuroimage 18, 505–516 (2003).

    Article  Google Scholar 

  45. Bilir, E. et al. Volumetric MRI of the limbic system: anatomical determinants. Neuroradiology 40, 138–144 (1998).

    Article  CAS  Google Scholar 

  46. Zahajszky, J. et al. A quantitative MR measure of the fornix in schizophrenia. Schizophr. Res. 47, 87–97 (2001).

    Article  CAS  Google Scholar 

  47. Cook, M.J., Fish, D.R., Shorvon, S.D., Straughan, K. & Stevens, J.M. Hippocampal volumetric and morphometric studies in frontal and temporal lobe epilepsy. Brain 115, 1001–1015 (1992).

    Article  Google Scholar 

  48. Insausti, R. et al. MR volumetric analysis of the human entorhinal, perirhinal and temporopolar cortices. AJNR Am. J. Neuroradiol. 19, 659–671 (1998).

    CAS  PubMed  Google Scholar 

  49. Pruessner, J.C. et al. Volumetry of temporopolar, perirhinal, entorhinal and parahippocampal cortex from high-resolution MR images: considering the variability of the collateral sulcus. Cereb. Cortex 12, 1342–1353 (2002).

    Article  Google Scholar 

  50. Howard, M.A., Roberts, N., García-Finana, M. & Cowell, P.E. Volume estimation of prefrontal cortical subfields using MRI and stereology. Brain Res. Brain Res. Protoc. 10, 125–138 (2003).

    Article  Google Scholar 

Download references

Acknowledgements

The authors would like to thank the participants and their families for their generous contributions to this project and the neurosurgeons for facilitating access to their patients. The authors would also like to acknowledge the contribution of D. McMackin in the initial stages of this research project. This work was funded by the UK Medical Research Council (grant G0001371).

Author information

Author notes

  1. Dimitris Tsivilis and Seralynne D Vann: These authors contributed equally to this work.

Authors and Affiliations

  1. School of Psychological Sciences, Zochonis Building, University of Manchester, Brunswick Street, Manchester, M13 9PL, UK

    Dimitris Tsivilis, Christine Denby, Andrew R Mayes & Daniela Montaldi

  2. School of Psychology, Cardiff University, Park Place, Cardiff, CF10 3AT, Wales, UK

    Seralynne D Vann & John P Aggleton

  3. Magnetic Resonance and Image Analysis Research Centre, University of Liverpool, Pembroke Place, Liverpool, L69 3GE, UK

    Neil Roberts

Authors
  1. Dimitris Tsivilis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Seralynne D Vann
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Christine Denby
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Neil Roberts
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Andrew R Mayes
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Daniela Montaldi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. John P Aggleton
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors helped design and analyze the findings. Psychometric testing was conducted by D.T. and S.D.V., and volumetric assessments were conducted by C.D.

Corresponding author

Correspondence to Dimitris Tsivilis.

Supplementary information

Supplementary Text and Figures

Supplementary Figure 1 and Supplementary Tables 1–5 (PDF 192 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Tsivilis, D., Vann, S., Denby, C. et al. A disproportionate role for the fornix and mammillary bodies in recall versus recognition memory. Nat Neurosci 11, 834–842 (2008). https://doi.org/10.1038/nn.2149

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nn.2149

This article is cited by

Search

Advanced search

Quick links

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