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.

  • Article
  • Published:

Isolating the neural mechanisms of age-related changes in human working memory

Nature Neuroscience volume 3, pages 509–515 (2000)Cite this article

Abstract

Working memory (WM), the process by which information is coded into memory, actively maintained and subsequently retrieved, declines with age. To test the hypothesis that age-related changes in prefrontal cortex (PFC) may mediate this WM decline, we used functional MRI to investigate age differences in PFC activity during separate WM task components (encoding, maintenance, retrieval). We found greater PFC activity in younger than older adults only in dorsolateral PFC during memory retrieval. Fast younger subjects showed less dorsolateral PFC activation during retrieval than slow younger subjects, whereas older adults showed the opposite pattern. Thus age-related changes in dorsolateral PFC and not ventrolateral PFC account for WM decline with normal aging.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1: Experimental design and analysis (a) Trial sequence of the behavioral task.
Figure 2: Regions of interest.
Figure 3: Age-group differences in activation by PFC region, memory-load condition and task period.
Figure 4: Neural activity in the fastest and slowest subjects in each age group.
Figure 5: Scatterplots of activation–performance relationships.
Figure 6: A sigmoid activation model of age-related differences in brain–behavior relationships.

Similar content being viewed by others

References

  1. Raz, N. et al. Selective aging of the human cerebral cortex observed in vivo: Differential vulnerability of the prefrontal gray matter. Cereb. Cortex, 7, 268–282 (1997).

    Article  CAS  Google Scholar 

  2. Heilbroner, P. L. & Kemper T. L., The cytoarchitectonic distribution of senile plaques in three aged monkeys. Acta Neuropathol. 81, 60–65 (1990).

    Article  CAS  Google Scholar 

  3. Haug, H. & Eggers, R. Morphometry of the human cortex cerebri and corpus striatum during aging. Neurobiol. Aging 12, 336–338 (1991).

    Article  CAS  Google Scholar 

  4. Goldman-Rakic, P. M., & Brown, R. M. Regional changes of monoamines in cerebral cortex and subcortical structures of aging rhesus monkeys. J. Neurosci, 6, 177–178 (1981).

    Article  CAS  Google Scholar 

  5. Waugh, N. C. & Norman, D. A. Primary memory. Psychol. Rev. 72, 89–104 (1965).

    Article  CAS  Google Scholar 

  6. Glanzer, M. & Razel, M. The size of the unit in short term storage. J. Verb. Learn. Verb. Behav. 13, 114–131 (1974).

    Article  Google Scholar 

  7. Craik, F. I. M. & Jennings, J. M. in The Handbook of Aging and Cognition (eds. Craik, F. I. M. & Salthouse, T. A.) 51–110 (Erlbaum, Hillsdale, New Jersey, 1992).

    Google Scholar 

  8. Awh, E. et al. Dissociation of storage and rehearsal in verbal working memory: evidence from PET. Psychol. Sci. 7, 25–31 (1996).

    Article  Google Scholar 

  9. Paulesu, E., Frith, C. & Frackowiak, R. The neural correlates of the verbal component of working memory. Nature 362, 342–345 (1991).

    Article  Google Scholar 

  10. Rypma, B., Prabhakaran, V., Desmond, J. E., Glover, G. H. & Gabrieli, J. D. E. Load-dependent roles of prefrontal brain regions in the maintenance of working memory. Neuroimage 9, 216–225 (1999).

    Article  CAS  Google Scholar 

  11. Rypma B. & D'Esposito, M. The roles of prefrontal brain regions in components of working memory: Effects of memory load and individual differences. Proc. Natl. Acad. Sci. USA 96, 6558–6563 (1999).

    Article  CAS  Google Scholar 

  12. D'Esposito, M., Postle, B. R., Ballard, D. & Lease, J, Maintenance versus manipulation of information held in working memory: An event-related fMRI study. Brain Cognit. 41, 66–86 (1999).

    Article  CAS  Google Scholar 

  13. Anders, T. R., Fozard, J. L. & Lillyquist, T. D. Effects of age upon retrieval from short-term memory. Dev. Psychol. 6, 214–217 (1972).

    Article  Google Scholar 

  14. Van der Linden, M., Bredart, S. & Beerten, A. Age-related differences in updating working memory. Br. J. Psychol. 85, 145–151 (1994).

    Article  Google Scholar 

  15. Fuster, J. M. The Prefrontal Cortex: Anatomy, Physiology, and Neuropsychology of the Frontal Lobes (Raven, New York, 1989).

    Google Scholar 

  16. Smith, E. E. & Jonides, J. Storage and executive processes in the frontal lobes. Science 283, 1657–1661 (1999).

    Article  CAS  Google Scholar 

  17. Petrides, M. in Handbook of Neuropsychology (eds. Boller, F. & Grafman, J.) 75–90 (Elsevier, Amsterdam, 1989).

    Google Scholar 

  18. Owen, A. M., Evans, A. C. & Petrides, M. Evidence for a two-stage model of spatial working memory processing within the lateral frontal cortex: a positron emission tomography study. Cereb. Cortex 6, 31–39 (1996).

    Article  CAS  Google Scholar 

  19. Belsley, D. A., Kuh, E. & Welsch, R. E. Regression Diagnostics: Identifying Influential Data and Sources of Collinearity (Wiley, New York, 1980).

    Book  Google Scholar 

  20. Sternberg, S. High speed scanning in human memory. Science 153, 652–654 (1966).

    Article  CAS  Google Scholar 

  21. Salthouse, T. A. The processing speed theory of adult age differences in cognition. Psychol. Rev. 103, 403–428 (1996).

    Article  CAS  Google Scholar 

  22. Myerson, J., Hale, S., Wagstaff, D., Poon, L. W. & Smith, G. A. The information-loss model: a mathematical theory of age-related cognitive slowing. Psychol. Rev. 97, 475–487 (1990).

    Article  CAS  Google Scholar 

  23. Servan-Schreiber, D., Printz, H. & Cohen, J. D. A network model of catecholamine effects: gain, signal to noise ratio, and behavior. Science 249, 892–895 (1990).

    Article  CAS  Google Scholar 

  24. Cohen, J. D. & Servan-Schreiber, D. Context, cortex, and dopamine: A connectionist approach to behavior and biology in schizophrenia. Psychol. Rev. 99, 45–77 (1992).

    Article  CAS  Google Scholar 

  25. Kimberg, D. Y., D'Esposito, M. & Farah, M. T. Effects of bromocriptine on human subjects depend on working memory capacity. Neuroreport 8, 3581–3585 (1997).

    Article  CAS  Google Scholar 

  26. Mitchell, K. J. et al. Aging and reflective processes of working memory: Binding and test load deficits. Psychol. Aging (in press).

  27. Zarahn, E., Aguirre, G. K. & D'Esposito, M. A trial based experimental design for functional MRI. Neuroimage 6, 122–138 (1997).

    Article  Google Scholar 

  28. Worsley, K. J. & Friston, K. J. Analysis of fMRI time-series revisited-again. Neuroimage 2, 173–182 (1995).

    Article  CAS  Google Scholar 

  29. Aguirre, G. K., Zarahn, E. & D'Esposito, M. The variability of human BOLD hemodynamic responses. Neuroimage 8, 360–369 (1998).

    Article  CAS  Google Scholar 

  30. Talairach, J. & Tournoux, P. Co-Planar Stereotaxic Atlas of the Human Brain (Thieme, New York, 1988).

    Google Scholar 

  31. Kleinbaum, D. G., Kupper, L. L. & Muller, K. E. Applied regression analysis (Duxbury, Belmont, California, 1988).

    Google Scholar 

  32. D'Esposito, M., Zarahn, E., Aguirre, G. K. & Rypma, B. The effect of normal aging on the coupling of neural activity to the BOLD hemodynamic response. Neuroimage 10, 6–14 (1999).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This research was supported by American Federation for Aging Research and NIH grants NS01762, AG15793 and AG13483. We thank Jeffrey S. Berger, Ron Collis, David Dorfman, Eric Zarahn and Geoff Aguirre for their support on this project. We thank Marcia K. Johnson, Karen Mitchell and Carol Raye for the design of replication experiment 2.

Author information

Authors and Affiliations

  1. Helen Wills Neuroscience Institute and Department of Psychology, University of California, Berkeley, 3210 Tolman Hall, Berkeley, 94720-1650, California, USA

    Bart Rypma & Mark D'Esposito

Authors
  1. Bart Rypma
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mark D'Esposito
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bart Rypma.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rypma, B., D'Esposito, M. Isolating the neural mechanisms of age-related changes in human working memory. Nat Neurosci 3, 509–515 (2000). https://doi.org/10.1038/74889

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/74889

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