Age-related differences in prefrontal glutamate are associated with increased working memory decay that gives the appearance of learning deficits
- University of California, Berkeley, United States
- Massachusetts Institute of Technology, United States
- Brown University, United States
Abstract
The ability to use past experience to effectively guide decision making declines in older adulthood. Such declines have been theorized to emerge from either impairments of striatal reinforcement learning systems (RL) or impairments of recurrent networks in prefrontal and parietal cortex that support working memory (WM). Distinguishing between these hypotheses has been challenging because either RL or WM could be used to facilitate successful decision making in typical laboratory tasks. Here we investigated the neurocomputational correlates of age-related decision making deficits using an RL-WMtask to disentangle these mechanisms, a computational model to quantify them, and magnetic resonance spectroscopy to link them to their molecular bases. Our results reveal that task performance is worse in older age, in a manner best explained by working memory deficits, as might be expected if cortical recurrent networks were unable to sustain persistent activity across multiple trials. Consistent with this, we show that older adults had lower levels of prefrontal glutamate, the excitatory neurotransmitter thought to support persistent activity, compared to younger adults. Individuals with the lowest prefrontal glutamate levels displayed the greatest impairments in working memory after controlling for other anatomical and metabolic factors. Together, our results suggest that lower levels of prefrontal glutamate may contribute to failures of working memory systems and impaired decision making in older adulthood.
Data availability
All data and code has been made available on OSF (available here: https://osf.io/2u7pm/?view_only=04046e75466645f884ba72a6b4c0e5e9).
Article and author information
Author details
Funding
National Institute on Aging (R00AG054732)
- Matthew R Nassar
National Institute on Aging (K99AG054732)
- Matthew R Nassar
National Science Foundation (NSF2020844)
- Anne GE Collins
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: All participants provided a written informed consent prior to beginning the experiment. All procedures were approved by the Brown University Institutional Review Board under protocol 0812992595 (behavioral session) and 1203000583 (MRS session).
Copyright
© 2023, Rmus et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Age-related differences in prefrontal glutamate are associated with increased working memory decay that gives the appearance of learning deficits
eLife 12:e85243.
https://doi.org/10.7554/eLife.85243
