Linking cognitive integrity to working memory dynamics in the aging human brain.

Aging is accompanied by a decline of working memory, an important cognitive capacity that involves stimulus-selective neural activity that persists after stimulus presentation. Here, we unraveled working memory dynamics in older human adults (male and female) including those diagnosed with mild cognitive impairment (MCI) using a combination of behavioral modeling, neuropsychological assessment, and magnetoencephalographic (MEG) recordings of brain activity. Younger adults (male and female) were studied with behavioral modeling only. Participants performed a visuo-spatial delayed match-to-sample task under systematic manipulation of the delay and distance between sample and test stimuli. Their behavior (match/non-match decisions) was fit with a computational model permitting the dissociation of noise in the internal operations underlying the working memory performance from a strategic decision threshold. Task accuracy decreased with delay duration and sample/test proximity. When sample/test distances were small, older adults committed more false alarms than younger adults. The computational model explained the participants' behavior well. The model parameters reflecting internal noise (not decision threshold) correlated with the precision of stimulus-selective cortical activity measured with MEG during the delay interval. The model uncovered an increase specifically in working memory noise in older compared to younger participants. Furthermore, in the MCI group, but not in the older healthy controls, internal noise correlated with the participants' clinically assessed cognitive integrity. Our results are consistent with the idea that the stability of working memory contents deteriorates in aging, in a manner that is specifically linked to the overall cognitive integrity of individuals diagnosed with MCI.Significance statement Several cognitive functions decline during aging, and this process is aggravated in MCI - a condition constituting a primary risk factor for developing dementia. One function susceptible to age-related cognitive decline is working memory: the ability to maintain information online for the flexible control of behavior, which entails persistent stimulus-selective neural activity in different regions of the cerebral cortex. We used computational modeling of behavioral and neural recordings to show that the stability of working memory contents is reduced in older human subjects and predicts overall cognitive decline in MCI patients. Our findings provide new mechanistic insight into cognitive aging and MCI and highlight working memory stability as an objective marker of the mechanisms underlying cognitive impairment.