Temporal pattern separation as a measure of successful cognitive aging

Ooh Ooh Ooh, They Finally Did It!

This post is about a research article I knew existed because I know the authors and I reviewed it. I have just been waiting for it to come out so I could finally celebrate the work. This research finally looked explicitly at temporal processing in humans using a paradigm that is similar to those used in rodents as well as controls for duration as well as sequential order. The manuscript I am describing is “Temporal discrimination deficits as a function of lag interference in older adults” in Hippocampus and is by Jared Roberts and colleagues in Mike Yassa’s lab now at UC Irvine.

An Innovative Approach!

What excites me about this research is that previous work looking at temporal processing in humans has ignored the rodent research and computational models that rely on rodent research for support. What the authors did in their experiments was to specifically design an experiment to test two things: 1) They are testing the potential role for an inability to gauge duration of time between stimuli in aging. And 2) they are looking at specifically whether or not there is a specific deficit for temporal ordering (or sequential ordering to be more precise) in aging.

They found that there was a relationship between the number of intervening items (“temporal lag”) and performance with age. Older adults showed deficits for task performance at medium and high temporal lags, but not low temporal lags. When they looked at potential confounds of primacy and recency, they found that this measure actually separated the older adults into the aged-impaired and ages-unimpaired groups often reported in studies such as these (in fact, they found that this measure was more reliable than the typical RAVLT used to separate groups into impaired and unimpaired groups in aging studies!). The unimpaired group was 2 standard deviations below the young group whereas the unimpaired group was on par with the young group performance levels.

When they looked at their data again, separating the older adults into the aged-impaired and aged-unimpaired groups, they found that the impaired group showed a global deficit at all temporal lags, whereas the aged-unimpired group only showed a deficit at the middle lag. They interpreted these data as suggesting the aged-impaired group had a more global memory deficit in the temporal domain but also extending beyond (perhaps to prefrontal cortex dysfunction, etc). The aged-unimpaired group, however, appeared to show a temporal pattern separation deficit as has been reported in a number of rodent studies.

As part of their validation, they set out to use the standard RAVLT separation of aged adults into groups, rather than try to explain their exults, I will quote them:

One pertinent question is whether or not standard neuropsychological testing that is commonly used to assess medial temporal lobe and prefrontal cortical function is sensitive to the age-related deficits reported herein. We examined scores on the RAVLT delayed recall (Rey 1941) a word list learning test that is sensitive to MTL dysfunction (Lezak et al. 2004). Although prior studies in humans have used scores on the RAVLT delayed recall as a criterion for dividing aged subjects into AI and AU groups, these studies examined memory for objects independent of temporal information. While the RAVLT assesses word list learning, it does not assess the temporal sequence in which those words were presented. Thus, we reasoned that it may not be sensitive to impairments affecting temporal memory specifically, and as such may not be the best criterion for discerning gross temporal memory impairment from more subtle impairment. We found that although there is an age-related decline in RAVLT delayed recall, consistent with prior work (Stark et al. 2013), there was no difference between the AI and AU groups. This suggests that our temporal memory task may be sensitive to more subtle impairments in memory function than standard neuropsychological testing and may offer potential avenues for diagnosis and prediction of cognitive decline.

In other words, they found their task to be more reliable and sensitive than neuropsychological tests. Which to me is not at all surprising.

Conclusion

Roberts and colleagues developed a task to test temporal pattern separation (as well as primacy and recency) in a cohort of young and aged adults. They were not only able to identify a clear pattern separation deficit in the temporal domain (which makes me very happy as I have been harping on their group to do so for quite a long time), but they also were able to identify successful and unsuccessful cognitive aging as well.

To me, the more important part of their work was that they developed a behavioral task that appears to be a rather sensitive marker for episodic memory deficits that emerge with age (at least the “when” component of episodic memory), and appears also to have a potential diagnostic value for early detection of age-related pathology. The authors obviously need to run a much larger cohort to see what individual differences exist in this task similar to their work with the behavioral pattern separation tasks (mnemonic discrimination tasks as now renamed), but it appears they are off to a great start.

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