Age-related changes in neural activity during performance matched working memory manipulation

Abstract

A long-standing assumption in the cognitive aging literature is that performance on working memory (WM) tasks involving serial recall is relatively unaffected by aging, whereas tasks that require the rearrangement of items prior to recall are more age-sensitive. Previous neuroimaging studies of WM have found age-related increases in neural activity in frontoparietal brain regions during simple maintenance tasks, but few have examined whether there are age-related differences that are specific to rearranging WM items. In the current study, older and younger adults' brain activity was monitored using functional magnetic resonance imaging (fMRI) as they performed WM tasks involving either maintenance or manipulation (letter–number sequencing). The paradigm was developed so that performance was equivalent across age groups in both tasks, and the manipulation condition was not more difficult than the maintenance condition. In younger adults, manipulation-related increases in activation occurred within a very focal set of regions within the canonical brain WM network, including left posterior prefrontal cortex and bilateral inferior parietal cortex. In contrast, older adults showed a much wider extent of manipulation-related activation within this WM network, with significantly increased activity relative to younger adults found within bilateral PFC. The results suggest that activation and age-differences in lateral PFC engagement during WM manipulation conditions may reflect strategy use and controlled processing demands rather than reflect the act of manipulation per se.

Introduction

The domain of working memory (WM) – which refers to temporary, on-line storage of information in a form that can be used to support on-going processing – has been an object of intense investigation across the disciplines of psychology and neuroscience, and has received particular focus in studies of cognitive aging. A long-standing assumption in the cognitive aging literature is that performance on serial recall tasks (referred to here as simple maintenance tasks; e.g., digit or letter span) is relatively unaffected by aging, whereas tasks that require the rearrangement of items prior to recall (referred to here as manipulation tasks; e.g., backward digit span, alphabet span) are more age-sensitive. This is presumed to be because manipulation tasks require greater prefrontal involvement than maintenance tasks, a view supported by current neuroimaging evidence (see Wager and Smith, 2003, for a review). That is, because normal aging is widely thought to be accompanied by changes in prefrontal cortex structure and function, age-related cognitive changes are most strongly observed in the tasks that are most strongly sensitive to frontal function (i.e., the so-called “frontal cortex theory of aging”, e.g., West, 1996), such as working memory tasks requiring manipulation more so than those requiring simple maintenance.

The behavioral evidence for older adults being particularly poor at manipulating items in working memory, however, is somewhat equivocal. For example, some studies indicate a larger age difference in backward recall than in forward (serial) recall (Babcock and Salthouse, 1990, Bopp and Verhaeghen, 2005), but other studies find equivalent age differences in forward and backward recall (Gregoire and Van der Linden, 1997, Myerson et al., 2003, Wilde et al., 2004). More complex manipulations of items in working memory, such as that required by alphabetical re-ordering or letter–number sequencing, often show larger age differences than simple serial or backward recall (Craik, 1986, Myerson et al., 2003), but this may be due to more general age-related memory deficits that are exacerbated by the manipulation requirement (Belleville et al., 1998, Emery et al., 2007).

The interpretation of the behavioral results is further complicated by recent neuroimaging studies of cognitive aging, which generally find that older adults show more activation than young adults do during the performance of many cognitive tasks. In studies of working memory, older adults often show more prefrontal activation than young adults in the hemisphere contralateral to the typical prefrontal activation location. That is, older adults show more right prefrontal activation than do young adults during the performance of verbal maintenance tasks (Reuter-Lorenz et al., 2000), and more left prefrontal activation than do young adults during the performance of nonverbal maintenance tasks (Grady et al., 1998, Reuter-Lorenz et al., 2000). To date, however, almost all of the published studies of working memory and aging have compared older and younger adults only on maintenance tasks (e.g., Grady et al., 1998, Reuter-Lorenz et al., 2000, Rypma et al., 2001), with no manipulation task for comparison. Therefore, although there are several pieces of evidence about how age differences in working memory maintenance are manifest in the brain, very little evidence exists regarding age-related differences in brain activation that are unique to manipulation tasks.

One exception is a recent study by Sun et al. (2005), in which older and younger adults were imaged while performing versions of the forward and backward digit span test. An Age Group × Recall Order interaction was found in right inferior frontal cortex (BA 44/45), such that older adults showed more activation in this area than did young adults, but only during backward digit span. In addition, the volume activated in this area was significantly correlated with backward digit span performance in the older adults but not in the younger adults. This would suggest that even though behavioral studies often show equivalent decline of forward and backward digit span, older and younger adults may be arriving at their backward digit span performance in different ways.

The current study expands on the imaging research conducted by Sun et al. using a more complex manipulation task with some unique properties. In the current study, we use a modified version of the WMS-III Letter–number sequencing task, an item-manipulation task that is in wide use in neuropsychological testing and often shows larger age differences than either forward or backward digit span (Myerson et al., 2003). In the paradigm used here, participants are shown a series of alternating letters and numbers presented one at a time on a computer screen. Before the items are presented, participants are told either that they will have to recall the items in the order they appeared (simple maintenance condition) or will recall the digits first, in ascending order, followed by the letters in alphabetical order (manipulation condition). In order to encourage participants to manipulate the items as they are being presented, the items are presented at a relatively slow rate. Under these conditions, previous research has shown a somewhat unexpected and striking phenomenon: both older and younger adults are able to remember at least as many or more items in the manipulation condition than in the maintenance condition (Emery et al., 2007; Robertson et al., 2006). This is presumably because, in the manipulation condition, when participants group and reorder the items as the items are being presented the resulting arrangement is more memorable. That is, remembering “257BKT” is easier than remembering “T2B7K5”, even though it takes some work to change the order from the latter order to the former. Thus, the current paradigm presents a unique opportunity to investigate a manipulation task in which performance is often equal to or better than its maintenance counterpart, testing the generalizability of previous results showing that manipulation produces greater prefrontal cortex activation than does maintenance.

In addition, the current study used a unique method of matching the performance of older and younger adults that improves upon previous methods of performance matching. One perennial problem in testing for age group differences in specific cognitive processes is the presence of differences in baseline performance. Because of these baseline performance differences, it can be difficult to rule out the possibility that different patterns of brain activity in older adults during working memory performance are due to differences in the subjective difficulty of the task (that is, are older adults just “working harder” than young adults?). The typical solution to this problem is to match young and older adults on observed performance, by testing older adults in a lower load condition than younger adults. Matching observable performance at one pair of load levels, however, does not necessarily eliminate the possibility that older adults are “working harder” to maintain that (smaller number) of items than younger adults are to maintain their (larger number) of items. This is particularly the case if, as described below, performance is near ceiling for both groups.

In the current study, participants’ performance was instead matched across a range of load levels, with older adults’ memory being tested from 3–6 items, and younger adults from 4–7 items. Pilot testing (conducted in both younger and older adults) indicated that, using these ranges, the two age groups were performance-matched across the entire range in both the maintenance and manipulation tasks. Although this does not completely eliminate the problem of “subjective difficulty”, it significantly improves upon previous types of matching for the following reason. In a typical memory span task, participants are asked to remember and recall several series of items that increase in series length. Performance typically remains very high when participants have a small number of items to remember, but drops precipitously when participants reach their “span”. A participant (or group of participants) may maintain high performance over many series lengths before reaching the point at which performance begins to fall. If groups are only matched at one series length (when participants in both groups are maintaining high performance), it is possible that participants in one group may be very near to their point of rapid performance drop, whereas the other group is still several items from that point. Thus, the former group is undoubtedly working harder to maintain the items (and experiencing greater subjective difficulty) than the latter, even though objective performance is equivalent. By matching observable performance across a range of series lengths, our aim was to span the point at which performance drops for both groups. As a result, it is possible to have greater confidence that each group was working equally “hard”.

The analyses were developed to answer two questions about brain activation as participants engaged in WM manipulation within the letter–number sequencing task: (1) is performance of the manipulation condition associated with increased activity in brain regions that are a part of the canonical WM manipulation network? And (2) are there subsets of these regions that show significant age differences in the effect of manipulation? To answer the first question, we conducted separate analyses in the younger and older adults, using an ROI-based approach. To answer the second question, we determined whether any of the identified brain regions showing manipulation effects further exhibited an Age × Task interaction.