Under conditions in which encoding stimuli and encoding tasks were held constant, and behavioral performance was equivalent between young and older adults, both groups showed neural activity in left ventrolateral PFC, left dorsolateral PFC, and right hippocampus during accurate retrieval. Whereas young adults’ neural activity in left posterior ventrolateral PFC and right hippocampus was modulated by the extent to which the retrieval task depended on relational processing, older adults activated these regions during the retrieval of relational, as well as item, information, suggesting an age-related reduction in processing specificity in these regions. No age-related differences in processing specificity, however, were observed in anterior ventrolateral PFC or dorsolateral PFC: activity in these regions was observed during retrieval of item and relational information for both groups, demonstrating that not all regions showed age-related reductions in specificity for our task.
Behaviorally, generation of encoding sentences, combined with increased repetition of information at encoding for older adults, equated relational memory performance between the young and older groups. Such findings demonstrate that with encoding support older adults can overcome their relational memory deficit. This finding is consistent with prior behavioral reports demonstrating the benefit of encoding support to older adults’ source memory performance. For example, Glisky and her colleagues (2001)
found that only a subset of their older adult participants showed deficits in source memory, namely those with below average frontal function, and these deficits could be eliminated by requiring participants at study to consider the relation between an item and its context. The current behavioral results extend these findings by demonstrating that memory for other types of contexts (i.e., the inter-item associations formed between two words) can be equated between young and older adults with encoding support (see Craik, 1977
; Craik and Simon, 1980
for examples of the use of external cues for environmental support).
In the current study, we explicitly equated memory performance across young adults and older adults to assess neural activity. Although there are several merits to equating performance across the age groups, a downside to such an approach is that performance is artificially equated, and as such, it is unclear what imaging results would have been obtained if group performance had varied naturally. Nonetheless, we chose to equate memory performance between groups to minimize several potential group differences, including those associated with task difficulty.
At the neural level, hippocampal activity in young adults was modulated by the extent to which the retrieval task depended upon relational processing. This finding is consistent with several findings indicating a critical role for the hippocampus during the encoding (Chua et al., 2007
; Davachi and Wagner, 2002
; Henke et al., 1999
; Jackson and Schacter, 2004
; Prince et al., 2005
; Sperling et al., 2001
; Sperling et al., 2003
) and retrieval of relational information (Giovanello et al., 2004
; Yonelinas et al., 2001
), and directly replicates our prior finding in young adults using the same paradigm, in which only the intact pair condition contributed to activity in the hippocampus (Giovanello, Schnyer, Verfaellie, 2004
). Importantly, greater hippocampal activation for the Intact Pair condition than for Recombined Pair condition in young adults suggests that the hippocampus plays a critical role in successful reinstatement of newly formed associations, rather than solely in the attempt to retrieve such information. Activity in left posterior ventrolateral PFC observed in the current study is consistent with prior reports that this region is involved in the retrieval of temporal order, spatial location, and presentation modality (Cabeza et al., 2003
; Hayes et al., 2004
; Henson, et al., 1999
; Nolde et al., 1998
; Ranganath, et al., 2000
), and may reflect the processing of relevant features (e.g., semantic, phonological, or orthographic) of stimuli (i.e., intra-item associations) or the degree of controlled selection that is engaged (see Blumenfeld and Ranganath, 2007
In contrast, older adults showed significant neural activity in right hippocampus and posterior ventrolateral PFC for accurate retrieval, but activity in these regions was observed for both item and relational memory conditions, suggesting a loss of regional specialization. Such age-related neural activity is consistent with a prior report that documented declining ventral visual cortex specificity in older adults for who face regions were also more responsive to places than in young adults where regions responded discriminately to one category (Park et al., 2004
). Moreover, Payer and colleagues (2006)
observed ventral visual dedifferentiation in older adults during working memory encoding, together with prefrontal overactivation, raising the possibility that frontal regions may compensate for lost perceptual specificity. In the current study, neural activity in bilateral middle and superior frontal regions was greater for older adults than for younger adults, again potentially suggesting that frontal regions may compensate for reduced hippocampal specificity, particularly under conditions in which no age-related behavioral differences are observed.
However, a different pattern emerged in the anterior ventrolateral PFC and dorsolateral PFC. In these regions, neural activity was similar between young and older adult groups, with activity present for both item and relational memory conditions. Prior studies in young adults suggest that activation of anterior ventrolateral PFC is enhanced during the general selection of semantic information, while dorsolateral PFC is involved in the organization or comparison of relationships among items that are active in memory (see Paller and Wagner, 2002
; Ranganath, 2010
). For instance, Murray and Ranganath (2007)
reported that anterior ventrolateral prefrontal (BA 45/47) activity at encoding predicted successfully memory for both items and relations, while dorsolateral prefrontal (BA 46) activity predicted successful memory for relational information only. The current findings in anterior ventrolateral PFC dovetail nicely with those of Murray and Ranganath (2007)
, extending their observation at encoding to activity at retrieval and documenting similar patterns of activity in this region in young and older adults. The current findings in dorsolateral PFC, however, appear inconsistent to those reported by Murray and Ranganath (2007)
, as we observed retrieval-related activity in this region for both item and relational information. Future studies will need to address whether this apparent inconsistency is due to the stage of memory examined (encoding versus retrieval) or some other factor.
We also examined neural regions showing a stronger correspondence to accurate memory in young adults than in older adults (young>old), as well as regions showing the opposite effect (old > young). For neural regions uniquely activated by young adults (i.e., young>old) during accurate memory retrieval, we observed activity in bilateral inferior and middle PFC, bilateral occipital cortex, and left hippocampus. These findings are consistent with several studies documenting retrieval-related activity in these regions in young adults (e.g., Badgaiyan et al., 2002
; Bunge et al. 2004
; Dobbins, et al., 2002
; Giovanello, Schnyer, and Verfaellie, 2004
; Rugg,, Fletcher et al., 1999
; Velanova et al., 2003
). Additionally, the contrasts selective for relational versus item memory showed that young adults recruited left posterior ventrolateral PFC (BA 44) and right hippocampus during relational retrieval, consistent with the pattern of observed in the region of interest data extracted from the accurate retrieval analysis.
For neural regions uniquely activated by older adults (i.e., old > young) during accurate memory retrieval, we observed activity in bilateral superior and middle frontal gyri, as well as left middle temporal gyrus. As noted above, such age-related over-recruitment, particularly in PFC, has been reported previously and may reflect frontal compensation, as it has been associated with underactivation in medial temporal and ventral visual cortex, as well as improved performance (e.g., Davis et al., 2007; Gutchess et al., 2005
). These findings, known as the posterior-to-anterior shift in aging (PASA
, Davis et al., 2007) have been observed previously under conditions of age-related under recruitment in posterior regions (i.e., MTL and ventral visual cortex). Finally, an examination of the neural regions uniquely activated by older (i.e., old > young) adults during accurate relational memory retrieval relative to accurate item memory retrieval yielded no statistically significant results, suggesting that older adults did not engage any regions beyond those of young adults for accurate relational, relative to item, retrieval.
It should be noted that the neural activity observed in the current study occurred under conditions in which the encoding task encouraged relational processing, while the retrieval tasks required relational memory or item memory. As such, there was a greater match between encoding and retrieval processes during relational retrieval than during item retrieval. Neural differences, particularly in the hippocampus, have been observed during relational retrieval when the stimulus
properties have been manipulated (i.e., a perceptual match between study and test; Giovanello, Schnyer, and Verfaellie, 2010
). Future research is needed to determine whether, and to what extent, the current findings reflect a differential match between encoding and retrieval process for the relational memory and item memory conditions. Additionally, because the current study contained only one condition that was seen at study, and then seen again in the exact format at test (intact pair condition), future research could examine whether age-related reductions in specificity would be observed under conditions in which stimuli in both item memory and
relational memory conditions were matched between study and test.
In summary, our data showed that left posterior ventrolateral PFC and bilateral hippocampal activity was modulated by the extent to which a retrieval task depended on relational processing in younger, but not older, adults. These findings suggest a reduction in ventrolateral PFC and hippocampal specificity with normal aging, and might help to understand such phenomena of normal aging as increased susceptibility to memory distortion. A number of studies have shown that older adults are sometimes more prone to making memory errors that reflect generic or nonspecific memory for previously studied information (e.g., Dodson and Schacter, 2002
; Jacoby and Rhodes, 2006
; Koutstaal and Schacter, 1997
). It will be interesting to examine whether susceptibility to such memory errors is related to the kind of reduced specificity of PFC and hippocampal processing documented here. Elsewhere we, as well as others, have provided evidence that hippocampal dysfunction may be implicated in some relational memory-based retrieval errors committed by older adults (Dennis, Kim, and Cabeza, 2008
; Giovanello, et al., 2010
), but further research is needed to examine whether reduced specificity of hippocampal or PFC processing also contributes to mistakes that older adults make when attempting to remember past events.
Finally, we defined specificity (specific versus general processes) at the level of a domain and included tests of item memory and relational memory that differed in the extent to which specific, detailed information was required at retrieval. Further work is needed to elucidate the exact mechanisms underlying this effect. For example, it is possible that the relational memory test used here requires more effort than does the item memory test, and that young adults modulated activity in ventrolateral PFC and hippocampus differentially for the more effortful task, whereas older adults did not (see Grady, 2002
for an example age-related neural differences based on cognitive effort). Alternatively, relational and item tests are thought to draw differentially on processes of recollection and familiarity (Hockley & Consoli, 1999
), which in turn could modulate the responses of ventrolateral PFC and hippocampus differently in younger and older adults (see Daselaar et al., 2006
for an example of age-related effects on the neural underpinnings of recollection and familiarity). Future research that explores these and other possibilities should help to increase our understanding of the mechanisms responsible for the age differences observed in the present study.