Abstract

Neuroimaging studies of episodic memory in young adults demonstrate greater functional neural activity in ventrolateral pFC and hippocampus during retrieval of relational information as compared with item information. We tested the hypothesis that healthy older adults—individuals who exhibit behavioral declines in relational memory—would show reduced specificity of ventrolateral prefrontal and hippocampal regions during relational retrieval. At study, participants viewed two nouns and were instructed to covertly generate a sentence that related the words. At retrieval, fMRIs were acquired during item and relational memory tasks. In the relational task, participants indicated whether the two words were previously seen together. In the item task, participants indicated whether both items of a pair were previously seen. In young adults, left posterior ventrolateral pFC and bilateral hippocampal activity was modulated by the extent to which the retrieval task elicited relational processing. In older adults, activity in these regions was equivalent for item and relational memory conditions, suggesting a reduction in ventrolateral pFC and hippocampal specificity with normal aging.

INTRODUCTION

Decades of cognitive aging research have shown that older adults do not perform as well as young adults on tests of episodic memory (for a review, see Hoyer & Verhaeghen, 2006). Episodic memory refers to the encoding and conscious retrieval of contextually specific information, such as an event that occurred at a particular place and time (Tulving, 1983). Age differences have been found in memory for several types of contextual attributes, including perceptual features (Pilotti, Meade, & Gallo, 2003; Naveh-Benjamin, 2000; McIntyre & Craik, 1987; Kausler & Puckett, 1981), spatial attributes (Denney, Dew, & Kihlstrom, 1992; Park, Puglisi, & Sovacool, 1983; Park, Puglisi, & Lutz, 1982), temporal order (Kausler & Puckett, 1981), and the source of information (Simons, Dodson, Bell, & Schacter, 2004; Johnson, Hashtroudi, & Lindsay, 1993; Schacter, Kaszniak, Kihlstrom, & Valdiserri, 1991). A review by Spencer and Raz (1995) and another, more recently, by Old and Naveh-Benjamin (2008) indicate that age differences in memory for contextual details are twice as large as age differences in memory for content items (but see Siedlecki, Salthouse, & Berish, 2005, for a different view).

Encoding and retrieval of contextual attributes is thought to rely on relational memory processing, which occurs when two previously unrelated items are linked together (e.g., Eichenbaum & Cohen, 2001). Two prominent theoretical views have been proposed to account for age-related deficits in contextual or relational memory. Whereas the binding deficit view suggests that older adults have a fundamental deficit in linking or integrating the separate elements of a to-be-remembered episode (Ryan, Leung, Turk-Browne, & Hasher, 2007; Lyle, Bloise, & Johnson, 2006; Bayen, Phelps, & Spaniol, 2000; Mitchell, Johnson, Raye, & D'Esposito, 2000; Naveh-Benjamin, 2000; Chalfonte & Johnson, 1996; Burke & Light, 1981), the control deficit view asserts that older adults experience more generalized age-related declines in the processes under cognitive control (Anderson & Craik, 2000; Light, Prull, LaVoie, & Healy, 2000; Smith, Park, Earles, Shaw, & Whiting, 1998; Moscovitch & Winocur, 1995; Jennings & Jacoby, 1993; Craik, 1986; Craik & Byrd, 1982), such as the strategic manipulation, organization, or evaluation of features or contextual attributes and the conscious, intentional retrieval of relational information (Dew & Giovanello, 2010).

Research in neuropsychology and cognitive neuroscience suggests that such binding and control processes depend primarily upon the medial-temporal lobe (MTL) and the pFC, respectively. Whereas the MTL, particularly the hippocampus, serves to bind elements together into a learning event (e.g., Eichenbaum, Yonelinas, & Ranganath, 2007; Moscovitch, 1992), pFC regions mediate consciously controlled bias mechanisms that operate under effortful, intentional conditions (Buckner, 2003). For example, functional neuroimaging studies in young adults have shown greater hippocampal activity during the encoding (Chua, Schacter, Rand-Giovannetti, & Sperling, 2007; Jackson & Schacter, 2004; Davachi & Wagner, 2002; Henke, Weber, Kneifel, Wieser, & Buck, 1999) and retrieval (Giovanello, Schnyer, & Verfaellie, 2004, Yonelinas, Hopfinger, Buonocore, Kroll, & Baynes, 2001) of relational information relative to item information. Additionally, fMRI studies in young adults have reported activity in left pFC during controlled encoding (Henson, Shallice, Joseph, & Dolan, 2002; Fletcher, Shallice, & Dolan, 2000; Lepage, Habib, Cormier, Houle, & McIntosh, 2000; Mottaghy et al., 1999) and intentional retrieval (Bunge, Burrows, & Wager, 2004; Velanova et al., 2003; Badgaiyan, Schacter, & Alpert, 2002; Dobbins, Foley, Schacter, & Wagner, 2002; Rugg, Fletcher, Chua, & Dolan, 1999) of relational information.

The notion that age-related declines in relational memory may be linked to dysfunction in pFC and MTL regions fits well with structural, volumetric magnetic resonance imaging studies of older adults demonstrating that age-related atrophy differs across brain regions. For example, the frontal lobes show the steepest rate of age-related atrophy (Raz et al., 2005; Resnick, Pham, Kraut, Zonderman, & Davatzikos, 2003; Pfefferbaum, Sullivan, Rosenbloom, Mathalon, & Lim, 1998), particularly inferior frontal subregions (Resnick et al., 2003), and this atrophy corresponds to cognitive deficits (e.g., Gunning-Dixon & Raz, 2003). Additionally, memory structures within the MTL (e.g., entorhinal cortex, hippocampus, and parahippocampal gryus) exhibit differential rates of decline, with the hippocampus showing substantial atrophy and the entorhinal cortex demonstrating minimal changes (Raz et al., 2005). Shrinkage of entorhinal cortex, however, has been shown to correspond with poorer memory performance whereas changes in pFC and hippocampus have not (Rodrigue & Raz, 2004). Persson and colleagues (2006) reported reduced hippocampal volume in a group of older adults whose episodic memory performance declined over time compared with that of a group whose memory performance remained stable. More recently, Yonelinas and colleagues (2007) demonstrated that reductions in hippocampal volume resulted in decreased recollection of episodic memories. Taken together, these findings suggest that age-related declines in pFC and the hippocampus may underlie the relational memory impairment observed in healthy older adults.

Prior functional neuroimaging studies of memory in healthy older adults have demonstrated age-related alterations in neural activity (see Park & Reuter-Lorenz, 2009; Grady, 2008; Cabeza, 2006, for a general discussion of relevant issues). Such alterations have taken the form of “underrecruitment” (i.e., failures to recruit specific brain regions to the same extent as young adults) or “nonselective recruitment” (i.e., recruitment of brain regions engaged beyond those of young adults), particularly when tasks place strong demands on relational processing. With regard to relational encoding, age-related underrecruitment has been observed during intentional learning of word pairs (Cabeza et al., 1997). Compared with young adults, older adults show weaker activity in left ventrolateral pFC, a region that has been associated with semantic processing and verbal encoding (for reviews, see Cabeza & Nyberg, 2000; Gabrieli, Poldrack, & Desmond, 1998).

The link between age-related relational memory deficits and MTL decline is supported by age-related decreases in MTL activity during encoding (e.g., Daselaar, Veltman, Rombouts, Raaijmakers, & Jonker, 2003; Mitchell et al., 2000). More recently, Dennis, Hayes, et al. (2008) examined the effects of aging on the neural correlates of successful item and source memory encoding and showed age-related reductions in both hippocampal and prefrontal regions that were more pronounced for source memory than for item memory. During relational retrieval, age-related changes in pFC activity have been observed (e.g., Cabeza, Anderson, Locantore, & McIntosh, 2002; Cabeza et al., 1997). In one study, Cabeza and colleagues (1997) scanned participants while recalling word pairs and found age-related decreases in right pFC activity. Additionally, older adults showed activation in the left ventrolateral pFC that was not displayed by young adults. As a result, prefrontal activity during relational memory retrieval was unilateral for young adults and bilateral for older adults—the neural pattern termed “nonselective” neural activity. Regarding MTL activity, event-related fMRI studies have documented age-related changes in MTL activity linked to relational memory performance (e.g., Cabeza et al., 2004; Mitchell et al., 2000). In one study (Mitchell et al., 2000), older adults showed weaker MTL activity when binding objects to their locations. In another study (Cabeza et al., 2004), older adults showed weaker activity in the hippocampus but stronger activity in the parahippocampal gyrus during a recognition task with remember/know responses.

Although prior functional neuroimaging studies of relational memory have demonstrated age-related neural alterations in the form of “underrecruitment” or “nonselective recruitment” in MTL and pFC regions, no studies have examined the specificity of activity in neural regions engaged by both young and older adult groups. Importantly, the term “specificity” has been used quite broadly, ranging from “information specificity” (e.g., how study–test changes in particular types of information affect priming), to “activation specificity” (e.g., the high degree of specificity in activation processes that give rise to false memories), to “monitoring specificity” (e.g., specificity in monitoring processes that can be used to reduce false memories, such as recall to reject or distinctiveness), to “specific versus general processes” at the level of a domain, such as with emotional or nonemotional processing (for a detailed discussion, see Schacter, Gallo, & Kensinger, 2007). Here, we use the term “specificity” to denote differences in the degree of specific, detailed information required at retrieval. In the current study, we operationalized specificity by inclusion of tests of relational memory and item memory. Successful relational retrieval requires recovery of more specific, detailed information than does successful item retrieval, which can be based on a general sense of prior occurrence. As such, inclusion of item memory and relational memory tests allowed us to assess, under conditions in which both young and older adults recruit the same neural regions (e.g., pFC and MTL regions) during retrieval, whether such regions mediate retrieval of the same specific, detailed information.

The current study addressed this aspect of processing specificity by examining the contribution of pFC and hippocampus during recognition of item and relational information in young and older adults. We compared retrieval of item information and relational information, holding constant the stimuli at encoding, as well as the encoding task for the two retrieval conditions (item and relational). In addition, we equated the level of recognition accuracy across young and older adult groups to assess whether age-related neural changes in pFC and hippocampus would occur under conditions of age-equivalent relational memory performance, and if not, whether hippocampal and prefrontal activity in older adults exhibited the same specificity for relational information as activity observed in these regions in young adults. We hypothesized that young and older adults would recruit the pFC and hippocampus during accurate retrieval, albeit for different memory conditions: We expected young adults to recruit pFC and the hippocampus during relational memory retrieval, whereas we expected older adults to recruit these regions for both item and relational memory conditions, thereby showing a reduction in processing specificity.

METHODS

Participants

Sixteen young adults between the ages of 20 and 29 years (M = 22.8 years, SD = 3.0 years; 8 women) and 16 older adults between the ages of 66 and 73 years (M = 69.6 years, SD = 2.3 years; 9 women) were paid for their participation. Young adults had a mean education of 15.8 years (SD = 0.04 years), and older adults had a mean education of 15.9 years (SD = 2.2 years). Young adults were recruited from flyers posted on the Harvard University campus, and older adults were recruited from Cambridge, Massachusetts, and the surrounding communities. Participants were right-handed, fluent English speakers with normal or corrected-to-normal vision. All participants were screened to ensure that they were healthy, reported no history of psychiatric (including depression and epilepsy) or neurological disorder (including diabetes), had no contraindications for fMRI, and were not taking psychotropic medication. Informed consent was obtained from all participants according to the institutional review board at Massachusetts General Hospital.

Neuropsychological Assessment

In addition, older adult participants were given a battery of neuropsychological tests to assess their mental functioning. The neuropsychological battery consisted of the Mini-Mental State Exam, subtests from the WAIS-Revised (Mental Arithmetic and Mental Control) and WAIS-III (Digit Span Backward), subtests from the Wechsler Memory Scale-Revised (Logical Memory I and Verbal Paired Associates), the California Verbal Learning Test, the WCST, and the Controlled Oral Word Association Test. The neuropsychological data, collected within 6 months of this study, are presented in Table 1. All participants scored within 1 SD of the mean for each test (i.e., no participants were excluded based on neuropsychological testing).

Table 1. 

Group Characteristics

Measure
Young (n = 16)
Old (n = 16)
Age, years  22.8 (3.0) 69.6 (2.3) 
Sex, women 11 
Education, % 15.8 (0.04) 15.9 (2.2) 
MMSE – 29.7/30 (0.06) 
California Verbal Learning Test – 13/16 (2.5) 
Controlled Oral Word Association Test – 44.9 (14.6) 
WAIS-R Mental Arithmetic – 14.1/19 (2.0) 
WAIS-R Mental Control – 6/6 (0.8) 
WAIS-III Backward Digit Span – 8.1/14 (2.3) 
WMS-R Logical Memory I – 39.9/50 (9.0) 
WMS-R Verbal Paired Associates I – 19.2/24 (4.3) 
WCST (categories) – 6/6 (0.3) 
Measure
Young (n = 16)
Old (n = 16)
Age, years  22.8 (3.0) 69.6 (2.3) 
Sex, women 11 
Education, % 15.8 (0.04) 15.9 (2.2) 
MMSE – 29.7/30 (0.06) 
California Verbal Learning Test – 13/16 (2.5) 
Controlled Oral Word Association Test – 44.9 (14.6) 
WAIS-R Mental Arithmetic – 14.1/19 (2.0) 
WAIS-R Mental Control – 6/6 (0.8) 
WAIS-III Backward Digit Span – 8.1/14 (2.3) 
WMS-R Logical Memory I – 39.9/50 (9.0) 
WMS-R Verbal Paired Associates I – 19.2/24 (4.3) 
WCST (categories) – 6/6 (0.3) 

Standard deviations are in parentheses. For the California Verbal Learning Test, the measure reported is the number of items retrieved on the long delay cued recall test.

Stimuli and Cognitive Task

Stimuli were 288 one- to three-syllable unrelated nouns (Mean Frequency = 56.3, SD = 63.5). After extensive practice outside the scanner, participants received two study/retrieval runs. During study, young participants simultaneously viewed two nouns (42 unrelated word pairs/run; total stimuli = 84) and were instructed to covertly create a sentence that incorporated the two words. For older participants, each study run consisted of the 42 unrelated word pair trials, with each trial randomly repeated three times throughout the course of the run (in an attempt to produce equivalent levels of recognition performance).1 As with young adults, older adults were instructed to covertly create a sentence that incorporated the two words. All participants indicated via button press that they had successfully created an encoding sentence for each trial. During retrieval, which started immediately following the study phase, functional MR images were acquired for a total of 192 trials while participants performed one of two recognition tasks (Associative and Item). In the Associative task, participants saw pairs of words previously seen together (Intact Pair [IP]), pairs of words previously seen but not together (Rearranged Pair [RP]), and pairs of novel words (New Pair [NP]). Test stimuli appeared for 6 sec each, during which participants indicated whether the two words were previously seen together. In the Item task, participants saw pairs of words previously seen, but not together (Rearranged Items [RI]),2 pairs consisting of one old word and one new word (Old/New Items [ONI]), and pairs consisting of two new words (New Items [NI]). They were asked to indicate whether both words of a pair were previously seen. Four task blocks alternated between self-paced associative recognition and item recognition (Figure 1). Each block consisted of 18 trials drawn from each of the task-appropriate experimental condition types (Associative Block: 6 IP, 6 RP, 6 NP; Item block: 6 RI, 6 ONI, 6 NI), as well as six control trials during which participants viewed ampersands and number signs, and were instructed to indicate on which side of the screen the ampersands had appeared. Control trials were also used to introduce jitter during each scanner run. Trials were randomized within each task block. Starting task and stimulus conditions were counterbalanced across participants.

Figure 1. 

Event-related task design with alternating blocked task periods of relational memory (“together previously?”) and item memory (“both old?”).

Figure 1. 

Event-related task design with alternating blocked task periods of relational memory (“together previously?”) and item memory (“both old?”).

fMRI Data Acquisition and Analysis

Whole-brain gradient-echo, echo-planar images were collected during the test phase (3-mm slices, repetition time = 2, echo time = 23) only using a Siemens 3T MR scanner. Slices were oriented along the long axis of the hippocampus with a resolution of 3.125 mm × 3.125 mm × 3 mm. High-resolution T1-weighted (MP-RAGE) structural images were collected for anatomic visualization. Stimuli were back-projected onto a screen and viewed in a mirror mounted above the participant's head. For those participants requiring vision correction, subjects were given MRI compatible glasses with prescriptions matching their own. The task was presented using MacStim software (CogState Ltd., Melbourne, Australia). Responses were recorded using an MR-compatible response box. Head motion was restricted using a pillow and foam inserts.

All preprocessing and data analysis were conducted using SPM2 (Statistical Parametric Mapping; Wellcome Department of Neurology, UK). Slice acquisition timing was corrected by resampling all slices in time relative to the first slice, followed by rigid body motion correction. The functional data were then normalized spatially to the standard T1 Montreal Neurological Institute (MNI) template. Images were resampled into 3-mm cubic voxels and smoothed spatially with a 5-mm FWHM isotropic Gaussian kernel.

For each participant, on a voxel-by-voxel basis, an event-related analysis was first conducted in which all instances of a particular event type were modeled through the convolution with a canonical hemodynamic response function. Each retrieval trial (6 sec in duration) was modeled as three 2-sec repetition times. Because our interest centered on neural recruitment during successful retrieval, as well as the fact that we designed the paradigm to elicit high levels of accuracy from each age group, all memory conditions were modeled for correct decisions only. Effects for each event type were estimated using a subject-specific, fixed effects model. These data were then entered into a second-order, random-effects analysis. Analyses contrasted activation as a function of recognition type (associative vs. item) using the appropriate trial types (IP, RP, NP, RI, ONI, NI). Regions consisting of at least five contiguous voxels that exceeded the threshold of p < .001 were considered reliable.

Conjunction analyses (using the masking function in SPM2) examined what neural regions were (1) commonly activated by young and older participants during retrieval and (2) differentially activated by young or older participants during retrieval.3 For conjunction analyses examining commonalities between groups, the threshold for each contrast entered into a conjunction analysis was set at p < .01 (such that the conjoint probability of the conjunction analysis, using Fisher's estimate, was p < .0001; Lazar, Luna, Sweeney, & Eddy, 2002; Fisher, 1950). For analyses examining differences between groups, the threshold for the first contrast entered in the analysis was set at p < .01, whereas the threshold for the second contrast entered into the analysis was set at p < .001 (such that the conjoint probability of the conjunction analysis, using Fisher's estimate was p < .00001). In this way, each region surpassed the .01 threshold in both groups, thereby being involved in the task for each group. Age differences occurred above and beyond that level. Additionally, we employed direct group contrasts to examine regions uniquely activated by each age group during relational memory, relative to item memory. Voxel coordinates are reported in MNI coordinates and reflect the most significant voxel within the cluster.

RESULTS

Behavioral Data

The proportion of studied and unstudied stimuli endorsed as “old” are shown in Table 2. Behaviorally, associative recognition accuracy was calculated as the difference between “old” judgments to intact stimulus pairs (hits) and “old” judgments to recombined stimulus pairs (false alarms), whereas item recognition was calculated as the difference in “old” judgments to recombined items (hits) and “old” judgments to NI (false alarms). An ANOVA with Memory Type (item, relational) and Response Type (IP hits, NP false alarms, RI hits, and NI false alarms) as within-subjects factors and Group (young old) as a between-subject factor revealed a main effect of Memory Type (F(1, 30) = 42.69, p < .0001), indicating that greater accuracy in the relational task than the item task, as well as a main effect of Response Type (F(1, 30) = 865.26, p < .0001), indicating that studied stimuli were correctly endorsed “old” at a higher rate than nonstudied relations or items. There was no main effect of group F < 1 nor a Group × Memory type × Condition interaction, indicating that both groups performed equivalently well on the item and relational memory tasks.

Table 2. 

Proportion of Studied and Unstudied Stimuli Endorsed as “Old” and Corrected Accuracy (Hits–False Alarms) as a Function of Age


Young
Old
Item memory 
 Recombined Items (hits) .74 (.14) .71 (.17) 
 ONI (false alarm) .26 (.15) .17 (.11) 
 NI (false alarms) .05 (.08) .05 (.09) 
Relational memory 
 IP (Hits) .87 (.10) .91 (.09) 
 Recombined Pair (false alarms) .08 (.10) .12 (.12) 
 NP (false alarms) .02 (.03) .02 (.05) 
Item accuracy .69 (.15) .66 (.18) 
Relational accuracy .79 (.16) .79 (.17) 

Young
Old
Item memory 
 Recombined Items (hits) .74 (.14) .71 (.17) 
 ONI (false alarm) .26 (.15) .17 (.11) 
 NI (false alarms) .05 (.08) .05 (.09) 
Relational memory 
 IP (Hits) .87 (.10) .91 (.09) 
 Recombined Pair (false alarms) .08 (.10) .12 (.12) 
 NP (false alarms) .02 (.03) .02 (.05) 
Item accuracy .69 (.15) .66 (.18) 
Relational accuracy .79 (.16) .79 (.17) 

Standard deviations are shown in parentheses.

Functional Neuroimaging Data

Neural Regions Commonly Associated with Young and Older Adults during Accurate Memory Retrieval

We hypothesized that young and older adults would recruit the pFC and the MTL (i.e., hippocampus) during accurate retrieval, albeit for different memory conditions. As such, we contrasted all memory conditions greater than the control condition (IP + RP + RI + ONI + NI > control) for both groups to assess common regions generally contributing to accurate memory performance. This approach allowed us to extract the percent signal change in the same regions for all memory conditions (IP + RP + RI + ONI + NI) in both age groups. The analysis revealed activity in several neural regions, including left ventrolateral and dorsolateral prefrontal (DLPF) cortex, left superior parietal cortex, left inferior frontal gyrus, and right hippocampus for both groups (see Table 3). To examine which conditions elicited retrieval-related activity in pFC and hippocampus, we extracted the signal change in these regions (left ventrolateral pFC, left dorsolateral pFC, and hippocampus) for each group. There were two clusters within the left ventrolateral pFC (one anterior region located in BA 47 and one posterior region located in BA 44), one cluster within dorsolateral pFC (BA 46), and one cluster within the right hippocampus. The data, shown in Figure 2, illustrate that young adults recruited right hippocampus and left posterior ventrolateral pFC during retrieval of relational information, whereas older adults recruited these regions during retrieval of item and relational information. More specifically, young adults showed greater hippocampal activity to IP than to any other memory condition, whereas older adults recruited right hippocampus for several mnemonic conditions, both relational and item. Similarly, young adults activated left posterior ventrolateral pFC during retrieval of intact and recombined pairs, whereas older adults activated this region during both relational and item memory. Such findings point to age-related reductions in processing specificity for hippocampal and left posterior ventrolateral pFC regions. A different pattern emerged, however, in left anterior ventrolateral pFC and left dorsolateral pFC (see Figure 2). Here, both groups recruited these regions during retrieval of item and relational information, indicating no loss of processing specificity with age.

Table 3. 

Regions of Significant Neural Activity in Young and Older Adults

Location
Hemisphere
BA
MNI Coordinates
t
x
y
z
Common Neural Activity for Young and Older Adults during Accurate Retrieval 
Inferior frontal gyrus 44 −42 33 7.09 
47 −39 33 6.70 
Thalamus n/a −12 −18 5.76 
Inferior frontal gyrus 45 −54 24 21 5.10 
Middle frontal gyrus 10 39 57 4.91 
Superior parietal −30 −69 42 4.88 
Lingual gyrus 19 24 −60 −3 4.86 
Inferior temporal gyrus 20 −48 −45 −18 4.61 
Middle frontal gyrus 46 −45 51 4.58 
Inferior frontal gyrus 47 −45 36 −6 4.50 
Hippocampus n/a 24 −21 −9 4.46 
Superior Occipital gyrus 19 −24 −78 24 4.43 
Middle frontal gyrus −42 54 4.39 
 
Neural Activity Greater for Younger than Older Adults during Accurate Retrieval 
Inferior frontal gyrus 47 39 27 −6 7.08 
Occipital cortex 19 15 −78 15 7.04 
Inferior frontal gyrus 47 33 33 5.53 
Superior parietal −30 −63 48 5.61 
−36 −57 48 5.52 
Middle frontal gyrus −45 54 5.44 
−39 51 5.43 
−30 −9 51 5.34 
Occipital cortex 18 −78 18 5.26 
19 −18 −78 15 5.21 
Inferior frontal gyrus 47 −36 27 5.15 
−36 27 −9 5.11 
Hippocampus n/a −24 −21 −9 4.63 
 
Neural Activity Greater for Older than Younger Adults during Accurate Retrieval 
Middle temporal gyrus 21 −51 −42 −3 6.30 
Middle frontal gyrus 10 42 60 −6 5.31 
Middle frontal gyrus −36 12 36 4.75 
Superior frontal gyrus 39 −12 30 4.60 
Superior frontal gyrus 10 −33 60 4.48 
 
Neural Activity Greater for Younger than Older Adults during Relational Retrieval, Relative to Item Retrieval 
Inferior frontal gyrus 44 −53 15 16 5.67 
Middle temporal gryus 39 −53 −60 25 5.39 
Superior temporal gryus 22 −48 −54 19 5.01 
Precuneus 15 −65 39 4.58 
Cuneus 19 −71 34 4.48 
Hippocampus n/a 35 −21 −12 4.42 
Superior Temporal Gyrus 22 −62 −43 19 4.14 
Location
Hemisphere
BA
MNI Coordinates
t
x
y
z
Common Neural Activity for Young and Older Adults during Accurate Retrieval 
Inferior frontal gyrus 44 −42 33 7.09 
47 −39 33 6.70 
Thalamus n/a −12 −18 5.76 
Inferior frontal gyrus 45 −54 24 21 5.10 
Middle frontal gyrus 10 39 57 4.91 
Superior parietal −30 −69 42 4.88 
Lingual gyrus 19 24 −60 −3 4.86 
Inferior temporal gyrus 20 −48 −45 −18 4.61 
Middle frontal gyrus 46 −45 51 4.58 
Inferior frontal gyrus 47 −45 36 −6 4.50 
Hippocampus n/a 24 −21 −9 4.46 
Superior Occipital gyrus 19 −24 −78 24 4.43 
Middle frontal gyrus −42 54 4.39 
 
Neural Activity Greater for Younger than Older Adults during Accurate Retrieval 
Inferior frontal gyrus 47 39 27 −6 7.08 
Occipital cortex 19 15 −78 15 7.04 
Inferior frontal gyrus 47 33 33 5.53 
Superior parietal −30 −63 48 5.61 
−36 −57 48 5.52 
Middle frontal gyrus −45 54 5.44 
−39 51 5.43 
−30 −9 51 5.34 
Occipital cortex 18 −78 18 5.26 
19 −18 −78 15 5.21 
Inferior frontal gyrus 47 −36 27 5.15 
−36 27 −9 5.11 
Hippocampus n/a −24 −21 −9 4.63 
 
Neural Activity Greater for Older than Younger Adults during Accurate Retrieval 
Middle temporal gyrus 21 −51 −42 −3 6.30 
Middle frontal gyrus 10 42 60 −6 5.31 
Middle frontal gyrus −36 12 36 4.75 
Superior frontal gyrus 39 −12 30 4.60 
Superior frontal gyrus 10 −33 60 4.48 
 
Neural Activity Greater for Younger than Older Adults during Relational Retrieval, Relative to Item Retrieval 
Inferior frontal gyrus 44 −53 15 16 5.67 
Middle temporal gryus 39 −53 −60 25 5.39 
Superior temporal gryus 22 −48 −54 19 5.01 
Precuneus 15 −65 39 4.58 
Cuneus 19 −71 34 4.48 
Hippocampus n/a 35 −21 −12 4.42 
Superior Temporal Gyrus 22 −62 −43 19 4.14 
Figure 2. 

Neural activity in right hippocampus, left ventrolateral pFC, and left DLPF cortex during accurate retrieval of item information and relational information in young and older adults. In each region, the mean percent signal change is graphed for each memory condition, and standard errors are shown.

Figure 2. 

Neural activity in right hippocampus, left ventrolateral pFC, and left DLPF cortex during accurate retrieval of item information and relational information in young and older adults. In each region, the mean percent signal change is graphed for each memory condition, and standard errors are shown.

Because statistical analysis of the ROI data shown in Figure 2 could be viewed as circular, we next directly compared relational memory and item memory for each group to statistically establish whether the results observed for the omnibus analysis (IP + RP + RI + ONI + NI > control) were still observed in contrasts selective for relational versus item memory. To this end, we compared all relational memory conditions to all item memory conditions for each group (IP + RP + NP > RI + ONI + NI). These results are reported below for each age group.

Regions Showing a Stronger Correspondence to Accurate Memory in Young Adults than in Older Adults

We examined neural regions activated by young adults, relative to older adults (i.e., young > old), during accurate memory retrieval. This contrast showed greater activity in bilateral inferior frontal gyrus, left middle frontal gyrus, left hippocampus, and bilateral occipital cortex for young adults relative to older adults (see Table 3). Next, we examined neural regions uniquely activated by young (i.e., young > old) adults during accurate relational memory retrieval relative to accurate item memory retrieval. This contrast showed greater activity in left inferior frontal gyrus (BA 44), left middle temporal gyrus (BA 39), bilateral superior temporal gyrus, right hippocampus, and right parietal cortex for young adults relative to older adults (see Table 3).

Regions Showing a Stronger Correspondence to Accurate Memory in Older Adults than in Younger Adults

We examined neural regions activated by older adults, relative to younger adults (i.e., old > young), during accurate memory retrieval. This contrast showed greater activity in bilateral superior and middle frontal gyri, as well as left middle temporal gyrus for older adults relative to young adults (see Table 3). Finally, we examined neural regions uniquely activated by older (i.e., old > young) adults during accurate relational memory retrieval relative to accurate item memory retrieval. This contrast showed no significant regions, indicating that older adults did not engage any regions beyond those of young adults for accurate relational retrieval, relative to item retrieval.

DISCUSSION

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 elicited relational processing, older adults activated these regions during the retrieval of relational information 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, Rubin, and Davidson (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 interitem associations formed between two words) can be equated between young and older adults with encoding support (see Craik & Simon, 1980; Craik, 1977, 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 elicited relational processing. This finding is consistent with several findings indicating a role for the hippocampus during the encoding (Chua et al., 2007; Prince, Daselaar, & Cabeza, 2005; Jackson & Schacter, 2004; Sperling et al., 2001, 2003; Davachi & Wagner, 2002; Henke et al., 1999) and retrieval of relational information (Giovanello, Schnyer, & Verfaellie, 2009; 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 IP condition contributed to activity in the hippocampus (Giovanello et al., 2004). Importantly, greater hippocampal activation for the IP condition than for Recombined Pair condition in young adults suggests that the hippocampus plays a 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 (Hayes, Ryan, Schnyer, & Nadel, 2004; Cabeza, Locantore, & Anderson, 2003; Ranganath, Johnson, & D'Esposito, 2000; Henson, Shallice, & Dolan, 1999; Nolde, Johnson, & D'Esposito, 1998) and may reflect the processing of relevant features (e.g., semantic, phonological, or orthographic) of stimuli (i.e., intraitem associations) or the degree of controlled selection that is engaged (see Blumenfeld & 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 whom 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, whereas dorsolateral pFC is involved in the organization or comparison of relationships among items that are active in memory (see Ranganath, 2010; Paller & Wagner, 2002). For instance, Murray and Ranganath (2007) reported that anterior ventrolateral prefrontal (BA 45/BA 47) activity at encoding successfully predicted memory for both items and relations, whereas DLPF (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 because of the stage of memory examined (encoding vs. retrieval) or some other factors.

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., Giovanello et al., 2004, 2009; Bunge et al., 2004; Velanova et al., 2003; Badgaiyan et al., 2002; Dobbins et al., 2002; Rugg et al., 1999). 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 observed in the ROI 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 overrecruitment, 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, Dennis, Daselaar, Fleck, & Cabeza, 2008; Gutchess et al., 2005). These findings, known as the posterior-to-anterior shift in aging (Davis et al., 2008) have been observed previously under conditions of age-related underrecruitment 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 retrieval, 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 whereas 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, & Verfaellie, 2009). 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 (IP 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 elicited 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., Jacoby & Rhodes, 2006; Dodson & Schacter, 2002; Koutstaal & 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 (Giovanello, Kensinger, Wong, & Schacter, 2010; Dennis, Kim, & Cabeza, 2008), 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 vs. 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 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 of 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, Fleck, Dobbins, Madden, & Cabeza, 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.

Acknowledgments

This research was supported by the National Institute on Aging at the National Institutes of Health grants AG023439 and AG08441.

Reprint requests should be sent to Kelly S. Giovanello, Department of Psychology, University of North Carolina, Campus Box 3270, Chapel Hill, NC 27713, or via e-mail: kgio@unc.edu.

Notes

1. 

Although not explicitly instructed to do so, all older adult participants reported that they generated the same encoding sentence for all repetitions of a word pair.

2. 

The primary reason for not having an “intact item” condition (but rather an RI condition) was that pilot testing indicated that participants often used the first word of a given pair to cue regeneration of the encoding sentence. As such, the RI condition was used to ensure that participants were making their recognition judgments on each item of the pair, thereby minimizing the contribution of relational processing in the item conditions.

3. 

We also conducted direct comparisons between young and older groups to examine group differences. Both the conjunction approach and direct comparison approach yielded the same results, providing confidence in the reported findings.

REFERENCES

REFERENCES
Anderson
,
N. D.
, &
Craik
,
F. I. M.
(
2000
).
Memory in the aging brain.
In E. Tulving & F. I. M. Craik (Eds.),
The Oxford handbook of memory
(pp.
411
426
).
Oxford
:
Oxford University Press
.
Badgaiyan
,
R.
,
Schacter
,
D. L.
, &
Alpert
,
N. M.
(
2002
).
Retrieval of relational information: A role for the left inferior prefrontal cortex.
Neuroimage
,
17
,
393
400
.
Bayen
,
U. J.
,
Phelps
,
M. P.
, &
Spaniol
,
J.
(
2000
).
Age-related differences in the use of contextual information in recognition memory: A global matching approach.
Journals of Gerontology: Psychological Sciences
,
55B
,
131
141
.
Blumenfeld
,
R. S.
, &
Ranganath
,
C.
(
2007
).
Prefrontal cortex and long-term memory encoding: An integrative review of findings from neuropsychology and neuroimaging.
Neuroscientist
,
13
,
280
291
.
Buckner
,
R. L.
(
2003
).
Functional–anatomic correlates of control processes in memory.
The Journal of Neuroscience
,
23
,
3999
4004
.
Bunge
,
S. A.
,
Burrows
,
B.
, &
Wager
,
A. D.
(
2004
).
Prefrontal and hippocampal contributions to visual associative recognition: Interactions between cognitive control and episodic retrieval.
Brain and Cognition
,
56
,
141
152
.
Burke
,
D. M.
, &
Light
,
L. L.
(
1981
).
Memory and aging: The role of retrieval processes.
Psychological Bulletin
,
90
,
513
546
.
Cabeza
,
R.
(
2006
).
Prefrontal and medial-temporal contributions to relational memory in young and older adults.
In H. D. Zimmer, A. Mecklinger, & U. Lindenberger (Eds.),
Binding in human memory: A neurocognitive perspective
(pp.
596
626
).
Oxford
:
Oxford University Press
.
Cabeza
,
R.
,
Anderson
,
N. D.
,
Locantore
,
J. K.
, &
McIntosh
,
A. R.
(
2002
).
Aging gracefully: Compensatory brain activity in high-performing older adults.
Neuroimage
,
17
,
1394
1402
.
Cabeza
,
R.
,
Daselaar
,
S. M.
,
Dolcos
,
F.
,
Prince
,
S. E.
,
Budde
,
M.
, &
Nyberg
,
L.
(
2004
).
Task-independent and task-specific age effects on brain activity during working memory, visual attention, and episodic retrieval.
Cerebral Cortex
,
14
,
364
375
.
Cabeza
,
R.
,
Grady
,
C. L.
,
Nyberg
,
L.
,
McIntosh
,
A. R.
,
Tulving
,
E.
,
Kapur
,
S.
,
et al
(
1997
).
Age-related differences in neural activity during memory encoding and retrieval: A positron emission tomography study.
Journal of Neuroscience
,
17
,
391
400
.
Cabeza
,
R.
,
Locantore
,
J. K.
, &
Anderson
,
N. D.
(
2003
).
Lateralization of prefrontal activity during episodic memory retrieval: Evidence for the production-monitoring hypothesis.
Journal of Cognitive Neuroscience
,
15
,
249
259
.
Cabeza
,
R.
, &
Nyberg
,
L.
(
2000
).
Imaging cognition II: An empirical review of 275 PET and fMRI studies.
Journal of Cognitive Neuroscience
,
12
,
1
47
.
Chalfonte
,
B. L.
, &
Johnson
,
M. K.
(
1996
).
Feature memory and binding in young and older adults.
Memory & Cognition
,
24
,
403
416
.
Chua
,
E. F.
,
Schacter
,
D. L.
,
Rand-Giovannetti
,
E.
, &
Sperling
,
R. A.
(
2007
).
Evidence for a specific role of the anterior hippocampal region in successful associative encoding.
Hippocampus
,
17
,
1071
1080
.
Craik
,
F. I. M.
(
1977
).
Age differences in human memory.
In J. E. Birren & K. W. Schaie (Eds.),
Handbook of psychology and aging
(3rd ed., pp.
384
420
).
New York
:
Van Nostrand Reinhold Company
.
Craik
,
F. I. M.
(
1986
).
A functional account of age differences in memory.
In F. Klix & H. Hagendorf (Eds.),
Human memory and cognitive capabilities, mechanisms, and performances
(pp.
409
422
).
North Holland, Netherlands
:
Elsevier
.
Craik
,
F. I. M.
, &
Byrd
,
M.
(
1982
).
Aging and cognitive deficits: The role of attentional resources.
In F. I. M. Craik & S. Trehub (Eds.),
Aging and cognitive processes
(pp.
199
211
).
New York
:
Plenum Press
.
Craik
,
F. I. M.
, &
Simon
,
E.
(
1980
).
Age differences in memory: The roles of attention and depth of processing.
In L. W. Poon, J. L. Fozard, L. S. Cermak, D. Arenberg, & L. W. Thompson (Eds.),
New directions in memory and aging: Procedures of the George A. Talland Memorial Conference
(pp.
95
112
).
Hillsdale, NJ
:
Lawrence Erlbaum Associates
.
Daselaar
,
S. M.
,
Fleck
,
M. S.
,
Dobbins
,
I. G.
,
Madden
,
D. J.
, &
Cabeza
,
R.
(
2006
).
Effects of healthy aging on hippocampal and rhinal memory functions: An event-related fMRI study.
Cerebral Cortex
,
16
,
1771
1782
.
Daselaar
,
S. M.
,
Veltman
,
D. J.
,
Rombouts
,
S. A.
,
Raaijmakers
,
J. G.
, &
Jonker
,
C.
(
2003
).
Deep processing activates the medial temporal lobe in young but not in older adults.
Neurobiology of Aging
,
24
,
1005
1011
.
Davachi
,
L.
, &
Wagner
,
A. D.
(
2002
).
Hippocampal contributions to episodic encoding: Insights from relational and item-based learning.
Journal of Neurophysiology
,
88
,
982
990
.
Davis
,
S. W.
,
Dennis
,
N. A.
,
Daselaar
,
S. M.
,
Fleck
,
M. S.
, &
Cabeza
,
R.
(
2008
).
Qué PASA? The posterior-anterior shift in aging.
Cerebral Cortex
,
18
,
1201
1209
.
Denney
,
N. W.
,
Dew
,
J. R.
, &
Kihlstrom
,
J. F.
(
1992
).
An adult developmental study of the encoding of spatial location.
Experimental Aging Research
,
18
,
25
32
.
Dennis
,
N. A.
,
Hayes
,
S. M.
,
Prince
,
S. E.
,
Madden
,
D. J.
,
Huettel
,
S. A.
, &
Cabeza
,
R.
(
2008
).
Effects of aging on the neural correlates of successful item and source memory encoding.
Journal of Experimental Psychology: Learning, Memory, and Cognition
,
34
,
791
808
.
Dennis
,
N. A.
,
Kim
,
H.
, &
Cabeza
,
R.
(
2008
).
Age-related differences in brain activity during true and false memory retrieval.
Journal of Cognitive Neuroscience
,
20
,
1390
1402
.
Dew
,
I. T. Z.
, &
Giovanello
,
K. S.
(
2010
).
Differential age effects for implicit and explicit associative memory.
Psychology and Aging
,
25
,
911
921
.
Dobbins
,
I. G.
,
Foley
,
H.
,
Schacter
,
D. L.
, &
Wagner
,
A. D.
(
2002
).
Executive control during episodic retrieval: Multiple prefrontal processes subserve source memory.
Neuron
,
35
,
989
996
.
Dodson
,
C. S.
, &
Schacter
,
D. L.
(
2002
).
Aging and strategic retrieval processes: Reducing false memories with a distinctiveness heuristic.
Psychology and Aging
,
17
,
405
415
.
Eichenbaum
,
H.
, &
Cohen
,
N. J.
(
2001
).
From conditioning to conscious recollection: Memory systems of the brain.
New York
:
Oxford University Press
.
Eichenbaum
,
H.
,
Yonelinas
,
A. P.
, &
Ranganath
,
C.
(
2007
).
The medial temporal lobe and recognition memory.
Annual Review of Neuroscience
,
30
,
123
152
.
Fisher
,
R. A.
(
1950
).
Statistical methods for research workers.
London
:
Oliver and Boyd
.
Fletcher
,
P. C.
,
Shallice
,
T.
, &
Dolan
,
R. J.
(
2000
).
“Sculpting the response space“—An account of left prefrontal activation at encoding.
Neuroimage
,
12
,
404
417
.
Gabrieli
,
J. D.
,
Poldrack
,
R. A.
, &
Desmond
,
J. E.
(
1998
).
The role of left prefrontal cortex in language and memory.
Proceedings of the National Academy of Sciences, U.S.A.
,
95
,
906
913
.
Giovanello
,
K. S.
,
Kensinger
,
E. A.
,
Wong
,
A. T.
, &
Schacter
,
D. L.
(
2010
).
Age-related neural changes during memory conjunction errors.
Journal of Cognitive Neuroscience
,
22
,
1348
1361
.
Giovanello
,
K. S.
,
Schnyer
,
D. M.
, &
Verfaellie
,
M.
(
2004
).
A critical role for the anterior hippocampus in relational memory: Evidence from an fMRI study comparing associative and item recognition.
Hippocampus
,
14
,
5
8
.
Giovanello
,
K. S.
,
Schnyer
,
D. M.
, &
Verfaellie
,
M.
(
2009
).
Distinct hippocampal regions make unique contributions to relational memory.
Hippocampus
,
19
,
111
117
.
Glisky
,
E. L.
,
Rubin
,
S. R.
, &
Davidson
,
P. S.
(
2001
).
Source memory in older adults: An encoding or retrieval problem?
Journal of Experimental Psychology: Learning, Memory, and Cognition
,
27
,
1131
1146
.
Grady
,
C.
(
2002
).
Age-related differences in face processing: A meta-analysis of three functional neuroimaging experiments.
Canadian Journal of Experimental Psychology
,
56
,
208
220
.
Grady
,
C.
(
2008
).
Cognitive neuroscience of aging.
Annals of the New York Academy of Sciences
,
1124
,
127
144
.
Gunning-Dixon
,
F. M.
, &
Raz
,
N.
(
2003
).
Neuroanatomical correlates of selected executive functions in middle-aged and older adults: A prospective MRI study.
Neuropsychologia
,
4
,
1929
1941
.
Gutchess
,
A. H.
,
Welsh
,
R. C.
,
Hedden
,
T.
,
Bangert
,
A.
,
Minear
,
M.
,
Liu
,
L. L.
,
et al
(
2005
).
Aging and the neural correlates of successful picture encoding: Frontal activations compensate for decreased medial-temporal activity.
Journal of Cognitive Neuroscience
,
17
,
84
96
.
Hayes
,
S. M.
,
Ryan
,
L.
,
Schnyer
,
D. M.
, &
Nadel
,
L.
(
2004
).
An fMRI study of episodic memory: Retrieval of object, spatial, and temporal information.
Behavioral Neuroscience
,
118
,
885
896
.
Henke
,
K.
,
Weber
,
B.
,
Kneifel
,
S.
,
Wieser
,
H. G.
, &
Buck
,
A.
(
1999
).
Human hippocampus associates information in memory.
Proceedings of the National Academy of Sciences, U.S.A.
,
86
,
5884
5889
.
Henson
,
R. N.
,
Shallice
,
T.
, &
Dolan
,
R. J.
(
1999
).
Right prefrontal cortex and episodic memory retrieval: A functional MRI test of the monitoring hypothesis.
Brain
,
122
,
1367
1381
.
Henson
,
R. N.
,
Shallice
,
T.
,
Joseph
,
O.
, &
Dolan
,
R. J.
(
2002
).
Functional magnetic resonance imaging of proactive interference during cued recall.
Neuroimage
,
17
,
543
558
.
Hockley
,
W. A.
, &
Consoli
,
A.
(
1999
).
Familiarity and recollection in item and associative recognition.
Memory and Cognition
,
27
,
657
664
.
Hoyer
,
W. J.
, &
Verhaeghen
,
P.
(
2006
).
Memory aging.
In J. Birren & K. W. Schaie (Eds.),
Handbook of the psychology of aging
(6th ed., pp.
209
232
).
Amsterdam
:
Elsevier
.
Jackson
,
O.
, &
Schacter
,
D. L.
(
2004
).
Encoding activity in anterior medial temporal lobe supports subsequent associative recognition.
Neuroimage
,
21
,
456
462
.
Jacoby
,
L. L.
, &
Rhodes
,
M. G.
(
2006
).
False remembering in the aged.
Current Directions in Psychological Science
,
15
,
49
53
.
Jennings
,
J. M.
, &
Jacoby
,
L. L.
(
1993
).
Automatic versus intentional uses of memory: Aging, attention, and control.
Psychology and Aging
,
8
,
283
293
.
Johnson
,
M. K.
,
Hashtroudi
,
S.
, &
Lindsay
,
D. S.
(
1993
).
Source monitoring.
Psychological Bulletin
,
114
,
3
28
.
Kausler
,
D. H.
, &
Puckett
,
J. M.
(
1981
).
Adult age differences in memory for sex of voice.
Journal of Gerontology
,
36
,
44
50
.
Koutstaal
,
W.
, &
Schacter
,
D. L.
(
1997
).
Gist-based false recognition of pictures in older and younger adults.
Journal of Memory and Language
,
37
,
555
583
.
Lazar
,
N. A.
,
Luna
,
B.
,
Sweeney
,
J. A.
, &
Eddy
,
W. F.
(
2002
).
Combining brains: A survey of methods for statistical pooling of information.
Neuroimage
,
16
,
538
550
.
Lepage
,
M.
,
Habib
,
R.
,
Cormier
,
H.
,
Houle
,
S.
, &
McIntosh
,
A. R.
(
2000
).
Neural correlates of semantic associative encoding in episodic memory.
Cognitive Brain Research
,
9
,
271
280
.
Light
,
L. L.
,
Prull
,
M. W.
,
LaVoie
,
D. J.
, &
Healy
,
M. R.
(
2000
).
Dual-process theories of memory in old age.
In T. J. Perfect & E. A. Maylor (Eds.),
Models of cognitive aging
(pp.
238
300
).
New York
:
Oxford University Press
.
Lyle
,
K. B.
,
Bloise
,
S. Z.
, &
Johnson
,
M. K.
(
2006
).
Age-related biding deficits and the content of false memories.
Psychology and Aging
,
21
,
86
95
.
McIntyre
,
J. S.
, &
Craik
,
F. I. M.
(
1987
).
Age differences in memory for item and source information.
Canadian Journal of Psychology
,
4
,
175
192
.
Mitchell
,
K. J.
,
Johnson
,
M. K.
,
Raye
,
C. L.
, &
D'Esposito
,
M.
(
2000
).
fMRI evidence of age-related hippocampal dysfunction in feature binding in working memory.
Brain Research, Cognitive Brain Research
,
10
,
197
206
.
Moscovitch
,
M.
(
1992
).
Memory and working-with-memory: A component process model based on modules central systems.
Journal of Cognitive Neuroscience
,
4
,
257
267
.
Moscovitch
,
M.
, &
Winocur
,
G.
(
1995
).
Frontal lobes, memory, and aging.
Annals of the New York Academy of Sciences
,
769
,
119
150
.
Mottaghy
,
F. M.
,
Shah
,
N. J.
,
Krause
,
B. J.
,
Schmidt
,
D.
,
Halsband
,
U.
,
Jancke
,
L.
,
et al
(
1999
).
Neuronal correlates of encoding and retrieval in episodic memory during a paired-word association learning task: A functional magnetic resonance imaging study.
Experimental Brain Research
,
128
,
332
342
.
Murray
,
L. J.
, &
Ranganath
,
C.
(
2007
).
The dorsolateral prefrontal cortex contributes to successful relational memory encoding.
Journal of Neuroscience
,
27
,
5515
5522
.
Naveh-Benjamin
,
M.
(
2000
).
Adult-age differences in memory performance: Tests of an associative deficit hypothesis.
Journal of Experimental Psychology: Learning, Memory, and Cognition
,
26
,
1170
1187
.
Nolde
,
S. F.
,
Johnson
,
M. K.
, &
D'Esposito
,
M. E.
(
1998
).
Left prefrontal activation during episodic remembering: An event-related fMRI study.
NeuroReport
,
9
,
3509
3514
.
Old
,
S. R.
, &
Naveh-Benjamin
,
M.
(
2008
).
Differential effects of age on item and associative measures of memory: A meta-analysis.
Psychology and Aging
,
23
,
104
118
.
Paller
,
K. A.
, &
Wagner
,
A. D.
(
2002
).
Observing the transformation of experience into memory.
Trends in Cognitive Science
,
6
,
93
102
.
Park
,
D.
, &
Reuter-Lorenz
,
P.
(
2009
).
Human neuroscience and the aging mind: A new look at old problems.
Journal of Gerontology, Series B, Psychological Science and Social Science
,
65
,
405
415
.
Park
,
D. C.
,
Polk
,
T. A.
,
Park
,
R.
,
Minear
,
M.
,
Savage
,
A.
, &
Smith
,
M. R.
(
2004
).
Aging reduces neural specialization in ventral visual cortex.
Proceedings of the National Academy of Sciences, U.S.A.
,
101
,
13091
13095
.
Park
,
D. C.
,
Puglisi
,
J. T.
, &
Lutz
,
R.
(
1982
).
Spatial memory in older adults: Effects of intentionality.
Journal of Gerontology
,
37
,
582
588
.
Park
,
D. C.
,
Puglisi
,
J. T.
, &
Sovacool
,
M.
(
1983
).
Memory for pictures, words, and spatial locations in older adults: Evidence for pictorial superiority.
Journal of Gerontology
,
38
,
582
588
.
Payer
,
D.
,
Marshuetz
,
C.
,
Sutton
,
B.
,
Hebrank
,
A.
,
Welsh
,
R. C.
, &
Park
,
D. C.
(
2006
).
Decreased neural specialization in old adults on a working memory task.
NeuroReport
,
17
,
487
491
.
Persson
,
J.
,
Nyberg
,
L.
,
Lind
,
J.
,
Larsson
,
A.
,
Nilsson
,
L. G.
,
Ingvar
,
M.
,
et al
(
2006
).
Structure-function correlates of cognitive decline in aging.
Cerebral Cortex
,
16
,
907
915
.
Pfefferbaum
,
A.
,
Sullivan
,
E. V.
,
Rosenbloom
,
M. J.
,
Mathalon
,
D. H.
, &
Lim
,
K. O.
(
1998
).
A controlled study of cortical gray matter and ventricular changes in alcoholic men over a 5-year interval.
Archives of General Psychiatry
,
55
,
905
912
.
Pilotti
,
M.
,
Meade
,
M. L.
, &
Gallo
,
D. A.
(
2003
).
Implicit and explicit measures of memory for perceptual information in young adults, healthy older adults, and patients with Alzheimer's disease.
Experimental Aging Research
,
29
,
15
32
.
Prince
,
S. E.
,
Daselaar
,
S. M.
, &
Cabeza
,
R.
(
2005
).
Neural correlates of relational memory: Successful encoding and retrieval of semantic and perceptual associations.
Journal of Neuroscience
,
25
,
1203
1210
.
Ranganath
,
C.
(
2010
).
Binding items and contexts: The cognitive neuroscience of episodic memory.
Current Directions in Psychological Science
,
19
,
131
137
.
Ranganath
,
C.
,
Johnson
,
M. K.
, &
D'Esposito
,
M.
(
2000
).
Left anterior prefrontal activation increases with demands to recall specific perceptual information.
Journal of Neuroscience
,
20
,
RC108
.
Raz
,
N.
,
Lindenberger
,
U.
,
Rodrigue
,
K. M.
,
Kennedy
,
K. M.
,
Head
,
D.
,
Williamson
,
A.
,
et al
(
2005
).
Regional brain changes in aging healthy adults: General trends, individual differences and modifiers.
Cerebral Cortex
,
15
,
1676
1689
.
Resnick
,
S. M.
,
Pham
,
D. L.
,
Kraut
,
M. A.
,
Zonderman
,
A. B.
, &
Davatzikos
,
C.
(
2003
).
Longitudinal magnetic resonance imaging studies of older adults: A shrinking brain.
Journal of Neuroscience
,
23
,
3295
3301
.
Rodrigue
,
K. M.
, &
Raz
,
N.
(
2004
).
Shrinkage of the entorhinal cortex over five years predicts memory performance in healthy adults.
Journal of Neuroscience
,
24
,
956
963
.
Rugg
,
M. D.
,
Fletcher
,
P. C.
,
Chua
,
P. M. L.
, &
Dolan
,
R. J.
(
1999
).
The role of the prefrontal cortex in recognition memory and memory for source: An fMRI study.
Neuroimage
,
10
,
520
529
.
Ryan
,
J. D.
,
Leung
,
G.
,
Turk-Browne
,
N. B.
, &
Hasher
,
L.
(
2007
).
Assessment of age-related inhibition and binding using eye-movement monitoring.
Psychology and Aging
,
22
,
239
250
.
Schacter
,
D. L.
,
Gallo
,
D. A.
, &
Kensinger
,
E. A.
(
2007
).
The cognitive neuroscience of implicit and false memories: Perspectives on processing specificity.
In J. S. Nairne (Ed.),
The foundations of remembering: Essays in honor of Henry L. Roediger III
(pp.
353
378
).
New York
:
Psychology Press
.
Schacter
,
D. L.
,
Kaszniak
,
A. W.
,
Kihlstrom
,
J. F.
, &
Valdiserri
,
M.
(
1991
).
The relation between source memory and aging.
Psychology and Aging
,
6
,
559
568
.
Siedlecki
,
K. L.
,
Salthouse
,
T. A.
, &
Berish
,
D. E.
(
2005
).
Is there anything special about the aging of source memory?
Psychology and Aging
,
20
,
19
32
.
Simons
,
J. S.
,
Dodson
,
C. S.
,
Bell
,
D.
, &
Schacter
,
D. L.
(
2004
).
Specific and partial source memory: Effects of aging.
Psychology and Aging
,
19
,
689
694
.
Smith
,
A. D.
,
Park
,
D. C.
,
Earles
,
J. L. K.
,
Shaw
,
R. J.
, &
Whiting
,
W. L.
(
1998
).
Age differences in context integration in memory.
Psychology and Aging
,
13
,
21
28
.
Spencer
,
W. D.
, &
Raz
,
N.
(
1995
).
Differential effects of aging on memory for content and context: A meta-analysis.
Psychology and Aging
,
10
,
527
539
.
Sperling
,
R. A.
,
Bates
,
J. A.
,
Cocchiarella
,
A. J.
,
Schacter
,
D. L.
,
Rosen
,
B. R.
, &
Albert
,
M. S.
(
2001
).
Encoding novel face-name associations: A functional MRI study.
Human Brain Mapping
,
14
,
129
139
.
Sperling
,
R. A.
,
Chua
,
E.
,
Cocchiarella
,
A.
,
Rand-Giovannetti
,
E.
,
Poldrack
,
R.
,
Schacter
,
D. L.
,
et al
(
2003
).
Putting names to faces: Successful encoding of associative memories activates the anterior hippocampus.
Neuroimage
,
20
,
1400
1410
.
Tulving
,
E.
(
1983
).
Elements of episodic memory.
Oxford, UK
:
Clarendon Press
.
Velanova
,
K.
,
Jacoby
,
L. L.
,
Wheeler
,
M. E.
,
McAvoy
,
M. P.
,
Peterson
,
S. E.
, &
Buckner
,
R. L.
(
2003
).
Functional-anatomic correlates of sustained and transient processing components engaged during controlled retrieval.
The Journal of Neuroscience
,
23
,
8460
8470
.
Yonelinas
,
A. P.
,
Hopfinger
,
J. B.
,
Buonocore
,
M. H.
,
Kroll
,
N. E. A.
, &
Baynes
,
K.
(
2001
).
Hippocampal, parahippocampal, and occipital-temporal contributions to associative and item recognition memory: An fMRI study.
NeuroReport
,
12
,
359
363
.
Yonelinas
,
A. P.
,
Widaman
,
K.
,
Mungas
,
D.
,
Reed
,
B.
,
Weiner
,
M. W.
, &
Chui
,
H. C.
(
2007
).
Memory in the aging brain: Doubly dissociating the contribution of the hippocampus and entorhinal cortex.
Hippocampus
,
17
,
1134
1140
.