Reduced Specificity of Hippocampal and Posterior Ventrolateral Prefrontal Activity during Relational Retrieval in Normal Aging

Neuroimaging studies of episodic memory in young adults demonstrate greater functional neural activity in ventrolateral prefrontal cortex and hippocampus during retrieval of relational, as compared to 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, functional magnetic resonance images 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 depended on 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

Reduced Specificity of Hippocampal and Posterior Ventrolateral Prefrontal Activity during Relational Retrieval in Normal Aging

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.Psycholog

Neural evidence for age-related differences in representational quality and strategic retrieval processes.

Mounting behavioral evidence suggests that declines in both representational quality and controlled retrieval processes contribute to episodic memory decline with age. The present study sought neural evidence for age-related change in these factors by measuring neural differentiation during encoding of paired associates and changes in regional blood oxygenation level-dependent activity and functional connectivity during retrieval conditions that placed low (intact pairs) and high (recombined pairs) demands on controlled retrieval processes. Pattern similarity analysis revealed age-related declines in the differentiation of stimulus representations at encoding, manifesting as both reduced pattern similarity between closely related events and increased pattern similarity between distinct events. During retrieval, both groups increased recruitment of areas within the core recollection network when endorsing studied pairs, including the hippocampus and angular gyrus. In contrast, only younger adults increased recruitment of, and hippocampal connectivity with, lateral prefrontal regions during correct rejections of recombined pairs. These results provide evidence for age-related changes in representational quality and in the neural mechanisms supporting memory retrieval under conditions of high, but not low, control demand

The source of the associative deficit in aging: the role of attentional resources for processing relational information

Previous studies have proposed an associative deficit hypothesis, which attributes part of older adults' deficient episodic memory performance to their difficulty in creating cohesive episodes. According to the ADH, older adults show disproportionate deficits in relational memory (RM) relative to item memory (IM). The disproportionate RM deficit in older adults has been demonstrated with a variety of memory tasks, such as word-word, word-font, and face-name pairs. Despite rich evidence of an age-related RM deficit, the source of this deficit remains unspecified. One of the most widely investigated factors is the reduction in attentional resources in older adults. To investigate the effect of reduced attentional resources on RM performance, previous researchers have imposed a secondary task load on young adults during encoding of memory lists to divide attentional resources into two different tasks. However, none of the existing studies have found a disproportionate RM impairment in young adults under divided attention conditions. The current project investigated whether a reduction in attentional resources for relational processing underlies the memory impairments observed in aging. Using behavioral and functional neuroimaging techniques, I conducted three studies aimed at determining: 1) whether imposing a secondary task load for relational processing makes young adults' memory performance mimic the age-related RM deficit, and 2) whether the effect of reduced attentional resources for relational processing on RM is similar to the effect of aging at the neural level, using functional magnetic resonance imaging (fMRI). The results from the two behavioral studies indicate that a reduction in attentional resources for relational processing in young adults during encoding equates their performance in RM to that of older adults. Furthermore, the results from the fMRI study demonstrate that both aging and reductions in relational attention processing in young adults significantly reduced activity in the brain areas critical for RM formation, namely, the ventrolateral and dorsolateral PFC, superior and inferior parietal regions, and left hippocampus. This converging evidence from behavioral and neuroimaging studies thus documents the first evidence that the reduction in attentional resources for relational processing is the critical factor for the age-related RM deficit

Inter-individual differences in associative memory : structural and functional brain correlates and genetic modulators

Our memory for personal experiences (e.g., the first day at school) is termed episodic memory. This form of memory involves the recollection of single information as well as the connection between these pieces of information (e.g., what happened when, and where), referred to as associative memory. Associative memory declines markedly in aging; however, some individuals have proficient associative memory even until late life. These individual differences in associative-memory performance are also observable at younger ages. The underlying sources of these individual differences remain unclear. In this thesis, we aimed to identify the neural underpinnings of individual differences in associative memory, with special regard to brain structure, function, and neurochemistry. In the first part of the thesis, we investigated structural brain correlates of and dopaminergic contributions to associative memory in healthy older adults (studies I and II). In study I, we examined the relationship between regional gray-matter volume and associative memory. Individuals with better associative memory had larger gray-matter volume in dorsolateral and ventrolateral prefrontal cortex, suggesting that organizational and strategic processes distinguish older adults with good from those with poor associative memory. In study II, we examined the influence of dopamine (DA) receptor genes on item and associative memory. Individuals with less beneficial DA genotypes performed worse in the associative-memory task compared with carriers of more beneficial genotypes. Because no such group differences were found with regard to item memory, this suggests that dopaminergic neuromodulation is particularly important for associative memory in older adults. In the second part of the thesis, we examined in a sample of younger adults how different task instructions influence associative encoding, as well as the structural-functional coupling between task-relevant brain regions during associative-memory formation (studies III and IV). In study III, we investigated the effect of encoding instruction on associative memory. Specifically, we examined functional brain correlates of intentional and incidental encoding and demonstrated differential involvement of anterior hippocampus in intentional relative to incidental associative encoding. This suggests that the intent to remember associative information triggers a binding process accomplished by this brain region. Finally, in study IV we explored how gray-matter volume is associated with brain activity during associative-memory formation. We observed a relationship between gray-matter volume in the medial-temporal lobe (MTL) and functional brain activity in the inferior frontal gyrus (IFG). Importantly, this structure-function coupling correlated with performance, such that younger individuals with a stronger MTL-IFG coupling had better associative memory. Collectively, these four studies show that the neural underpinnings of individual differences in associative memory are many-faceted, interacting with each other and vary with regard to age and specific features of the associative task

Medial temporal lobe contributions to intra-item associative recognition memory in the aging brain

Aging is associated with a decline in episodic memory function. This is accompanied by degradation of and functional changes in the medial temporal lobe (MTL) which subserves mnemonic processing. To date no study has investigated age-related functional change in MTL substructures during specific episodic memory processes such as intra-item associative memory. The aim of this study was to characterize age-related change in the neural correlates of intra-item associative memory processing. Sixteen young and 10 older subjects participated in a compound word intra-item associative memory task comprising a measure of associative recognition memory and a measure of recognition memory. There was no difference in performance between groups on the associative memory measure but each group recruited different MTL regions while performing the task.The young group recruited the left anterior hippocampus and posterior parahippocampal gyrus whereas the older participants recruited the hippocampus bilaterally. In contrast, recognition memory was significantlyworse in the older subjects.The left anterior hippocampuswas recruited in the young group during successful recognition memory whereas the older group recruited a more posterior region of the left hippocampus and showed a more bilateral activation of frontal brain regions than was observed in the young group. Our results suggest a reorganization of the neural correlates of intra-item associative memory in the aging brain

Effects of healthy ageing on the precision of episodic memory

Episodic memory decline is one of the hallmarks of human cognitive ageing, but our understanding of the neurocognitive mechanisms underlying this decline remains limited. In particular, it is unclear whether healthy ageing differentially affects distinct components of episodic memory retrieval; specifically, the probability of successfully retrieving information from memory, and the quality, or precision, of the retrieved memory representations. The research reported in this PhD thesis used continuous measures of memory retrieval to dissociate these two alternative sources of age-related memory deficits and their cognitive and neural underpinnings, providing more detailed insight into the nature of age-related episodic memory decline. Two behavioural experiments reported in Chapter 2 provided initial evidence for differential effects of healthy ageing on the success and precision of episodic memory retrieval, suggesting greater sensitivity of mnemonic precision to age-related declines. Chapter 3 assessed whether these decreases in memory precision are specific to long-term memory or may be explained by age-related decreases in the fidelity of perceptual or working memory processes. The results from this experiment demonstrated that age-related reductions in the precision of episodic memory retrieval persisted after controlling for decreases in the fidelity of perception and working memory, suggesting a predominantly long-term memory basis for this deficit. The functional and structural magnetic resonance imaging experiments reported in Chapters 4 and 5 sought to elucidate the neural basis of age-related changes in the success and precision of episodic memory retrieval. Results from Chapter 4 revealed distinct encoding and retrieval contributions to the decreases in these two aspects of memory retrieval exhibited by older adults. At retrieval, age-related reductions in activity associated with successful memory retrieval were observed in the hippocampus, while decreases in activity underlying the precision of memory retrieval were evident in the angular gyrus. Furthermore, at encoding, age-related decreases in activity predicting both later success and precision of memory retrieval were evident in the fusiform gyrus, while prefrontal reductions were observed in the encoding activity predicting the subsequent success of memory retrieval only. In addition to these functional changes, Chapter 5 provided evidence for the role of structural integrity of the lateral parietal cortex in individual differences in mnemonic precision across older adults. Together, the results reported in this thesis highlight the sensitivity of memory precision to age-related cognitive decline, and suggest both distinct and common factors underlying age-related decreases in the success and precision of episodic memory retrieval

Age-related changes in overcoming proactive interference in associative memory: the role of VLPFC-mediated post-retrieval selection

Behavioral evidence has shown that older adults are less able to overcome proactive interference in memory than young adults. However, it is unclear what underlies this deficit. Imaging studies in the young suggest overcoming interference may require post-retrieval selection, a process thought to be mediated by the left mid-ventrolateral prefrontal cortex (VLPFC). Further, selection may resolve interference by enhancing or suppressing perceptual processing. The present fMRI study investigated whether age-related changes in VLPFC-mediated post-retrieval selection underlie older adults' deficits in overcoming interference in associative memory. Participants were tasked with remembering which associate (face or scene) objects were paired with most recently during study, under conditions of high or low proactive interference. Behavioral results demonstrated that as interference increased, memory performance decreased similarly across groups. Across groups, activity in the left mid-VLPFC also increased with interference. However, right PFC post-retrieval monitoring effects, but not left mid-VLPFC, distinguished successful vs. unsuccessful resolution of interference for both young and older adults, suggesting selection alone may be insufficient for successful resolution of interference. Age-related memory deficits may be related to reduced recruitment of relational processing effects in the dorsolateral and anterior PFC, as well as reduced memory retrieval effects in the hippocampus. Lastly, results showed evidence that selection may modulate perceptual processing of retrieved memory representations. Namely, activity in the parahippocampal place area (PPA) was greater when participants selected scene, versus face, regardless of accuracy. Further, older adults showed reduced effects in the PPA, possibly reflecting reduced differentiation of perceptual processing. Taken together, these results suggest age-related deficits in overcoming proactive interference are not related to post-retrieval selection, but reduced recruitment of PFC-mediated relational processes, coupled with reduced associative memory retrieval.Ph.D

Event-Related Functional Magnetic Resonance Imaging Changes during Relational Retrieval in Normal Aging and Amnestic Mild Cognitive Impairment

Abstract The earliest cognitive deficits observed in amnestic mild cognitive impairment (aMCI) appear to center on memory tasks that require relational memory (RM), the ability to link or integrate unrelated pieces of information. RM impairments in aMCI likely reflect neural changes in the medial temporal lobe (MTL) and posterior parietal cortex (PPC). We tested the hypothesis that individuals with aMCI, as compared to cognitively normal (CN) controls, would recruit neural regions outside of the MTL and PPC to support relational memory. To this end, we directly compared the neural underpinnings of successful relational retrieval in aMCI and CN groups, using event-related functional magnetic resonance imaging (fMRI), holding constant the stimuli and encoding task. The fMRI data showed that the CN, compared to the aMCI, group activated left precuneus, left angular gyrus, right posterior cingulate, and right parahippocampal cortex during relational retrieval, while the aMCI group, relative to the CN group, activated superior temporal gyrus and supramarginal gyrus for this comparison. Such findings indicate an early shift in the functional neural architecture of relational retrieval in aMCI, and may prove useful in future studies aimed at capitalizing on functionally intact neural regions as targets for treatment and slowing of the disease course. (JINS, 2012, 18, 886-897