M. Natasha Rajah

Age-related changes in prefrontal cortex activity are associated with behavioural deficits in both temporal and spatial context memory retrieval in older adults

Aging is associated with decrements in both spatial and temporal context retrieval. Functional neuroimaging studies of young adults suggest that there are differences in left versus right lateral prefrontal cortex (PFC) contributions to spatial versus temporal source (recency) retrieval, respectively. The goal of the current study was to determine if age-related decreases in temporal and spatial context retrieval are due to common or distinct changes in PFC function. To address this goal we conducted an event-related functional magnetic resonance imaging (fMRI) study in which young and older adults performed recognition, recency and spatial context retrieval tasks using face stimuli to identify event-related PFC regions associated with these retrieval tasks in both age groups. Our behavioural results indicated that older adults did not differ on recognition performance, but did exhibit a deficit in both context retrieval tasks, compared to young adults. The fMRI results suggest that age-related deficits in both spatial and temporal context retrieval may be linked to functional changes in right dorsolateral and left medial anterior PFC (APFC) function. In addition, based on brain-behaviour correlations in older adults, our results imply that older adults attempt to compensate for these deficits by engaging left dorsolateral PFC during spatial context retrieval and right APFC during temporal context retrieval.

Group differences in anterior hippocampal volume and in the retrieval of spatial and temporal context memory in healthy young versus older adults

The ability to retrieve temporal and spatial context information from memory declines with healthy aging. The hippocampus (HC) has been shown to be associated with successful encoding and retrieval of spatio-temporal context, versus item recognition information (Davachi, Mitchell, & Wagner, 2003; Nadel, Samsonovich, Ryan, & Moscovitch, 2000; Ross & Slotnick, 2008). Aging has been linked to volume reduction in the HC (Bouchard, Malykhin, Martin, Hanstock, Emery, Fisher, & Camicioli, 2008; Malykhin, Bouchard, Camicioli, & Coupland, 2008; Raz et al., 2005). As such, age-associated reductions in anterior HC volume may contribute to the context memory deficits observed in older adults. In the current MRI study we investigated whether item recognition, spatial context and temporal context memory performance would be predicted by regional volumes in HC head (HH), body (HB) and tail (HT) volumes, using within group multiple regression analyses in a sample of 19 healthy young (mean age 24.3) and 20 older adults (mean age 67.7). We further examined between age-group differences in the volumes of the same HC sub-regions. Multiple regression analyses revealed that in younger adults both spatial and temporal context retrieval performance was predicted by anterior HC volume. Older age was associated with significant volume reductions in HH and HB, but not HT; and with reduced ability to retrieve spatial and temporal contextual details from episodic memory. However, HC volumes did not predict context retrieval performance in older adults. We conclude that individual differences in anterior, not posterior, HC volumes predict context memory performance in young adults. With age there may be a posterior-to-anterior shift from using HC-related processes, due to HC volume loss, to employing the prefrontal cortex to aid in the performance of cognitively demanding context memory tasks. However, due to concomitant changes in the prefrontal system with age, there are limits to compensation in the aging brain.

Age-related differences in brain activity in the subsequent memory paradigm: A meta-analysis

Healthy aging is associated with declines in episodic memory. This reduction is thought to be due in part to age-related differences in encoding-related processes. In the current study, we performed an activation likelihood estimation meta-analysis of functional magnetic resonance imaging (fMRI) studies assessing age-related differences in the neural correlates of episodic encoding. Only studies using the subsequent memory paradigm were included. We found age-related under-recruitment of occipital and fusiform cortex, but over-recruitment in a set of regions including bilateral middle/superior frontal gyri, anterior medial frontal gyrus, precuneus and left inferior parietal lobe. We demonstrate that all of the regions consistently over-recruited by older adults during successful encoding exhibit either direct overlap, or occur in close vicinity to regions consistently involved in unsuccessful encoding in young adults. We discuss the possibility that this overall pattern of age-related differences represents an age-related shift in focus: away from perceptual details, and toward evaluative and personal thoughts and feelings during memory tasks. We discuss whether these age-related differences in brain activation benefit performance in older adults, and additional considerations.

Association between prefrontal activity and volume change in prefrontal and medial temporal lobes in aging and dementia: A review

Functional neuroimaging studies have consistently reported age-related changes in prefrontal cortex (PFC) activity during a variety of cognitive tasks, including episodic memory. These changes are often interpreted within the context of one of the following three neural models of age-related changes in brain function: dedifferentiation, neural inefficiency, and neural plasticity and compensation models. Distinguishing between these competing models has proven difficult when interpreting results using functional imaging data alone. In this paper we suggest that a more accurate interpretation of age-related changes in PFC activity requires consideration of age-related differences in gray matter volume (GMv) in PFC and the medial temporal lobes (MTL). We review fMRI studies of cognitive aging that have directly examined the relationship between PFC activity and both local (PFC) and distal (MTL) GMv in older versus younger adults. We also considered how structure-function relationships may be further modified in pathological aging (i.e. mild cognitive impairment (MCI) and Alzheimers disease (AD)). We found that when task performance was matched between age-groups there was a negative association between regional PFC volume and activity in older adults. However, when older adults performed worse than young adults we observed a positive association between volume and activity in right lateral PFC. Additionally during memory tasks, several studies revealed that PFC activity is positively related to GM volume in MTL in healthy older adults, but negatively related in MCI and AD patients. We conclude that PFC activity is related to age-related changes in local and distal GM volume reductions and that consideration of these structural measures aids the interpretation of fMRI results. Furthermore, the study of structure-function relationships may provide important insights into the biological mechanisms underlying healthy versus pathological aging.

Prefrontal contributions to domain-general executive control processes during temporal context retrieval

Neuroimaging studies have reported increased prefrontal cortex (PFC) activity during temporal context retrieval versus recognition memory. However, it remains unclear if these activations reflect PFC contributions to domain-general executive control processes or domain-specific retrieval processes. To gain a better understanding of the functional roles of these various PFC regions during temporal context retrieval we propose it is necessary to examine PFC activity across tasks from different domains, in which parallel manipulations are included targeting specific cognitive processes. In the current fMRI study, we examined domain-general and domain-specific PFC contributions to temporal context retrieval by increasing stimulus (but maintaining response number) and increasing response number (but maintaining stimulus number) across temporal context memory and ordering control tasks, for faces. The control task required subjects to order faces from youngest to oldest. Our behavioral results indicate that the combination of increased stimulus and response numbers significantly increased task difficulty for temporal context retrieval and ordering tasks. Across domains, increasing stimulus number, while maintaining response numbers, caused greater right lateral premotor cortex (BA 6/8) activity; whereas increasing response number, while maintaining stimulus number, caused greater domain-general left DLPFC (BA 9) and VLPFC (BA 44/45) activity. In addition, we found domain-specific right DLPFC (BA 9) activity only during retrieval events. These results highlight the functional heterogeneity of frontal cortex, and suggest its involvement in temporal context retrieval is related to its role in various cognitive control processes.

Age-related changes in frequency of mind-wandering and task-related interferences during memory encoding and their impact on retrieval

During the performance of cognitive tasks such as memory encoding, attention can become decoupled from the external environment and instead focused on internal thoughts related to the appraisal of the current task (task-related interferences; TRI), or personal thoughts unrelated to the task at hand (mind-wandering; MW). However, the association between the frequency of these thoughts experienced at encoding and retrieval accuracy in young and older adults remains poorly understood. In this study young and older adults encoded lists of words using one of two encoding tasks: judging whether words are man-made/natural (objective task), or whether they are pleasant/neutral (subjective task). We measured the frequency of TRI and MW at encoding, and related them to retrieval accuracy in both age groups. We found that encoding task influenced the type of internal thoughts experienced by young, but not older, adults: young exhibited greater MW in the subjective vs the objective task, and greater TRI in the objective vs subjective encoding task. Second, across both tasks we found marked age-related decreases in both MW and TRI at encoding, and frequency of these thoughts negatively impacted memory retrieval in young adults only. We discuss these findings in relation to current theories of ageing, attention and memory.

Dissociable roles of default-mode regions during episodic encoding

We investigated the role of distinct regions of the default-mode network (DMN) during memory encoding with fMRI. Subjects encoded words using either a strategy that emphasized self-referential (pleasantness) processing, or one that emphasized semantic (man-made/natural) processing. During encoding subjects were intermittently presented with thought probes to evaluate if they were concentrated and on-task or exhibiting task-unrelated thoughts (TUT). After the scanning session subjects performed a source retrieval task to determine which of two judgments they performed for each word at encoding. Source retrieval accuracy was higher for words encoded with the pleasantness vs. the man-made/natural task and there was a trend for higher performance for words preceding on-task vs. TUT reports. fMRI results show that left anterior medial PFC and left angular gyrus activity was greater during successful vs. unsuccessful encoding during both encoding tasks. Greater activity in left anterior cingulate and bilateral lateral temporal cortex was related successful vs. unsuccessful encoding only in the pleasantness task. In contrast, posterior cingulate, right anterior cingulate and right temporoparietal junction were activated to a greater extent in unsuccessful vs. successful encoding across tasks. Finally, activation in posterior cingulate and bilateral dorsolateral prefrontal cortex was related to TUT across tasks; moreover, we observed a conjunction in posterior cingulate between encoding failure and TUT. We conclude that DMN regions play dissociable roles during memory formation, and that their association with subsequent memory may depend on the manner in which information is encoded and retrieved.

Context Memory Decline in Middle Aged Adults is Related to Changes in Prefrontal Cortex Function

The ability to encode and retrieve spatial and temporal contextual details of episodic memories (context memory) begins to decline at midlife. In the current study, event-related fMRI was used to investigate the neural correlates of context memory decline in healthy middle aged adults (MA) compared with young adults (YA). Participants were scanned while performing easy and hard versions of spatial and temporal context memory tasks. Scans were obtained at encoding and retrieval. Significant reductions in context memory retrieval accuracy were observed in MA, compared with YA. The fMRI results revealed that overall, both groups exhibited similar patterns of brain activity in parahippocampal cortex, ventral occipito-temporal regions and prefrontal cortex (PFC) during encoding. In contrast, at retrieval, there were group differences in ventral occipito-temporal and PFC activity, due to these regions being more activated in MA, compared with YA. Furthermore, only in YA, increased encoding activity in ventrolateral PFC, and increased retrieval activity in occipital cortex, predicted increased retrieval accuracy. In MA, increased retrieval activity in anterior PFC predicted increased retrieval accuracy. These results suggest that there are changes in PFC contributions to context memory at midlife.

Age-related changes in the three-way correlation between anterior hippocampus volume, whole-brain patterns of encoding activity and subsequent context retrieval.

Age-related declines in memory for context have been linked to volume loss in the hippocampal head (HH) with age. However, it remains unclear how this volumetric decline correlates with age-related changes in whole-brain activity during context encoding, and subsequent context retrieval. In the current study we examine this. We collected functional magnetic resonance imaging data in young and older adults during the encoding of item, spatial context and temporal context. HH volume and subsequent retrieval performance was measured in all participants. In young adults only there was a positive three-way correlation between larger HH volumes, better memory retrieval, and increased activity in right hippocampus, right ventrolateral prefrontal cortex (VLPFC) and midline brain regions during episodic encoding. In contrast, older adults exhibited a positive three-way association between HH volume, generalized activity in bilateral hippocampus and dorsolateral PFC across all encoding tasks, and subsequent spatial context retrieval. Young adults also engaged this network, but only during the most difficult temporal context encoding task and activity in this network correlated with subsequent temporal context retrieval. We conclude that age-related volumetric reductions in HH disrupted the structure-function association between the hippocampus and activity in the first general encoding network recruited by young adults. Instead, older adults recruited those brain regions young adults only engaged for the most difficult temporal task, at lower difficulty levels. This altered pattern of association correlated with spatial context retrieval in older adults, but was not sufficient to maintain context memory abilities overall.

Similarities in the patterns of prefrontal cortex activity during spatial and temporal context memory retrieval after equating for task structure and performance.

Event-related functional magnetic resonance imaging was used to assess healthy adults while they performed spatial and temporal context memory tasks matched in task structure. After equating task structure between spatial versus temporal context tasks, subjects reported using similar strategies across tasks and we observed no significant differences in accuracy and reaction time performance between tasks. We used three methods of statistical analysis to interrogate similarities and differences in whole-brain activity across retrieval tasks, while focussing on prefrontal cortex (PFC) activations: multivariate partial least squares analysis (PLS), univariate statistical parametric mapping (SPM) and conjunction analysis. The PLS and conjunction analyses indicated that the overall pattern of PFC activity was similar across both temporal and spatial context retrieval tasks; but the SPM results indicated that some of these PFC regions exhibited differences in the degree to which they were engaged between tasks. However, none of these methods identified unique PFC activations specific to mediating spatial and/or temporal context retrieval. These results indicate that, overall, similar patterns of PFC activity were observed during temporal and spatial context memory retrieval once task structure and performance were equated.