Dissociative Effects of Age on Neural Differentiation at the Category and Item Levels.

Increasing age is associated with age-related neural dedifferentiation, a reduction in the selectivity of neural representations, which has been proposed to contribute to cognitive decline in older age. Recent findings indicate that when operationalized in terms of selectivity for different perceptual categories, age-related neural dedifferentiation and the apparent age-invariant association of neural selectivity with cognitive performance are largely restricted to the cortical regions typically recruited during scene processing. It is currently unknown whether this category-level dissociation extends to metrics of neural selectivity defined at the level of individual stimulus items. Here, we examined neural selectivity at the category and item levels using multivoxel pattern similarity analysis (PSA) of fMRI data. Healthy young and older male and female adults viewed images of objects and scenes. Some items were presented singly, while others were either repeated or followed by a "similar lure." In agreement with recent findings, category-level PSA revealed robustly lower differentiation in older than in younger adults in scene-selective, but not object-selective, cortical regions. By contrast, at the item level, robust age-related declines in neural differentiation were evident for both stimulus categories. Additionally, we identified an age-invariant association between category-level scene selectivity in the parahippocampal place area and subsequent memory performance, but no such association was evident for item-level metrics. Lastly, category- and item-level neural metrics were uncorrelated. Thus, the present findings suggest that age-related category- and item-level dedifferentiation depend on distinct neural mechanisms.

Dissociative effects of age on neural differentiation at the category and item level.

Increasing age is associated with age-related neural dedifferentiation, a reduction in the selectivity of neural representations which has been proposed to contribute to cognitive decline in older age. Recent findings indicate that when operationalized in terms of selectivity for different perceptual categories, age-related neural dedifferentiation, and the apparent age-invariant association of neural selectivity with cognitive performance, are largely restricted to the cortical regions typically recruited during scene processing. It is currently unknown whether this category-level dissociation extends to metrics of neural selectivity defined at the level of individual stimulus items. Here, we examined neural selectivity at the category and item levels using multivoxel pattern similarity analysis (PSA) of fMRI data. Healthy young and older male and female adults viewed images of objects and scenes. Some items were presented singly, while others were either repeated or followed by a 'similar lure'. Consistent with recent findings, category-level PSA revealed robustly lower differentiation in older than younger adults in scene-selective, but not object-selective, cortical regions. By contrast, at the item level, robust age-related declines in neural differentiation were evident for both stimulus categories. Moreover, we identified an age-invariant association between category-level scene-selectivity in the parahippocampal place area and subsequent memory performance, but no such association was evident for item-level metrics. Lastly, category and item-level neural metrics were uncorrelated. Thus, the present findings suggest that age-related category- and item-level dedifferentiation depend on distinct neural mechanisms.

Cortical thickness, gray matter volume, and cognitive performance: a crosssectional study of the moderating effects of age on their interrelationships.

In a sample comprising younger, middle-aged, and older cognitively healthy adults (N = 375), we examined associations between mean cortical thickness, gray matter volume (GMV), and performance in 4 cognitive domains-memory, speed, fluency, and crystallized intelligence. In almost all cases, the associations were moderated significantly by age, with the strongest associations in the older age group. An exception to this pattern was identified in a younger adult subgroup aged <23 years when a negative association between cognitive performance and cortical thickness was identified. Other than for speed, all associations between structural metrics and performance in specific cognitive domains were fully mediated by mean cognitive ability. Cortical thickness and GMV explained unique fractions of the variance in mean cognitive ability, speed, and fluency. In no case, however, did the amount of variance jointly explained by the 2 metrics exceed 7% of the total variance. These findings suggest that cortical thickness and GMV are distinct correlates of domain-general cognitive ability, that the strength and, for cortical thickness, the direction of these associations are moderated by age, and that these structural metrics offer only limited insights into the determinants of individual differences in cognitive performance across the adult lifespan.

The Retrieval-Related Anterior Shift Is Moderated by Age and Correlates with Memory Performance.

Recent research suggests that episodic memory is associated with systematic differences in the localization of neural activity observed during memory encoding and retrieval. The retrieval-related anterior shift is a phenomenon whereby the retrieval of a stimulus event (e.g., a scene image) is associated with a peak neural response which is localized more anteriorly than the response elicited when the stimulus is experienced directly. Here, we examine whether the magnitude of the anterior shift (i.e., the distance between encoding- and retrieval-related response peaks) is moderated by age, and also whether the shift is associated with memory performance. Younger and older human subjects of both sexes underwent fMRI as they completed encoding and retrieval tasks on word-face and word-scene pairs. We localized peak scene and face selectivity for each individual participant within the face-selective precuneus and in three scene-selective (parahippocampal place area [PPA], medial place area, occipital place area) ROIs. In line with recent findings, we identified an anterior shift in the PPA and occipital place area in both age groups and, in older adults only, in the medial place area and precuneus also. Of importance, the magnitude of the anterior shift was larger in older than in younger adults. The shift within the PPA exhibited an age-invariant across-participant negative correlation with source memory performance, such that a smaller displacement between encoding- and retrieval-related neural activity was associated with better performance. These findings provide novel insights into the functional significance of the anterior shift, especially in relation to memory decline in older age.SIGNIFICANCE STATEMENT Cognitive aging is associated with reduced ability to retrieve precise details of previously experienced events. The retrieval-related anterior shift is a phenomenon in which category-selective cortical activity at retrieval is localized anterior to the peak activity at encoding. The shift is thought to reflect a bias at retrieval in favor of semantic and abstract information at the expense of low-level perceptual detail. Here, we report that the anterior shift is exaggerated in older relative to younger adults, and we demonstrate that a larger shift in the parahippocampal place area is associated with poorer memory performance. These findings suggest that the shift is sensitive to increasing age and that it is moderated by the quality and content of the retrieved episode.

Effects of age on goal-dependent modulation of episodic memory retrieval.

Retrieval gating refers to the ability to modulate the retrieval of features of a single memory episode according to behavioral goals. Recent findings demonstrate that younger adults engage retrieval gating by attenuating the representation of task-irrelevant features of an episode. Here, we examine whether retrieval gating varies with age. Younger and older adults incidentally encoded words superimposed over scenes or scrambled backgrounds that were displayed in one of three spatial locations. Participants subsequently underwent fMRI as they completed two memory tasks: the background task, which tested memory for the word's background, and the location task, testing memory for the word's location. Employing univariate and multivariate approaches, we demonstrated that younger, but not older adults, exhibited attenuated reinstatement of scene information when it was goal-irrelevant (during the location task). Additionally, in younger adults only, the strength of scene reinstatement in the parahippocampal place area during the background task was related to item and source memory performance. Together, these findings point to an age-related decline in the ability to engage retrieval gating.

Neural Differentiation is Moderated by Age in Scene-Selective, But Not Face-Selective, Cortical Regions.

The aging brain is characterized by neural dedifferentiation, an apparent decrease in the functional selectivity of category-selective cortical regions. Age-related reductions in neural differentiation have been proposed to play a causal role in cognitive aging. Recent findings suggest, however, that age-related dedifferentiation is not equally evident for all stimulus categories and, additionally, that the relationship between neural differentiation and cognitive performance is not moderated by age. In light of these findings, in the present experiment, younger and older human adults (males and females) underwent fMRI as they studied words paired with images of scenes or faces before a subsequent memory task. Neural selectivity was measured in two scene-selective (parahippocampal place area (PPA) and retrosplenial cortex (RSC)] and two face-selective [fusiform face area (FFA) and occipital face area (OFA)] regions using both a univariate differentiation index and multivoxel pattern similarity analysis. Both methods provided highly convergent results, which revealed evidence of age-related reductions in neural dedifferentiation in scene-selective but not face-selective cortical regions. Additionally, neural differentiation in the PPA demonstrated a positive, age-invariant relationship with subsequent source memory performance (recall of the image category paired with each recognized test word). These findings extend prior findings suggesting that age-related neural dedifferentiation is not a ubiquitous phenomenon, and that the specificity of neural responses to scenes is predictive of subsequent memory performance independently of age.

Age-related neural dedifferentiation and cognition.

This review focuses on possible contributions of neural dedifferentiation to age-related cognitive decline. Neural dedifferentiation is held to reflect a breakdown in the functional specificity of brain regions and networks that compromises the fidelity of neural representations supporting episodic memory and related cognitive functions. The evidence for age-related dedifferentiation is robust when it is operationalized as neural selectivity for different categories of perceptual stimuli or as decreased segregation or modularity of resting-state functional brain networks. Neural dedifferentiation for perceptual categories appears to demonstrate a negative, age-invariant relationship with performance on tests of memory and fluid processing. Whether this pattern extends to network-level measures of dedifferentiation cannot currently be determined due to insufficient evidence. The existing data highlight the importance of further examination of neural dedifferentiation as a factor contributing to episodic memory and to cognitive performance more generally.

Semantic Relatedness Corrects the Age-Related Binding Deficit in Working Memory and Episodic Memory.

OBJECTIVES: It is well known that age differentially impacts aspects of long-term episodic memory (EM): Whereas a binding deficit indicates that older adults are less capable than younger adults to encode or retrieve associations between information (e.g., the pairing between two memoranda, such as lock - race), item memory is relatively intact (e.g., recognizing lock without its original pairing). METHOD: We tested whether this deficit could be corrected by facilitating establishment of the bindings in working memory (WM) through adapting the semantic relatedness of studied pairs according to participants' ongoing performance (Experiments 1 and 2). We also examined whether this was evident for the long-term retention of pairs that were not tested in WM (Experiment 2). RESULTS: The results revealed matched binding and item memory in WM and EM between age groups. Most importantly, older adults required increased semantic strength between word pairs to achieve similar performance to that of younger adults, regardless of whether pairs were immediately tested during the WM task. DISCUSSION: These findings indicate that relying on their superior semantic memory can correct the commonly exhibited profound deficit in binding memory in older age.