The relationship between age, neural differentiation, and memory performance.

Healthy aging is associated with decreased neural selectivity (dedifferentiation) in category-selective cortical regions. This finding has prompted the suggestion that dedifferentiation contributes to age-related cognitive decline. Consistent with this possibility, dedifferentiation has been reported to negatively correlate with fluid intelligence in older adults. Here, we examined whether dedifferentiation is associated with performance in another cognitive domain - episodic memory - that is also highly vulnerable to aging. Given the proposed role of differentiation in age-related cognitive decline, we predicted there would be a stronger link between dedifferentiation and episodic memory performance in older than in younger adults. Young (18-30 yrs) and older (64-75 yrs) male and female humans underwent fMRI scanning while viewing images of objects and scenes prior to a subsequent recognition memory test. We computed a differentiation index in two regions-of-interest (ROIs): parahippocampal place area (PPA) and lateral occipital complex (LOC). This index quantified the selectivity of the BOLD response to an ROI's preferred versus non-preferred category (scenes for PPA, objects for LOC). The differentiation index in the PPA, but not the LOC, was lower in older than in younger adults. Additionally, the PPA differentiation index predicted recognition memory performance for the studied items. This relationship was independent of and not moderated by age. The PPA differentiation index also predicted performance on a latent 'fluency' factor derived from a neuropsychological test battery; this relationship was also age invariant. These findings suggest that two independent factors, one associated with age, and the other with cognitive performance, drive neural differentiation. SIGNIFICANCE STATEMENT Aging is associated with neural dedifferentiation - reduced neural selectivity in 'category selective' cortical brain regions - which has been proposed to mediate cognitive aging. Here, we examined whether neural differentiation is predictive of episodic memory performance, and whether the relationship is moderated by age. A neural differentiation index was estimated for scene- (PPA) and object- (LOC) selective cortical regions while participants studied images for a subsequent memory test. Age related reductions were observed for the PPA, but not the LOC, differentiation index. Importantly, the PPA differentiation index demonstrated age invariant correlations with subsequent memory performance and a fluency factor derived from a neuropsychological battery. Together, these findings suggest that neural differentiation is associated with two independent factors: age and cognitive performance.