Neural Selectivity, Retrieval-Related Reinstatement, and Age-Related MemoryDecline

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Project Summary Episodic memory declines substantially and, relative to other forms of memory, disproportionately, with age. Understanding the cognitive and neural bases of age-related episodic decline in healthy subjects is important because even the modest impairment (by clinical standards) typical of healthy individuals entering their 70’s is sufficient to have a detrimental impact on quality of life. Identifying the specific cognitive processes, and their neural substrates, which are most responsible for age-related memory decline is a crucial precursor to the development of potential rehabilitative interventions. Equally important, a full understanding of the much more severe memory impairments characteristic of age-related neurodegenerative diseases such as Alzheimer’s Disease will be difficult to achieve without knowledge of how memory and its neural substrates vary over the course of the healthy lifespan. The aim of the present research is to investigate the possible role in age-related memory decline of the strength of encoding-related neural selectivity (neural differentiation) and retrieval- related neural reinstatement, as well as the relationship between encoding- and retrieval-related neural activity. The starting point for the proposed research is recent findings indicating that, i) neural selectivity and reinstatement are weaker in older than in younger adults, are strongly correlated regardless of age and, in the case of selectivity, predict memory performance across- subjects, and ii) differences in the locations of the peaks of category-selective encoding- and retrieval-related activity (the ‘anterior shift’) are exaggerated in older adults and, in the parahippocampal cortex, correlate negatively across subjects with memory performance. Building on these findings, the proposed research will use functional and structural fMRI to examine the cross-sectional profile of neural selectivity, reinstatement, and the anterior shift, and their relationships with memory performance, in a large (N=160) lifespan sample of cognitively healthy adults (age range 18-90 years). The older cohort (aged 65-90 years) will be followed up after 3 years to assess whether selectivity, reinstatement or shift metrics obtained at baseline are predictive of longitudinal change in cognitive performance or brain structure. For the structural analyses we will focus on anterior medial temporal regions that have been strongly implicated in pre-clinical and early Alzheimer’s Disease, with the aim of examining the sensitivity of the functional metrics to incipient Alzheimer’s pathology. A second study will employ a lifespan sample to assess whether the findings described above generalize to the auditory modality. A third study will employ an extreme age group design to examine the role of retrieval demands (recall of general vs. specific details from the study event) on age differences in the anterior shift.