Increased prefrontal activity with aging reflects nonspecific neural responses rather than compensation

Abstract

Elevated prefrontal cortex activity is often observed in healthy older adults despite declines in their memory and other cognitive functions. According to one view, this activity reflects a compensatory functional posterior-to-anterior shift, which contributes to maintenance of cognitive performance when posterior cortical function is impaired. Alternatively, the increased prefrontal activity may be less efficient or less specific, owing to structural and neurochemical changes accompanying aging. These accounts are difficult to distinguish on the basis of average activity levels within brain regions. Instead, we used a novel model-based multivariate analysis technique, applied to two independent functional magnetic resonance imaging datasets from an adult-lifespan human sample (N=123 and N=115; approximately half female). Standard analysis replicated the age-related increase in average prefrontal activation, but multivariate tests revealed that this activity did not carry additional information. The results contradict the hypothesis of a compensatory posterior-to-anterior shift. Instead, they suggest that the increased prefrontal activation reflects reduced efficiency or specificity, rather than compensation.\n\nSignificance statementFunctional brain imaging studies have often shown increased activity in prefrontal brain regions in older adults. This has been proposed to reflect a compensatory shift to greater reliance on prefrontal cortex, helping to maintain cognitive function. Alternatively, activity may become less specific as people age. This is a key question in the neuroscience of aging. In this study, we used novel tests of how different brain regions contribute to long- and short-term memory. We found increased activity in prefrontal cortex in older adults, but this activity carried less information about memory outcomes than activity in visual regions. These findings are relevant for understanding why cognitive abilities decline with age, suggesting that optimal function depends on successful brain maintenance rather than compensation.