Human neuroimaging research on cognitive aging has brought significant advances to our understanding of the neural mechanisms underlying age-related cognitive decline and successful aging. However, interpreting age-related changes and differences in brain structure, activation, and functional connectivity is an ongoing challenge. Ambiguous terminology is a major source of this challenge. For example, the terms ‘compensation,’ ‘maintenance,’ and ‘reserve’ are used in different ways and researchers disagree about the kinds of evidence or patterns of results required to interpret findings related to these concepts. As such inconsistencies can impede theoretical and empirical progress, we here aim to clarify these key terms and to propose consensual definitions of maintenance, reserve, and compensation.

The concept of reserve arose from the mismatch between the extent of brain changes or pathology and the clinical manifestations of these brain changes. The cognitive reserve hypothesis posits that individual differences in the flexibility and adaptability of brain networks underlying cognitive function may allow some people to cope better with brain changes than others. Although there is ample epidemiologic evidence for cognitive reserve, the neural substrate of reserve is still a topic of ongoing research. Here we review some representative studies from our group that exemplify possibilities for the neural substrate of reserve including neural reserve, neural compensation, and generalized cognitive reserve networks. We also present a schematic overview of our ongoing research in this area.

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Objectives-To examine patterns of brain activation while performing a working memory task in persons with moderate to severe traumatic brain injury (TBI) and healthy controls. It is well established that working memory is an area of cognition that is especially vulnerable to disruption after TBI. Although much has been learned about the system of cerebral representation of working memory in healthy people, little is known about how this system is disrupted by TBI. Methods-Functional magnetic resonance imaging (fMRI) was used to assess brain activation during a working memory task (a modified version of the paced auditory serial addition test) in nine patients with TBI and seven healthy controls. Results-Patients with TBI were able to perform the task, but made significantly more errors than healthy controls. Cerebral activation in both groups was found in similar regions of the frontal, parietal, and temporal lobes, and resembled patterns of activation found in previous neuroimaging studies of working memory in healthy persons. However, compared with the healthy controls, the TBI group displayed a pattern of cerebral activation that was more regionally dispersed and more lateralised to the right hemisphere. Differences in lateralisation were particularly evident in the frontal lobes. Conclusions-Impairment of working memory in TBI seems to be associated with alterations in functional cerebral activity. (J Neurol Neurosurg Psychiatry 2001;71:161-168)

This study investigated the relationship between education and physical activity and the difference between a physiological prediction of age and chronological age. Cortical and subcortical grey matter regional volumes were calculated from 331 healthy adults (range: 19-79 years). Multivariate analyses identified a covariance pattern of brain volumes best predicting chronological age (CA)(R2 = 47%). Individual expression of this brain pattern served as a physiologic measure of brain age (BA). The difference between CA and BA was predicted by education and self-report measures of physical activity. Education and the daily number of flights of stairs climbed were the only two significant predictors of decreased brain age. Effect sizes demonstrated that brain age decreased by 0.95 years for each year of education and by 0.58 years for one additional daily FOSC. Effects of education and FOSC on regional brain volume were largely driven by temporal and subcortical volumes. These results demonstrate that higher levels of education and daily FOSC are related to larger brain volume than predicted by chronological age which supports the utility of regional grey matter volume as a biomarker of healthy brain aging.