Widespread fMRI BOLD signal overactivations during cognitive control in older adults are not matched by corresponding increases in fPET glucose metabolism.

A common observation in functional magnetic resonance imaging (fMRI) studies using the blood-oxygenation level-dependent (BOLD) signal is that older adults, compared to young adults, show overactivations, particularly during less demanding tasks. The neuronal underpinnings of such overactivations are not known, but a dominant view is that they are compensatory in nature and involve recruitment of additional neural resources. We scanned 23 young (20-37y) and 34 older (65-86y) healthy human adults of both sexes with hybrid positron emission tomography (PET)/MRI. The radioligand [18F]fluoro-deoxyglucose (FDG) was used to assess dynamic changes in glucose metabolism as a marker of task-dependent synaptic activity, along with simultaneous fMRI BOLD imaging. Participants performed two verbal working memory (WM) tasks, one involving maintenance (easy) and one requiring manipulation (difficult) of information in WM. Converging activations to the WM tasks versus rest were observed for both imaging modalities and age groups in attentional, control and sensorimotor networks. Upregulation of activity to WM-demand, comparing the more difficult to the easier task, also converged between both modalities and age groups. For regions in which older adults showed task-dependent BOLD overactivations when compared to the young adults, no corresponding increases in glucose metabolism were found. To conclude, findings from the current study show that task-induced changes in the BOLD signal and synaptic activity as measured by glucose metabolism generally converge but overactivations observed with fMRI in older adults are not coupled with increased synaptic activity, which suggests that these overactivations are not neuronal in origin. SIGNIFICANCE STATEMENT: Findings of increased functional magnetic resonance imaging (fMRI) activations in older as compared to younger adults have been suggested to reflect increased use of neuronal resources to cope with reduced brain function. The physiological underpinnings of such compensatory processes are poorly understood however, and rest on the assumption that vascular signals accurately reflect neuronal activity. Comparing fMRI and simultaneously acquired functional positron emission tomography (fPET) as an alternative index of synaptic activity we show that age-related overactivations do not appear to be neuronal in origin. This result is important because mechanisms underlying compensatory processes in aging are potential targets for interventions aiming to prevent age-related cognitive decline.