Calibrated fMRI during a cognitive Stroop task reveals reduced metabolic response with increasing age

fMRI studies of aging have revealed increased blood oxygenation level dependent (BOLD) response to tasks of executive function with advancing age, which is generally interpreted as increased neural activity. However, changes in the cerebrovascular system with age can alter the BOLD signal, complicating this interpretation. Arterial spin labeling (ASL) allows simultaneous acquisition of BOLD and cerebral blood flow (CBF) information and can be used to quantify the component parts of the BOLD signal. We used this calibrated BOLD approach in 58 healthy participants over an age range of 18-71 years to determine the relative vascular and neuronal contributions to the age-related BOLD changes in response to a Stroop task. The percentage BOLD response increased significantly with increasing age but the percentage CBF response did not alter, such that the BOLD increase is attributed to a significant reduction in the oxygen metabolism response with increasing age. Hence, in this study, the BOLD increase with age should be interpreted as a reduction in neural activity. The greatest percentage BOLD increases with age were found in the left and right medial frontal gyri and the primary motor cortex and were again linked to a reduction in oxygen metabolism. On separating the participants into three groups (young, old high performers and old low performers), age-related differences in percentage BOLD response and oxygen metabolism response could be attributed to the low performing old group. This study demonstrates the need to take into account alterations in vascular-metabolic coupling and resting blood volume when interpreting changes in the BOLD response with aging.

► Cerebrovascular alterations contribute to age-related change in the BOLD signal. ► Calibrated fMRI separates vascular and neuronal components of the BOLD signal. ► The BOLD increase with age is due to a reduction in oxygen metabolism response. ► Age-related reductions in oxygen metabolism response are related to low-performance. ► Care is needed in interpretation of BOLD signal differences across age or disease.