Interpreting fMRI studies in populations with cerebrovascular risk: the use of a subject-specific hemodynamic response function

Functional magnetic resonance imaging (fMRI) is commonly used to investigate the neural bases of aging and psychological disorders. However, the BOLD signal captured by fMRI is affected by many factors that are non-neural in origin. We tested how vascular health risks, which often go unmeasured in neuroimaging studies, and aging interact to modify the shape and/or timing of the HRF, which then affect the differences in patterns of brain activity in a task-evoked memory encoding paradigm. Adult participants (aged 20–74) answered questions about their health and underwent two fMRI tasks: viewing a flashing checkerboard and a memory encoding task. Aging and vascular risk had the largest impacts on the maximum peak value of the HRF. Using a subject-specific HRF resulted in a dampening of brain activity in task-positive and task-negative regions. Across three vascular risk factors, using a subject-specific HRF resulted in more consistent brain regions that reached significance and larger effect sizes compared with the canonical HRF. These findings serve as a cautious tail when interpreting task-evoked fMRI activity, especially in populations experiencing alterations to brain vasculature including many older adults and people with neurocognitive disorders like Alzheimer’s disease and related dementias.