Examining the significance of hemodynamic response function variability to psychopathology and development

Abstract

The hemodynamic response function (HRF) model is used in neuroimaging studies to characterize the blood oxygen level dependent (BOLD) response to a stimulus (typically assumed to be neuronal activity). Recent work utilizing resting-state functional magnetic resonance imaging (rs-fMRI) data has shown that in some brain regions, adults diagnosed with internalizing disorders show an altered HRF shape relative to controls. However, associations between internalizing disorders and rs-fMRI HRF remain unexamined in late childhood and adolescence. This gap in the literature was addressed in this work through two studies leveraging data from the Human Connectome Project – Development (HCP-D) sample (ages 8 – 17 years). The first study followed a confirmatory analytic approach by seeking to replicate and extend previous work reporting associations between depression and HRF response height (RH) in frontal-rostral brain regions. Following multiplicity correction, a statistically significant negative association was found between a dimensional measure of depression and RH in right Brodmann area 25. The second study followed an exploratory approach by conducting a brain-wide association study examining HRF shape parameter associations with internalizing scores. The largest effects corresponded to the RH parameter, and notably associations were found in both positive and negative directions. These findings establish and characterize, for the first time, associations between HRF shape and internalizing psychopathology in youth.