PROJECT SUMMARY/ABSTRACT Traumatic brain injury (TBI) is widespread and potentially debilitating, and multiple mild head impacts can potentially cause chronic traumatic encephalopathy (CTE). Despite its importance, the underlying mechanics of the brain’s response to skull acceleration are not fully understood. This project is designed to identify and characterize natural modes of oscillation in the living human brain, using magnetic resonance imaging (MRI) of the brain during mild head accelerations (either very light impacts or low-amplitude vibration). Modes of oscillation are types of motion to which the brain is particularly vulnerable; such modes can be activated by skull motion in specific directions with particular frequency components. In preliminary studies I have identified seemingly consistent modes of oscillation in brains of 19 human subjects, by analyzing displacement and strain data sets from tagged MRI with a method known as dynamic mode decomposition. In this project, I hypothesize that the dominant natural modes of oscillation in particular, and the dynamic response of the brain to skull excitation in general, will be similar across all subjects, but the parameters of the response will differ quantitatively in subjects of different age and gender (due to differences in size, shape, and stiffness). In Aim 1, I will identify and characterize modes of oscillation in the human brain, again using dynamic mode decomposition of tagged MRI data, in groups of subjects of different ages and genders. Specifically I will quantify the damped natural frequencies, damping ratios, modal coefficients, and spatial patterns (mode shapes) that characterize each mode. These quantities will be obtained for male and female subjects in three age groups, during two different types of head motion: (i) anterior-posterior motion (neck extension, or “yes” nodding) and (ii) axial rotation (neck rotation, or “no” nodding). In Aim 2 I will determine the frequency response of the human brain to harmonic skull motion using magnetic resonance elastography (MRE), again in subjects of different ages and genders. This will be done to determine whether the harmonic brain deformations observed in MRE reflect anatomical or physiological differences due to age or sex. MRE studies will be performed over a range of frequencies, with either occipital excitation (anterior-posterior motion) or lateral excitation (right-left motion). A key feature of the brain’s response is the amplitude of brain deformation (shear strain amplitude) relative to the amplitude of skull acceleration. This ratio is expected to vary with the direction and frequency of skull motion, as well as with age and sex. Successful completion of these Aims will provide quantitative understanding of how skull motion leads to brain deformation in specific regions of the brain, under different impact scenarios, and allow quantitative assessment of computer models of TBI. This understanding will ultimately be cr...