Multi-variate and multi-modal modelling of neuroimaging data to better understand brain ageing

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Understanding variation in ageing requires sophisticated techniques that can examine brain structure and function across volumetric, microstructural, and functional dimensions. Here, we leverage recent developments from my group for the integration of multi-modal MRI data (using non negative matrix factorization [NMF]) to build models that allow for an improved understanding of how variation in brain structure and function integrate and are related to cognition, with specific focus on the hippocampus. We will use publicly available data (the Human Connectome Project) containing state-of-the-art MRI of brain microstructure related myelin content and axonal properties in addition normative brain function using resting state functional MRI (rsfMRI). We will relate cognitive and functional tasks back to MRI-derived measures. Finally, we will use these techniques in a machine learning-based prediction model for individual age in a well-characterized healthy elderly sample. The goal would be to identify patterns of covariance that best predict cognitive function and age using an integrated analysis strategy that leverages NMF to define components of variance and then to examine the association of each component across cognitive measures using partial least squares (PLS). Compared to common decomposition techniques such as principal and independent component analysis, NMF outputs are more interpretable, sparse, and more spatially contiguous and non overlapping. Research Goals: 1) Microstructural parcellation of the human hippocampus and its relationship with cognition: NMF outputs individual weightings for each subject will be estimated to assess microstructural variability across the 330 unrelated study participants in HCP. Inputs to the NMF will be indices from structural MRI thought to reflect myelin content (T1/T2 ratio) and indices from diffusion MRI (fractional anisotropy and mean diffusivity). Subject-specific component weighting will be related back to 32 cognitive tests administered by the HCP using PLS. 2) Functional parcellation of the human hippocampus and its relationship with cognition: Here we will use a hippocampus-whole-brain approach to derive a rsfMRI based parcellation. Once again the relationship between our parcellation will be related back to the 32 cognitive measures using PLS. 3) Using NMF to predict individual age in a normative population: We will use existing data from the Whitehall II Imaging Sub-study, collected in the FMRIB Centre at Oxford. This dataset includes structural and diffusion MRI, as well as resting-state fMRI scans from 800 community-dwelling adults aged 60-85 years old. The development of an accelerated ageing biomarker has potential relevance to ageing studies in the future focused on heterogeneity of ageing trajectories and developing as a method that can help to better understand the variance in normative ageing. predicting future ageing trajectory.