Towards the implementation and interpretation of masked ICA for identifying signatures of autonomic activation in the brainstem with resting-state BOLD fMRI

The brainstem is the site of key exchanges between the autonomic and central nervous systems but has historically presented a challenging target for study with BOLD fMRI. A potentially powerful although under-characterized approach to identifying nucleic activation within the brainstem is masked independent component analysis (mICA), which restricts signal decomposition to the brainstem itself, thus aiming to reduce the strong effect of physiological noise in nearby regions such as ventricles and large arteries. In this study, we systematically investigate the use of mICA to uncover signatures of autonomic activation in the brainstem at rest. We apply mICA on 40 subjects in a high-resolution resting state 7T dataset following different strategies for dimensionality selection, denoising, and component classification. We show that among the noise mitigation techniques investigated, cerebrospinal fluid denoising makes the largest impact in terms of mICA outcomes. We further demonstrate that across preprocessing pipelines and previously reported results the majority of components are spatially reproducible, but temporal outcomes differ widely depending on denoising strategy. Evaluating both hand-labelling and whole-brain specificity criteria, we develop an intuitive framework for mICA classifications. Finally, we make a comparison between mICA and atlas-based segmentations of brainstem nuclei, finding little consistency between these two approaches. Based on our evaluation of the effects of methodology on mICA and its relationship to other signals of interest in the brainstem, we provide recommendations for future uses of mICA to identify autonomically-relevant BOLD fluctuations in subcortical structures.