Applications of Gradient Representations in Resting-State fMRI

Abstract

Classical models of brain organization have often considered the brain to be made up of a mosaic of patches that are demarcated by discrete boundaries, often defined histologically. In contrast, emerging views have pointed towards an alternative paradigm – referred to as gradients – by conceptualizing brain organization as sets of organizational axes that characterizes spatial variation of differing connectivity principles over the extent of a region. Such organizational axes provide a well-suited framework for elucidating underpinnings of brain connectivity and has garnered widespread attention across various domains of neuroimaging. This work seeks to explore various applications of gradient estimation techniques, in combination with resting-state functional connectivity data, across the fields of basic, comparative, and clinical neuroscience. First, gradient estimation was performed on resting-state functional connectivity (RSFC) patterns of the primary somatosensory cortex to unveil a secondary organizational axis that spans the region’s anterior-posterior axis, akin to circuitry fundamental to sensory cortical information processing. Second, gradient techniques were used in a cross-species comparison study to unify connectivity principles of humans and marmosets by mapping them simultaneously onto a set of organizational axes. In doing so, this provided a systematic framework to compare the functional architecture of both species, facilitating novel insight of a well-integrated default-mode network in humans, compared to marmosets. Third, connectivity gradients, along with a myriad of other resting-state fMRI features were used to explore the implications of focal lesion pathophysiology on functional organization of the thalamus in individuals with Multiple Sclerosis. A lack of focal changes to resting-state related features was observed suggesting the limited role of focal thalamic lesions to functional organization in MS. Together, these different avenues of research highlight the capacity for a gradient-centric view in neuroimaging to provide profound insights into brain organization, and its utility across the applications of basic, comparative, and clinical neuroscience

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