Geddes, M. R. | Search bioRxiv

bioRxiv2020

Asymmetric Functional Gradients in the Human Subcortex

A central principle in our understanding of cerebral cortical organization is that homotopic left and right areas are functionally linked to each other, and also connected with structures that share similar functions within each cerebral cortical hemisphere. Here we refer to this concept as interhemispheric functional symmetry (IHFS). While multiple studies have described the distribution and variations of IHFS in the cerebral cortex, descriptions of IHFS in the subcortex are largely absent in the neuroscientific literature. Further, the proposed anatomical basis of IHFS is centered on callosal and other commissural tracts. These commissural fibers are present in virtually all cerebral cortical areas, but almost absent in the subcortex. There is thus an important knowledge gap in our understanding of subcortical IHFS. What is the distribution and variations of subcortical IHFS, and what are the anatomical correlates and physiological implications of this important property in the subcortex? Using fMRI functional gradient analyses in a large dataset (Human Connectome Project, n=1003), here we explored IHFS in human thalamus, lenticular nucleus, cerebellar cortex, and caudate nucleus. Our detailed descriptions provide an empirical foundation upon which to build hypotheses for the anatomical and physiological basis of subcortical IHFS. Our results indicate that direct or driver cerebral cortical afferent connectivity, as opposed to indirect or modulatory cerebral cortical afferent connectivity, is associated with stronger subcortical IHFS in thalamus and lenticular nucleus. In cerebellar cortex and caudate, where there is no variability in terms of either direct vs. indirect or driver vs. modulatory cerebral cortical afferent connections, connectivity to cerebral cortical areas with stronger cerebral cortical IHFS is associated with stronger IHFS in the subcortex. These two observations support a close relationship between subcortical IHFS and connectivity between subcortex and cortex, and generate new testable hypotheses that advance our understanding of subcortical organization.

neuroscience↗

bioRxiv2020

Resting-State Connectivity of Auditory and Reward Systems in Alzheimer's Disease and Mild Cognitive Impairment

Music-based interventions have become increasingly widely adopted for dementia and related disorders. Previous research shows that music engages reward-related regions through functional connectivity with the auditory system. Here we characterize intrinsic connectivity of the auditory and reward systems in healthy aging, mild cognitive impairment (MCI) - a predementia phase of cognitive dysfunction, and Alzheimers disease (AD). Using resting-state fMRI data from the Alzheimers Database Neuroimaging Initiative, we tested functional connectivity within and between auditory and reward systems in older adults with MCI, AD, and age-matched healthy controls (N=105). Seed-based correlations were assessed from regions of interest (ROIs) in the auditory network, i.e. anterior superior temporal gyrus (aSTG), posterior superior temporal gyrus (pSTG), Heschls Gyrus, and reward network (i.e., nucleus accumbens, caudate, putamen, and orbitofrontal cortex [OFC]). AD individuals were lower in both within-network and between-network functional connectivity in the auditory network and reward networks compared to MCI and healthy controls. Furthermore, graph theory analyses showed that MCI individuals had higher clustering, local efficiency, degrees, and strengths than both AD individuals and healthy controls. Together, the auditory and reward systems show preserved within- and between-network connectivity in MCI relative to AD. These results suggest that music-based interventions have the potential to make an early difference in individuals with MCI, due to the preservation of functional connectivity in reward-related regions and between auditory and reward networks at that initial stage of neurodegeneration.

neuroscience↗