Caudate functional networks influence brain structural changes with aging

Abstract

Neurogenesis decline with aging may be associated with brain atrophy. Subventricular zone (SVZ) neuron precursor cells possibly modulate striatal neuronal activity via the release of soluble molecules. Neurogenesis decay in SVZ may result in structural alterations of brain regions connected to the caudate, particularly to its medial component. The aim of this study was to investigate how the functional organization of caudate networks relates to structural brain changes with aging. 152 normal subjects were recruited: 52 young healthy adults (≤ 35 years old), 42 middle-aged (36≤ 60 years old) and 58 elderly subjects (≥ 60 years old). In young adults, stepwise functional connectivity (SFC) was used to characterize regions that connect to medial and lateral caudate at different levels of link-step distances. Statistical comparison between the connectivity of medial and lateral caudate in young subjects was useful to define medial- (MCR) and lateral- (LCR) caudate connected regions. Atrophy of MCR and LCR caudate connected regions was estimated in young, middle-aged and elderly subjects using T1-weighted images. Results showed that middle-aged and elderly adults exhibited decreased SFC at one-link step from the caudate, particularly in frontal, parietal, temporal, and occipital brain regions, compared to young subjects. Elderly individuals showed increased SFC in frontal, parietal, temporal, and occipital lobes compared to both young and middle-aged adults. Additionally, elderly adults displayed decreased SFC compared to middle-aged subjects in specific parietal and subcortical areas. Moreover, in young adults, medial-caudate showed higher direct connectivity to basal ganglia (left thalamus), superior, middle and inferior frontal and inferior parietal gyri (MCR) relative to the lateral-caudate. Considering the opposite contrast, lateral-caudate showed a stronger connectivity to basal ganglia (right pallidum), orbitofrontal, rostral-anterior cingulate and insula cortices (LCR) compared to medial-caudate. In elderly subjects, MCR showed greater atrophy relative to LCR. Brain regions linked to medial-caudate appear to be more vulnerable to aging than lateral-caudate connected areas. The adjacency to SVZ may, at least partially, explain these findings. SFC analysis can be useful to evaluate the role of the SVZ in the network disruptions in age-related neurodegenerative disorders.