From Synchrony to Asynchrony: Cerebellar–Basal Ganglia Functional Circuits in Young and Older Adults

Abstract

Resting state functional magnetic resonance imaging (rs-fMRI) has indicated disruptions in functional connectivity in older (OA) relative to young adults (YA). While age differences in cortical networks are well studied, differences in subcortical networks are poorly understood. Both the cerebellum and the basal ganglia are of particular interest given their role in cognitive and motor functions, and work in non-human primates has demonstrated direct reciprocal connections between these regions. Here, our goal was twofold. First, we were interested in delineating connectivity patterns between distinct regions of the cerebellum and basal ganglia, known to have topologically distinct connectivity patterns with cortex. Our second goal was to quantify age-differences in these cerebellar-striatal circuits. We performed a targeted rs-fMRI analysis of the cerebellum and basal ganglia in 33 YA and 31 OA individuals. In the YA, we found significant connectivity both within and between the cerebellum and basal ganglia, in patterns supporting semi-discrete circuits that may differentially subserve motor and cognitive performance. We found a shift in connectivity, from one of synchrony in YA, to asynchrony in OA, resulting in substantial age differences. Connectivity was also associated with behavior. These findings significantly advance our understanding of cerebellar-basal ganglia interactions in the human brain.

Cerebellar Dentate Connectivity Across Adulthood: A Large-Scale Resting State Functional Connectivity Investigation

“…We followed the standard preprocessing pipeline in CONN, including functional realignment and unwarping, functional centering of the image to (0, 0, 0) coordinates, slice-timing correction, structural centering to (0, 0, 0,) coordinates, structural segmentation and normalization to MNI space, functional normalization to MNI space, and spatial smoothing with a smoothing kernel of 6mm FWHM. This paralleled the approach taken in recent investigations conducted by our group (Bernard et al 2017; Hausman et al 2020). Because of the potential confounding effects of motion and signal outliers (Power et al 2012; Van Dijk et al 2012) these procedures also included processing using the Artifact Rejection Toolbox (ART).…”

“…However, changes in neurotransmitter systems may also contribute to the age differences in dentate connectivity. Previously, we have demonstrated marked differences in connectivity between the cerebellum and basal ganglia in OA relative to YA (Bernard et al 2013; Hausman et al 2020) using lobular cerebellar seeds. We speculated that age differences in dopamine may be contributing, at least in part, to the differences in connectivity in advanced age.…”

“…Though our understanding of cerebellar connectivity, particularly that of the cerebellar dentate nucleus has greatly expanded in recent years, it remains unknown whether networks of the dentate nucleus are different across the lifespan. While prior work has demonstrated that connectivity of the cerebellar lobules is lower in OA Hausman et al 2020), to date, the dentate nucleus has not been investigated across the adult lifespan. While cerebellar lobular approaches are informative and reflect purported changes in processing and communication with the cerebral cortex, given that the dentate nucleus is a critical aspect of this circuit as the primary output region to the cerebral cortex, further investigation is warranted.…”

“…Work over the past two decades has increasingly pointed to the cerebellum as a contributor to age-related performance differences when investigating volume (MacLullich et al 2004; Bernard and Seidler 2013; Miller et al 2013; Koppelmans et al 2015, 2017), and we have known for quite some time that cerebellar volume is smaller in older adults and declines in volume over time (Raz et al 1998, 2005, 2010, 2013; Han et al 2020). Furthermore, there are age differences in lobular cerebellar connectivity as well (Bernard et al 2013), and subcortically, differing patterns of connectivity between the cerebellum and basal ganglia (Hausman et al 2020).…”

Cerebellar and Prefrontal-Cortical Engagement During Higher-Order Rule Learning in Older Adulthood

“…Indeed, this subcortical structure may provide key scaffolding for cognition, as has been suggested in motor tasks (Filip, Gallea, Lehéricy, Lungu, & Bareš, 2019). Critically, there is evidence that the cerebellum and its resting state networks are negatively impacted with age in behaviorally relevant ways (smaller volume, decreased connectivity; Abe et al, 2008;Bernard et al, 2013;Bernard & Seidler, 2014;Hausman, Jackson, Goen, & Bernard, 2019), further underscoring the importance of investigating cerebellar function in advanced age.…”