Disrupted cortico-cerebellar connectivity in older adults

Abstract

Healthy aging is marked by declines in a variety of cognitive and motor abilities. A better understanding of the aging brain may aid in elucidating the neural substrates of these behavioral effects. Investigations of resting state functional brain connectivity have provided insights into pathology, and to some degree, healthy aging. Given the role of the cerebellum in both motor and cognitive behaviors, as well as its known volumetric declines with age, investigating cerebellar networks may shed light on the neural bases of age-related functional declines. We mapped the resting state networks of the lobules of the right hemisphere and the vermis of the cerebellum in a group of healthy older adults and compared them to those of young adults. We report disrupted cortico-cerebellar resting state network connectivity in older adults. These results remain even when controlling for cerebellar volume, signal-to-noise ratio, and signal-to-fluctuation noise ratio. Specifically, there was consistent disruption of cerebellar connectivity with both the striatum and the medial temporal lobe. Associations between connectivity strength and both sensorimotor and cognitive task performance indicate that cerebellar engagement with the default mode network and striatal pathways is associated with better performance for older adults. These results extend our understanding of the resting state networks of the aging brain to include cortico-cerebellar networks, and indicate that age differences in network connectivity strength are important for behavior.

Moving forward: Age effects on the cerebellum underlie cognitive and motor declines

“…A role for the cerebellum in both cognitive and motor behavior has been postulated for quite some time (Leiner et al, 1993, 1989, 1986; Schmahmann and Sherman, 1998); moreover, recent work in non-human primates has demonstrated segregated cognitive and motor cerebello-cortical closed-loop circuits (Kelly and Strick 2003; Dum and Strick 2009; for a review see Strick et al 2009). Similar distinct circuits have also been demonstrated in the human brain using fcMRI (Bernard et al, 2012; Bernard et al, 2013; Habas et al, 2009; Krienen and Buckner, 2009; O'Reilly et al, 2010), and crucially, a functional topography has been demonstrated in the cerebellum with fMRI and meta-analysis (Stoodley and Schmahmann, 2010, 2009; Stoodley et al, 2012). Together, this work underscores the importance of investigations of cerebellar sub-regions, as aging may differentially impact regions of the cerebellum associated with cognitive and motor function, and indeed some work has begun to address this question.…”

“…A complete overview of the findings of studies investigating connectivity in aging is beyond the scope of this review, and it has recently been reviewed elsewhere (Ferreira and Busatto, 2013). However, the utility of fcMRI to better understand the aging brain is clear, though there has been relatively little work to date investigating cerebello-cortical networks, with the exception of one study (Bernard et al, 2013). With that said, some of the work investigating resting state networks in the aging brain has implicated the cerebellum.…”

“…Recently, we directly investigated cerebello-cortical resting state networks in young and older adults (Bernard et al, 2013). Using masks of each lobule of the right hemisphere and vermis, we were able to compare resting state networks in older adults to those that we had previously defined in young adults (Bernard et al, 2012), while controlling for lobular volume.…”

“…Importantly, decreased connectivity in the cerebello-cortical networks was also behaviorally relevant. That is, connectivity strength was correlated with both motor (manual dexterity, timing, balance confidence) and cognitive (working memory) performance in older adults (Bernard et al, 2013), with greater connectivity strength associated with better performance. While more work investigating cerebello-cortical networks in older adults is needed, these findings further highlight the role of the cerebellum in aging.…”

“…Altered interactions between the cerebellum and the cortex or basal ganglia due in part to the process of normal aging have the potential to result in a variety of behavioral disruptions. In particular, the disrupted cortico-cerebellar networks (Bernard et al, 2013), along with both the morphological and functional differences between the cerebella of young and older adults (eg. Bernard and Seidler, 2013; Bo et al, 2011b; Carp et al, 2011; Eckert et al, 2010; Raz et al, 2000) may affect the formation of new internal models, and/or result in the degradation of existing internal models of both motor and cognitive behaviors.…”