Abstract
Healthy aging is associated with decline in basic motor functioning and higher motor control. Here, we investigated age-related differences in the brain-wide functional connectivity (FC) pattern of the subthalamic nucleus (STN), which plays an important role in motor response control. As earlier studies revealed functional coupling between STN and basal ganglia, which both are known to influence the conservativeness of motor responses on a superordinate level, we tested the hypothesis that STN FC with the striatum becomes dysbalanced with age. To this end, we performed a seed-based resting-state analysis of fMRI data from 361 healthy adults (mean age: 41.8, age range: 18–85) using bilateral STN as the seed region of interest. Age was included as a covariate to identify regions showing age-related changes of FC with the STN seed. The analysis revealed positive FC of the STN with several previously described subcortical and cortical regions like the anterior cingulate and sensorimotor cortex, as well as not-yet reported regions including central and posterior insula. With increasing age, we observed reduced positive FC with caudate nucleus, thalamus, and insula as well as increased positive FC with sensorimotor cortex and putamen. Furthermore, an age-related reduction of negative FC was found with precuneus and posterior cingulate cortex. We suggest that this reduced de-coupling of brain areas involved in self-relevant but motor-unrelated cognitive processing (i.e. precuneus and posterior cingulate cortex) from the STN motor network may represent a potential mechanism behind the age-dependent decline in motor performance. At the same time, older adults appear to compensate for this decline by releasing superordinate motor control areas, in particular caudate nucleus and insula, from STN interference while increasing STN-mediated response control over lower level motor areas like sensorimotor cortex and putamen.
Highlights
The proportion of the world’s population over 60 years of age will presumably double from about 11–22% between the years 2000 and 20501
The subthalamic nucleus (STN) is an integral part of current models of basal ganglia motor functions, which differentiate direct and indirect striatal output pathways, originating from different neuronal populations and which are characterized by opposite end-effects (Weintraub and Zaghloul, 2013)
The STN’s functional connectivity (FC) with the caudate nucleus and with the central insula declined with age, but at the same time increased with the putamen and right M1
Summary
The proportion of the world’s population over 60 years of age will presumably double from about 11–22% (i.e., amounting to 2 billion people) between the years 2000 and 20501. 1www.who.int/ageing a more widespread involvement of prefrontal cortex and basal ganglia, which might reflect an increased reliance on cognitive control mechanisms, in compensation for lower level sensorimotor processing deficits (Seidler et al, 2010). The STN is an integral part of current models of basal ganglia motor functions, which differentiate direct and indirect striatal output pathways, originating from different neuronal populations and which are characterized by opposite end-effects (Weintraub and Zaghloul, 2013). The direct pathway represents inhibitory circuits from the striatum to the internal segment of the globus pallidus, leading to a decreased inhibition of the ventrolateral thalamic nucleus, which in turn is associated with motor facilitation
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