Resting‐state functional connectivity of subcortical locomotor centers explains variance in walking capacity

Abstract

Walking capacity influences the quality of life and disability in normal aging and neurological disease, but the neural correlates remain unclear and subcortical locomotor regions identified in animals have been more challenging to assess in humans. Here we test whether resting-state functional MRI connectivity (rsFC) of midbrain and cerebellar locomotor regions (MLR and CLR) is associated with walking capacity among healthy adults. Using phenotypic and MRI data from the Nathan Kline Institute Rockland Sample (n =119, age 18-85), the association between walking capacity (6-min walk test distance) and rsFC was calculated from subcortical locomotor regions to 81 other gait-related regions of interest across the brain. Additional analyses assessed the independence and specificity of the results. Walking capacity was associated with higher rsFC between the MLR and superior frontal gyrus adjacent to the anterior cingulate cortex, higher rsFC between the MLR and paravermal cerebellum, and lower rsFC between the CLR and primary motor cortex foot area. These rsFC correlates were more strongly associated with walking capacity than phenotypic variables such as age, and together explained 25% of the variance in walking capacity. Results were specific to locomotor regions compared with the other brain regions. The rsFC of locomotor centers correlates with walking capacity among healthy adults. These locomotion-related biomarkers may prove useful in future work aimed at helping patients with reduced walking capacity.

The Functional and Structural Neural Correlates of Dynamic Balance Impairment and Recovery in Persons with Acquired Brain Injury

“…The role of the putamen in gait and gait kinematics has been demonstrated in studies involving healthy adults [27,48] , and in stroke [21,49] . Lastly, the resting state FC analysis revealed a correlation between cerebro-cortical areas and dynamic balance recovery (10MWT) which is also consistent with previous studies highlighting the involvement of the cerebellum and the cerebral cortices in gait and balance control in relation to healthy subjects [50,27] , and post-brain injury [51,52] . Our results highlight the potential contribution of these cortical and subcortical brain areas to dynamic balance and gait related recovery following brain injury.…”

Deep brain activation patterns involved in virtual gait without and with a doorway: An fMRI study

“…During mental imagery of simple or unobstructed gait in healthy subjects, functional magnetic resonance imaging has shown similar brain area activations including SMA, parahippocampal, fusiform and lingual gyri, precuneus and cuneus, posterior cingulate, and visual cortices, putamen, subthalamic nucleus, MLR and cerebellar vermis and cortex activation, with decreased activity in the vestibular and somatosensory cortices [7–14]. Recently, resting state functional MRI connectivity of the MLR and cerebellar locomotor region was found to be related to gait capacity [15], and activation of the left PPN of the MLR to the speed of imaginary gait [10]. Very few studies have examined mental imagery of complex gait.…”

Resting state connectivity within the basal ganglia and gait speed in older adults with cerebral small vessel disease and locomotor risk factors

“…Evidence for a link between connectivity and gait speed is recent, and primarily for cortical networks ( Boyne et al, 2018 , Crockett et al, 2017 , Di Scala et al, 2019 , He et al, 2016 , Hsu et al, 2018 , Hsu et al, 2014 , Hugenschmidt et al, 2014 , Liem et al, 2017 , Lo et al, 2018 , Poole et al, 2019 , Taniwaki et al, 2007 , Yuan et al, 2015 , Zwergal et al, 2012 ), with few studies examining subcortical regions and basal ganglia in particular ( Boyne et al, 2018 , Zwergal et al, 2012 ). Previous studies have shown both higher and lower connectivity in relation with faster gait.…”

“…Higher co-activation at rest among regions is interpreted as a measure of higher intrinsic connectivity or cohesiveness between those regions. Initial evidence suggests that higher connectivity between basal ganglia and other regions predicts better motor performance in patients with Parkinsonian Syndromes ( Filippi et al, 2019 ) and in healthy adults ( Boyne et al, 2018 , Zwergal et al, 2012 ). However, prior studies have not accounted for the contribution of impairment of other age-related factors influencing locomotion including muscle strength ( McLean et al, 2014 ), vision ( Chaudhry et al, 2010 ), joint pain ( White et al, 2013 ), and obesity ( Vincent et al, 2010 ) as well as WMH and brain volume ( Rosso et al, 2017 ).…”