Person:

Zhou, Junhong

Background: Impaired motor control is one of the most common symptoms of multiple system atrophy (MSA). It arises from dysfunction of the cerebellum and its connected neural networks, including the primary motor cortex (M1), and is associated with altered spontaneous (i.e., resting-state) brain network activity. Non-invasive repetitive transcranial magnetic stimulation (rTMS) selectively facilitates the excitability of supraspinal networks. Repeated rTMS sessions have been shown to induce long-term changes to both resting-state brain dynamics and behavior in several neurodegenerative diseases. Here, we hypothesized that a multi-session rTMS intervention would improve motor control in patients with MSA, and that such improvements would correlate with changes in resting-state brain activity. Methods: Nine participants with MSA received daily sessions of 5 Hz rTMS for 5 days. rTMS targeted both the cerebellum and the bilateral M1. Before and within 3 days after the intervention, motor control was assessed by the motor item of the Unified Multiple System Atrophy Rating Scale (UMSARS). Resting-state brain activity was recorded by blood-oxygen-level dependency (BOLD) functional magnetic resonance imaging. The “complexity” of resting-state brain activity fluctuations was quantified within seven well-known functional cortical networks using multiscale entropy, a technique that estimates the degree of irregularity of the BOLD time-series across multiple scales of time. Results: The rTMS intervention was well-attended and was not associated with any adverse events. Average motor scores were lower (i.e., better performance) following the rTMS intervention as compared to baseline (t8 = 2.3, p = 0.003). Seven of nine participants exhibited such pre-to-post intervention improvements. A trend toward an increase in resting-state complexity was observed within the motor network (t8 = 1.86, p = 0.07). Participants who exhibited greater increases in motor network resting-state complexity demonstrated greater improvement in motor control (r2= 0.72, p = 0.004). Conclusion: This pilot study demonstrated that a five-session rTMS intervention targeting the cerebellum and bilateral M1 is feasible and safe for those with MSA. More definitive, well-controlled trials are warranted to confirm our preliminary results that rTMS may alleviate the severity of motor dysfunction and modulate the multiscale dynamics of motor network brain activity.

Gait speed and gait variability are clinically meaningful markers of locomotor control that are suspected to be regulated by multiple supraspinal control mechanisms. The purpose of this study was to evaluate the relationships between these gait parameters and the functional connectivity of brain networks in functionally limited older adults. Twelve older adults with mild-to-moderate cognition “executive” dysfunction and relatively slow gait, yet free from neurological diseases, completed a gait assessment and a resting-state fMRI. Gait speed and variability were associated with the strength of functional connectivity of different brain networks. Those with faster gait speed had stronger functional connectivity within the frontoparietal control network (R = 0.61, p = 0.04). Those with less gait variability (i.e., steadier walking patterns) exhibited stronger negative functional connectivity between the dorsal attention network and the default network (R = 0.78, p < 0.01). No other significant relationships between gait metrics and the strength of within- or between- network functional connectivity was observed. Results of this pilot study warrant further investigation to confirm that gait speed and variability are linked to different brain networks in vulnerable older adults.