Effects of rhythmic auditory stimulation on upper-limb movements and functions, and its neural mechanism in people with Parkinson's disease

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the degeneration of the substantia nigra, leading to dopamine deficiency and motor symptoms—such as bradykinesia—that significantly affect daily functions. Although dopaminergic medications offer initial symptomatic relief, their long-term use is frequently associated with diminished efficacy and undesirable side effects, highlighting the need for other therapeutic strategies. Rhythmic auditory stimulation (RAS) offers a promising non-pharmacological approach to ameliorate the symptoms. It uses rhythmic auditory cues to facilitate movements by engaging auditory-motor circuits, which potentially bypass impaired basal ganglia pathways. RAS has demonstrated effects on enhancing gait in patients with PD. Upper-limb bradykinesia is also a prominent symptom in PD that impairs daily activities by reducing movement speed and amplitude during tasks such as buttoning clothes, writing, and eating. However, current research has paid less attention to the sequelae of upper-limb impairments on PD, and the effects of RAS on the neural mechanism of improving the upper limb in patients with PD remain unclear. Therefore, this dissertation aimed to determine effects of RAS on upper-limb movements, daily functions, and neural activity in patients with PD. Study 1 employed a repeated-measures design to investigate immediate effects of different RAS tempi on upper-limb movements in patients with PD. Faster RAS induced faster upper-limb movements in both patients with PD and healthy controls, providing preliminary evidence for RAS effectiveness on upper-limb movements in patients with PD. To establish neural responses to RAS without PD pathology interference, we first studied healthy older people for understanding on the underpinning mechanism. Study 2 employed a repeated-measures design using electroencephalography to investigate the immediate effects of RAS tempi on finger tapping and neural activity in healthy older people. Faster RAS induced faster finger tapping, but motor cortex activation remained constant across tempi. These findings may suggest that RAS facilitated movements through timing rather than cortical activation. Study 3 was a randomized controlled trial (RCT) to investigate effects of 7-day upper-limb training involving RAS on upper-limb movements, daily functions, and neural activity in healthy older people. RAS improved upper-limb movements and daily functions as well as increased neural activation in motor and auditory cortices was found. These findings supported effectiveness of RAS incorporated in training on upper-limb movements and daily functions in healthy older people and provided new insights into underlying mechanisms of RAS. Study 4 was an RCT to investigate effects of 21-day upper-limb training involving RAS on upper-limb movements, daily functions, and neural activity in patients with PD. RAS improved upper-limb movements, daily functions, and changed neural activation in motor and auditory cortices in patients with PD. The neural activation in healthy older people (Study 3) and patients with PD (Study 4) responded to RAS in different ways. Our findings supported effectiveness of RAS in combination with rehabilitation training on enhancing upper-limb movements and daily functions in patients with PD and provided new insights into PD-specific neural changes to RAS. In conclusion, these studies substantiated immediate effects of RAS and effects of RAS incorporated in training on upper-limb movements, daily functions, and neural activity in both healthy older people and patients with PD respectively. These studies in this thesis provided healthcare practitioners with new guidelines of addressing upper-limb bradykinesia and daily dysfunction in patients with PD. These studies in this thesis also shed lights for new insights in the cortical neural changes in response to RAS, which may inspire optimized interventions involving RAS for upper limb training for patients with PD in future.