Master of Science (MSc)
Faculty of Science
Quincy J. Almeida
It has been well established that motor symptoms in Parkinson’s disease (PD) are primarily associated with dopaminergic degeneration in the basal ganglia. However, symptoms which respond poorly to dopaminergic replacement, such as tremor, gait, and balance deficits, point to an alternative pathology to dysfunction of the basal ganglia. Over-activity of the cerebellum has been demonstrated in PD, however it is not entirely clear how the cerebellum might be affecting motor symptoms. A lack of consensus exists regarding how cerebellar over-activity might be influencing PD tremor, and whether resting and postural tremor are differentially influenced by cerebellar dysfunction. It is also unclear how cerebellar over-activity might be affecting gait and balance deficits in PD, even though the cerebellum is an important subcortical structure for the control of gait and balance. Thus, the aim of the current thesis was to assess how cerebellar over-activity may be influencing symptoms which respond poorly to dopamine replacement in PD by inhibiting cerebellar activity using repetitive transcranial magnetic stimulation (rTMS). Additionally, a direct comparison was made between the effects of stimulation targeted to the medial versus lateral cerebellum with the aim to localize the effect of cerebellar over-activity. Fifty PD participants were randomly assigned to receive stimulation over either the medial cerebellum (n=20), lateral cerebellum (n=20) or sham stimulation (n=10). 900 pulses at 1Hz were delivered at an intensity of 120% resting motor threshold determined from the first dorsal interosseous muscle representation in the primary motor cortex. Tremor was assessed quantitatively using a wireless finger accelerometer to record tremor. Balance was measured with objective, computerized protocols: modified clinical test of sensory integration and balance (m-CTSIB) and postural stability testing (PST). Spatiotemporal gait parameters were measured quantitatively during self-paced walking. All assessments were performed before and after either real or sham stimulation. Resting tremor frequency was reduced in tremor-dominant individuals, regardless of whether stimulation was applied over the medial (p=0.024) or lateral (p=0.033) cerebellum, but not in the sham group. Additionally, inhibition of the cerebellum did not result in modulation of gait and balance outcome measures. Hence, dysfunction of the cerebellum may be a contributing factor to resting tremor, but not gait and balance deficits in PD. Importantly, the improvements in resting tremor occurred without detriment to gait or balance, demonstrating the therapeutic potential of this stimulation protocol. Low frequency rTMS over the medial or lateral cerebellum provides promise of an alternative treatment for resting tremor in PD, a symptom that is poorly responsive to dopaminergic replacement.
Lefaivre, Shannon C., "The Contribution of the Cerebello-thalamo-cortical Circuit to the Pathology of Non-dopaminergic Responsive Parkinson's Disease Symptoms" (2016). Theses and Dissertations (Comprehensive). 1832.