Neurophysiology and Neuromodulation: Incorporating Task Training to Harness Cerebellar Neuroplasticity in Rehabilitation

Abstract

Dystonia is a neurologic movement disorder characterized by involuntary muscular contractions that may be sustained or intermittent, resulting in abnormal movement and postures. The burden associated with dystonia is considerable as there is no cure or known pathophysiology. Despite the immediate need for innovative treatments, alternative interventions are barred by a lack of understanding of the pathology and mechanism of dystonia. To develop and refine effective rehabilitative interventions for patients with focal dystonia, the pathology must be better understood and methods to assess corticospinal excitability refined. There are emerging lines of evidence that suggest there is an altered balance of inhibition and excitation contributing to the cause of dystonia. This may be due to dysfunctional interplays between the cerebellum, basal ganglia and motor cortex that generate network dysfunction. One strategy to study the affected brain regions in people with dystonia is via the use of non-invasive brain stimulation to measure and modulate motor cortical excitability. The overall goal of this dissertation is to evaluate the use of non-invasive brain stimulation, using both transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), to assess and modulate aspects of neurophysiology and neuroplasticity in people with cervical dystonia (CD) and healthy controls. Four studies were designed to achieve this research goal. 1) The first study evaluated the validity of using fine-wire electrodes to record motor evoked responses. Fine-wire electrodes were found to be a valid means to record muscle responses, allowing the investigation of motor cortical excitability in small or intrinsic muscles that can be affected by dystonia. 2) The second study evaluated the use of cerebellar neuromodulation with simultaneous task training in healthy adults. This investigation revealed that cerebellar neuromodulation interfered with practice-related changes in corticospinal excitability. 3) The third study evaluated ipsilateral and contralateral motor evoked responses in the upper trapezius between people with CD and controls and provided evidence that inhibitory responses are asymmetrically regulated in people with CD. 4) The fourth study explored the use of cerebellar tDCS to modulate eye-blink classical conditioning and measures of motor cortical excitability. The results suggest poor conditioning responses in all participants, limiting the interpretation of the study; however, no differences between groups were detected in outcomes of motor cortical excitability. These studies add to our understanding of how non-invasive brain stimulation may be used to assess measures of excitation and inhibition in-vivo to probe aspects of neuroplasticity and the effects of neuromodulation.