Co-Administration of Galvanic Vestibular Stimulation and Transauricular Vagus Nerve Stimulation in Parkinson's Disease

Parkinson's disease (PD) is a chronic, disabling neurodegenerative condition affecting a growing worldwide population. There is no cure, and prevailing drug therapies provide only partial relief. Therapeutic interest has therefore increased in non-invasive brain stimulation (NIBS). In most studies, however, the different forms of stimulation have been applied singularly rather than together. Drawing on the facilitative effects of multisensory integration, this thesis investigated, for the first time in PD, the safety, feasibility and potential effects of co-administering transauricular vagus nerve stimulation (ta-VNS) and galvanic vestibular stimulation (GVS). Chapter 1 develops the rationale for this dual-stimulation approach. Chapter 2 reports Study 1, in which participants allocated by matching to ta-VNS, GVS or dual stimulation received sham and active stimulation blocks. Co-administration was not associated with serious adverse events or an increased frequency of minor reactions, and participant compliance was high. Chapter 3 reports Study 2, a single-blind active-comparator study of six stimulation sessions delivered over two weeks, with assessments at baseline, post-stimulation and four-week follow-up. Baseline-adjusted linear mixed models identified Time × Stimulation Type interactions for global cognition and sleep quality however these did not confer an advantage for dual stimulation over unilateral stimulation. As a general pattern, participants across all three treatment arms improved similarly over the course of study. Heart rate variability analyses indicated that all three active conditions increased the mean interval between successive heartbeats within sessions, with this response reaching asymptote earlier during dual stimulation. Chapter 4 examines participant and companion interviews thematically and integrates the qualitative motor findings with UPDRS Part III Motor Examination change. Thirty-two of 40 participants contributed at least one positive qualitative motor code, and 22 showed individual-level convergence between a positive qualitative finding and objective motor improvement. However, neither the presence nor the number of positive motor codes was significantly associated with UPDRS Part III improvement at sample level. Exploratory analyses also did not establish physical activity, age, disease duration, medication burden, cognition, mood, sleep, fatigue or physical comorbidity as reliable predictors of motor response after correction for multiple comparisons. Together, these findings indicate that co-administered ta-VNS and GVS is feasible and tolerable and may produce a distinctive temporal pattern of cardiac autonomic response. As Study 2 did not include a sham condition, improvement common to all active groups cannot be separated from expectancy, repeated assessment, researcher contact, regression to the mean or natural fluctuation in PD. Adequately powered sham-controlled studies are therefore required before absolute efficacy or superiority of dual stimulation can be established.