Doctor of Philosophy (PhD)
Kinesiology and Nutrition Sciences
First Committee Member
Second Committee Member
Third Committee Member
Fourth Committee Member
Number of Pages
Parkinson's disease (PD) is the most common movement disorder and the second most common neurodegenerative disorder. PD is characterized by dopaminergic cell loss in the substantia nigra pars compacta, which leads to a reduction in dopamine in the striatum. These physiological mechanisms lead to a number of motor impairments such as bradykinesia, rigidity, tremor, and postural instability that severely limit the ability of individuals with PD to perform many essential daily living activities. Although current pharmacological, surgical, and physical exercise treatment approaches are valuable they are either only mildly effective, expensive, or associated with a variety of side effects. Therefore, development of new adjunct interventions that are effective and have a realistic potential to be implemented into clinical practice would be highly beneficial.
The current pharmaceutical, surgical, and management strategies for PD are directed towards relieving the symptoms associated with PD. Levodopa combined with other medications represents the standard treatment for PD, but their efficacy diminishes over time and leads to side effects such as dyskinesia. For advanced PD, deep brain stimulation is the established surgical approach and can improve motor function and quality of life. Nonetheless, deep brain stimulation is associated with surgical contraindications, high costs, neuropsychiatric side effects, and is not effective in treating non-motor PD symptoms. Physical exercise is also commonly prescribed in PD primarily based on animal studies, but the magnitude of these positive effects has generally not been achieved in humans. However, not all patients have the ability, financial resources, available facilities, or determination to engage in long-term high intensity exercise programs to realize their benefit. While several forms of exercise can induce clinically significant motor improvements in PD, the most successful strategy to improve motor function would likely entail pairing adjunctive therapies with rehabilitation to enhance or complement the effects of exercise.
Non-invasive brain stimulation methods such as repetitive transcranial magnetic stimulation (rTMS) have shown promise in alleviating PD symptoms, but practical limitations as well as inconsistent or mild positive effects limit its clinical applicability. Recently, transcranial direct current stimulation (tDCS) has emerged as a powerful brain stimulation technique that can enhance motor performance and cortical function in PD. Most importantly, tDCS is now regarded to be a more effective form of non-invasive brain stimulation compared to rTMS in PD. In addition, tDCS offers several important advantages over rTMS such as portability, safety, ease of administration, ability to be delivered during motor activities, a superior ability to blind participants with SHAM stimulation, and low cost (as low as $400 versus $20,000-100,000 for rTMS). Taken together, these lines of reasoning strongly suggest that tDCS may represent such an intervention with a realistic potential to be translated into clinical practice.
Anodal tDCS of motor cortex (M1) improves motor performance in young adults, older adults, stroke, and in PD. This involves passing a current over M1 through surface electrodes, which increases M1 excitability for ~90 minutes. Accordingly, most M1-tDCS studies have found improvements in motor performance of approximately 10-15% during or after a single 10-20 minute session when compared to motor practice alone in young adults and old adults as well as in PD. Most importantly, longer-term studies lasting between 3 days and 2 weeks have documented that these improvements in performance can be increased to up about 20-30% compared to a single M1-tDCS session in healthy adults and in one notable study in PD. Despite these positive findings involving M1-tDCS in PD, development of new non-invasive brain stimulation techniques or the targeting of additional brain areas could provide additional avenues to improve motor function in PD. Recently, tDCS delivered to the cerebellum (c-tDCS) has also been reported to significantly improve motor skill in young and old adults. The ability of c-tDCS to impact motor skill learning in older adults is particularly interesting because accumulating evidence suggests that the cerebellum may be the primary brain area responsible for the movement impairments often observed in by older adults. Similarly, the cerebellum has recently been implicated in contributing to the motor deficits associated with PD. Despite these observations, no studies have examined the influence of c-tDCS on motor learning in PD, given that most individuals with PD are older adults.
The M1 projections to upper limb motor neurons play a predominant role in the generation and execution of skilled movements. However, M1 output depends on inputs from sources such as premotor cortex, contralateral M1, and basal ganglia along with crucial contributions from cerebellum, which is strongly involved in movement timing, multi-joint coordination, agonist and antagonist muscle interactions, and error detection in goal-directed movements. Although PD is primarily a basal ganglia disorder, the widespread cerebellar involvement in PD pathophysiology based on mounting anatomical, physiological, and clinical evidence forms the basis for targeting it with c-tDCS. In addition, more specific evidence provides further rationale for c-tDCS in PD treatment: 1) previously unknown bi-directional pathways have recently been discovered between basal ganglia and cerebellum and M1-tDCS has been shown in animal and human physiological studies to induce remote effects in anatomically interconnected CNS regions (basal ganglia, thalamus, pain centers, spinal cord). For example, M1-tDCS increased striatal extracellular dopamine levels in rats and improved their motor function. The evidence for tDCS remote effects provides support for the idea that c-tDCS may indirectly impact basal ganglia in PD; 2) impaired cerebellar function in PD may be a compensatory mechanism that attempts to diminish the negative influences of abnormal basal ganglia activity as PD patients with greater cerebellar activity exhibit better motor function. Thus, c-tDCS may improve function by enhancing these compensatory processes by increasing cerebellar activity; 3) c-tDCS improves motor performance in young and older adults and tDCS of M1 improves performance in these populations and in PD; 4) tDCS efficacy scales with age and impairment level due to motor disorders making improvements in PD more likely to occur; and 5) c-tDCS led to greater improvements in an arm movement task compared to M1-tDCS in young adults. Collectively, these factors and the positive effects on motor performance obtained in several studies involving c-tDCS in young and older adults provide strong rationale for the investigation of c-tDCS for PD treatment. Despite these interrelated lines of reasoning, no studies have examined the influence of c-tDCS on motor performance in PD in either the short or long-term.
Therefore, the overall purpose of this dissertation was to determine the influence of c-tDCS on motor skill acquisition, motor learning, and transfer of motor learning in PD. This was accomplished through a series of 3 interrelated studies. For the first study (Chapter 2), the primary purpose was to examine the influence of a single session of c-tDCS on motor performance in a complex, visuomotor isometric precision grip task (PGT) in PD. The secondary purpose was to determine the influence of c-tDCS on the transfer of motor performance in PD. Based on c-tDCS studies involving practice of hand and arm tasks in young and older adults and M1-tDCS studies in PD, it was hypothesized that c-tDCS would increase motor performance in the PGT and in the transfer tasks to a greater extent than SHAM stimulation in PD. Therefore, the major methodological aspects of study 1 that distinguished it from the subsequent studies included: 1) it involved acute application of c-tDCS in a single experimental session; 2) it utilized only one primary motor task that was performed concurrently with administration of c-tDCS; 3) it also investigated the influence of c-tDCS on transfer of motor performance to motor tasks not performed simultaneously with c-tDCS and not practiced extensively; and 4) all experimental testing was conducted while participants were off of their medications; and 5) it utilized a within-participants design. Therefore each participant underwent both the c-tDCS and SHAM conditions. The within-participants design was chosen in this study as it has the advantage of being able to minimize the possible inter-individual response to c-tDCS. The main findings of the study were that a single session of c-tDCS did not elicit improvements in motor performance or transfer of motor performance in hand and arm tasks in PD
In the second study (Chapter 3), the purpose was to determine the effects of c-tDCS on motor performance in PD while participants were on medications. This was accomplished by having participants perform two motor tasks with their most affected hand in a baseline condition and in an experimental condition. Most importantly, one group of participants received c-tDCS during performance of the motor tasks in the experimental condition, whereas the other group received SHAM stimulation. The major methodological features of study 2 that distinguished it in most aspects from the two other studies included: 1) it involved acute application of c-tDCS in a single experimental session; 2) it comprised two different motor tasks that were performed concurrently with administration of c-tDCS; 3) it did not investigate the influence of c-tDCS on transfer of motor performance to untrained tasks; 4) all experimental testing was conducted while participants were on their medications; 5) it utilized a between-participants design. Thus, two groups of PD participants were utilized and allocated into either a c-tDCS or SHAM group. The main findings of the study were that a single session of c-tDCS did not elicit enhancements in motor performance in either of the hand and arm tasks performed concurrent with c-tDCS in PD.
In the third study (Chapter 4), the primary purpose was to determine the influence of long-term application of c-tDCS on motor learning in PD. The secondary purpose was to examine the influence of long-term application of c-tDCS on transfer of motor learning in PD. This was accomplished by employing a long-term training study. Specifically, 9 practice sessions were performed over a 2 week period that involved extensive practice of an isometric pinch grip task (PGT) and a rapid arm movement task (AMT). These practice tasks were performed over a 25 minute period concurrent with either c-tDCS or SHAM stimulation. A set of transfer tasks that included clinical rating scales, manual dexterity tests, and lower extremity function assessments were quantified in test sessions at Baseline, 1, 14, and 28 days after the end of practice (EOP). Thus, the major methodological features of study 3 that distinguished it in most aspects from the two other studies included: 1) it involved chronic application of c-tDCS over 9 practice sessions and was concerned with the effect of c-tDCS on long-term motor learning; 2) it comprised two different motor tasks that were performed concurrently with administration of c-tDCS; 3) it investigated the influence of c-tDCS on transfer of motor learning to untrained tasks; 4) experimental testing was conducted while participants were both off and on their medications; 5) it utilized a between-participants design. Thus, participants were allocated into either a c-tDCS or SHAM group. The main findings of the study were that long-term application of c-tDCS concurrent with motor practice did not enhance motor learning to a greater extent than practice alone in PD. Similarly, long-term application of c-tDCS did not increase transfer of motor learning in PD.
In summary, this dissertation examined the influence of c-tDCS on motor skill acquisition, motor learning, and transfer of motor learning in PD. Collectively, the findings provided no evidence that c-tDCS applied in either the short or the long-term is an effective intervention to improve motor function in PD.
Brain Stimulation; Cerebellum; Motor Control; Parkinson's Disease; Pinch Grip; Skill Acquisition
Kinesiology | Medical Neurobiology | Neuroscience and Neurobiology | Neurosciences
University of Nevada, Las Vegas
Lima De Albuquerque, Lidio, "The Influence of Cerebellar Transcranial Direct Current Stimulation on Motor Function in Parkinson’s Disease" (2020). UNLV Theses, Dissertations, Professional Papers, and Capstones. 4006.
IN COPYRIGHT. For more information about this rights statement, please visit http://rightsstatements.org/vocab/InC/1.0/