Transcranial direct current stimulation (tDCS) is a non-invasive stimulation technique that modulates brain function by increasing or decreasing cortical excitability (Nitsche & Paulus, 2001). In chronic stroke patients tDCS has been shown to improve function of the affected arm when combined with rehabilitative motor training (e.g. Lindenberg et al., 2010) and thus has the potential to accelerate motor learning. Its potential as a treatment for upper limb function in hemiplegic cerebral palsy (CP) had not been explored, which was the principle aim of this doctorate. After literature reviews on CP and tDCS (Chapter 1) feasibility work in healthy subjects was conducted to develop and validate the experimental procedures (Chapters 2 to 5). Chapter 2 examined whether tDCS improved motor performance of the non-preferred hand in healthy right-handed adults. The sophisticated kinematic outcome measures detected changes in performance due to learning, but no effect of tDCS was found. In Chapter 3, a novel motor learning task was developed and validated in healthy children and adolescents. This task was added to the study protocol and using a revised study design tDCS was found again to have no benefit on either motor performance or motor learning in healthy adults (Chapter 4). Tolerability, perception and acceptance of electrical stimulation were explored in Chapters 5 and 6, with the former showing that tDCS was well tolerated by healthy adults. Using a qualitative research methodology Chapter 6 established that teenagers with CP and their parents had concerns over the application of electricity on the scalp and how little is currently known of tDCS effects in CP. In Chapter 7, tDCS was applied to a teenager with hemiplegic CP with no clear beneficial effects. Finally, the contribution of this doctoral work with regard to the use of tDCS for the rehabilitation of motor function in CP is discussed in Chapter 8.

Anorexia Nervosa (AN) has the highest mortality rate of any psychiatric condition, and despite its recognition for centuries, remains a significant treatment challenge. Marked by firmly entrenched maladaptive beliefs about body, weight and food, as well as high rates of psychiatric comorbidity, AN is a chronic illness in a large proportion of patients. The neural substrates of AN are now beginning to emerge, and appear to be related to dysfunctional, primarily limbic, circuits driving pathological thoughts and behaviours. Deep Brain Stimulation (DBS) is a neurosurgical procedure where implanted electrodes are used to regulate activity in critical nodes comprising such aberrant circuits. The promise of DBS in motor-circuit conditions, such as Parkinson’s Disease, has driven it’s investigation in other circuit-based disorders, including some psychiatric conditions. Converging evidence from clinical and imaging literatures suggests that AN is in large part a disorder of emotional processing, wherein disordered mood, anxiety, and affective dysregulation contribute to disease maintenance and are obstacles to effective treatment. The subcallosal cingulate (SCC), a key medial frontal structure involved in affective processing, has further been directly implicated in AN relevant pathways. As such, this work had three broad objectives: i) to establish the safety and initial efficacy of SCC DBS in a group of chronic and highly-refractory AN patients; ii) to show that SCC DBS can have network wide cerebral metabolic influence, on AN-relevant circuits and structures; and, iii) to investigate whether structural brain features, including hippocampal volume changes, are correlated with clinical outcomes of DBS. Our results showed that DBS is safe in AN, and associated in some patients with significant improvements in mood, anxiety and, over time, weight and treatment-response. Imaging results further showed DBS to be associated with substantial changes in glucose utilization in disease-relevant circuits, with preliminary evidence supporting a relationship between hippocampal volume changes and clinical improvements. In the context of highly refractory disease, these promising results suggest that DBS can inform AN circuit models, and be explored as a novel therapeutic option for treatment-resistant patients.

Anorexia Nervosa (AN) has the highest mortality rate of any psychiatric condition, and despite its recognition for centuries, remains a significant treatment challenge. Marked by firmly entrenched maladaptive beliefs about body, weight and food, as well as high rates of psychiatric comorbidity, AN is a chronic illness in a large proportion of patients. The neural substrates of AN are now beginning to emerge, and appear to be related to dysfunctional, primarily limbic, circuits driving pathological thoughts and behaviours. Deep Brain Stimulation (DBS) is a neurosurgical procedure where implanted electrodes are used to regulate activity in critical nodes comprising such aberrant circuits. The promise of DBS in motor-circuit conditions, such as Parkinson’s Disease, has driven it’s investigation in other circuit-based disorders, including some psychiatric conditions. Converging evidence from clinical and imaging literatures suggests that AN is in large part a disorder of emotional processing, wherein disordered mood, anxiety, and affective dysregulation contribute to disease maintenance and are obstacles to effective treatment. The subcallosal cingulate (SCC), a key medial frontal structure involved in affective processing, has further been directly implicated in AN relevant pathways. As such, this work had three broad objectives: i) to establish the safety and initial efficacy of SCC DBS in a group of chronic and highly-refractory AN patients; ii) to show that SCC DBS can have network wide cerebral metabolic influence, on AN-relevant circuits and structures; and, iii) to investigate whether structural brain features, including hippocampal volume changes, are correlated with clinical outcomes of DBS. Our results showed that DBS is safe in AN, and associated in some patients with significant improvements in mood, anxiety and, over time, weight and treatment-response. Imaging results further showed DBS to be associated with substantial changes in glucose utilization in disease-relevant circuits, with preliminary evidence supporting a relationship between hippocampal volume changes and clinical improvements. In the context of highly refractory disease, these promising results suggest that DBS can inform AN circuit models, and be explored as a novel therapeutic option for treatment-resistant patients.

This research examines the summation characteristics of the neural network subserving self-stimulation reward. The data show that the neural network has two integrators that sum the signals produced by brain stimulation. The time constant of the first integrator is approximately 450 msec, whereas that of the second integrator is approximately 6.5 sec. Furthermore, these integrators are sensitive to the spatiotemporal arrival of the signals. / When prolonged stimulation is delivered at a high pulse frequency, the initial pulses contribute the most to the rewarding effect. Later pulses are affected by the reduced ability of the neurons or synapses to transmit signals along the neural network due to fatigue. / A fatigue effect may be dissipated by splitting a pulse train into two parts by an interval of no stimulation. This should increase the rewarding effectiveness of the pulse train. However, the rewarding effectiveness is dependent upon the duration of the interval of no stimulation and the magnitude of the two pulse-train halves. A long interval of no stimulation combined with a low stimulation magnitude may cause a frustration response and a decay in memory of the associations between the response, first pulse-train half, and second pulse-train half. These would make the rewarding effectiveness of the two pulse-train halves lower than that of a continuous pulse train. / Previous models of summation are unable to predict the present results. The data are explained in terms of a newly developed model of summation involving two central integrators and fatigue.

The phenomenon of self-stimulation has been used to map the neural circuitry of reinforcement and determine its neurophysiological and neurochemical characteristics. More recently, it has been proposed that drugs of abuse control behavior by their effects on the same neural systems. However, drug effects rise and fall over minutes or hours while conventional brain stimulation trains have abrupt onset and offset and last less than one second. Possibly because of this, the pattern of responding produced by drug reinforcers is different from the pattern produced by conventional brain stimulation. Furthermore, pharmacological antagonists of drug reinforcement increase the rate of drug self-administration while antagonists of brain stimulation reinforcement depress self-stimulation. To test the hypothesis that the differences in the characteristics of brain stimulation and drugs as reinforcers are due to differences in the kinetics of drugs and brain stimulation, we have modelled drug kinetics with frequency modulated brain stimulation trains. It is reported that animals will self-administer such brain stimulation and that, under these conditions, dopamine antagonists can induce an increase in the rate of self-administration.

Parkinson’s disease (PD) is a neurodegenerative movement disorder and a leading cause of neurological disability in the older adult population. Historically, the research and treatment of PD has focused on the associated motor symptoms. Now the non-motor symptoms such as sleep disturbance are becoming an increased focus for researchers. Deep brain stimulation (DBS) is a surgical intervention that has proven to be beneficial for PD motor symptom management. There are claims from the literature that DBS may assist with the phenomenon of sleep disturbance. A case study analysis was done to explore this concept in the DBS-PD patient population using the framework of the Symptom Management Theory. From the analysis of the subjective and objective data gathered it is clear that the phenomenon of sleep disturbance in this population is multifaceted and that DBS may play a role in managing the phenomenon of sleep disturbance for this population.

No description available.

Parkinson’s disease (PD) is a neurodegenerative movement disorder and a leading cause of neurological disability in the older adult population. Historically, the research and treatment of PD has focused on the associated motor symptoms. Now the non-motor symptoms such as sleep disturbance are becoming an increased focus for researchers. Deep brain stimulation (DBS) is a surgical intervention that has proven to be beneficial for PD motor symptom management. There are claims from the literature that DBS may assist with the phenomenon of sleep disturbance. A case study analysis was done to explore this concept in the DBS-PD patient population using the framework of the Symptom Management Theory. From the analysis of the subjective and objective data gathered it is clear that the phenomenon of sleep disturbance in this population is multifaceted and that DBS may play a role in managing the phenomenon of sleep disturbance for this population.

Thesis (Ph.D.) -- McMaster University, 1999. / Includes bibliographical references (leaves 130-151). Also available via World Wide Web.

Thesis (Ph.D.)--University of Western Australia, 2007.