Thesis (Ph. D.)--Rutgers University, 2009. / "Graduate Program in Integrative Neuroscience." Includes bibliographical references (p. 203-218).

Thesis (Ph. D.)--Washington State University, December 2009. / Title from PDF title page (viewed on Dec. 9, 2009). "College of Education." Includes bibliographical references (p. 84-88).

Thesis (Ph. D.)--York University, 2000. Graduate Programme in Psychology. / Typescript. Includes bibliographical references (leaves 209-273). Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: http://wwwlib.umi.com/cr/yorku/fullcit?pNQ59157.

Electrical stimulation has been a controversial treatment option for acquired dysphagia since the initial study by Freed, Freed, Chatburn, and Christian (2001). This report investigates the efficacy of electrical stimulation by addressing three issues related to the use of this technique: 1) the movement of the hyolaryngeal complex during stimulation, 2) the population(s) for which electrical stimulation is efficacious, and 3) the necessity of combining electrical stimulation with traditional treatments for the treatment to be effective. Twenty-two studies were evaluated and revealed overall positive findings for the use of electrical stimulation as a treatment technique. To further analyze the strength of these findings, the studies were evaluated for methodological limitations with regards to participant selection, treatment design, and outcome measure selection. This analysis revealed two main methodological limitations: 1) a lack of established treatment protocol which led to differences in how and with what other techniques electrical stimulation was used and 2) an absence of follow-up measures. While these factors do not appear to affect the applicability of the study findings, future research should focus developing a treatment protocol and investigating the long-term benefits of electrical stimulation treatment. / text

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.

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Electrical potentials are the fundamental currency of communication in the nervous system. The advanced executive functions of the prefrontal cortex and the motor commands delivered to the neuromuscular junction, though involved with very different aspects of behavior, both rely on time-varying electrical signals. It is possible to "listen to" the internal communications of the nervous system by measuring the electrical potentials in the extra-cellular space. However, this is only meaningful if there is some way to interpret these signals, which are incredibly complicated and information rich. This dissertation represents an attempt to decode some of these signals in order to reveal their significance for behavior and function. The first study is an investigation of the relationship between different elements of the local field potential in the prefrontal cortex and memory consolidation. It is shown that certain electrographic signatures of non-rapid eye movement sleep, namely K-complexes and low-voltage spindles, are correlated with neuronal replay of recent experiences. It is also shown that the global fluctuations of activity in the population of cells, known as up/down states, is correlated with neuronal replay. Finally, it is shown that high-voltage spindles are not correlated with memory replay, and are therefore functionally different from low-voltage spindles. The second study focuses on the relationship between movements of the upper limb and the coordinated neural control, as measured by the electromyogram (EMG), of the muscles generating that movement. We show that different probability-based models can be used to predict what the pattern of EMG in the different muscles will be for any given kinematic state of the hand. In the third study it is demonstrated that the kinematic output associated with a particular pattern of EMG can be reproduced with electrical stimulation. Thus, it is not only possible to understand the commands issued by the nervous system, it is also possible to issue commands by interfacing with the nervous system directly. Finally, the design for an experiment that would combine EMG prediction with translation of EMG into electrical stimulus patterns is presented. The objective of this study would be to use these methods to fully control the upper limb in a way that would be useful for a functional electrical stimulation-based neuroprosthetic for spinal cord injured 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.

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.