Neural Oscillations in Health and Disease

大多数神经和精神疾病是由复杂的神经回路驱动的。震颤就是这样一种疾病，由参与运动控制的大脑区域过度的节奏活动驱动。到目前为止，对疾病循环仍然知之甚少，治疗选择有限。由于长期治疗震颤的药物治疗的局限性，脑深部电刺激已成为疾病症状管理的普遍替代方案。脑深部电刺激是一种有效的外科治疗方法，它涉及通过电池供电的脑起搏器对关键脑区域进行定期和高频电刺激。刺激是有效的，但不幸的是，可能会影响其他功能，产生副作用，影响患者的语言，平衡和冲动。这是因为目前应用的刺激形式无法区分患病和正常的大脑活动。封闭的研究计划旨在改变刺激的传递方式，使其优先破坏与疾病相关的大脑活动，使正常活动相对保留。为此，我将开发理论模型来了解大脑在健康和疾病中是如何组织的。理论模型是一种强有力的工具，可以用来研究大脑功能的不同层次的细节，并完善临床可检验的假设。我将询问理论模型，以确定如何选择性地破坏与疾病相关的大脑活动，并随后在一组帕金森病和原发性震颤患者中试验这种新型刺激模式，这些患者已经植入了深部脑刺激电极用于治疗震颤。这项工作将为我们理解大脑在疾病期间是如何组织的做出重大贡献，并且至关重要的是，将告诉我们如何改进治疗以使其具有病理特异性，减少不必要的副作用。

Most neurological and psychiatric disorders are driven by complicated neural circuits. Tremor is one such disorder, driven by exaggerated rhythmic activity in brain regions involved in motor control. To date, disease circuit remains poorly understood and treatment options limited. Due to limitations of pharmacological therapy for long-term treatment of tremor, deep brain stimulation has become a prevalent alternative for management of disease symptoms. Deep brain stimulation is an effective surgical treatment, which involves regular and high frequency electrical stimulation of key brain regions by a battery powered brain pacemaker. Stimulation is effective, but unfortunately may affect other functions giving rise to side effects, impacting patients' speech, balance and impulsivity. This is because the form of stimulation presently applied cannot distinguish between diseased and normal brain activities. Enclosed research programme aims to alter the way stimulation is delivered so that it preferentially disrupts disease-related brain activities, leaving normal activity relatively spared. To this end, I will develop theoretical models to understand how brain is organized in health and disease. Theoretical models are powerful tools that can be used to investigate brain function in different levels of detail and to refine clinically testable hypothesis. I will interrogate theoretical models to determine how to selectively disrupt disease related brain activities and subsequently pilot this novel stimulation pattern in a group of Parkinson's disease and Essential Tremor patients, who have already been implanted with deep brain stimulation electrodes for treatment of their tremor. This work will provide significant contributions to our understanding of how brain is organized during disease, and crucially will inform us how treatment can be improved to be pathology specific, reducing unwanted side effects.