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。震颤就是这样一种障碍，是由参与运动控制的大脑区域夸大的节律活动引起的。到目前为止，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，脑深部刺激已成为治疗疾病症状的一种普遍选择。脑深部刺激是一种有效的外科治疗方法，它通过电池供电的脑起搏器对大脑关键区域进行常规和高频的电刺激。刺激是有效的，但不幸的是，可能会影响其他功能，从而产生副作用，影响患者的言语、平衡和冲动。这是因为目前使用的刺激形式不能区分疾病和正常的大脑活动。封闭式研究计划旨在改变刺激的传递方式，使其优先扰乱与疾病相关的大脑活动，使正常活动相对较少。为此，我将开发理论模型，以了解大脑在健康和疾病中是如何组织的。理论模型是一种强大的工具，可以用来研究不同细节水平的大脑功能，并改进临床可检验的假说。我将询问理论模型，以确定如何有选择地扰乱与疾病相关的大脑活动，并随后在一组帕金森病和特发性震颤患者中试验这种新的刺激模式，这些患者已经植入了大脑深部刺激电极来治疗他们的震颤。这项工作将为我们理解疾病期间大脑是如何组织的做出重大贡献，并至关重要的是将告诉我们如何改进治疗方法，使其具有病理学特异性，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.