Dynamic Neuromodulation

据估计，英国4%的人口患有原发性震颤，而大约127，000人患有帕金森病，使这些疾病的长期治疗成为医疗保健系统面临的主要挑战之一。脑深部电刺激是一种常用的治疗干预，它涉及对关键脑区的电刺激。最先进的刺激模式减弱了驱动疾病症状并导致症状抑制的大脑活动。然而，刺激也抑制与帕金森病和特发性震颤的运动症状无关的大脑活动，在高达50%的接受脑深部刺激治疗的患者中引起副作用。我相信，开发选择性地针对大脑活动驱动疾病症状的治疗策略可以减少刺激引起的副作用，并显着改善患者的生活质量。该提议源于临床需要，以改善刺激特异性，从而减少患者经历的副作用，并将这种强大的治疗干预的使用扩展到其他难以治疗的神经障碍。该提案的第一个目的是通过仔细定时刺激来选择性地抑制与疾病相关的大脑活动。关键是，我的目标是实现状态依赖性脑深部电刺激，它根据患者症状的严重程度动态调整治疗的关键方面（例如，提供多少刺激和刺激模式）。神经调节不仅可用于抑制导致疾病症状的大脑活动，还可用于增强在控制我们日常行为中起关键作用的神经活动。我的目标是开发刺激技术，以选择性地增强被认为有助于反应抑制和动作选择等行为的神经过程。促进神经活动以补偿损伤的可能性可能在未来管理强迫症和冲动性等治疗难治性疾病中发挥重要作用。该提案的第二个目的是从基本神经过程中学习，以设计更“自然”的治疗干预措施。帕金森病和特发性震颤的运动症状的脑活动可以被自发地抑制。例如，当患有震颤的患者进行运动时，震颤幅度显著降低。受我们大脑中发生的自然过程的启发，即使在疾病期间，治疗干预也可能提供一种有效的方法来减少疾病症状，同时保留与疾病过程无关的大脑活动。这项研究计划将产生令人兴奋的理论和实验工具，可用于了解不同的大脑区域如何交流和控制行为。至关重要的是，模仿我们的大脑通过刺激容易地控制疾病相关的神经活动的方式的概念是一种创新的途径，可以导致开发新型的治疗干预措施，不仅用于帕金森病和原发性震颤，而且用于由类似类型的大脑活动驱动的其他运动和精神疾病。

It is estimated that 4% of UK's population suffer from essential tremor while approximately 127,000 people live with Parkinson's disease, making long-term treatment of these conditions one of the key challenges facing the healthcare system. Deep brain stimulation is a commonly used therapeutic intervention, which involves electrical stimulation of key brain regions. State of the art stimulation patterns attenuate brain activity that drives disease symptoms and lead to symptom suppression. However, stimulation also suppresses brain activity not linked with motor symptoms of Parkinson's disease and essential tremor, inducing side effects in up to 50 % of the patients treated with deep brain stimulation. I believe developing therapeutic strategies that selectively target brain activity driving disease symptoms could reduce stimulation-induced side effects and significantly improve patients' quality of life. This proposal emerges from a clinical need to improve stimulation specificity in order to reduce side effects experienced by patients, and to expand the use of this powerful therapeutic intervention to other difficult to treat neurological disorders. The first aim of the proposal is to selectively suppress disease related brain activity by carefully timing stimulation. Critically, I aim to achieve state-dependent deep brain stimulation, which adjusts key aspects of the therapy (e.g. how much stimulation is delivered and pattern of stimulation) dynamically according to patients' symptom severity. Neuromodulation can be used not only to suppress brain activities driving disease symptoms but also to enhance neural activity that play a critical role in controlling our every day actions. I aim to develop stimulation techniques in order to selectively enhance neural processes believed to contribute to behaviors such as response inhibition and action selection. The possibility of promoting neural activity to compensate for impairment may play an important role in the future for managing treatment-refractory disorders such as obsessive-compulsive disorder and impulsivity. The second aim of the proposal is to learn from fundamental neural processes in order to design more "natural" therapeutic interventions. Brain activity driving motor symptoms of Parkinson's disease and essential tremor can be spontaneously suppressed. For instance, when patients with tremor make a movement, tremor amplitude reduces significantly. Therapeutic interventions inspired by natural processes that take place in our brains even during disease, may provide an effective method for reducing disease symptoms while sparing brain activity not linked to disease processes. This research programme will generate exciting theoretical and experimental tools, which could be used to understand how different brain regions communicate and control behavior. Critically, the notion of mimicking the way our brains readily control disease related neural activity through stimulation is an innovative path that could lead to the development of new types of therapeutic interventions not only for Parkinson's disease and essential tremor but also for other movement and psychiatric disorders driven by similar types of brain activity.