Personalised neurostimulation for Parkinson's inspired by neurophysiological improvements observed after physical exercise

帕金森氏症的个性化神经刺激受到体育锻炼后观察到的神经生理学改善的启发

• 批准号: MR/Y014863/1
• 负责人: Petra Fischer
• 金额: $ 72.23万
• 依托单位: University of Bristol
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FY014863%2F1
• 关键词: Personalised; neurostimulation; Parkinson; inspired; neurophysiological

Parkinson's causes a wide range of symptoms that vary strongly between individuals. Patients are burdened with different combinations of symptoms, including tremor, slowness, muscle cramps, walking difficulties and impulsivity, and would thus benefit from a personalized therapeutic approach.The two currently leading therapies are dopaminergic medication and deep brain stimulation (DBS), which can be highly effective in the early and middle stages of the disease. However, high medication doses in later stages can cause side effects including hallucinations, impulsivity, and excessive uncontrollable movements. DBS could deliver personalized therapies and minimize side effects as it can theoretically be programmed to adjust to symptom fluctuations. However, it requires invasive surgery, can also negatively affect cognition, in particular memory, and is thus available to only few patients (~10%). Non-invasive neurostimulation can also be personalized and could be more cost-effective and more accessible than DBS and would thus be preferrable - if protocols could be developed to be similarly effective or were able to improve unmet needs. My aim is to develop novel personalized non-invasive neurostimulation protocols for Parkinson's to improve both motor and cognitive control abilities beyond what existing therapies achieve. I will achieve this by characterizing in detail how brain areas communicate with each other when optimally tuned for movement control. How can we access "optimal tuning"?People with Parkinson's reportedly feel at their best within 2-4 hours after engaging in intense physical exercise. Some even report they briefly feel they do not have Parkinson's at all. I will capitalize on the striking acute benefits of exercise to identify which brain activity patterns should be restored. I will then program non-invasive neurostimulation tools to restore the identified patterns and test how well it improves individual symptoms.What will we gain?The changes in brain activity that we will observe following exercise will inform the design of a personalized neurostimulation protocol for each patient. This is a big step forwards from delivering the same stimulation essentially blindly to all participants. We aim to support specifically the brain activity patterns that are associated with symptom improvements in each individual to account for the large variability of symptoms across patients. To do this I will employ a combination of stimulation tools, including electrical stimulation and sensory stimulation using vibration. We will also use computational modelling to find the maximally effective stimulation parameters. My approach is timely as new devices now have the capability to precisely coordinate stimulation of multiple sites while also measuring brain activity. Combining tools and orchestrating stimulation of multiple brain areas likely will be clinically more effective than interacting with one target area alone. Additionally, my work has the potential to inspire improvements in current practises of assessing treatment success (e.g. when adjusting medication or DBS parameters). In summary, stepping away from a one-fits-all approach towards brain-activity based, and in this case also exercise-inspired, personalization of neurostimulation could revolutionize the way we treat Parkinson's and other movement disorders.

帕金森氏症引起的各种症状在个人之间差异很大。患者承担着不同症状组合的负担，包括震颤，缓慢，肌肉痉挛，步行困难和冲动性，因此将受益于个性化的治疗方法。目前两种领先的治疗方法是多巴胺能药物和深脑刺激（DBS），这在早期和中期都可以非常有效。但是，在后期的高剂量可能会导致副作用，包括幻觉，冲动和过度无法控制的运动。 DBS可以提供​​个性化疗法并最大程度地减少副作用，因为它可以从理论上编程以适应症状波动。但是，它需要侵入性手术，也可能对认知，特别是记忆力，因此仅对少数患者使用（约10％）。非侵入性神经刺激也可以个性化，并且可能比DBS更具成本效益，更容易访问，因此可以优选 - 如果可以开发协议以类似有效或能够提高未满足的需求。我的目的是为帕金森氏症开发新型的个性化非侵入性神经刺激方案，以提高运动能力和认知控制能力，超出现有疗法的实现。我将通过详细描述大脑区域在最佳调整进行运动控制时如何相互通信来实现这一目标。我们如何访问“最佳调整”？据报道，患有帕金森氏症的人在进行激烈的体育锻炼后的2-4小时内会感觉最好。有些人甚至报告说，他们简短地认为他们根本没有帕金森氏症。我将利用锻炼的惊人急性好处，以确定应恢复哪些大脑活动模式。然后，我将对非侵入性神经刺激工具进行编程，以恢复已确定的模式并测试它如何改善个人症状。我们将获得什么？锻炼后我们将观察到的大脑活动的变化将为每个患者的个性化神经刺激方案设计。这是向所有参与者盲目地盲目提供相同的刺激迈出的一大步。我们旨在特别支持与每个人症状改善相关的大脑活动模式，以解释患者症状的巨大变化。为此，我将使用刺激工具的组合，包括使用振动的电刺激和感觉刺激。我们还将使用计算建模来找到最大有效的刺激参数。我的方法是及时的，因为新设备现在具有精确协调多个位点刺激的能力，同时还可以测量大脑活动。组合工具和策划多个大脑区域的刺激可能比仅与一个目标区域进行互动更有效。此外，我的工作有可能激发当前评估治疗成功实践的改善（例如，在调整药物或DBS参数时）。总而言之，远离基于脑活动的全部方法，在这种情况下，在运动启发的情况下，神经刺激的个性化可能会彻底改变我们对待帕金森氏和其他运动障碍的方式。