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A "Circuits-First" Platform for Personalized Neurostimulation Treatment

用于个性化神经刺激治疗的“电路优先”平台

基本信息

批准号：
10214488
负责人：
Amit Etkin
金额：
$ 101.5万
依托单位：
ALTO NEUROSCIENCE, INC.
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-10-15 至 2023-07-31
项目状态：
已结题

项目摘要

SUMMARY/ABSTRACT Mental illnesses are the largest source of healthcare utilization costs in the US, and the costliest of non- communicable diseases worldwide – estimated to result in $6 Trillion in annual societal burden by 2030. The way in which we have defined psychiatric diagnoses (i.e. based only on symptom clusters) and identified treatments (i.e. capitalizing on serendipity), has failed to substantially mitigate the disabling burden of these diseases, which typically appear early in life and persist. Not surprisingly, individual psychiatric diagnoses are highly clinically and biologically heterogeneous, with as much or greater variability within a diagnosis as between diagnoses. The number of mechanistically distinct psychiatric drug targets has also not grown in decades, and typically only half of patients respond well in clinical trials. Public stigma towards psychiatric disorders remains palpable, as lay understanding of the brain bases of these conditions contrasts with the growing excitement amongst scientists for the potential of grounding diagnosis and treatment directly in neurobiology. Neuroimaging, as the dominant tool in human neuroscience, however, has been used largely for comparing these arbitrarily-defined diagnoses against healthy individuals not for robustly characterizing individual patients in objective biological terms. Imaging is also a purely observational method, and thus cannot by itself provide the causal understanding of circuitry that is necessary for transitioning from a descriptive to a circuit-based mechanistic understanding of mental illness that can directly guide novel interventions. Here, I propose a new diagnostic and treatment development framework that transcends the arbitrariness and heterogeneity of traditional diagnoses, the limitations of group-level imaging analyses and current trial-and- error approaches to treatment planning. Rather, this “Circuits-First” platform focuses on understanding causality in the brain circuits of individual patients as a means for personalized diagnosis and treatment using individually-tailored plasticity-inducing neurostimulation, establishing direct linkage between circuits and clinical outcome. Successful implementation of this “Circuits-First” approach will establish a platform for rapid translation to other psychiatric disorders, and beyond to specific neurological disorders (e.g. stroke, Parkinson’s) where circuit perturbations are prominent. Importantly, despite its novelty, my approach will create a readily scalable platform that, with simple modifications, can have the potential to transform clinical practice in the near term. This is facilitated by the use of broadly-applicable, already FDA-approved tools (e.g. transcranial magnetic stimulation (TMS) and electroencephalography (EEG)), and the fact that it can be performed in the office-based settings of the clinical practitioner, thus not restricted to specialized research labs.

摘要/摘要： -- 精神疾病是美国最大的医疗保健和医疗费用来源，也是非精神疾病最昂贵的医疗费用来源。据估计，到2030年，传染病将在全球范围内造成约60万亿美元的年度社会经济负担。在这种方式下，我们可以定义精神疾病的诊断方法(即，仅基于症状和簇)以及识别的方法。治疗方法(即利用机缘巧合)未能从根本上减轻这些疾病的致残和负担。通常出现在生命早期的疾病通常会持续存在。不足为奇的是，个体精神疾病的诊断越来越少。在临床上高度异质性，在生物学上是异质性的，在一个新的诊断结果中具有高达10%或更大的变异性。在两次诊断之间。近年来，机械性和独特的精神科药物治疗靶点的数量也没有增加。几十年来，中国和印度通常只有一半的患者在临床试验中反应良好。公众对精神病患者的耻辱倾向于他们。障碍仍然是显而易见的，因为他们需要了解这些疾病的大脑和基础，并将其与健康形成对比。越来越多的科学家感到兴奋，他们期待着这种将诊断和治疗直接联系在一起的技术的潜在价值。神经生物学。神经成像，被认为是人类和神经科学中最主要的研究工具，然而，它在很大程度上还没有被用于治疗。将这些随意定义的诊断结果与健康的健康个体进行比较，不能很好地刻画出他们的特征。个别患者是在客观的生物学条件下进行检查的。影像检查也不是一种纯粹的观察性检查方法，因此无法进行检查。它本身就提供了对电路的基本因果关系和理解能力，即它是从一个描述性电路过渡到一个电路的必要步骤。以电路为基础的、机械式的对精神疾病的理解能力，可以直接指导新的心理干预措施。提出了一种新的、超越传统的随意性的诊断、治疗和发展框架。传统医学诊断的异质性，克服了组级医学成像和分析的局限性，以及当前的临床试验和研究出错的方法涉及到治疗和规划。相反，这个名为“电路第一”的软件平台的重点是解决问题的理解。因果关系存在于个体癌症患者的大脑和神经回路中，是实现个性化诊断和合理治疗的重要手段。为个人量身定做的可塑性诱导神经刺激，以及建立电路和临床之间的直接医疗联系。结果。这一方法的成功实施将为快速解决方案建立一个新的平台。翻译到其他精神障碍，从精神障碍到特定的神经功能障碍(例如中风，)。帕金森氏症)，这是一个电路和扰动非常突出的地方。重要的是，尽管它很新奇，但我的方法将不会创造。一个易于扩展的医疗平台，只需进行简单的技术修改，就可以拥有彻底转变其临床医疗实践的潜在能力。在短期内，这项工作将通过推广广泛适用的、已经获得FDA批准的可再生工具的使用来促进这一进程。经颅磁刺激(TMS)和脑电(EEG)，证实了这样一个事实：它是不可能的。在临床医学从业者的办公室工作环境中表现良好，因此不受限制于专业医学研究。实验室。