权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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.

总结/摘要精神疾病是美国医疗保健利用成本的最大来源，也是非医疗保健费用最高的来源。世界范围内的传染病--估计到2030年，每年将造成6万亿美元的社会负担。我们定义精神病诊断的方式（即仅基于症状群）和识别治疗（即利用意外发现）未能实质上减轻这些疾病的致残负担。通常在生命早期出现并持续存在的疾病。毫不奇怪，高度临床和生物学异质性，诊断中的变异性与在不同的诊断之间，机械上不同的精神病药物靶点的数量也没有增加，几十年来，通常只有一半的患者在临床试验中反应良好。疾病仍然是显而易见的，因为外行对这些疾病的大脑基础的理解与科学家们越来越兴奋地认为，然而，神经成像作为人类神经科学中的主导工具，已经被大量用于将这些任意定义的诊断与健康个体进行比较，成像也是一种纯粹的观察方法，因此不能它本身提供了对电路的因果理解，这是从描述性过渡到对精神疾病的基于电路的机械理解，可以直接指导新的干预措施。在这里，我提出一个新的诊断和治疗发展框架，超越任意性，传统诊断的异质性、组间水平影像学分析的局限性以及当前试验的局限性治疗计划的错误方法。相反，这个“电路-电路优先”平台专注于理解个体患者脑回路中的因果关系作为个性化诊断和治疗的手段，个体定制的可塑性-诱导神经刺激，建立电路和临床之间的直接联系这种“电路优先”方法的成功实施将建立一个快速转化为其他精神疾病，以及更进一步转化为特定的神经疾病（例如中风，重要的是，尽管我的方法很新奇，一个易于扩展的平台，只需简单修改，就有可能改变临床实践这是通过使用广泛适用的、已经获得FDA批准的工具（例如，经颅磁刺激（TMS）和脑电图（EEG）），以及它可以在临床医生的办公室环境中进行，因此不限于专门研究 labs.