Tractography-Activation Models for Neuropsychiatric Deep Stimulation

描述(申请人提供)：脑深部刺激(DBS)是一种公认的运动障碍的临床治疗方法，并有望成为治疗神经精神障碍的一种方法。扣带下脑白质DBS具有改善难治性抑郁症患者生活的潜力；然而，负责从刺激中获得治疗益处的特定白质通路(S)尚不清楚。该项目的目标是确定治疗性中西医结合DBS直接刺激的关键轴突通路。我们将结合患者特定的扩散加权成像(DWI)和神经刺激建模，以实现对轴突路径的概率识别，这些路径的直接激活与SCCWM DBS患者测量的临床结果指标的变化有关。我们假设，SCCWM DBS的治疗益处依赖于与腹内侧额前皮质(VmPFC)及其皮质下连接相关的通路的激活。我们将通过分析参加SCCWM DBS(FDA IDE G060028和FDA IDE G130107)研究人员发起的临床试验的患者，使用患者特定的气管造影术激活模型(TAMS)来评估我们的假设。我们的具体目标要求在35名SCCWM DBS患者中开发TAMS。这些模型的结果将使我们能够发展我们对刺激目标路径的假设，并通过创建概率刺激图谱(PSA)来帮助我们区分治疗和非治疗路径。我们还将比较我们的SCCWM结果与来自腹侧包膜(VC)DBS的TAM用于TRD，因为在不同的手术靶点之间可能存在共同的靶道。最后，我们将使用我们的TAM来研究在理论上刺激我们的PSA识别的靶通路的最佳方法。这项研究的结果具有巨大的潜力，有助于神经精神病学DBS技术的发展，并有助于指导未来的临床方案。

DESCRIPTION (provided by applicant): Deep brain stimulation (DBS) is an established clinical therapy for movement disorders and is positioned to grow as a treatment for neuropsychiatric disorders. Subcallosal cingulate white matter (SCCWM) DBS has potential to improve the lives of patients with treatment-resistant depression (TRD); however, the specific white matter pathway(s) responsible for therapeutic benefit from stimulation remain unknown. The goal of this project is to identify the key axonal pathways directly stimulated by therapeutic SCCWM DBS. We will combine patient-specific diffusion-weighted imaging (DWI) based tractography with neurostimulation modeling to enable probabilistic identification of the axonal pathways whose direct activation is linked to changes in clinical outcome metrics measured in SCCWM DBS patients. We hypothesize that therapeutic benefit from SCCWM DBS is dependent upon activation of pathways associated with the ventromedial pre-frontal cortex (vmPFC) and its subcortical connections. We will use patient-specific tractography-activation models (TAMs) to evaluate our hypothesis by analyzing patients enrolled in investigator initiated clinical trials of SCCWM DBS (FDA IDE G060028 & FDA IDE G130107). Our specific aims call for the development of TAMs in a cohort of 35 total SCCWM DBS patients. Results from these models will enable us to evolve our hypothesis on the target pathways for stimulation and help us to differentiate between therapeutic and non-therapeutic pathways by creating a probabilistic stimulation atlas (PSA). We will also compare our SCCWM results with TAMs derived from ventral capsule (VC) DBS for TRD, as it may be possible that common target pathways exist between the different surgical targets. Finally, we will use our TAMs to investigate theoretically optimal methods for stimulating our PSA-identified target pathways. The results of this study have great potential to assist in the evolution of neuropsychiatric DBS technology and help guide future clinical protocols.