Tractography-Activation Models for Neuropsychiatric Deep Stimulation

描述（由申请人提供）：脑深部电刺激（DBS）是一种已确立的运动障碍临床治疗方法，并有望成为神经精神疾病的治疗方法。胼胝体下扣带回白色物质（SCCWM）DBS有可能改善难治性抑郁症（TRD）患者的生活;然而，负责刺激治疗获益的特定白色物质通路仍不清楚。该项目的目标是确定治疗SCCWM DBS直接刺激的关键轴突通路。我们将结合联合收割机基于患者特异性弥散加权成像（DWI）的纤维束成像与神经刺激建模，以实现轴突通路的概率识别，其直接激活与SCCWM DBS患者中测量的临床结局指标的变化相关。我们假设SCCWM DBS的治疗益处取决于腹内侧前额叶皮层（vmPFC）及其皮层下连接相关通路的激活。我们将使用患者特异性纤维束成像激活模型（TAM），通过分析研究者发起的SCCWM DBS临床试验（FDA IDE G 060028和FDA IDE G130107）中招募的患者来评估我们的假设。我们的具体目标是在35例SCCWM DBS患者中开发TAM。这些模型的结果将使我们能够发展我们对刺激靶通路的假设，并帮助我们通过创建概率刺激图谱（PSA）来区分治疗和非治疗通路。我们还将比较SCCWM结果与腹侧囊（VC）DBS治疗TRD的TAM，因为不同手术靶点之间可能存在共同的靶通路。最后，我们将使用我们的TAM来研究理论上最佳的方法来刺激我们的PSA识别的靶向通路。这项研究的结果有很大的潜力，以协助神经精神DBS技术的发展，并帮助指导未来的临床协议。

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.