Tractography-Activation Models for Neuropsychiatric Deep Stimulation

描述（由申请人提供）：深部脑刺激（DBS）是一种已建立的运动障碍临床治疗方法，并定位为神经精神疾病的治疗方法。胼胝体下扣带白质（SCCWM） DBS有可能改善难治性抑郁症（TRD）患者的生活；然而，具体的白质通路(s)负责治疗效益的刺激仍然未知。该项目的目标是确定治疗性SCCWM DBS直接刺激的关键轴突通路。我们将基于患者特异性弥散加权成像（DWI）的神经束造影与神经刺激建模相结合，以实现轴突通路的概率识别，其直接激活与SCCWM DBS患者临床结果指标的变化有关。我们假设SCCWM DBS的治疗效果依赖于与腹内侧前额叶皮层（vmPFC）及其皮层下连接相关的通路的激活。我们将使用患者特异性牵引图激活模型（tam）来评估我们的假设，通过分析参与研究者发起的SCCWM DBS （FDA IDE G060028和FDA IDE G130107）临床试验的患者。我们的具体目标是在35名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关于刺激目标途径的假设，并通过创建概率刺激图谱（PSA）帮助我们区分治疗和非治疗途径。我们还将SCCWM结果与腹侧囊（VC） DBS治疗TRD的TAMs结果进行比较，因为不同手术靶点之间可能存在共同的靶标通路。最后，我们将使用我们的tam来研究理论上最优的方法来刺激我们的psa识别的目标通路。本研究的结果对神经精神DBS技术的发展有很大的帮助，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.