Longitudinal study of functional connectivity among cocaine users in treatment

描述（申请人提供）：长期使用可卡因是最难治疗的药物使用障碍之一。高复发率可能是由于边缘系统和认知因素的综合作用，包括易受边缘系统提示的影响和执行控制的丧失。这可能是由于边缘系统神经回路的功能连接性提高所致。在一些实施例中，执行控制电路中的功能连接性降低（例如，内侧前额叶皮层（MPFC）和腹侧纹状体之间的功能连接性降低）和/或执行控制电路中的功能连接性降低（例如，背外侧前额叶皮层（DLPFC）和背侧纹状体之间的功能连接性降低）。这项纵向成像研究的首要目标是使用新型TMS/fMRI探针来确定执行和边缘回路完整性之间的关系，因为它涉及到 强化门诊治疗计划后的即时和长期结果。这将通过评估寻求治疗的可卡因使用者和基线时非药物使用对照的功能连接（Aim 1）以及28天认知行为治疗计划（仅限使用者）后功能连接的变化来实现（Aim 2）。我们还将确定这些回路的完整性与基线后60天和90天（目标3）有临床意义的结局指标之间的关系。从这些目标中产生的关于执行（例如DLPFC）和边缘系统（例如MPFC）回路连接对成瘾治疗结果的重要性的基本神经科学知识。这些数据将提供一个关键的基础 从该领域可以开发基于证据的脑刺激治疗策略（如重复TMS），以扩大寻求治疗的个体之间的DLPFC连接。

DESCRIPTION (provided by applicant): Chronic cocaine use is among the most difficult substance-use disorders to treat. High relapse rates are likely due to a combination of limbic and cognitive factors, including vulnerability to salient limbic cues and loss of executive control This may be due to elevated functional connectivity in limbic neural circuitry (e.g. between the medial prefrontal cortex (MPFC) and ventral striatum) and/or lower functional connectivity in executive control circuitry (e.g. between the dorsolateral prefrontal cortex (DLPFC) and dorsal striatum). The overarching goal of this longitudinal imaging study is to use the novel TMS/fMRI probe to determine the relationship between executive and limbic circuit integrity as it relates to immediate and extended outcomes after an intensive outpatient treatment program. This will be achieved by assessing functional connectivity in treatment-seeking cocaine users and non-drug using controls at baseline (Aim1) and the change in functional connectivity after a 28-day cognitive- behavioral treatment program (users only)(Aim 2). We will also determine the relationship between the integrity of these circuits and clinically meaningful outcome measures 60 days and 90 days after baseline (Aim 3). The fundamental neuroscience knowledge resulting from these aims regarding the importance of executive (e.g. DLPFC) and limbic (e.g. MPFC) circuit connectivity to addiction treatment outcomes. These data will provide a critical foundation from which the field can develop evidence-based brain stimulation treatment strategies (such as repetitive TMS) to amplify DLPFC connectivity among treatment-seeking individuals.