Translational Research to Enhance Cognitive Control

包括抽动症在内的慢性抽动障碍(CTD)是一种相对常见的典型损害 儿童期的神经发育障碍。CTD与认知控制缺陷有关，包括 工作记忆和反应抑制，以及皮质-纹状体回路功能障碍。虽然药物 靶向这些回路在减少CTD症状、习惯逆转训练方面有一定的效果 (HRT)，一种行为技术，在提供持久的症状缓解方面显示出有效性，而不会出现严重的 与药物治疗相关的副作用。该项目旨在澄清功能 对CTD青少年认知控制关键回路的解剖，以检验假说 与HRT相关的认知增强机制，并将这些机制与 被确定为ADHD的药物治疗。确定行为的神经基础 干预措施，如激素替代疗法，并建立这些发现的概括性，有可能 大大加强制定经改进的CTD治疗战略，包括制定 针对个别患者的最佳治疗方案。因此，这些目标与 CIDAR的总体目标。共有60名患有DSM-IV慢性抽动障碍的青少年(7-16岁)将 接受8周的HRT，使用我们开发的和之前测试的手动治疗方案 一群人。青少年还将在基线水平上接受全面的临床、认知/EEG和功能磁共振成像评估 和后处理。减少的临床和认知/EEG电池也将在治疗中期和 三个月的随访(仅限于应答者)，以检查反应的进程和持久性。所有参与者将首先被招募，并由 研究评估单位(RAU)，也将招募匹配的正常对照样本，以允许 基线临床、EEG/fMRI与CTD和Project III ADHD患者样本的比较。功能磁共振成像和 这项研究的脑电/认知部分将通过与成像和 研究方法(RMC)核心。最后，这个项目中与治疗相关的发现将是 系统地与项目III中的数据进行比较，以证明神经的潜在共性 跨越多种疾病和治疗模式的治疗反应机制。

Chronic Tic Disorder, including Tourette Syndrome, (CTD) is a relatively common and typically impairing neurodevelopmental disorder of childhood. CTD is associated with deficits in cogntive control, including working memory and response inhibition, and dysfunction of cortico-striatal circuits. Although medications targeting these circuits have been moderately effective in reducing CTD symptoms, Habit Reversal Training (HRT), a behavioral technique, has shown efficacy in providing durable symptom relief without the serious side effects associated with pharmacotherapy. This project aims to clarify the functional anatomy of key circuits subserving cognitive control in youngsters with CTD, to examine hypothesized mechanisms of cognitive enhancement associated with HRT, and to compare these mechanisms to those identified for medication treatment of ADHD. Determining the neural basis of behavioral interventions, such as HRT, and establishing the generalizability of these findings, has the potential to significantly enhance development of improved treatment strategies for CTD, including the development of optimal treatment regimes for individual patients. As such, the aims are highly consistent with the overal goals of the CIDAR. A total of 60 youngsters (aged 7-16) with a DSM-IV Chronic Tic Disorder will receive eight weeks of HRT using a manualized treatment protocol developed and previously tested by our group. Youngsters will also undergo comprehensive clinical, cognitive/EEG, and fMRI evaluation at baseline and post-treatment. A reduced clinical and cognitive/EEG battery will also be collected mid-treatment and three month follow-up (responders only) to examine course and durability of response. All participants will be initially recruited and screened by the Research Assessment Unit (RAU) which will also recruit a matched sample of normal controls to allow for baseline clinical, EEG/fMRI comparison with the CTD and Project III ADHD patient samples. The fMRI and EEG/Cognitive components of the study will be executed through close collaboration with the Imaging and Research Methods (RMC) Cores, respectively. Finally, treatment-related findings from this project will be systematically compared to those from Project III in order to document the potential commonality of neural mechanisms of treatment response across multiple disorders and treatment modalities.