tDCS and cognitive training as a neurodevelopmental intervention in FASD

项目摘要/摘要 胎儿酒精谱系障碍(FASD)包括产前酒精暴露的一系列影响 (PAE)包括神经异常、认知和行为障碍、生长迟缓、 还有颅面畸形。很少有治疗方法被研究过，尽管有巨大的 FASD造成的公共卫生负担。认知是干预的自然目标，因为缺陷 造成适应能力、社交技能和独立生活的问题。十年来 研究表明，认知训练对大脑功能网络有好处-- 调节各种神经发育和心理健康状况下的认知。我们相信这一点 可以改善FASD患者的认知表现。我们现有的主要目标是 神经调节研究和建议的RCT是利用tdcs的能力来增强 皮质兴奋性和神经可塑性，以最大限度地提高儿童的认知训练效益 以及患有FASD的青少年。 最近，我们进行了一项关于tdcs-增强认知的试点随机对照试验。 培训以证明这种方法在FASD儿童中的安全性和可行性(Boroda， Krueger等人，2020年)。我们表明，在这些人群中，干预是安全的，并且可以很好地耐受。 此外，尽管应用了相对较低剂量的tdcs和认知训练，我们发现 在注意任务上，接受主动-tDC训练的人比接受小组训练的人表现出更大的进步 收到假的-tdcs。这些有希望的试点结果值得在更大的临床试验中复制。 我们建议对60名(在完成时)儿童进行完全有效的随机对照试验，并 患有FASD的青少年将在TDC的基础上接受认知训练。我们假设 与认知训练相结合，五次积极的tDC初始课程将产生 持续注意(CPT)的改善显著高于假TDC。我们也 假设，在认知训练的同时，总共10个活跃的tDC课程将 在持续注意力(CPT)方面比五次积极活动的改善要大得多 Tdcs。我们还致力于建立神经认知改善的长期持久性和 Tdcs和认知训练导致的相关行为变化。最后，我们计划使用 显示功能网络变化的干预前和干预后静息状态fMRI数据 与干预相关并量化剂量和功能网络之间的关系 改变。试验结果将直接指导未来认知训练的临床实施和 TDCs作为一种潜在的神经发育干预。

PROJECT SUMMARY / ABSTRACT Fetal alcohol spectrum disorders (FASDs) comprise a range of effects from prenatal alcohol exposure (PAE) including neurological abnormalities, cognitive and behavioral impairments, growth retardation, and craniofacial anomalies. Very few treatments have been investigated despite the tremendous public health burden posed by FASD. Cognition is a natural target for intervention because deficits contribute to problems with adaptive functioning, social skills, and independent living. A decade of research suggests that cognitive training has beneficial effects on functional brain networks - mediating cognition in a variety of neurodevelopmental and mental health conditions. We believe it can improve cognitive performance in individuals with FASD. The primary objective of our existing line of neuromodulation research and the proposed RCT is to leverage the ability of tDCS to enhance cortical excitability and neural plasticity in order to maximize the cognitive training benefits in children and adolescents with FASD. Recently we carried out a pilot randomized controlled trial of tDCS-augmented cognitive training to demonstrate the safety and feasibility of this approach in children with FASD (Boroda, Krueger, et al., 2020). We showed that the intervention was safe and well-tolerated in this population. Further, despite applying a relatively low-dose of tDCS and cognitive training, we found that the group receiving active-tDCS demonstrated greater improvements on an attention task than a group receiving sham-tDCS. These promising pilot results merit replication in a larger clinical trial. We propose a fully-powered randomized controlled trial of 60 (at completion) children and adolescents with FASD who will receive cognitive training in combination with tDCS. We hypothesize that, in conjunction with cognitive training, five initial sessions of active tDCS will produce a significantly greater improvement in sustained attention (CPT) than sham tDCS. We also hypothesize that, in conjunction with cognitive training, a total of ten sessions of active tDCS will produce a significantly greater improvement in sustained attention (CPT) than five sessions of active tDCS. We also aim to establish the long-term durability of neurocognitive improvements and associated behavioral changes resulting from tDCS and cognitive training. Finally, we plan to use pre-intervention and post-intervention resting-state fMRI data to show functional network changes related to the intervention and to quantify the relationship between dose and functional network changes. Results of the trial will directly inform future clinical implementation of cognitive training and tDCS as a potential neurodevelopmental intervention.