tDCS and cognitive training as a neurodevelopmental intervention in FASD

项目概要/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， 和颅面畸形很少有治疗方法被研究，尽管有巨大的 FASD造成的公共卫生负担。认知是一个自然的干预目标，因为赤字 导致适应功能，社交技能和独立生活的问题。十年的 研究表明，认知训练对大脑功能网络有有益的影响， 在各种神经发育和心理健康状况中调节认知。我们认为 可以改善FASD患者的认知能力。我们现有的主要目标 神经调节研究和拟议的RCT是利用tDCS的能力， 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 和患有FASD的青少年 最近，我们进行了一项tDCS增强认知功能的初步随机对照试验， 培训以证明这种方法在患有FASD的儿童中的安全性和可行性（Boroda， Krueger等人，2020年）。我们证明了干预在这一人群中是安全的，耐受性良好。 此外，尽管应用了相对低剂量的tDCS和认知训练，我们发现， 接受主动tDCS的人在注意力任务上比接受主动tDCS的人表现出更大的改善。 接受假tDCS这些有希望的试点结果值得在更大的临床试验中复制。 我们提出了一个充分的权力随机对照试验60（完成）的儿童和 将接受认知训练与tDCS相结合的FASD青少年。我们假设 在认知训练的同时，五次主动tDCS的初始训练将产生一个 持续注意力（CPT）的改善显著大于假tDCS。我们也 假设，结合认知训练，总共10次主动tDCS将 产生显着更大的改善持续注意力（CPT）比五个积极的会议 tDCS。我们还旨在建立神经认知改善的长期持久性， 与tDCS和认知训练相关的行为变化。最后，我们计划使用 干预前和干预后静息状态fMRI数据，以显示功能网络变化 并量化剂量与功能网络之间的关系 变化试验结果将直接为未来认知训练的临床实施提供信息， tDCS作为一种潜在的神经发育干预措施。

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.