Data_Sheet_5_Neural Connectivity Changes Facilitated by Familiar Auditory Sensory Training in Disordered Consciousness: A TBI Pilot Study.DOCX

For people with disordered consciousness (DoC) after traumatic brain injury (TBI), relationships between treatment-induced changes in neural connectivity and neurobehavioral recovery have not been explored. To begin building a body of evidence regarding the unique contributions of treatments to changes in neural network connectivity relative to neurobehavioral recovery, we conducted a pilot study to identify relationships meriting additional examination in future research. To address this objective, we examined previously unpublished neural connectivity data derived from a randomized clinical trial (RCT). We leveraged these data because treatment efficacy, in the RCT, was based on a comparison of a placebo control with a specific intervention, the familiar auditory sensory training (FAST) intervention, consisting of autobiographical auditory-linguistic stimuli. We selected a subgroup of RCT participants with high-quality imaging data (FAST n = 4 and placebo n = 4) to examine treatment-related changes in brain network connectivity and how and if these changes relate to neurobehavioral recovery. To discover promising relationships among the FAST intervention, changes in neural connectivity, and neurobehavioral recovery, we examined 26 brain regions and 19 white matter tracts associated with default mode, salience, attention, and language networks, as well as three neurobehavioral measures. Of the relationships discovered, the systematic filtering process yielded evidence supporting further investigation of the relationship among the FAST intervention, connectivity of the left inferior longitudinal fasciculus, and auditory-language skills. Evidence also suggests that future mechanistic research should focus on examining the possibility that the FAST supports connectivity changes by facilitating redistribution of brain resources. For a patient population with limited treatment options, the reported findings suggest that a simple, yet targeted, passive sensory stimulation treatment may have altered functional and structural connectivity. If replicated in future research, then these findings provide the foundation for characterizing the unique contributions of the FAST intervention and could inform development of new treatment strategies. For persons with severely damaged brain networks, this report represents a first step toward advancing understanding of the unique contributions of treatments to changing brain network connectivity and how these changes relate to neurobehavioral recovery for persons with DoC after TBI.
Clinical Trial Registry: NCT00557076, The Efficacy of Familiar Voice Stimulation During Coma Recovery (http://www.clinicaltrials.gov).

针对创伤性脑损伤（Traumatic Brain Injury, TBI）后意识障碍（Disordered Consciousness, DoC）患者，目前尚未探索治疗诱导的神经连接变化与神经行为恢复之间的关联。
为构建相关证据体系，阐明相较于神经行为恢复，各类治疗对神经网络连接变化的独特贡献，我们开展了一项先导性研究，以识别未来研究中值得进一步探究的关联。
为达成这一研究目标，我们分析了来自一项随机对照试验（Randomized Clinical Trial, RCT）的未公开神经连接数据。选用该数据集的原因在于，此项RCT的治疗疗效评估基于安慰剂对照组与特定干预措施——熟悉听觉感官训练（Familiar Auditory Sensory Training, FAST）——的对比，该训练由自传体听觉语言刺激构成。我们选取了该RCT中具备高质量成像数据的亚组参与者（FAST组n=4，安慰剂组n=4），以探究治疗相关的脑网络连接变化，以及此类变化是否、如何与神经行为恢复产生关联。
为挖掘FAST干预、神经连接变化与神经行为恢复之间的潜在关联，我们分析了与默认模式、突显、注意力及语言网络相关的26个脑区和19条白质束，同时纳入3项神经行为评估指标。经系统筛选流程后，我们获得了可支持进一步探究FAST干预、左侧下纵束连接性与听觉语言技能三者间关联的证据。另有证据表明，未来的机制性研究可聚焦于FAST是否通过促进脑资源重分配来推动连接变化这一假说。
对于治疗选择有限的患者群体而言，本研究结果提示，一种简便却具有针对性的被动感官刺激疗法，或可改变大脑的功能与结构连接。若该研究结果在后续工作中得以重复验证，将为阐明FAST干预的独特贡献奠定基础，并可为新型治疗策略的开发提供参考。对于脑网络严重受损的患者而言，本报告为推进理解治疗如何改变脑网络连接、以及此类变化与TBI后DoC患者神经行为恢复的关联迈出了第一步。
临床试验注册信息：NCT00557076，《昏迷恢复期间熟悉声音刺激的疗效》（http://www.clinicaltrials.gov）。