Zhuang Yutong, Zhai Weihang, Li Qinghua, Jiao Haoyang, Ge Qianqian, Rong Peijing, He Jianghong
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Department of Neurosurgery, The Second Clinical College of Southern Medical University, Guangzhou, China.
Front Neurol. 2023 Aug 24;14:1165145. doi: 10.3389/fneur.2023.1165145. eCollection 2023.
Non-invasive brain stimulation (NIBS) techniques are now widely used in patients with disorders of consciousness (DOC) for accelerating their recovery of consciousness, especially minimally conscious state (MCS). However, the effectiveness of single NIBS techniques for consciousness rehabilitation needs further improvement. In this regard, we propose to enhance from bottom to top the thalamic-cortical connection by using transcutaneous auricular vagus nerve stimulation (taVNS) and increase from top to bottom cortical-cortical connections using simultaneous high-definition transcranial direct current stimulation (HD-tDCS) to reproduce the network of consciousness.
METHODS/DESIGN: The study will investigate the effect and safety of simultaneous joint stimulation (SJS) of taVNS and HD-tDCS for the recovery of consciousness. We will enroll 84 MCS patients and randomize them into two groups: a single stimulation group (taVNS and HD-tDCS) and a combined stimulation group (SJS and sham stimulation). All patients will undergo a 4-week treatment. The primary outcome will be assessed using the coma recovery scale-revised (CRS-R) at four time points to quantify the effect of treatment: before treatment (T0), after 1 week of treatment (T1), after 2 weeks of treatment (T2), and after 4 weeks of treatment (T3). At the same time, nociception coma scale-revised (NCS-R) and adverse effects (AEs) will be collected to verify the safety of the treatment. The secondary outcome will involve an analysis of electroencephalogram (EEG) microstates to assess the response mechanisms of dynamic brain networks to SJS. Additionally, CRS-R and AEs will continue to be obtained for a 3-month follow-up (T4) after the end of the treatment.
This study protocol aims to innovatively develop a full-time and multi-brain region combined neuromodulation paradigm based on the mesocircuit model to steadily promote consciousness recovery by restoring thalamocortical and cortical-cortical interconnections.
非侵入性脑刺激（NIBS）技术目前广泛应用于意识障碍（DOC）患者，以加速其意识恢复，尤其是微意识状态（MCS）。然而，单一NIBS技术用于意识康复的有效性仍需进一步提高。在这方面，我们建议通过经皮耳迷走神经刺激（taVNS）从下至上增强丘脑-皮质连接，并使用同步高清经颅直流电刺激（HD-tDCS）从上至下增加皮质-皮质连接，以重建意识网络。
方法/设计：本研究将调查taVNS与HD-tDCS同步联合刺激（SJS）对意识恢复的效果及安全性。我们将招募84例MCS患者，并将他们随机分为两组：单一刺激组（taVNS和HD-tDCS）和联合刺激组（SJS和假刺激）。所有患者将接受为期4周的治疗。主要结局将在四个时间点使用昏迷恢复量表修订版（CRS-R）进行评估，以量化治疗效果：治疗前（T0）、治疗1周后（T1）、治疗2周后（T2）和治疗4周后（T3）。同时，将收集疼痛昏迷量表修订版（NCS-R）和不良反应（AE）以验证治疗的安全性。次要结局将包括对脑电图（EEG）微状态的分析，以评估动态脑网络对SJS的反应机制。此外，在治疗结束后3个月的随访（T4）中，将继续获取CRS-R和AE。
本研究方案旨在基于中环路模型创新性地开发一种全时程、多脑区联合神经调节模式，通过恢复丘脑皮质和皮质-皮质互连来稳步促进意识恢复。
