Computational, Cognitive and Clinical Imaging Lab, Division of Brain Sciences, Department of Medicine, Imperial College London, UK.
UK DRI Centre for Care Research and Technology, Imperial College London, UK.
Brain. 2019 Oct 1;142(10):3280-3293. doi: 10.1093/brain/awz252.
Non-invasive brain stimulation has been widely investigated as a potential treatment for a range of neurological and psychiatric conditions, including brain injury. However, the behavioural effects of brain stimulation are variable, for reasons that are poorly understood. This is a particular challenge for traumatic brain injury, where patterns of damage and their clinical effects are heterogeneous. Here we test the hypothesis that the response to transcranial direct current stimulation following traumatic brain injury is dependent on white matter damage within the stimulated network. We used a novel simultaneous stimulation-MRI protocol applying anodal, cathodal and sham stimulation to 24 healthy control subjects and 35 patients with moderate/severe traumatic brain injury. Stimulation was applied to the right inferior frontal gyrus/anterior insula node of the salience network, which was targeted because our previous work had shown its importance to executive function. Stimulation was applied during performance of the Stop Signal Task, which assesses response inhibition, a key component of executive function. Structural MRI was used to assess the extent of brain injury, including diffusion MRI assessment of post-traumatic axonal injury. Functional MRI, which was simultaneously acquired to delivery of stimulation, assessed the effects of stimulation on cognitive network function. Anodal stimulation improved response inhibition in control participants, an effect that was not observed in the patient group. The extent of traumatic axonal injury within the salience network strongly influenced the behavioural response to stimulation. Increasing damage to the tract connecting the stimulated right inferior frontal gyrus/anterior insula to the rest of the salience network was associated with reduced beneficial effects of stimulation. In addition, anodal stimulation normalized default mode network activation in patients with poor response inhibition, suggesting that stimulation modulates communication between the networks involved in supporting cognitive control. These results demonstrate an important principle: that white matter structure of the connections within a stimulated brain network influences the behavioural response to stimulation. This suggests that a personalized approach to non-invasive brain stimulation is likely to be necessary, with structural integrity of the targeted brain networks an important criterion for patient selection and an individualized approach to the selection of stimulation parameters.
非侵入性脑刺激已被广泛研究作为治疗一系列神经和精神疾病的潜在手段，包括脑损伤。然而，脑刺激的行为效果是可变的，其原因还不太清楚。这对于创伤性脑损伤来说是一个特别的挑战，因为损伤的模式及其临床效果是异质的。在这里，我们检验了这样一个假设，即在创伤性脑损伤后接受经颅直流电刺激的反应取决于刺激网络内的白质损伤。我们使用了一种新的同步刺激磁共振成像（MRI）方案，对 24 名健康对照者和 35 名中度/重度创伤性脑损伤患者应用阳极、阴极和假刺激。刺激施加于右侧下额叶/前岛叶突显网络节点，选择该节点是因为我们之前的工作表明它对执行功能很重要。刺激在执行停止信号任务时进行，该任务评估反应抑制，这是执行功能的一个关键组成部分。结构 MRI 用于评估脑损伤的程度，包括创伤后轴突损伤的扩散 MRI 评估。同时进行的功能 MRI 用于评估刺激对认知网络功能的影响。在对照组中，阳极刺激改善了反应抑制，而在患者组中则没有观察到这种效果。突显网络内的创伤性轴突损伤程度强烈影响了对刺激的行为反应。连接刺激的右侧下额叶/前岛叶与突显网络其余部分的束状结构损伤程度越大，刺激的有益效果就越低。此外，阳极刺激使反应抑制不良的患者的默认模式网络激活正常化，这表明刺激调节了支持认知控制的网络之间的通信。这些结果证明了一个重要原则：刺激脑网络内连接的白质结构影响了对刺激的行为反应。这表明，非侵入性脑刺激的个性化方法可能是必要的，目标脑网络的结构完整性是患者选择的重要标准，而刺激参数的个体化选择也是如此。
