Department of Neurosurgery,
Department of Psychiatry and Behavioral Sciences.
J Neurosci. 2018 Jun 6;38(23):5384-5398. doi: 10.1523/JNEUROSCI.1088-17.2018. Epub 2018 May 21.
How does human brain stimulation result in lasting changes in cortical excitability? Uncertainty on this question hinders the development of personalized brain stimulation therapies. To characterize how cortical excitability is altered by stimulation, we applied repetitive direct electrical stimulation in eight human subjects (male and female) undergoing intracranial monitoring. We evaluated single-pulse corticocortical-evoked potentials (CCEPs) before and after repetitive stimulation across prefrontal ( = 4), temporal ( = 1), and motor ( = 3) cortices. We asked whether a single session of repetitive stimulation was sufficient to induce excitability changes across distributed cortical sites. We found a subset of regions at which 10 Hz prefrontal repetitive stimulation resulted in both potentiation and suppression of excitability that persisted for at least 10 min. We then asked whether these dynamics could be modeled by the prestimulation connectivity profile of each subject. We found that cortical regions (1) anatomically close to the stimulated site and (2) exhibiting high-amplitude CCEPs underwent changes in excitability following repetitive stimulation. We demonstrate high accuracy (72-95%) and discriminability (81-99%) in predicting regions exhibiting changes using individual subjects' prestimulation connectivity profile, and show that adding prestimulation connectivity features significantly improved model performance. The same features predicted regions of modulation following motor and temporal cortices stimulation in an independent dataset. Together, baseline connectivity profile can be used to predict regions susceptible to brain changes and provides a basis for personalizing brain stimulation. Brain stimulation is increasingly used to treat neuropsychiatric disorders by inducing excitability changes at specific brain regions. However, our understanding of how, when, and where these changes are induced is critically lacking. We inferred plasticity in the human brain after applying electrical stimulation to the brain's surface and measuring changes in excitability. We observed excitability changes in regions anatomically and functionally closer to the stimulation site. Those in responsive regions were accurately predicted using a classifier trained on baseline brain network characteristics. Finally, we showed that the excitability changes can potentially be monitored in real-time. These results begin to fill basic gaps in our understanding of stimulation-induced brain dynamics in humans and offer pathways to optimize stimulation protocols.
人类大脑刺激如何导致皮质兴奋性的持久变化?这个问题的不确定性阻碍了个性化脑刺激疗法的发展。为了描述刺激如何改变皮质兴奋性,我们在 8 名接受颅内监测的人类受试者(男性和女性)中应用重复的直接电刺激。我们在额(=4)、颞(=1)和运动(=3)皮质之前和之后评估了单次皮质-皮质诱发电位(CCEPs)。我们询问单次重复刺激是否足以在分布的皮质部位诱导兴奋性变化。我们发现,在额皮质的 10 Hz 重复刺激下,有一部分区域既增强了兴奋性,又抑制了兴奋性,这种变化至少持续了 10 分钟。然后,我们询问这些动态是否可以通过每个受试者的刺激前连通性特征来建模。我们发现,皮质区域(1)与刺激部位解剖上接近,(2)表现出高振幅 CCEPs,在重复刺激后兴奋性发生变化。我们使用个体受试者的刺激前连通性特征,在预测表现出变化的区域方面表现出高准确性(72-95%)和可区分性(81-99%),并表明添加刺激前连通性特征显著提高了模型性能。相同的特征可以预测在独立数据集在运动和颞皮质刺激后调制的区域。总之,基线连通性特征可用于预测易受大脑变化影响的区域,并为个性化脑刺激提供基础。脑刺激通过在特定脑区诱导兴奋性变化,越来越多地用于治疗神经精神障碍。然而,我们对这些变化是如何、何时以及何地产生的理解严重不足。我们在向大脑表面施加电刺激并测量兴奋性变化后,推断了人类大脑的可塑性。我们观察到与刺激部位在解剖和功能上更接近的区域的兴奋性变化。使用基于基线大脑网络特征训练的分类器,可以准确预测响应区域的变化。最后,我们表明可以实时监测兴奋性变化。这些结果开始填补我们对人类刺激诱导大脑动力学理解的基本空白,并为优化刺激方案提供途径。