Modulation of Cortical Oscillations by Low-Frequency Direct Cortical Stimulation Is State-Dependent.
Modulation of Cortical Oscillations by Low-Frequency Direct Cortical Stimulation Is State-Dependent.
复制标题
DOI：
10.1371/journal.pbio.1002424
复制
发表时间：
2016-03
期刊：
影响因子：
9.8
通讯作者：
Frӧhlich F
中科院分区：
文献类型：
--
作者：
Alagapan S;Schmidt SL;Lefebvre J;Hadar E;Shin HW;Frӧhlich F
皮层振荡在组织大规模功能性大脑网络中发挥着重要作用。已经提出了具有时间模式化波形的非侵入性脑刺激，例如重复经颅磁刺激（rTMS）和经颅交流刺激（tACS），以调制这些振荡。因此，这些刺激方式代表了治疗这些振荡受损的精神疾病的有前途的新方法。然而，周期性大脑刺激改变内源性振荡动力学的机制仍存在争议，并且似乎取决于大脑状态。在这里，我们证明了一个静态模型和一个神经振荡器模型，经常性的兴奋在丘脑-皮层电路，再加上招聘的皮质-皮质连接，可以解释增强的振荡，脑刺激作为一个功能的大脑状态。然后，我们进行了并发的侵入性记录和刺激的人皮层表面，以阐明皮层振荡周期性刺激的反应，并支持从计算模型的结果。我们发现（1）刺激增强了目标振荡功率，（2）这种增强持续刺激，（3）刺激的效果取决于行为状态。总之，我们的研究结果表明，成功的目标参与振荡周期性脑刺激，并强调内源性网络振荡和刺激之间的非线性相互作用的作用。这些机制的见解将有助于设计自适应，更有针对性的刺激范例。这项研究提出了数学模型，解释了时间模式的电刺激对皮层振荡的影响，并提供了支持证据，使用直接记录的数据从人类皮层在经颅电刺激。大脑中的节奏被认为在认知中起着重要作用。这些振荡的中断与许多神经和精神疾病有关。因此，针对这些振荡的非侵入性脑刺激技术提供了作为治疗工具的希望。特别地，经颅交流电刺激（tACS）应用周期性刺激波形以参与皮质中的特定振荡。虽然最近的研究提供了证据的调制皮层振荡的tACS，确切的机制，产生的影响是知之甚少。我们提出了两个数学模型的周期性电刺激和持续的大脑活动之间的相互作用，可以解释tACS的影响。此外，我们提出了一个独特的数据集，其中我们用硬膜下电极刺激患者的皮层表面，并观察相邻电极对刺激的反应。我们发现，刺激增强持续振荡期间和刺激后立即。这种增强依赖于大脑状态，从而支持我们提出的模型。我们的研究结果证明了电刺激对皮层振荡的影响，并强调了在设计用于中枢神经系统疾病的电刺激疗法时考虑大脑状态的重要性。
Cortical oscillations play a fundamental role in organizing large-scale functional brain networks. Noninvasive brain stimulation with temporally patterned waveforms such as repetitive transcranial magnetic stimulation (rTMS) and transcranial alternating current stimulation (tACS) have been proposed to modulate these oscillations. Thus, these stimulation modalities represent promising new approaches for the treatment of psychiatric illnesses in which these oscillations are impaired. However, the mechanism by which periodic brain stimulation alters endogenous oscillation dynamics is debated and appears to depend on brain state. Here, we demonstrate with a static model and a neural oscillator model that recurrent excitation in the thalamo-cortical circuit, together with recruitment of cortico-cortical connections, can explain the enhancement of oscillations by brain stimulation as a function of brain state. We then performed concurrent invasive recording and stimulation of the human cortical surface to elucidate the response of cortical oscillations to periodic stimulation and support the findings from the computational models. We found that (1) stimulation enhanced the targeted oscillation power, (2) this enhancement outlasted stimulation, and (3) the effect of stimulation depended on behavioral state. Together, our results show successful target engagement of oscillations by periodic brain stimulation and highlight the role of nonlinear interaction between endogenous network oscillations and stimulation. These mechanistic insights will contribute to the design of adaptive, more targeted stimulation paradigms. This study presents mathematical models that explain the effect of temporally patterned electrical stimulation on cortical oscillations and provides supporting evidence using data recorded directly from human cortex during transcranial electrical stimulation. Rhythms in the brain are believed to play an important role in cognition. Disruptions in these oscillations are associated with a number of neurological and psychiatric disorders. Therefore, noninvasive brain stimulation techniques that target these oscillations offer promise as therapeutic tools. In particular, transcranial alternating current stimulation (tACS) applies a periodic stimulation waveform to engage specific oscillations in the cortex. Although recent studies provide evidence for the modulation of cortical oscillations by tACS, the exact mechanism by which the effects are produced is poorly understood. We propose two mathematical models of interaction between periodic electrical stimulation and ongoing brain activity that may explain the effects of tACS. In addition, we present a unique dataset in which we stimulated the patients’ cortical surface with subdural electrodes and observed the responses to stimulation in neighboring electrodes. We found that stimulation enhanced ongoing oscillations both during and immediately after stimulation. This enhancement depended on the brain state, thereby supporting our proposed models. Our results demonstrate the effect of electrical stimulation on cortical oscillations and highlight the importance of considering the state of the brain when designing electrical stimulation therapies for disorders of the central nervous system.