Objective. Invasive simultaneous stimulation and recording from intracranial electrodes and microwire arrays were used to investigate direct cortical responses to single pulses of electrical stimulation in humans. Approach. Microwire contacts measured surface potentials in cortical microdomains at a distance of 2–6 mm from the intracranial electrode. Direct cortical responses to stimulation (<20 ms) consisted of a larger surface negative potentials. Main results. The latencies of these responses were directly or inversely correlated with distances between the intracranial electrode and microwire contacts. We hypothesize that surface negative potentials reflected local synchronous depolarization of apical dendrites of pyramidal neurons in cortical microdomains in the superficial cortical layer and resulted from the activation of gray matter axons that delivered excitatory inputs to apical dendrites after cortical stimulation. We further hypothesized that the positive or inverse distance-latency correlations of the recorded negative responses were measured depending on whether activation of neurons originated at one (crown) or multiple (crown, lip, bank) sites throughout the gyrus simultaneously. The inverse distance-latency correlations then reflected the spatiotemporal superposition of different nearby sources of neuronal recruitment in the gyrus. To prove this hypothesis, we built an anatomically informed and biophysically realistic cortical network model and simulated early responses of cortical neurons to electrical stimulation in this cortical network model. The model simulations yielded negative potentials in simulated microdomains in the cortical model consistent with those recorded from humans. The model predicted sensitivity of cortical responses to the alignment of the stimulating electrode and microwire array with respect to the cortical gyrus and confirmed that gyral geometry has a major impact on direct neuronal recruitment, the timing, and the time course of neuronal activation in cortical microdomains. Significance. In this work, we demonstrated how the high-resolution forward network models can be used for better understanding and detailed prediction of cortical stimulation effects. Accurate predictive modeling tools are needed for the progress of brain stimulation therapies.

客观的。来自颅内电极和微线阵列的侵入性同步刺激和记录用于研究人类对单脉冲电刺激的直接皮层反应。方法。微线触点在距颅内电极 2-6 毫米处测量皮质微区的表面电位。对刺激的直接皮质反应 (<20 ms) 由较大的表面负电位组成。主要结果. 这些反应的潜伏期与颅内电极和微丝接触之间的距离成正比或负相关。我们假设表面负电位反映了浅表皮层皮层微区锥体神经元顶端树突的局部同步去极化，并且是由于灰质轴突的激活，在皮层刺激后向顶端树突传递兴奋性输入。我们进一步假设，所记录的负反应的正或反距离-延迟相关性的测量取决于神经元的激活是同时起源于整个脑回的一个（冠部）还是多个（冠部、唇部、堤岸）位点。然后，反距离-延迟相关性反映了脑回中不同附近神经元募集源的时空叠加。为了证明这一假设，我们建立了一个解剖学信息和生物物理现实的皮层网络模型，并在这个皮层网络模型中模拟了皮层神经元对电刺激的早期反应。模型模拟在皮层模型的模拟微域中产生负电位，与人类记录的一致。该模型预测了皮层反应对刺激电极和微线阵列相对于皮层回的对齐的敏感性，并证实了回旋几何对皮层微域中神经元激活的直接神经元募集、时间和时间过程有重大影响. 我们建立了一个解剖学信息和生物物理现实的皮层网络模型，并在这个皮层网络模型中模拟了皮层神经元对电刺激的早期反应。模型模拟在皮层模型的模拟微域中产生负电位，与人类记录的一致。该模型预测了皮层反应对刺激电极和微线阵列相对于皮层回的对齐的敏感性，并证实了回旋几何对皮层微域中神经元激活的直接神经元募集、时间和时间过程有重大影响. 我们建立了一个解剖学信息和生物物理现实的皮层网络模型，并在这个皮层网络模型中模拟了皮层神经元对电刺激的早期反应。模型模拟在皮层模型的模拟微域中产生负电位，与人类记录的一致。该模型预测了皮层反应对刺激电极和微线阵列相对于皮层回的对齐的敏感性，并证实了回旋几何对皮层微域中神经元激活的直接神经元募集、时间和时间过程有重大影响. 模型模拟在皮层模型的模拟微域中产生负电位，与人类记录的一致。该模型预测了皮层反应对刺激电极和微线阵列相对于皮层回的对齐的敏感性，并证实了回旋几何对皮层微域中神经元激活的直接神经元募集、时间和时间过程有重大影响. 模型模拟在皮层模型的模拟微域中产生负电位，与人类记录的一致。该模型预测了皮层反应对刺激电极和微线阵列相对于皮层回的对齐的敏感性，并证实了回旋几何对皮层微域中神经元激活的直接神经元募集、时间和时间过程有重大影响.意义。在这项工作中，我们展示了高分辨率前向网络模型如何用于更好地理解和详细预测皮层刺激效应。脑刺激疗法的进展需要准确的预测建模工具。