Data from: Resolving the mesoscopic missing link: biophysical modeling of EEG from cortical columns in primates

Event-related potentials (ERP) are among the most widely measured indices for studying human cognition. While their timing and magnitude provide valuable insights, their usefulness is limited by our understanding of their neural generators at the circuit level. Inverse source localization offers insights into such generators, but their solutions are not unique. To address this problem, scientists have assumed the source space generating such signals comprises a set of discrete equivalent current dipoles, representing the activity of small cortical regions. Based on this notion, theoretical studies have employed forward modeling of scalp potentials to understand how changes in circuit-level dynamics translate into macroscopic ERPs. However, experimental validation is lacking because it requires in vivo measurements of intracranial brain sources. Laminar local field potentials (LFP) offer a mechanism for estimating intracranial current sources. Yet, a theoretical link between LFPs and intracranial brain sources is missing. Here, we present a forward modeling approach for estimating mesoscopic intracranial brain sources from LFPs and predict their contribution to macroscopic ERPs. We evaluate the accuracy of this LFP-based representation of brain sources utilizing synthetic laminar neurophysiological measurements and then demonstrate the power of the approach in vivo to clarify the source of a representative cognitive ERP component. To that end, LFP was measured across the cortical layers of visual area V4 in macaque monkeys performing an attention demanding task. We show that area V4 generates dipoles through layer-specific transsynaptic currents that biophysically recapitulate the ERP component through the detailed forward modeling. The constraints imposed on EEG production by this method also revealed an important dissociation between computational and biophysical contributors. As such, this approach represents an important bridge between laminar microcircuitry, through the mesoscopic activity of cortical columns to the patterns of EEG we measure at the scalp.

事件相关电位（Event-related potentials, ERP）是当前研究人类认知功能最常用的测量指标之一。其潜伏期与幅值可为认知机制提供宝贵的研究视角，但学界对其在环路层面的神经发生源的认知局限，限制了该技术的应用价值。逆源定位（Inverse source localization）可用于揭示这类神经源，但其解并非唯一。为解决这一难题，研究者通常假设产生此类信号的源空间由一组离散的等效电流偶极子构成，以此代表局部皮层区域的神经活动。基于这一假设，已有理论研究通过头皮电位正向建模，探究环路层面的神经动态变化如何转化为宏观层面的事件相关电位。然而，此类研究缺乏实验验证，因为其需要获取颅内脑源的在体测量数据。层状局部场电位（Laminar local field potentials, LFP）为颅内电流源的估算提供了可行途径，但目前仍缺乏LFP与颅内脑源之间的理论关联机制。本研究提出了一种基于LFP估算介观层面颅内脑源的正向建模方法，并可预测其对宏观ERP的贡献。我们首先利用合成的层状神经生理测量数据，评估了该基于LFP的脑源表征方法的准确性；随后通过在体实验，展示了该方法在解析典型认知ERP成分神经源方面的强大能力。为此，我们在执行高注意力需求任务的猕猴视觉皮层V4区的各皮层层中采集了LFP信号。研究发现，V4区通过层特异性跨突触电流产生偶极子，经详细的正向建模，该生物物理过程可精准复现对应的ERP成分。该方法对脑电（Electroencephalogram, EEG）生成过程施加的约束，还揭示了计算贡献与生物物理贡献之间存在重要的解离现象。综上，该方法搭建了一座重要的桥梁，连接了层状微环路、皮层柱的介观活动，直至我们在头皮处记录到的脑电信号模式。