Department of Physiology and Biomedical Engineering, Mayo Clinic Rochester, Rochester, Minnesota 55902.
Department of Neurology, Mayo Clinic Rochester, Rochester, Minnesota 55902.
J Neurosci. 2023 Sep 27;43(39):6697-6711. doi: 10.1523/JNEUROSCI.2201-22.2023. Epub 2023 Aug 24.
Stimulation-evoked signals are starting to be used as biomarkers to indicate the state and health of brain networks. The human limbic network, often targeted for brain stimulation therapy, is involved in emotion and memory processing. Previous anatomic, neurophysiological, and functional studies suggest distinct subsystems within the limbic network (Rolls, 2015). Studies using intracranial electrical stimulation, however, have emphasized the similarities of the evoked waveforms across the limbic network. We test whether these subsystems have distinct stimulation-driven signatures. In eight patients (four male, four female) with drug-resistant epilepsy, we stimulated the limbic system with single-pulse electrical stimulation. Reliable corticocortical evoked potentials (CCEPs) were measured between hippocampus and the posterior cingulate cortex (PCC) and between the amygdala and the anterior cingulate cortex (ACC). However, the CCEP waveform in the PCC after hippocampal stimulation showed a unique and reliable morphology, which we term the "limbic Hippocampus-Anterior nucleus of the thalamus-Posterior cingulate, HAP-wave." This limbic HAP-wave was visually distinct and separately decoded from the CCEP waveform in ACC after amygdala stimulation. Diffusion MRI data show that the measured end points in the PCC overlap with the end points of the parolfactory cingulum bundle rather than the parahippocampal cingulum, suggesting that the limbic HAP-wave may travel through fornix, mammillary bodies, and the anterior nucleus of the thalamus (ANT). This was further confirmed by stimulating the ANT, which evoked the same limbic HAP-wave but with an earlier latency. Limbic subsystems have unique stimulation-evoked signatures that may be used in the future to help network pathology diagnosis. The limbic system is often compromised in diverse clinical conditions, such as epilepsy or Alzheimer's disease, and characterizing its typical circuit responses may provide diagnostic insight. Stimulation-evoked waveforms have been used in the motor system to diagnose circuit pathology. We translate this framework to limbic subsystems using human intracranial stereo EEG (sEEG) recordings that measure deeper brain areas. Our sEEG recordings describe a stimulation-evoked waveform characteristic to the memory and spatial subsystem of the limbic network that we term the "limbic HAP-wave." The limbic HAP-wave follows anatomic white matter pathways from hippocampus to thalamus to the posterior cingulum and shows promise as a distinct biomarker of signaling in the human brain memory and spatial limbic network.
刺激诱发的信号开始被用作生物标志物，以指示大脑网络的状态和健康。常被用于脑刺激治疗的人类边缘网络，参与情绪和记忆处理。先前的解剖学、神经生理学和功能研究表明，边缘网络内存在不同的子系统（Rolls，2015）。然而，使用颅内电刺激的研究强调了边缘网络中诱发波形的相似性。我们测试这些子系统是否具有独特的刺激驱动特征。在 8 名（男 4 名，女 4 名）耐药性癫痫患者中，我们用单脉冲电刺激刺激边缘系统。可靠的皮质间诱发电位（CCEPs）在海马和后扣带回（PCC）之间以及杏仁核和前扣带回（ACC）之间进行了测量。然而，海马刺激后 PCC 中的 CCEP 波形显示出独特而可靠的形态，我们称之为“边缘海马-丘脑前核-后扣带回，HAP 波”。这个边缘的 HAP 波在视觉上是不同的，并且可以从杏仁核刺激后 ACC 中的 CCEP 波形中单独解码。弥散 MRI 数据显示，在 PCC 中测量的终点与嗅球纤维束的终点重叠，而不是海马旁回纤维束的终点，这表明边缘的 HAP 波可能通过穹窿、乳头体和丘脑前核（ANT）传播。刺激 ANT 进一步证实了这一点，刺激 ANT 会引起相同的边缘 HAP 波，但潜伏期更早。边缘子系统具有独特的刺激诱发特征，未来可能用于帮助网络病理学诊断。边缘系统在多种临床情况下经常受到影响，如癫痫或阿尔茨海默病，描述其典型的电路反应可能提供诊断见解。刺激诱发的波形已用于运动系统中，以诊断电路病理学。我们使用测量深部脑区的人类颅内立体脑电图（sEEG）记录将该框架转换为边缘子系统。我们的 sEEG 记录描述了一种刺激诱发的波形，该波形是边缘网络记忆和空间子系统的特征，我们称之为“边缘 HAP 波”。边缘 HAP 波沿着从海马到丘脑到后扣带回的解剖白质通路，有望成为人类大脑记忆和空间边缘网络中信号的独特生物标志物。
