Laboratory of Behavioral and Cognitive Neuroscience, Human Intracranial Cognitive Electrophysiology Program, Stanford University School of Medicine, Stanford, CA 94305.
Department of Neurology and Neurological Sciences, Stanford School of Medicine, Stanford, CA 94305.
Proc Natl Acad Sci U S A. 2024 Aug 6;121(32):e2316021121. doi: 10.1073/pnas.2316021121. Epub 2024 Jul 30.
For the human brain to operate, populations of neurons across anatomical structures must coordinate their activity within milliseconds. To date, our understanding of such interactions has remained limited. We recorded directly from the hippocampus (HPC), posteromedial cortex (PMC), ventromedial/orbital prefrontal cortex (OFC), and the anterior nuclei of the thalamus (ANT) during two experiments of autobiographical memory processing that are known from decades of neuroimaging work to coactivate these regions. In 31 patients implanted with intracranial electrodes, we found that the presentation of memory retrieval cues elicited a significant increase of low frequency (LF < 6 Hz) activity followed by cross-regional phase coherence of this LF activity before select populations of neurons within each of the four regions increased high-frequency (HF > 70 Hz) activity. The power of HF activity was modulated by memory content, and its onset followed a specific temporal order of ANT→HPC/PMC→OFC. Further, we probed cross-regional causal effective interactions with repeated electrical pulses and found that HPC stimulations cause the greatest increase in LF-phase coherence across all regions, whereas the stimulation of any region caused the greatest LF-phase coherence between that particular region and ANT. These observations support the role of the ANT in gating, and the HPC in synchronizing, the activity of cortical midline structures when humans retrieve self-relevant memories of their past. Our findings offer a fresh perspective, with high temporal fidelity, about the dynamic signaling and underlying causal connections among distant regions when the brain is actively involved in retrieving self-referential memories from the past.
为了使人类大脑能够运作，跨越解剖结构的神经元群体必须在毫秒内协调它们的活动。迄今为止，我们对这种相互作用的理解仍然有限。我们在两个自传体记忆处理实验中直接记录了海马体（HPC）、后内侧皮层（PMC）、腹侧/眶额前皮质（OFC）和丘脑前核（ANT）的活动，这些实验在神经影像学工作的几十年中已知会共同激活这些区域。在 31 名植入颅内电极的患者中，我们发现记忆检索线索的呈现会引起低频（LF<6 Hz）活动的显著增加，随后在四个区域中的每个区域内的选定神经元群体增加高频（HF>70 Hz）活动之前，这种 LF 活动的跨区域相位相干性增加。HF 活动的功率受记忆内容的调制，其起始遵循特定的时间顺序，即 ANT→HPC/PMC→OFC。此外，我们用重复的电脉冲探测跨区域的因果有效相互作用，发现 HPC 刺激会导致所有区域 LF 相位相干性的最大增加，而任何区域的刺激都会导致该特定区域与 ANT 之间的 LF 相位相干性最大增加。这些观察结果支持 ANT 在门控中的作用，以及 HPC 在协调人类检索过去自我相关记忆时皮质中线结构活动中的作用。我们的研究结果提供了一个新的视角，以高时间保真度展示了大脑在主动检索过去自我参照记忆时，远距离区域之间的动态信号和潜在的因果联系。
