Electrophysiological connections linking medial pulvinar, anterior nuclei of the thalamus and the hippocampus

IF 11.7 1区医学 Q1 CLINICAL NEUROLOGY

Brain Pub Date : 2025-10-06 DOI:10.1093/brain/awaf342

Masaya Togo, Dian Lyu, Weichen Huang, Sofia Pantis, Robert Fisher, Riki Matsumoto, Vivek Buch, Josef Parvizi

{"title":"Electrophysiological connections linking medial pulvinar, anterior nuclei of the thalamus and the hippocampus","authors":"Masaya Togo, Dian Lyu, Weichen Huang, Sofia Pantis, Robert Fisher, Riki Matsumoto, Vivek Buch, Josef Parvizi","doi":"10.1093/brain/awaf342","DOIUrl":null,"url":null,"abstract":"The Papez circuit traditionally highlights the anterior nuclei of the thalamus (ANT) as the main relay of hippocampal (HPC) output to the cortex, a view that has shaped neuromodulation strategies in temporal lobe epilepsy (TLE). However, recent studies suggest that the medial subregion of the pulvinar (mPLV)— a thalamic nucleus that has undergone significant evolutionary expansion throughout the mammalian brain evolution— also forms functional connections with medial temporal lobe (MTL) structures, including the hippocampus (HPC). To date, however, there is a lack of causal evidence directly comparing the connectivity between the HPC and the two thalamic nuclei (mPLV and ANT) and between the two thalamic structures within the same brains. In this study, we investigated 41 patients with medial (mTLE, N=22) and non-medial temporal lobe epilepsy (non-mTLE, N=19) implanted with simultaneous depth electrodes in the HPC, ANT, and mPLV. Repeated single-pulse electrical stimulations were applied to compare the causal electrophysiological connectivity of these regions within the same individuals. Our intra-subject analysis revealed that anterior HPC stimulation evoked strong responses in both ANT and mPLV, with mPLV responses occurring significantly later than those in the ANT [linear mixed-effect model (LMM), Mean: 10.19ms, 95% CI [1.78, 18.59], (FDR corrected P = 0.040)]. In contrast, stimulation of the posterior HPC resulted in stronger (and a trend for earlier) responses in mPLV compared to ANT [LMM: Mean: 0.117, 95% CI [0.033, 0.201] (FDR corrected P = 0.012)]. This finding suggests anterio-posterior gradient of HPC connectivity. Furthermore, we found robust bilateral and bidirectional connectivity between ANT and mPLV. Stimulation of either elicited responses in the other, including contralateral thalamus. This represents clear evidence for both intra-thalamic and inter-thalamic connectivity within the human brain. Our findings offer new insights about the connectivity of human HPC with the thalamus and strong intra-thalamic exchange of electrophysiological activity within the human brain.","PeriodicalId":9063,"journal":{"name":"Brain","volume":"94 1","pages":""},"PeriodicalIF":11.7000,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Brain","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/brain/awaf342","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

The Papez circuit traditionally highlights the anterior nuclei of the thalamus (ANT) as the main relay of hippocampal (HPC) output to the cortex, a view that has shaped neuromodulation strategies in temporal lobe epilepsy (TLE). However, recent studies suggest that the medial subregion of the pulvinar (mPLV)— a thalamic nucleus that has undergone significant evolutionary expansion throughout the mammalian brain evolution— also forms functional connections with medial temporal lobe (MTL) structures, including the hippocampus (HPC). To date, however, there is a lack of causal evidence directly comparing the connectivity between the HPC and the two thalamic nuclei (mPLV and ANT) and between the two thalamic structures within the same brains. In this study, we investigated 41 patients with medial (mTLE, N=22) and non-medial temporal lobe epilepsy (non-mTLE, N=19) implanted with simultaneous depth electrodes in the HPC, ANT, and mPLV. Repeated single-pulse electrical stimulations were applied to compare the causal electrophysiological connectivity of these regions within the same individuals. Our intra-subject analysis revealed that anterior HPC stimulation evoked strong responses in both ANT and mPLV, with mPLV responses occurring significantly later than those in the ANT [linear mixed-effect model (LMM), Mean: 10.19ms, 95% CI [1.78, 18.59], (FDR corrected P = 0.040)]. In contrast, stimulation of the posterior HPC resulted in stronger (and a trend for earlier) responses in mPLV compared to ANT [LMM: Mean: 0.117, 95% CI [0.033, 0.201] (FDR corrected P = 0.012)]. This finding suggests anterio-posterior gradient of HPC connectivity. Furthermore, we found robust bilateral and bidirectional connectivity between ANT and mPLV. Stimulation of either elicited responses in the other, including contralateral thalamus. This represents clear evidence for both intra-thalamic and inter-thalamic connectivity within the human brain. Our findings offer new insights about the connectivity of human HPC with the thalamus and strong intra-thalamic exchange of electrophysiological activity within the human brain.

查看原文本刊更多论文

连接内侧枕核、丘脑前核和海马体的电生理连接

传统上，Papez电路强调丘脑前核（ANT）是海马（HPC）输出到皮层的主要中继，这一观点已经形成了颞叶癫痫（TLE）的神经调节策略。然而，最近的研究表明，枕侧内侧亚区（mPLV）——一个在哺乳动物大脑进化过程中经历了显著进化扩张的丘脑核——也与内侧颞叶（MTL）结构，包括海马体（HPC）形成功能联系。然而，到目前为止，还缺乏直接比较HPC和两个丘脑核（mPLV和ANT）之间以及同一大脑内两个丘脑结构之间连通性的因果证据。在本研究中，我们研究了41例内侧颞叶癫痫（mTLE， N=22）和非内侧颞叶癫痫（non-mTLE， N=19）患者在HPC、ANT和mPLV同时植入深度电极。应用重复的单脉冲电刺激来比较同一个体内这些区域的因果电生理连接。我们的受试者内部分析显示，前路HPC刺激在ANT和mPLV中都引起了强烈的反应，mPLV反应明显晚于ANT[线性混合效应模型（LMM）， Mean: 10.19ms, 95% CI [1.78, 18.59], (FDR校正P = 0.040)]。相比之下，与ANT相比，刺激后HPC导致mPLV的反应更强（并且有更早的趋势）[LMM：平均值：0.117,95% CI [0.033, 0.201] (FDR校正P = 0.012)]。这一发现提示HPC连接的前后梯度。此外，我们发现ANT和mPLV之间存在强大的双边和双向连接。刺激任何一方都会引起另一方的反应，包括对侧丘脑。这是人类大脑中丘脑内和丘脑间连通性的明确证据。我们的发现为人类HPC与丘脑的连通性以及人类大脑中强大的丘脑内电生理活动交换提供了新的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Brain 医学-临床神经学

CiteScore

20.30

自引率

4.10%

发文量

458

审稿时长

3-6 weeks

期刊介绍： Brain, a journal focused on clinical neurology and translational neuroscience, has been publishing landmark papers since 1878. The journal aims to expand its scope by including studies that shed light on disease mechanisms and conducting innovative clinical trials for brain disorders. With a wide range of topics covered, the Editorial Board represents the international readership and diverse coverage of the journal. Accepted articles are promptly posted online, typically within a few weeks of acceptance. As of 2022, Brain holds an impressive impact factor of 14.5, according to the Journal Citation Reports.