Investigating the neural mechanisms of human cognitive function through intracranial recordings

通过颅内记录研究人类认知功能的神经机制

• 批准号: 10915992
• 负责人: Kareem Zaghloul
• 金额: $ 312.07万
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10915992
• 关键词: Anterior; Area; Behavior; Brain; Brain region; Categories; Cells; Characteristics; Clinical; Code; Cognition; Cognitive; Communication; Cortical Column; Data; Dedications; Diamond; Dimensions; Electric Stimulation; Electrodes; Electroencephalography; Epilepsy; Episodic memory; Etiology; Event; Exhibits; Foundations; Functional Magnetic Resonance Imaging; Goals; Human; Human Characteristics; Image; Implanted Electrodes; Individual; Intractable Epilepsy; Knowledge; Learning; Link; Manuscripts; Medial; Memory; Methods; Monitor; Nature; Neurons; Neurosciences; Neurosurgical Procedures; Operative Surgical Procedures; Participant; Pathologic; Patients; Pattern; Physiological; Play; Preparation; Process; Publications; Publishing; Research; Role; Seizures; Semantics; Short-Term Memory; Site; Source; Stereotyping; Stimulus; Structure; Techniques; Temporal Lobe; Time; Vertebral column; Work; clinical center; cognitive function; cognitive task; combinatorial; design; experience; individual variation; insight; long term memory; member; memory encoding; memory retrieval; microstimulation; neural; neuromechanism; neurophysiology; neurosurgery; neurotransmission; patient engagement; recruit; response; temporal measurement; tool

FY2023 has seen significant progress towards realizing our goals and objectives. We have continued our efforts capturing and analyzing intracranial recordings while participants engage in cognitive tasks designed to probe memory encoding and retrieval. Patients with drug resistant epilepsy receiving intracranial electrodes and surgical treatment at the Clinical Center have been recruited for these studies. Our work takes advantage of the opportunities to record both intracranial EEG and single unit spiking activity from these implanted electrodes as participants perform a variety of cognitive tasks during the monitoring period. Our efforts are focused on understanding changes in human brain activity across these different spatial scales. In order to probe how memories are formed and retrieved in the brain, we have focused our efforts on understanding how information is represented in the neural signals that we record. To this end, we have uncovered a number of important phenomena. In particular, we have found that spiking activity in the human anterior temporal lobe cortex is often organized into bursts of spiking activity, and these bursts of neuronal firing are organized into temporal sequences. Our recent efforts have focused on understanding how these sequences may be relevant for neural coding. Our hypothesis has been that this sequential order of spiking activity may be a fundamental building block for representing information in the brain. By examining these sequences of spiking activity as participants view images drawn from different semantic categories, we have now found direct evidence that the specific order of neuronal firing in the anterior temporal lobe can distinguish different semantic categories, and therefore temporal order of neural activity seems to play a role in representing different semantic information. We have recently submitted a manuscript for publication describing this work in detail (Wittig JH, Xie W, Jackson SJ, Inati SK, Zaghloul KA (2023) In Review). This finding aligns with our previous work showing that the order of spiking activity that is present as individuals encode items into their memory is replayed when they retrieve those same items, suggesting that the order of spiking activity carries specific information about the items we are representing in our brains. We are now linking these findings with another phenomenon that we have recently described in our work related to how connectivity at the smallest spatial scales may provide insights into the functional organization and structure of the human cortex, and how such organization may be relevant for encoding information. We have previously found that small local patches of cortex, which we refer to as modules, are highly connected and that activity within these modules is differentially modulated by different stimuli, suggesting that these modules encode different functional information. These modules exhibit the same spatial dimensions and functional characteristics of cortical columns that are hypothesized to exist throughout the human cortex. Examining the sequences of spiking activity, we have now found that each sequence is composed of smaller sub-sequences that arise from the activity of neurons in the different cortical modules that we have identified. During any given burst of spiking activity, the neurons in some but not all modules within a patch of cortex are actively involved. Hence, any one individual sequence is in fact composed of spiking activity drawn in combinatorial manner from the spiking activity in different cortical modules. We are currently preparing a manuscript describing this work (Chapeton J, Swift K, Wittig JH, Inati SK, Zaghloul KA (2022) In Preparation). Given these fundamental insights into how neural activity may be organized across these different spatial scales, we have also spent much of our effort over the past year building upon this foundation in order to gain better insights into the neural mechanisms that underlie human episodic memory formation. We have recently completed a study in which we identified that the specific sequences of spiking activity that we observe in our data are both specific to individual items being represented in the brain but also are relatively constrained in their overall order. The spiking sequences observed in an individual patch of cortex during different times are, in general, somewhat similar to one another. Our data therefore suggest that the spiking activity of any patch of cortex can be characterized by a relatively stable backbone of sequential firing, around which individual variations in spiking order may enable the representations of item-specific information. We have recently published a manuscript describing this work (Vaz AP, Wittig JH, Inati SK, Zaghloul KA (2023) Nature Communications). In another study, we have also examined how network interactions at a larger spatial scale may be relevant for memory encoding and retrieval. We specifically examined large scale connectivity in the brain and identified pairs of regions that demonstrate stable time delays in their correlated activity. The presence of a reliable and consistent time delay suggests that indeed two brain regions may have a reliable connection. Based on these pairs alone, we then examined how the moment-to-moment fluctuations in connectivity form a unique pattern of connectivity for every item that we remember, and how these patterns are reinstated when retrieving these memories. These changes in connectivity that form a neural signature of the item being remembered are dissociable from changes in spectral power, suggesting that connectivity itself contains information about the events we encode into memory. We have completed this work and recently submitted a manuscript describing this work for publication (Phan AP, Xie W, Chapeton J, Inati SK, Zaghloul KA (2023) In Review). We have also examined how long-term episodic memory may interact with short-term memory (STM). There are significant parallels between the computations required for the precision of STM and those required to minimize mnemonic interference for long-term memory, a process referred to as pattern separation that has traditionally been ascribed to the medial temporal lobe (MTL). We have recently uncovered direct evidence supporting the hypothesis that the circuitry of the MTL, long viewed as a dedicated module for distinguishing similar neural representations of information in long-term memory, also supports STM precision. We recently published a manuscript describing this work (Xie W, Wittig JH, Bhasin S, Zawora C, Inati SK, Zhang W, Zaghloul KA (2022) Nature Human Behaviour). Finally, we have also spent much effort over the past year examining how these recordings may provide us some insight into the basic mechanisms of epilepsy, and how seizures begin and propagate throughout the brain. We have found that discharges appear to observe a stereotyped and constrained pattern of propagation. Because of this constraint, we can use the pattern of propagation to estimate the pathological source of the discharges. We have recently published a manuscript describing this work in detail (Diamond JM, Withers CP, Chapeton JI, Rahman S, Inati SK, Zaghloul KA (2023) Brain). We have also examined the role of direct electrical stimulation in modulating neural activity. We routinely use stimulation for clinical purposes, and one of our long-term goals is to use direct stimulation to investigate questions of causality. We have found that neurons can be selectively excited or inhibited by microstimulation, and that different stimulation sites may have different effects on the same neurons. We have completed this work and recently published a manuscript describing this study (Yousef D, Wittig JH, Inati SK, Zaghloul KA (2023) J Neuroscience).

2023 财年，我们在实现目标和目标方面取得了重大进展。 我们继续努力捕获和分析颅内记录，同时参与者参与旨在探测记忆编码和检索的认知任务。 这些研究已招募在临床中心接受颅内电极和手术治疗的耐药性癫痫患者。当参与者在监测期间执行各种认知任务时，我们的工作利用这些机会记录颅内脑电图和来自这些植入电极的单个单元尖峰活动。 我们的努力重点是了解人类大脑活动在这些不同空间尺度上的变化。 为了探究大脑中记忆是如何形成和检索的，我们集中精力了解信息如何在我们记录的神经信号中表示。为此，我们发现了一些重要的现象。特别是，我们发现人类前颞叶皮质中的尖峰活动通常被组织成尖峰活动的爆发，并且这些神经元放电的爆发被组织成时间序列。我们最近的工作重点是了解这些序列如何与神经编码相关。我们的假设是，这种尖峰活动的顺序可能是表示大脑中信息的基本构建块。通过检查参与者观看来自不同语义类别的图像时的这些尖峰活动序列，我们现在发现了直接证据，表明前颞叶神经元放电的特定顺序可以区分不同的语义类别，因此神经活动的时间顺序似乎在表示不同语义信息方面发挥了作用。我们最近提交了一份详细描述这项工作的手稿（Wittig JH, Xie W, Jackson SJ, Inati SK, Zaghloul KA (2023) In Review）。这一发现与我们之前的工作相一致，表明个体将项目编码到记忆中时出现的尖峰活动顺序在他们检索相同项目时会重放，这表明尖峰活动的顺序携带了有关我们在大脑中代表的项目的特定信息。我们现在将这些发现与我们最近在工作中描述的另一个现象联系起来，该现象涉及最小空间尺度的连接如何可以提供对人类皮层的功能组织和结构的见解，以及这种组织如何与编码信息相关。我们之前发现，皮层的局部小块（我们称之为模块）是高度连接的，并且这些模块内的活动受到不同刺激的差异调节，这表明这些模块编码不同的功能信息。这些模块表现出与皮质柱相同的空间维度和功能特征，假设这些模块存在于整个人类皮质中。检查尖峰活动的序列，我们现在发现 每个序列都由较小的子序列组成，这些子序列是由我们已识别的不同皮质模块中的神经元活动产生的。在任何给定的脉冲活动爆发期间，皮层内的一些但不是所有模块中的神经元都会积极参与。因此，任何一个单独的序列实际上都是由不同皮质模块中的尖峰活动以组合方式提取的尖峰活动组成的。我们目前正在准备一份描述这项工作的手稿（Chapeton J、Swift K、Wittig JH、Inati SK、Zaghloul KA（2022）准备中）。 鉴于这些关于神经活动如何在这些不同空间尺度上组织的基本见解，我们在过去一年中也在此基础上投入了大量精力，以便更好地了解人类情景记忆形成背后的神经机制。我们最近完成了一项研究，其中我们发现，我们在数据中观察到的尖峰活动的特定序列既特定于大脑中所代表的单个项目，又相对地受到其整体顺序的限制。一般来说，在不同时间在单个皮层斑块中观察到的尖峰序列彼此有些相似。因此，我们的数据表明，任何一块皮层的尖峰活动都可以通过相对稳定的顺序放电主干来表征，围绕该主干，尖峰顺序的个体变化可能能够表示特定项目的信息。我们最近发表了一篇描述这项工作的手稿（Vaz AP、Wittig JH、Inati SK、Zaghloul KA (2023) Nature Communications）。在另一项研究中，我们还研究了更大空间尺度的网络交互如何与记忆编码和检索相关。我们专门检查了大脑中的大规模连接性，并确定了在相关活动中表现出稳定时间延迟的区域对。可靠且一致的时间延迟的存在表明，确实两个大脑区域可能具有可靠的连接。仅基于这些对，我们就研究了连通性的即时波动如何为我们记住的每个项目形成独特的连通性模式，以及在检索这些记忆时如何恢复这些模式。这些形成所记忆项目的神经特征的连接性变化与光谱功率的变化是分离的，这表明连接性本身包含有关我们编码到记忆中的事件的信息。我们已经完成了这项工作，并最近提交了一份描述这项工作的手稿以供出版（Phan AP, Xie W, Chapeton J, Inati SK, Zaghloul KA (2023) In Review）。我们还研究了长期情景记忆如何与短期记忆（STM）相互作用。 STM 精度所需的计算与最小化长期记忆助记干扰所需的计算之间存在显着的相似之处，这一过程被称为模式分离，传统上归因于内侧颞叶 (MTL)。我们最近发现了支持以下假设的直接证据：MTL 电路长期以来被视为区分长期记忆中信息的相似神经表征的专用模块，也支持 STM 精度。我们最近发表了一篇描述这项工作的手稿（Xie W、Wittig JH、Bhasin S、Zawora C、Inati SK、Zhang W、Zaghloul KA (2022) Nature Human Behaviour）。 最后，我们在过去的一年里还花费了大量的精力来研究这些记录如何让我们深入了解癫痫的基本机制，以及癫痫发作如何在大脑中开始和传播。我们发现放电似乎观察到一种刻板且受限的传播模式。由于这个限制，我们可以使用传播模式来估计放电的病理源。我们最近发表了一份详细描述这项工作的手稿（Diamond JM、Withers CP、Chapeton JI、Rahman S、Inati SK、Zaghloul KA (2023) Brain）。我们还研究了直接电刺激在调节神经活动中的作用。我们通常将刺激用于临床目的，我们的长期目标之一是使用直接刺激来研究因果关系问题。我们发现，微刺激可以选择性地兴奋或抑制神经元，并且不同的刺激部位对同一神经元可能产生不同的影响。我们已经完成了这项工作，并最近发表了一份描述这项研究的手稿（Yousef D、Wittig JH、Inati SK、Zaghloul KA (2023) J Neuroscience）。

项目成果

Human subthalamic nucleus activity during non-motor decision making.

在非运动决策过程中，人丘脑核核活性。

• DOI: 10.7554/elife.31007
• 发表时间: 2017-12-15
• 期刊: eLife
• 影响因子: 7.7
• 作者: Zavala BA;Jang AI;Zaghloul KA
• 通讯作者: Zaghloul KA

The subthalamic nucleus, oscillations, and conflict.

• DOI: 10.1002/mds.26072
• 发表时间: 2015-03
• 期刊: MOVEMENT DISORDERS
• 影响因子: 8.6
• 作者: Zavala, Baltazar;Zaghloul, Kareem;Brown, Peter
• 通讯作者: Brown, Peter

Surface based electrode localization and standardized regions of interest for intracranial EEG.

• DOI: 10.1002/hbm.23876
• 发表时间: 2018-03
• 期刊: Human brain mapping
• 影响因子: 4.8
• 作者: Trotta MS;Cocjin J;Whitehead E;Damera S;Wittig JH Jr;Saad ZS;Inati SK;Zaghloul KA
• 通讯作者: Zaghloul KA

Risk of seizures induced by intracranial research stimulation: analysis of 770 stimulation sessions.

• DOI: 10.1088/1741-2552/ab4365
• 发表时间: 2019-11-11
• 期刊: Journal of neural engineering
• 影响因子: 4
• 作者: Goldstein HE;Smith EH;Gross RE;Jobst BC;Lega BC;Sperling MR;Worrell GA;Zaghloul KA;Wanda PA;Kahana MJ;Rizzuto DS;Schevon CA;McKhann GM;Sheth SA
• 通讯作者: Sheth SA

Language functional MRI and direct cortical stimulation in epilepsy preoperative planning.

• DOI: 10.1002/ana.24899
• 发表时间: 2017-04
• 期刊: Annals of neurology
• 影响因子: 11.2
• 作者: Austermuehle A;Cocjin J;Reynolds R;Agrawal S;Sepeta L;Gaillard WD;Zaghloul KA;Inati S;Theodore WH
• 通讯作者: Theodore WH