The adaptive human frontal cortex Flexibly switching between different tasks is a fundamental human cognitive ability that allows us to make selective use of only the information needed for a given decision. Minxha et al. used single-neuron recordings from patients to understand how the human brain retrieves memories on demand when needed for making a decision and how retrieved memories are dynamically routed in the brain from the temporal to the frontal lobe. When memory was not needed, only medial frontal cortex neural activity was correlated with the task. However, when outcome choices required memory retrieval, frontal cortex neurons were phase-locked to field potentials recorded in the medial temporal lobe. Therefore, depending on demands of the task, neurons in different regions can flexibly engage and disengage their activity patterns. Science, this issue p. eaba3313 Information stored in memory is selectively routed to the human frontal cortex only when a decision requires access to memory. INTRODUCTION Decision-making in complex environments relies on flexibly combining stimulus representations with context, goals, and memories. A central component of cognitive flexibility is to selectively retrieve information from memory and utilize the retrieved information to make decisions. The medial frontal cortex (MFC) plays a critical role in this process by representing task sets, context, and outcomes. During decision-making, the MFC is thought to selectively engage memory retrieval by representing memory-based choices and mediating interactions between the frontal lobes and the hippocampus and amygdala (HA) through phase-locking of MFC activity to oscillations in the HA. It remains unknown what features of decisions and context are represented in the human MFC and what functional interactions between the MFC and HA mediate dynamic memory retrieval during a task. RATIONALE We recorded single neurons and local field potentials in the human MFC and HA in patients implanted with depth electrodes. Subjects switched between two tasks: recognition memory and categorization. To identify signatures of task demands, we compared the strength of encoding of stimulus familiarity, category, and choices between tasks and tested whether decoders trained in one task generalized to the other task. Such cross-task generalizability would indicate abstract representations of the underlying variables. We hypothesized that this approach would reveal neural signatures of the representations and functional interactions that permit memory-based decisions. RESULTS We recorded from 1430 single neurons in the HA and MFC [dorsal anterior cingulate cortex (dACC) and the pre-supplementary motor area (pre-SMA)] across 13 patients. Subjects made “yes” or “no” decisions using button presses or saccades (eye movements) to indicate whether an image was novel or familiar, or whether an image belonged to a given visual category. Instructions were given before each block of trials, explaining the task and response modality to use (i.e., task set). Examining the underlying neural representations at the single-neuron and population levels revealed the following: (i) Cells in the MFC represented task set during baseline periods. These contextual signals emerged rapidly after a task switch and generalized across all response and task-type combinations in the MFC but not the HA. (ii) The strength and geometry of representations of familiarity were task-insensitive in the HA but not in the MFC. The responses of these memory-selective cells were a reflection of memory strength rather than decisions about the memory. (iii) The visual category of stimuli was represented more strongly during the memory task in both the MFC and HA. This encoding of category generalized across tasks fully in the HA but not the MFC. (iv) Choices in both tasks were most strongly represented by cells in the MFC. This choice representation differed in its population-level geometry between the two tasks but was insensitive to response modality (button press or saccade). One subset of MFC cells signaled only memory-based choices, and these cells signaled decisions about the memory. (v) MFC cells phase-locked their activity to theta-frequency band oscillation in the HA preferentially in the memory task, with memory-choice cells also phase-locking in the gamma-frequency band. The strength of this interareal phase-locking in both frequency bands of the MFC cells that signaled memory-based choices was predictive of behavior. CONCLUSION We leveraged the opportunity to record from single neurons in humans to identify representations of choices, task sets, stimulus category, and familiarity in the human MFC and HA. We found that neuronal populations within the MFC formed two separate decision axes: one for memory-based decisions and another for categorization-based decisions. MFC-HA theta-frequency functional connectivity was selectively enhanced during memory retrieval. This work reveals a neuronal mechanism in the human brain whereby oscillation-mediated coordination of activity between distant brain regions and accompanying changes in strength of representation and/or geometry implements task-dependent retrieval of memory. Flexible representations of choices in the human frontal lobe. (A) Recording locations. LFP, local field potential. (B) Population response of all recorded neurons (left) and example of a cell signaling memory-based choices (right). (C and D) Representational geometry analysis reveals that different subspaces are used by the two tasks, establishing a memory-specific decision axis. (E) Theta- and gamma-band coherence of MFC choice cells with HA LFPs increased during the memory task. Decision-making in complex environments relies on flexibly using prior experience. This process depends on the medial frontal cortex (MFC) and the medial temporal lobe, but it remains unknown how these structures implement selective memory retrieval. We recorded single neurons in the MFC, amygdala, and hippocampus while human subjects switched between making recognition memory–based and categorization-based decisions. The MFC rapidly implemented changing task demands by using different subspaces of neural activity and by representing the currently relevant task goal. Choices requiring memory retrieval selectively engaged phase-locking of MFC neurons to amygdala and hippocampus field potentials, thereby enabling the routing of memories. These findings reveal a mechanism for flexibly and selectively engaging memory retrieval and show that memory-based choices are preferentially represented in the frontal cortex when required.

中文翻译：

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人类内侧额叶皮层灵活招募基于记忆的选择表征


适应性人类额叶皮层 在不同任务之间灵活切换是人类的一项基本认知能力，它使我们能够选择性地仅使用给定决策所需的信息。明夏等人。使用患者的单神经元记录来了解人脑如何在需要做出决定时按需检索记忆，以及检索到的记忆如何在大脑中从颞叶动态路由到额叶。当不需要记忆时，只有内侧额叶皮层神经活动与任务相关。然而，当结果选择需要记忆检索时，额叶皮层神经元被锁相到内侧颞叶记录的场电位。因此，根据任务的需要，不同区域的神经元可以灵活地参与和脱离其活动模式。科学，本期第 14 页。 eaba3313 仅当决策需要访问内存时，存储在内存中的信息才会有选择地路由到人类额叶皮层。引言复杂环境中的决策依赖于刺激表征与背景、目标和记忆的灵活结合。认知灵活性的核心组成部分是有选择地从记忆中检索信息并利用检索到的信息做出决策。内侧额叶皮层 (MFC) 在此过程中通过表示任务集、上下文和结果发挥着关键作用。在决策过程中，MFC 被认为通过代表基于记忆的选择并通过 MFC 活动与 HA 振荡的锁相来调节额叶、海马体和杏仁核 (HA) 之间的相互作用来选择性地参与记忆检索。 目前尚不清楚人类 MFC 中代表了哪些决策和上下文特征，以及 MFC 和 HA 之间的哪些功能交互在任务期间介导动态记忆检索。基本原理 我们记录了植入深度电极的患者 MFC 和 HA 中的单个神经元和局部场电位。受试者在两项任务之间切换：识别记忆和分类。为了识别任务需求的特征，我们比较了任务之间的刺激熟悉度、类别和选择的编码强度，并测试了在一项任务中训练的解码器是否可以推广到另一项任务。这种跨任务的通用性将表明底层变量的抽象表示。我们假设这种方法将揭示允许基于记忆的决策的表征和功能交互的神经特征。结果 我们记录了 13 名患者的 HA 和 MFC [背侧前扣带皮层 (dACC) 和前辅助运动区 (pre-SMA)] 的 1430 个单个神经元。受试者通过按下按钮或扫视（眼球运动）来做出“是”或“否”决定，以表明图像是新颖的还是熟悉的，或者图像是否属于给定的视觉类别。在每个试验块之前给出说明，解释要使用的任务和响应模式（即任务集）。检查单神经元和群体水平的潜在神经表征揭示了以下内容：（i）MFC 中的细胞代表基线期间的任务集。这些上下文信号在任务切换后迅速出现，并泛化到 MFC 中的所有响应和任务类型组合，但不包括 HA。 (ii) 熟悉度表示的强度和几何形状在 HA 中对任务不敏感，但在 MFC 中则不然。这些记忆选择性细胞的反应反映了记忆强度，而不是关于记忆的决定。 (iii) 在 MFC 和 HA 的记忆任务中，视觉刺激的表现更为强烈。这种类别编码完全在 HA 中泛化到任务，但在 MFC 中不泛化。 (iv) 这两项任务中的选择最强烈地由 MFC 中的单元格代表。这种选择表示​​在两个任务之间的群体水平几何形状上有所不同，但对响应方式（按钮按下或扫视）不敏感。 MFC 细胞的一个子集仅发出基于记忆的选择信号，而这些细胞则发出有关记忆的决策信号。 (v) MFC 细胞在记忆任务中优先将其活动锁相到 HA 中的 θ 频带振荡，记忆选择细胞也在伽马频带中锁相。 MFC 细胞两个频段的区域间锁相强度表明基于记忆的选择，可以预测行为。结论 我们利用记录人类单个神经元的机会来识别人类 MFC 和 HA 中的选择、任务集、刺激类别和熟悉程度的表示。我们发现 MFC 内的神经元群体形成了两个独立的决策轴：一个用于基于记忆的决策，另一个用于基于分类的决策。 MFC-HA θ频率功能连接在记忆检索过程中被选择性增强。 这项工作揭示了人脑中的一种神经元机制，通过振荡介导的遥远大脑区域之间的活动协调以及伴随的表征和/或几何强度的变化实现了任务依赖性的记忆检索。人类额叶中选择的灵活表示。 (A) 录音地点。 LFP，本地场潜力。 (B) 所有记录的神经元的群体反应（左）和基于记忆的细胞信号选择的示例（右）。 （C 和 D）表征几何分析表明，两个任务使用不同的子空间，建立特定于内存的决策轴。 (E) MFC 选择细胞与 HA LFP 的 Theta 和 gamma 频带一致性在记忆任务期间增加。复杂环境下的决策依赖于灵活运用先前的经验。这个过程依赖于内侧额叶皮层（MFC）和内侧颞叶，但这些结构如何实现选择性记忆检索仍然未知。当人类受试者在基于识别记忆和基于分类的决策之间切换时，我们记录了 MFC、杏仁核和海马体中的单个神经元。 MFC 通过使用不同的神经活动子空间并表示当前相关的任务目标，快速实现不断变化的任务需求。需要记忆检索的选择选择性地将 MFC 神经元锁相至杏仁核和海马体场电位，从而实现记忆的路由。这些发现揭示了一种灵活、选择性地参与记忆检索的机制，并表明基于记忆的选择在需要时优先在额叶皮层中呈现。