Soldado-Magraner Joana, Minai Yuki, Yu Byron M, Smith Matthew A
Department of Electrical and Computer Engineering, Carnegie Mellon University, Pittsburgh 15213, Pennsylvania, USA.
Center for the Neural Basis of Cognition, Carnegie Mellon University and University of Pittsburgh, Pittsburgh 15213, Pennsylvania, USA.
J Neurosci. 2025 May 30. doi: 10.1523/JNEUROSCI.2197-24.2025.
Delay period activity in the dorso-lateral prefrontal cortex (dlPFC) has been linked to the maintenance and control of sensory information in working memory. The stability of working memory related signals found in such delay period activity is believed to support robust memory-guided behavior during sensory perturbations, such as distractors. Here, we directly probed dlPFC's delay period activity with a diverse set of activity perturbations, and measured their consequences on neural activity and behavior. We applied patterned microstimulation to the dlPFC of two male rhesus macaques implanted with multi-electrode arrays by electrically stimulating different electrodes in the array while they performed a memory-guided saccade task. We found that the microstimulation perturbations affected spatial working memory-related signals in individual dlPFC neurons. However, task performance remained largely unaffected. These apparently contradictory observations could be understood by examining different dimensions of the dlPFC population activity. In dimensions where working memory related signals naturally evolved over time, microstimulation impacted neural activity. In contrast, in dimensions containing working memory related signals that were stable over time, microstimulation minimally impacted neural activity. This dissociation could explain how working memory-related information may be stably maintained in dlPFC despite the activity changes induced by microstimulation. Thus, working memory processes are robust to a variety of activity perturbations in the dlPFC. Memory-guided behavior is remarkably robust to sensory perturbations, such as distractors. The dorso-lateral prefrontal cortex (dlPFC) is believed to underlie this robustness, given that it stably maintains working memory-related information in the presence of distractors. Here, we sought to understand the extent to which dlPFC circuits can robustly maintain working memory information during memory-guided behavior. We found that behavior was robust to electrical microstimulation perturbations in dlPFC, and that working memory signals were stably maintained in dlPFC despite widespread changes in the neural activity caused by the perturbations. Our findings indicate that working memory is robust to direct activity perturbations in the dlPFC, an ability that may be due to the processes that mediate similar robustness in the face of distractors.
背外侧前额叶皮层（dlPFC）的延迟期活动与工作记忆中感觉信息的维持和控制有关。在这种延迟期活动中发现的与工作记忆相关信号的稳定性被认为有助于在感觉干扰（如干扰物）期间进行强大的记忆引导行为。在这里，我们用多种活动干扰直接探测了dlPFC的延迟期活动，并测量了它们对神经活动和行为的影响。我们通过在两只植入了多电极阵列的雄性恒河猴执行记忆引导扫视任务时电刺激阵列中的不同电极，对dlPFC进行了模式化微刺激。我们发现微刺激干扰影响了单个dlPFC神经元中与空间工作记忆相关的信号。然而，任务表现基本未受影响。通过检查dlPFC群体活动的不同维度，可以理解这些明显矛盾的观察结果。在与工作记忆相关信号随时间自然演变的维度中，微刺激影响神经活动。相比之下，在包含随时间稳定的与工作记忆相关信号的维度中，微刺激对神经活动的影响最小。这种分离可以解释尽管微刺激引起了活动变化，但与工作记忆相关的信息如何在dlPFC中稳定维持。因此，工作记忆过程对dlPFC中的各种活动干扰具有鲁棒性。记忆引导行为对诸如干扰物之类的感觉干扰具有显著的鲁棒性。背外侧前额叶皮层（dlPFC）被认为是这种鲁棒性的基础，因为它在存在干扰物的情况下稳定地维持与工作记忆相关的信息。在这里，我们试图了解dlPFC回路在记忆引导行为期间能够在多大程度上稳健地维持工作记忆信息。我们发现行为对dlPFC中的电微刺激干扰具有鲁棒性，并且尽管干扰引起了神经活动的广泛变化，但工作记忆信号仍在dlPFC中稳定维持。我们的研究结果表明，工作记忆对dlPFC中的直接活动干扰具有鲁棒性，这种能力可能归因于在面对干扰物时介导类似鲁棒性的过程。
