Montreal Neurological Institute, McGill University, Montreal, Québec, H3A 2B4, Canada.
Institute for Neurophysiology and Pathophysiology, University Medical Center Hamburg-Eppendorf 20251, Hamburg, Germany.
eNeuro. 2019 Mar 4;6(1). doi: 10.1523/ENEURO.0371-18.2018. eCollection 2019 Jan-Feb.
Methylphenidate (MPH), commonly known as Ritalin, is the most widely prescribed drug worldwide to treat patients with attention deficit disorders. Although MPH is thought to modulate catecholamine neurotransmission in the brain, it remains unclear how these neurochemical effects influence neuronal activity and lead to attentional enhancements. Studies in rodents overwhelmingly point to the lateral prefrontal cortex (LPFC) as a main site of action of MPH. To understand the mechanism of action of MPH in a primate brain, we recorded the responses of neuronal populations using chronic multielectrode arrays implanted in the caudal LPFC of two macaque monkeys while the animals performed an attention task ( = 2811 neuronal recordings). Over different recording sessions ( = 55), we orally administered either various doses of MPH or a placebo to the animals. Behavioral analyses revealed positive effects of MPH on task performance at specific doses. However, analyses of individual neurons activity, noise correlations, and neuronal ensemble activity using machine learning algorithms revealed no effects of MPH. Our results suggest that the positive behavioral effects of MPH observed in primates (including humans) may not be mediated by changes in the activity of caudal LPFC neurons. MPH may enhance cognitive performance by modulating neuronal activity in other regions of the attentional network in the primate brain.
哌醋甲酯（MPH），通常被称为利他林，是世界上最广泛用于治疗注意力缺陷障碍患者的处方药物。尽管 MPH 被认为可以调节大脑中的儿茶酚胺神经递质传递，但这些神经化学效应如何影响神经元活动并导致注意力增强仍不清楚。啮齿动物研究几乎无一例外地指出外侧前额叶皮层（LPFC）是 MPH 的主要作用部位。为了了解 MPH 在灵长类动物大脑中的作用机制，我们使用植入两只猕猴尾侧 LPFC 的慢性多电极阵列记录神经元群体的反应，同时动物执行注意任务（=2811 个神经元记录）。在不同的记录会话（=55）中，我们通过口服给予动物不同剂量的 MPH 或安慰剂。行为分析显示，在特定剂量下，MPH 对任务表现有积极影响。然而，使用机器学习算法对单个神经元活动、噪声相关性和神经元集合活动进行分析，没有发现 MPH 的影响。我们的结果表明，在灵长类动物（包括人类）中观察到的 MPH 的积极行为效应可能不是由尾侧 LPFC 神经元活动的变化介导的。MPH 可能通过调节灵长类动物注意力网络中其他区域的神经元活动来增强认知表现。
