Influence of glutamatergic and GABA-ergic neurotransmission on perception and decision making: a novel pharmacological approach based on computational models.

关于人类认知理论模型的两个中心假设将感知和决策过程与γ-氨基丁酸和GABA能（γ-氨基丁酸）活性的网络效应联系起来。因此，脑电皮层活动被认为是对知觉和相关决策产生自上而下的预测。GABA能活动被认为是自下而上控制所需的相关生成的预测编码的记忆。虽然这些假说在认知神经科学领域被广泛接受，但关于这两种假说的神经药理学证据尚未收集。在随机和双盲条件下，参与者接受一组药理学药物（D-环丝氨酸、右甲氧啡、劳拉西泮、氟桂利嗪、安慰剂），这些药物可有效调节多巴胺能和GABA能网络活性。将结合两个既定任务（概率反应时间任务;瓮任务）和两个计算模型（分层高斯滤波器，马尔可夫决策过程）评估药理学干预对感知和决策的影响。因此，该研究提案提出了一个步骤，以了解在人类体内模型的感知和决策的多巴胺能和GABA能网络的影响。建立概述的转化研究框架是实现精神分裂症患者未来研究项目的关键，在精神分裂症患者中，多巴胺能和GABA能网络的病理功能障碍以及决策和感知障碍已被反复描述。因此，研究建议构成的基础，以解决未来的研究问题，精神分裂症患者使用概述的新的研究方法。

Two central hypotheses concerning theoretical models of human cognition have linked processes of perception and decision making to network effects of both glutamatergic and GABA-ergic (gamma-aminobutyric acid) activity. Thus, glutamatergic cortical activity is supposed to generate top-down predictions about perceptions and related decisions. And GABA-ergic activity is assumed to be required for the bottom-up control relating the generated predictions to encoded memories. Although these hypotheses are widely accepted in the field of cognitive neuroscience, neuropharmacological evidence has yet to be collected concerning both hypotheses. Under randomized and double-blind conditions participants receive a set of pharmacological agents (D-Cycloserine, Dextromethorphane, Lorazepam, Flunarizine, Placebo), which efficiently modulate glutamatergic and GABA-ergic network activity. The influence of the pharmacological interventions on perception and decision making will be assessed combining two established tasks (probabilistic-reaction-time task; urn task) and two computational bayesian models (Hierarchical-Gaussian-Filter, Markow-decision-processes). Thus, the research proposal presents a step toward understanding the glutamatergic and GABA-ergic network effects on perception and decision making in a human in-vivo model. Establishing the outlined translational research-framework is key to enable future research projects on patients with schizophrenia, where pathological dysfunction of glutamatergic and GABA-ergic networks as well as impairments in decision making and perception have repeatedly been described. The research proposal therefore constitutes the foundation to adress future research issues in schizophrenia patients using the outlined novel research approach.