Ward Ryan D, Winiger Vanessa, Higa Kerin K, Kahn Julia B, Kandel Eric R, Balsam Peter D, Simpson Eleanor H
Department of Psychology, Columbia University.
Department of Neuroscience and Psychiatry, Columbia University.
Behav Neurosci. 2015 Jun;129(3):292-9. doi: 10.1037/bne0000051. Epub 2015 Apr 27.
Interactions between motivation and cognition are implicated in producing functional impairments and poor quality of life in psychiatric patients. This interaction, however, is not well understood at either the behavioral or neural level. We developed a procedure for mice in which a cognitive measure, sustained attention, is modulated by a motivationally relevant signal that predicts reward probability on a trial-by-trial basis. Using this paradigm, we tested the interaction between motivation and cognition in mice that model the increased striatal D2 receptor activity observed in schizophrenia patients (D2R-OE mice). In control mice, attention was modulated by signaled-reward probability. In D2R-OE mice, however, attention was not modulated by reward-related cues. This impairment was not due to any global deficits in attention or maintenance of the trial-specific information in working memory. Turning off the transgene in D2R-OE mice rescued the motivational modulation of attention. These results indicate that deficits in motivation impair the ability to use reward-related cues to recruit attention and that improving motivation improves functional cognitive performance. These results further suggest that addressing motivational impairments in patients is critical to achieving substantive cognitive and functional gains.
动机与认知之间的相互作用与精神疾病患者的功能障碍和生活质量低下有关。然而，这种相互作用在行为或神经层面都尚未得到充分理解。我们为小鼠开发了一种程序，其中一种认知测量指标，即持续注意力，由一个与动机相关的信号调节，该信号在逐次试验的基础上预测奖励概率。利用这一范式，我们在模拟精神分裂症患者中观察到的纹状体D2受体活性增加的小鼠（D2R-OE小鼠）中测试了动机与认知之间的相互作用。在对照小鼠中，注意力受信号奖励概率的调节。然而，在D2R-OE小鼠中，注意力不受奖励相关线索的调节。这种损伤并非由于注意力的任何整体缺陷或工作记忆中特定试验信息的维持。在D2R-OE小鼠中关闭转基因可挽救注意力的动机调节。这些结果表明，动机缺陷会损害利用奖励相关线索来吸引注意力的能力，而改善动机则能提高功能性认知表现。这些结果进一步表明，解决患者的动机障碍对于实现实质性的认知和功能改善至关重要。
