Novel Cross-Species Neurophysiological Assays of Reward and Cognitive Domains

奖励和认知领域的新型跨物种神经生理学测定

• 批准号: 10249528
• 负责人: Diego A Pizzagalli
• 金额: $ 22.95万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10249528
• 关键词: Address; Administrative Supplement; Affect; Animal Testing; Animals; Award; Behavior; Behavioral; Behavioral Assay; Biological Assay; COVID-19 pandemic; Characteristics; Chronic; Cognition; Cognition Disorders; Cognitive; Collaborations; Data; Development; Disease; Electroencephalography; Event-Related Potentials; Feedback; Frequencies; Funding; Goals; Grant; Healthcare; Home; Hospitals; Human; Learning; Measures; Modafinil; Morbidity - disease rate; National Institute of Mental Health; Performance; Pharmacology; Phase; Rattus; Recovery of Function; Research; Research Activity; Reversal Learning; Rewards; Ritalin; Rodent; Site; Techniques; Testing; Time; Work; cognitive control; effective therapy; experimental study; flexibility; improved; negative affect; neural circuit; neurophysiology; neuropsychiatric disorder; novel; pre-clinical; virtual

Project Summary Deficits across the domains of reward and cognition are defining characteristics of virtually all neuropsychiatric disorders, and have deleterious effects on functional recovery, disease chronicity, and morbidity. Development of effective treatments is hindered by the lack of well-validated preclinical measures of target engagement that are functionally similar across species. Capitalizing on a partnership among basic and translational neuroscientists with a strong track record of collaborations, the overarching goal of UH2/UH3 MH109334 is to develop new translational assessments of reward and cognition in which the neurophysiological and behavioral metrics are identical across species. We have addressed this objective by modifying and validating assessments of reward learning, cognitive control, and cognitive flexibility, each of which is disrupted across illnesses. During the UH2 phase, we have developed (or modified), tested and optimized human and rodent versions of a flanker task (cognitive control) and a probabilistic reversal learning task (PRL; cognitive flexibility), such that task parameters are analogous between humans and rats. Additionally, we have recorded EEG data in both humans and rats during performance of each task. In both species, EEG data were analyzed using several techniques, including time- frequency wavelet analyses and time-domain event-related potential (ERP) analyses. These analyses yielded a priori EEG and behavioral variables (e.g., theta oscillations, error-related negativity, feedback-related negativity) that were manipulated in the UH3 phase, which included modafinil (Year 3) and methylphenidate (Year 4) challenges. Due to the COVID-19 pandemic, the human methylphenidate studies could not be started owing to work- from-home orders from Partners HealthCare and McLean Hospital. Similarly, the preclinical methylphenidate component at McLean Hospital (target: Flanker Task) was severely affected, with only limited research activities allowed between mid-March and mid-August. The preclinical methylphenidate component at UCSD (target: Probabilistic Reversal Learning Task) was also affected, although less severely. The current administrative supplement requests funding to complete the Year 4 methylphenidate experiments at all sites. Ultimately, these studies will provide novel measures of reward and/or cognition in both humans and rats that show clear parallels in behavior and neurophysiology that can be manipulated with putative treatments across species. Such tasks will help narrow the existing translational gap between preclinical animal and human research and will promote the development of urgently needed treatments for reward and cognitive disorders.

项目概要 奖励和认知领域的缺陷定义了几乎所有神经精神疾病的特征 疾病，并对功能恢复、疾病慢性化和发病率产生有害影响。发展 由于缺乏经过充分验证的目标参与临床前措施，阻碍了有效治疗的发展 不同物种之间的功能相似。利用基础和转化之间的伙伴关系 UH2/UH3 MH109334 的首要目标是 开发新的奖励和认知转化评估，其中神经生理学和行为 不同物种的指标是相同的。 我们通过修改和验证奖励学习、认知能力的评估来实现这一目标 控制力和认知灵活性，每一项都会因疾病而受到干扰。在 UH2 阶段，我们有 开发（或修改）、测试和优化人类和啮齿动物版本的侧翼任务（认知控制） 以及概率逆向学习任务（PRL；认知灵活性），使得任务参数是类似的 人类和老鼠之间。此外，我们还记录了人类和大鼠的脑电图数据 每项任务的执行情况。在这两个物种中，脑电图数据都使用多种技术进行分析，包括时间- 频率小波分析和时域事件相关电位（ERP）分析。这些分析得出 先验脑电图和行为变量（例如，theta 振荡、与错误相关的消极性、与反馈相关的 阴性），在 UH3 阶段进行操作，其中包括莫达非尼（第 3 年）和哌醋甲酯 （第四年）挑战。 由于 COVID-19 大流行，人类哌醋甲酯研究因工作原因而无法启动 Partners HealthCare 和 McLean Hospital 的在家订单。同样，临床前哌甲酯 麦克莱恩医院的部分（目标：侧翼任务）受到严重影响，仅进行了有限的研究 三月中旬至八月中旬之间允许进行的活动。加州大学圣地亚哥分校的临床前哌甲酯成分 （目标：概率逆转学习任务）也受到了影响，尽管不太严重。目前的 行政补充要求提供资金以完成所有地点的第 4 年哌醋甲酯实验。 最终，这些研究将为人类和大鼠提供新的奖励和/或认知测量方法 在行为和神经生理学方面显示出明显的相似之处，可以通过假定的治疗来操纵 跨物种。这些任务将有助于缩小临床前动物和临床前动物之间现有的转化差距。 人类研究并将促进急需的奖励和认知治疗方法的开发 失调。

项目成果

Concurrent electrophysiological recording and cognitive testing in a rodent touchscreen environment.

• DOI: 10.1038/s41598-021-91091-9
• 发表时间: 2021-06-03
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Kangas BD;Iturra-Mena AM;Robble MA;Luc OT;Potter D;Nickels S;Bergman J;Carlezon WA Jr;Pizzagalli DA
• 通讯作者: Pizzagalli DA

Error-related Alpha Suppression: Scalp Topography and (Lack of) Modulation by Modafinil.

错误相关的阿尔法抑制：头皮地形和莫达非尼（缺乏）调节。

• DOI: 10.1162/jocn_a_01836
• 发表时间: 2022
• 期刊: Journal of cognitive neuroscience
• 影响因子: 3.2
• 作者: Schroder,HansS;Iturra-Mena,AnnM;Breiger,Micah;Linton,SamanthaR;Robble,MykelA;Kangas,BrianD;Bergman,Jack;Nickels,Stefanie;Vitaliano,Gordana;Der-Avakian,Andre;Barnes,SamuelA;Carlezon,WilliamA;Pizzagalli,DiegoA
• 通讯作者: Pizzagalli,DiegoA