George Sophie A, Rodriguez-Santiago Mariana, Riley John, Abelson James L, Floresco Stan B, Liberzon Israel
Department of Psychiatry, University of Michigan, 4250 Plymouth Road, Ann Arbor, MI, 48109, USA; Ann Arbor Veterans Affairs Hospital, 2215 Fuller Road, Ann Arbor, MI, 49105, USA.
Department of Psychiatry, University of Michigan, 4250 Plymouth Road, Ann Arbor, MI, 48109, USA.
Behav Brain Res. 2015 Jun 1;286:256-64. doi: 10.1016/j.bbr.2015.02.051. Epub 2015 Mar 5.
Exposure to stressful or traumatic events is associated with increased vulnerability to post-traumatic stress disorder (PTSD). This vulnerability may be partly mediated by effects of stress on the prefrontal cortex (PFC) and associated circuitry. The PFC mediates critical cognitive functions, including cognitive flexibility, which reflects an organism's ability to adaptively alter behavior in light of changing contingencies. Prior work suggests that chronic or acute stress exerts complex effects on different forms of cognitive flexibility, via actions on the PFC. Similarly, PFC dysfunction is reported in PTSD, as are executive function deficits. Animal models that permit study of the effects of stress/trauma on cognitive flexibility may be useful in illuminating ways in which stress-linked cognitive changes contribute to PTSD. Here, we examined the behavioral effects of a rodent model of PTSD - single prolonged stress (SPS) - on performance of two forms of cognitive flexibility: reversal learning and strategy set-shifting. SPS did not impair acquisition of either a response or visual-cue discrimination but did cause slight impairments in the retrieval of the visual-cue rule. During response discrimination reversal, SPS rats made more perseverative errors. In comparison, during set-shifting from the visual-cue to response discrimination, SPS rats did not show enhanced perseveration, but did display increased never-reinforced errors, indicative of impairment in selecting a novel strategy. These data demonstrate that SPS leads to a complex and intriguing pattern of deficits in flexible responding and suggest that impairments in executive functioning associated with PTSD could, in part, be a neuro-cognitive consequence of trauma exposure.
暴露于应激或创伤事件与创伤后应激障碍(PTSD)易感性增加有关。这种易感性可能部分是由应激对前额叶皮质(PFC)及相关神经回路的影响介导的。PFC介导关键的认知功能,包括认知灵活性,它反映了生物体根据变化的意外情况适应性改变行为的能力。先前的研究表明,慢性或急性应激通过对PFC的作用,对不同形式的认知灵活性产生复杂影响。同样,PTSD患者中也有PFC功能障碍的报道,执行功能缺陷也是如此。允许研究应激/创伤对认知灵活性影响的动物模型,可能有助于阐明应激相关的认知变化对PTSD的影响方式。在这里,我们研究了PTSD啮齿动物模型——单次长时间应激(SPS)——对两种认知灵活性形式表现的行为影响:逆向学习和策略转换。SPS并未损害反应或视觉线索辨别学习的获得,但确实在视觉线索规则的提取上造成了轻微损害。在反应辨别逆向学习过程中,SPS大鼠出现了更多的持续性错误。相比之下,在从视觉线索辨别转换到反应辨别的过程中,SPS大鼠并未表现出更强的持续性,但确实出现了更多未强化错误,这表明在选择新策略方面存在损害。这些数据表明,SPS导致了灵活反应中复杂且有趣的缺陷模式,并表明与PTSD相关的执行功能损害可能部分是创伤暴露的神经认知后果。