Hodges Travis E, Lee Grace Y, Noh Sophia H, Galea Liisa A M
Department of Psychology, University of British Columbia, Canada.
Graduate Program in Neuroscience, University of British Columbia, Canada.
Neurobiol Stress. 2022 May 6;18:100458. doi: 10.1016/j.ynstr.2022.100458. eCollection 2022 May.
Cognitive symptoms of depression, including negative cognitive bias, are more severe in women than in men. Current treatments to reduce negative cognitive bias are not effective and sex differences in the neural activity underlying cognitive bias may play a role. Here we examined sex and age differences in cognitive bias and functional connectivity in a novel paradigm. Male and female rats underwent an 18-day cognitive bias procedure, in which they learned to discriminate between two contexts (shock paired context A, no-shock paired context B), during either adolescence (postnatal day (PD 40)), young adulthood (PD 100), or middle-age (PD 210). Cognitive bias was measured as freezing behaviour in response to an ambiguous context (context C), with freezing levels akin to the shock paired context coded as negative bias. All animals learned to discriminate between the two contexts, regardless of sex or age. However, adults (young adults, middle-aged) displayed a greater negative cognitive bias compared to adolescents, and middle-aged males had a greater negative cognitive bias than middle-aged females. Females had greater neural activation of the nucleus accumbens, amygdala, and hippocampal regions to the ambiguous context compared to males, and young rats (adolescent, young adults) had greater neural activation in these regions compared to middle-aged rats. Functional connectivity between regions involved in cognitive bias differed by age and sex, and only adult males had negative correlations between the frontal regions and hippocampal regions. These findings highlight the importance of examining age and sex when investigating the underpinnings of negative cognitive bias and lay the groundwork for determining what age- and sex-specific regions to target in future cognitive bias studies.
抑郁症的认知症状，包括消极认知偏差，在女性中比男性更严重。目前减少消极认知偏差的治疗方法并不有效，认知偏差背后的神经活动中的性别差异可能起到了一定作用。在这里，我们在一种新的范式中研究了认知偏差和功能连接中的性别与年龄差异。雄性和雌性大鼠接受了为期18天的认知偏差程序，在此过程中它们学会区分两种情境（电击配对情境A，无电击配对情境B），实验在青春期（出生后第40天（PD 40））、成年早期（PD 100）或中年期（PD 210）进行。认知偏差通过对模糊情境（情境C）的僵住行为来衡量，类似于电击配对情境的僵住水平被编码为消极偏差。所有动物都学会了区分这两种情境，无论性别或年龄如何。然而，与青少年相比，成年动物（成年早期、中年）表现出更大的消极认知偏差，中年雄性大鼠的消极认知偏差比中年雌性大鼠更大。与雄性相比，雌性大鼠对模糊情境在伏隔核、杏仁核和海马区域有更强的神经激活，与中年大鼠相比，年轻大鼠（青少年、成年早期）在这些区域有更强的神经激活。参与认知偏差的区域之间的功能连接因年龄和性别而异，只有成年雄性大鼠的额叶区域和海马区域之间存在负相关。这些发现突出了在研究消极认知偏差的基础时考察年龄和性别的重要性，并为确定未来认知偏差研究中针对特定年龄和性别的区域奠定了基础。
