Department of Psychology, Ludwig-Maximilians Universität München, Germany; NeuroImaging Core Unit Munich (NICUM), University Hospital, Ludwig-Maximilians Universität München, Germany.
Department of General Psychiatry, Center for Psychosocial Medicine, Heidelberg University, Germany.
Neuropharmacology. 2024 Jun 15;251:109930. doi: 10.1016/j.neuropharm.2024.109930. Epub 2024 Mar 25.
This study extended a classic self-referential learning paradigm by investigating the effects of intranasally-administered oxytocin in high and low socially anxious participants during social learning, as a function of social anxiety levels and sex.
In a randomized double-blinded design, 160 participants were either given intranasal oxytocin (24 I.U.) or placebo. Subsequently, while lying in an MR scanner, participants were shown neutral faces that were paired with positively, neutrally, or negatively valenced self-referential sentences, during which we measured self-reported arousal and sympathy of the facial stimuli, pupil dilation, and changes in the brain-oxygen-level dependent signal. Four-factor mixed analyses of variance with the between-subjects factors group (high socially anxious vs. low socially anxious), substance (oxytocin vs. placebo), and sex (male vs. female) and the within-subjects factor sentence valence (positive vs. neutral vs. negative) were conducted for each measure, respectively.
Administration of intranasal oxytocin yielded an increase in sympathy ratings in high socially anxious compared to low socially anxious individuals and decreased arousal ratings for positively-conditioned faces in low socially anxious participants. As an objective physiological measure of arousal, pupil dilation mirrored the behavioral results. Oxytocin effects on neural activation in the insula interacted with anxiety levels and sex: low socially anxious individuals yielded lower activation under oxytocin than placebo; the converse was observed in high socially anxious individuals. This interaction also differed between sexes, as men yielded higher activation levels than women. These findings were more prominent for positively- and negatively-conditioned faces. Within the amygdala, high socially anxious men yielded higher activation than high socially anxious women in the left hemisphere, and low socially anxious men yielded higher activation than low socially anxious women from positively- and negatively-conditioned faces, though no influence of oxytocin was detected.
These results suggest oxytocin-induced behavioral, physiological, and neural changes as a function of social learning in socially low and high anxious individuals. These findings challenge the amygdalocentric view of the role of emotions in social learning, instead contributing to the growing body of findings implicating the insula therein, revealing an interaction between oxytocin, sex, and emotional valence. Such discoveries raise an interesting set of questions regarding the computational goals of regions such as the insula in emotional learning and how neural activity can play a diagnostic or prognostic role in social anxiety, potentially leading to new treatment opportunities that may combine oxytocin and neurofeedback differentially for men and women.
本研究通过考察社交焦虑水平和性别的影响，在社交学习中，将经鼻给予的催产素应用于高、低社交焦虑参与者，扩展了经典的自我参照学习范式。
在随机双盲设计中，160 名参与者分别接受经鼻催产素（24IU）或安慰剂。随后，参与者躺在磁共振扫描仪中，观看中性面孔，并与积极、中性或消极的自我参照句子配对，在此期间，我们测量了参与者对刺激的自我报告唤醒和同情程度、瞳孔扩张以及脑血氧水平依赖信号的变化。对于每个测量指标，分别进行了四因素混合方差分析，其中组间因素为（高社交焦虑组与低社交焦虑组）、物质（催产素与安慰剂）和性别（男性与女性），以及内因素句子效价（积极、中性和消极）。
经鼻给予催产素可增加高社交焦虑个体对同情的评价，降低低社交焦虑个体对积极条件化面孔的唤醒评价。作为唤醒的客观生理测量指标，瞳孔扩张反映了行为结果。岛叶的催产素对神经激活的影响与焦虑水平和性别相互作用：低社交焦虑个体在接受催产素后比接受安慰剂时的激活水平更低；在高社交焦虑个体中观察到相反的结果。这种相互作用在性别之间也不同，因为男性的激活水平高于女性。这些发现对积极和消极条件化面孔更为明显。在杏仁核内，与高社交焦虑女性相比，高社交焦虑男性的左侧半球对积极和消极条件化面孔的激活水平更高，而与低社交焦虑女性相比，低社交焦虑男性的激活水平更高。
这些结果表明，在社交焦虑程度低和高的个体中，催产素诱导的行为、生理和神经变化是社会学习的一种功能。这些发现挑战了情绪在社会学习中以杏仁核为中心的观点，相反，为越来越多的发现提供了支持，这些发现表明岛叶在其中的作用，揭示了催产素、性别和情绪效价之间的相互作用。这些发现提出了一系列有趣的问题，涉及到岛叶等区域在情绪学习中的计算目标，以及神经活动如何在社交焦虑中发挥诊断或预后作用，这可能为男性和女性的催产素和神经反馈治疗提供新的机会。
