Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge CB2 3EB, United Kingdom.
Department of Psychology, University of Cambridge, Cambridge CB2 3EB, United Kingdom.
Neuroimage Clin. 2017 Aug 8;16:286-294. doi: 10.1016/j.nicl.2017.08.007. eCollection 2017.
Functional neurological disorder (FND) is an elusive disorder characterized by unexplained neurological symptoms alongside aberrant cognitive processing and negative affect, often associated with amygdala reactivity.
We examined the effect of negative conditioning on cognitive function and amygdala reactivity in 25 FND patients and 20 healthy volunteers (HV). Participants were first conditioned to stimuli paired with negative affective or neutral (CS +/CS -) information. During functional MRI, subjects then performed an instrumental associative learning task to avoid monetary losses in the context of the previously conditioned stimuli. We expected that FND patients would be better at learning to avoid losses when faced with negatively conditioned stimuli (increased harm avoidance). Multi-echo resting state fMRI was also collected from the same subjects and a robust denoising method was employed, important for removing motion and physiological artifacts.
FND subjects were more sensitive to the negative CS + compared to HV, demonstrated by a reinforcement learning model. Contrary to expectation, FND patients were generally more impaired at learning to avoid losses under both contexts (CS +/CS -), persisting to choose the option that resulted in a negative outcome demonstrated by both behavioural and computational analyses. FND patients showed enhanced amygdala but reduced dorsolateral prefrontal cortex responses when they received negative feedback. Patients also had increased resting state functional connectivity between these two regions.
FND patients had impaired instrumental avoidance learning, findings that parallel previous observations of impaired action-outcome binding. FND patients further show enhanced behavioural and neural sensitivity to negative information. However, this did not translate to improved avoidance learning. Put together, our findings do not support the theory of harm avoidance in FND. We highlight a potential mechanism by which negative contexts interfere with adaptive behaviours in this under-explored disorder.
功能性神经障碍（FND）是一种难以捉摸的疾病，其特征是存在无法解释的神经系统症状，同时伴有认知加工和负性情绪的异常，通常与杏仁核反应有关。
我们研究了 25 名 FND 患者和 20 名健康对照者（HV）的负性条件作用对认知功能和杏仁核反应的影响。参与者首先接受与负性情感或中性（CS+/CS-）信息配对的刺激的条件作用。在功能磁共振成像期间，受试者随后执行一项工具性联想学习任务，以避免先前条件刺激背景下的金钱损失。我们预计 FND 患者在面对负性条件刺激时会更好地学习避免损失（增加回避）。我们还从同一受试者收集了多回波静息态 fMRI，并采用了一种强大的去噪方法，这对于去除运动和生理伪影很重要。
与 HV 相比，FND 受试者对负性 CS+更敏感，这是由强化学习模型证明的。与预期相反，FND 患者在两种情况下（CS+/CS-）学习避免损失的能力通常都较差，行为和计算分析都表明，他们更倾向于选择导致负面结果的选项。FND 患者在收到负面反馈时表现出增强的杏仁核但减少的背外侧前额叶皮质反应。患者在这些区域之间还表现出增加的静息状态功能连接。
FND 患者的工具性回避学习受损，这与先前观察到的动作-结果结合受损的发现一致。FND 患者进一步表现出对负性信息的行为和神经敏感性增强。然而，这并没有转化为更好的回避学习。综上所述，我们的发现不支持 FND 中回避危害的理论。我们强调了一种潜在的机制，即负性情境干扰了这种探索不足的疾病中的适应性行为。
