Meeten Frances, Davey Graham C L, Makovac Elena, Watson David R, Garfinkel Sarah N, Critchley Hugo D, Ottaviani Cristina
Institute of Psychology, Psychiatry and Neuroscience, King's College LondonLondon, UK; Department of Psychiatry, Brighton and Sussex Medical School, University of SussexBrighton, UK.
School of Psychology, University of Sussex Brighton, UK.
Front Hum Neurosci. 2016 Nov 2;10:553. doi: 10.3389/fnhum.2016.00553. eCollection 2016.
Excessive and uncontrollable worry is a defining feature of Generalized Anxiety Disorder (GAD). An important endeavor in the treatment of pathological worry is to understand why some people are unable to stop worrying once they have started. Worry perseveration is associated with a tendency to deploy goal-directed worry rules (known as "as many as can" worry rules; AMA). These require attention to the goal of the worry task and continuation of worry until the aims of the "worry bout" are achieved. This study examined the association between the tendency to use AMA worry rules and neural and autonomic responses to a perseverative cognition induction. To differentiate processes underlying the AMA worry rule use from trait worry, we also examined the relationship between scores on the Penn State Worry Questionnaire (PSWQ) and neural and autonomic responses following the same induction. We used resting-state functional magnetic resonance brain imaging (fMRI) while measuring emotional bodily arousal from heart rate variability (where decreased HRV indicates stress-related parasympathetic withdrawal) in 19 patients with GAD and 21 control participants. Seed-based analyses were conducted to quantify brain changes in functional connectivity (FC) with the amygdala. The tendency to adopt an AMA worry rule was associated with validated measures of worry, anxiety, depression and rumination. AMA worry rule endorsement predicted a stronger decrease in HRV and was positively associated with increased connectivity between right amygdala and locus coeruleus (LC), a brainstem noradrenergic projection nucleus. Higher AMA scores were also associated with increased connectivity between amygdala and rostral superior frontal gyrus. Higher PSWQ scores amplified decreases in FC between right amygdala and subcallosal cortex, bilateral inferior frontal gyrus, middle frontal gyrus, and areas of parietal cortex. Our results identify neural mechanisms underlying the deployment of AMA worry rules. We propose that the relationship between AMA worry rules and increased connectivity between the amygdala and prefrontal cortex (PFC) represents attempts by high worriers to maintain arousal and distress levels in order to feel prepared for future threats. Furthermore, we suggest that neural mechanisms associated with the PSWQ represent effortful inhibitory control during worry. These findings provide unique information about the neurobiological processes that underpin worry perseveration.
过度且无法控制的担忧是广泛性焦虑症（GAD）的一个决定性特征。治疗病理性担忧的一项重要工作是理解为什么有些人一旦开始担忧就无法停止。担忧持续存在与采用目标导向性担忧规则（称为“尽可能多”担忧规则；AMA）的倾向有关。这些规则要求关注担忧任务的目标，并持续担忧直到“担忧发作”的目标实现。本研究考察了使用AMA担忧规则的倾向与对持续性认知诱导的神经和自主反应之间的关联。为了区分AMA担忧规则使用背后的过程与特质性担忧，我们还考察了宾夕法尼亚州立大学担忧问卷（PSWQ）得分与相同诱导后神经和自主反应之间的关系。我们对19名广泛性焦虑症患者和21名对照参与者进行静息态功能磁共振脑成像（fMRI），同时通过心率变异性测量情绪性身体唤醒（心率变异性降低表明与压力相关的副交感神经退缩）。进行基于种子的分析以量化与杏仁核功能连接（FC）的脑变化。采用AMA担忧规则的倾向与经过验证的担忧、焦虑、抑郁和沉思测量指标相关。AMA担忧规则认同预测心率变异性有更强的降低，并且与右侧杏仁核和蓝斑（LC）之间连接性增加呈正相关，蓝斑是脑干去甲肾上腺素能投射核。较高的AMA得分还与杏仁核和喙侧额上回之间连接性增加有关。较高的PSWQ得分放大了右侧杏仁核与胼胝体下皮质、双侧额下回、额中回以及顶叶皮质区域之间FC的降低。我们的结果确定了AMA担忧规则使用背后的神经机制。我们提出，AMA担忧规则与杏仁核和前额叶皮质（PFC）之间连接性增加的关系代表了高担忧者为了为未来威胁做好准备而维持唤醒和痛苦水平的尝试。此外，我们认为与PSWQ相关的神经机制代表了担忧期间的努力抑制控制。这些发现提供了关于支撑担忧持续存在的神经生物学过程的独特信息。
