Testing a Neuropsychological Model of Depersonalization with TMS

去人格化障碍(DPD)是一种精神疾病，影响大约1%的人口。它包括痛苦和无处不在的感觉和情感麻木的虚幻。最近使用大脑成像和身体唤醒测量(使用皮肤电导反应(SCR))的研究表明，这类患者在调节和控制情绪的方式上存在异常。作为大脑的一部分，右腹外侧前额叶皮质通常控制着包括被称为脑岛的区域在内的“情绪大脑”。我们将验证DPD源于脑岛前额叶抑制异常增加的假设，并预测减少DPD患者的额叶抑制应能缓解症状。DPD患者的SCR降低，这与支持情绪的大脑区域的激活减少有关，而与情绪调节有关的前额叶区域的激活增加。我们可以安全和暂时地抑制这种增加的前额叶激活，方法是将重复的磁脉冲施加到头部外部约15分钟，称为重复的经颅磁刺激(RTMS)。这通常被用作神经科学的研究工具，当给药几天或几周时，可以治疗包括抑郁症在内的几种精神疾病。我们可以使用标准磁共振成像(MRI)脑扫描和链接到TMS设备的计算机程序，将rTMS定位到我们感兴趣的精确大脑区域。我们将对比低频(抑制)和高频(刺激)TMS的效果，以及感觉像TMS但没有磁场的伪装条件。我们将研究3组20名健康志愿者，随机分为高、低或假rTMS组，以及2组20名DPD患者，随机分为低频率组或假频率组。我们将测量参与者在观看一组情绪照片时的SCR和主观唤醒评级。还将评估DPD的症状。我们预测：1.在DPD患者中，低频rTMS诱导的前额叶活动抑制将导致：与TMS前相比，SCR增加，对唤醒图片的情绪主观评分增加(加上症状减少)。2.在健康志愿者中，高频rTMS刺激将激活相同的前额叶区域，导致与TMS前水平类似的主观反应和SCR反应的一过性钝化。低频(和伪装)应该没有效果。这项研究将有助于了解情绪调节在健康和疾病中的作用，如果呈阳性，将为rTMS在DPD中的治疗试验铺平道路。

Depersonalization disorder (DPD) is a psychiatric condition affecting about 1% of the population. It comprises distressing and pervasive feelings of and emotional numbing unreality. Recent research using brain imaging and measures of bodily arousal (using skin conductance responses (SCR)) - a bit like the 'lie detector' - suggests abnormalities in the way such patients regulate and control their emotions. A part of the brain, the right ventro-lateral prefrontal cortex normally controls the 'emotional brain' including a region called the insula. We will test the hypothesis that DPD stems from abnormally increased prefrontal inhibition of the insula and predict that reducing frontal inhibition in patients with DPD should alleviate symptoms. Patients with DPD have reduced SCR which is linked to reduced activation in brain areas underpinning emotion affect, and by increased activation in prefrontal areas involved in emotion regulation. We can safely and temporarily dampen down this increased prefrontal activation using repeated magnetic pulses applied to the outside of the head for about 15 minutes, called repetitive transcranial magnetic stimulation (rTMS). This is commonly used as a research tool in neuroscience and when given over a period of days or weeks, a treatment for several psychotic conditions including depression. We can target the rTMS to the precise brain region we are interested in using standard magnetic resonance imaging (MRI) brain scans and a computer program linked to the TMS equipment. We will contrast the effects of low frequency (inhibitory) and high frequency (stimulatory) TMS and also a pretend or sham condition which feels like TMS but there is no magnetic field. We will study 3 groups of 20 healthy volunteers randomised to high, low or sham rTMS and 2 groups of 20 DPD patients, randomised to low-frequency or sham. We will measure participants' SCR and subjective arousal ratings when looking at a set of emotional photos. Symptoms of DPD will also be assessed. We predict that: 1. in DPD patients, low-frequency rTMS induced suppression of prefrontal activity will result in: increased SCR and enhanced subjective ratings of emotion to arousing pictures (plus reduced symptoms) versus pre-TMS levels. 2. in healthy volunteers, high-frequency rTMS stimulation will activate the same prefrontal regions leading to transient blunting of subjective and SCR responses resembling those of depersonalized participants, versus pre-TMS level. Low frequency (and sham) should have no effect. The study will contribute to knowledge of emotional regulation in health and disease and if positive, will pave the way for a therapeutic trial of rTMS in DPD.