Testing a Neuropsychological Model of Depersonalization with TMS

人格解体障碍（DPD）是一种精神疾病，影响约1%的人口。它包括痛苦和普遍的感觉和情感麻木的不现实。最近的研究使用大脑成像和身体唤醒的措施（使用皮肤电导反应（SCR））-有点像“测谎仪”-表明这些患者调节和控制情绪的方式异常。作为大脑的一部分，右腹外侧前额叶皮层通常控制着“情绪大脑”，包括一个叫做“情绪区”的区域。我们将检验这一假设，即DPD源于异常增加的前额叶抑制，并预测减少DPD患者的额叶抑制应缓解症状。DPD患者的SCR降低，这与支持情绪影响的大脑区域的激活减少有关，并且与参与情绪调节的前额叶区域的激活增加有关。我们可以安全地暂时抑制这种增加的前额叶激活，使用重复的磁脉冲施加到头部外部约15分钟，称为重复经颅磁刺激（rTMS）。这通常被用作神经科学的研究工具，当在几天或几周内给予时，可以治疗包括抑郁症在内的几种精神病。我们可以使用标准的磁共振成像（MRI）脑部扫描和与TMS设备相连的计算机程序，将rTMS瞄准我们感兴趣的精确大脑区域。我们将对比低频（抑制性）和高频（刺激性）经颅磁刺激的效果，以及感觉像经颅磁刺激但没有磁场的假装或假条件。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，随机分为低频率或假rTMS组。我们将测量参与者在观看一组情绪照片时的SCR和主观唤醒等级。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：与前TMS水平相比，SCR增加和对唤起图片的情绪的主观评级增强（加上症状减轻）。2.在健康志愿者中，高频rTMS刺激将激活相同的前额叶区域，导致主观和SCR反应的短暂钝化，类似于与前TMS水平相比去个性化参与者的主观和SCR反应。低频率（和假手术）应该没有影响。这项研究将有助于了解健康和疾病中的情绪调节，如果是积极的，将为DPD的rTMS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.