Using Magnetoencephalography to Investigate Aberrant Neural Synchrony in Prodromal Schizophrenia: A Translational Biomarker Approach

精神分裂症是一种常见的精神障碍，与一系列主诉有关，包括语音听力(幻觉)和奇怪的想法(妄想症)以及明显的记忆和注意力障碍。由于这些症状会导致思维过程的崩溃，被诊断患有这种疾病的人往往无法独立生活，目前也没有有效的治疗方法。精神分裂症通常在从青春期到成年期早期被诊断出来，这是一个对社会和职业发展至关重要的时期。因此，目前研究的一个重要目标是确定在精神分裂症全面爆发之前有更高风险发展成精神分裂症的个人。如果可能，这可以减少甚至防止人们生活中发生的深刻而持久的干扰。早期干预的一个重要前提是诊断技术，这种技术可以可靠地预测那些可能有特别高机会发展成这种疾病的人。在目前的研究中，我们将使用一种大脑成像技术，即所谓的脑磁图仪或MEG，这是一种能够以优异的时间分辨率测量大脑活动的机器，以开发一种新的诊断测试。特别是，我们有兴趣找出大脑产生的神经活动节奏的变化，即所谓的“振荡”，在精神障碍爆发之前是否会受到损害，以及这些变化是否有助于预测患精神分裂症的风险。大脑振荡已被证明发生在正常的大脑功能中，并与感知、记忆和注意信息的能力密切相关。此外，从以前的研究中我们知道，确诊的精神分裂症患者在产生这些振荡方面表现出明显的障碍，这可能是他们认知困难以及幻觉和妄想的原因之一。因此，大脑振荡似乎是了解精神障碍原因的关键。在拟议的项目中，我们将从爱丁堡和格拉斯哥的精神科服务机构招募大量表现出行为和心理问题的个人，并进行详细的访谈。如果他们的精神状态显示出某些可能表明精神分裂症的迹象，但还不符合完整的诊断标准，我们将进行脑磁图测量和磁共振成像扫描。后者也将使我们能够评估大脑中两种神经递质的存在，这两种神经递质对大脑的正常运作非常重要。在最初的大脑成像之后，我们将对这些参与者进行长达两年的跟踪，以评估他们的精神状态是否发生了变化。如果个人在此期间经历了精神健康状况的恶化，我们将通过延长面谈时间再次对他们进行评估。除了有精神分裂症风险的参与者外，我们还将从普通人群中招募一组个人，以便将他们的大脑活动模式与可能有精神分裂症风险的人进行比较。通过我们的研究，我们希望找到一种早期利用脑成像技术诊断精神分裂症的方法，这可能是防止严重的行为和脑功能障碍发生的重要一步。此外，通过我们对大脑振荡和相关神经化学物质的测量，我们希望深入了解可能对开发新疗法重要的潜在原因。

Schizophrenia is a common mental disorder which is associated with a range of complaints, including voice-hearing (hallucinations) and strange thoughts (delusions) as well as pronounced impairments in memory and attention. Because these symptoms lead to a breakdown of thought-processes, people who are diagnosed with the disorder often cannot live independently and no effective cure currently exists. Schizophrenia is typically diagnosed during the transition from puberty to early adulthood, a period critical for social and occupational development. Accordingly, one important goal of current research is to identify individuals who have an elevated risk of developing schizophrenia prior to the full outbreak of the disorder. If possible, this could reduce or even prevent the profound and long-lasting disruptions that occur to people's lives. One important prerequisite for early intervention are diagnostic techniques which allow reliable prediction of those individuals who may have a particularly high chance of developing the disorder. In the current study, we will use a brain imaging technique, so-called Magnetoencephalograph or MEG, which is a machine that allows the measurement of brain activity with excellent temporal resolution, to develop a novel diagnostic test. In particular, we are interested in finding out whether changes in rhythms of neural activity that the brain generates, so-called "oscillations", may be impaired prior to the outbreak of the disorder and whether those can be useful for predicting the risk of developing schizophrenia. Brain oscillations have been shown to occur during normal brain functioning and are closely linked to the ability to perceive, memorize and attend to information. Moreover, we know from previous studies that patients with established schizophrenia show prominent impairments in the generation of these oscillations which could be one reason for their cognitive difficulties as well as for their hallucinations and delusions. Thus, it appears that brain oscillations could be a key to understanding the causes of the disorder.For the proposed project, we will recruit a large sample of individuals from psychiatric services in Edinburgh and Glasgow who show already behavioural and psychological problems and conduct detailed interviews. If their mental state shows certain signs which could be indicative of schizophrenia but do not meet yet the full diagnostic criteria, we will perform a MEG-measurement as well as a magnetic resonance imaging scan. The latter will also allow us to assess the presence of two neurotransmitters in the brain which are important for proper brain functioning.After the initial brain imaging, we will follow-up these participants for a period of up to two years to assess whether their mental state has changed. If individuals during this period experience a deterioration in their mental health, we will assess them again with an extended interview. In addition to participants at risk for the development of schizophrenia, we will also recruit a group of individuals from the general populations in order to compare their patterns of brain activity with those who may be at-risk for schizophrenia. Through our research, we hope to find a way of diagnosing schizophrenia with brain imaging techniques earlier which could represent an important step to prevent the occurrence of the profound deficits in behavior and brain functioning. Moreover, through our measurements of brain oscillations and associated neurochemicals, we hope to gain in insight into the underlying causes which could be important for the development of novel therapies.