Identifying Neural Signatures of Auditory-Predictive Processing in Schizophrenia: A Multi-Modal Imaging Approach

了解大脑如何处理和传输信息是当前基础和医学研究的基本挑战之一。最近的证据表明，可以区分两大类过程，它们似乎支持不同的功能，并以不同的生物学相关性为特征：1）“前馈”模式，根据传入刺激的特征传递信息; 2）“反馈”模式，由大脑的内部活动控制，例如对事件的预期和预测。这种区别可能是获得新的见解大脑如何在正常情况下运作，以及如何在这两个不同的模式的变化可能会导致精神疾病，如精神分裂症（ScZ）的基础上，到目前为止，区分这些不同的大脑模式使用非侵入性脑成像，如功能磁共振成像（fMRI）或脑磁图（MEG），一直具有挑战性。然而，来自基础解剖学和生物学的新证据表明，不同频率的不同脑波以及特定的大脑层可能支持这些不同的大脑模式。因此，我们将首次尝试通过使用最先进的大脑成像来识别这些大脑模式，从而对大脑如何传输信息以及这些过程如何有助于ScZ获得新的理解。在该项目的第一部分，我们将向健康志愿者展示他们看电影时的声音序列。在这项任务中，我们用脑磁图仪测量他们的脑电波。特别是，我们有兴趣找出是否在神经活动的节奏变化，所谓的“振荡”，可能会受到存在的声音，偏离持续时间的影响。特别是，我们的目标是表明大脑区域之间的这些振荡流动将根据声音是否不同而变化。MEG记录将伴随7特斯拉下的fMRI测量。与大多数在3特斯拉场强下进行的fMRI研究相反，我们预计7特斯拉的fMRI记录揭示了传统fMRI机器无法观察到的大脑活动的新细节。特别是，基于我们在这一领域的先前工作，我们希望我们可以观察到不同层次的大脑活动，这对于获得大脑如何使用不同渠道进行交流的新见解至关重要。基于这些新的见解，我们将应用这个框架来了解ScZ患者和患有这种疾病的高风险年轻人的大脑活动变化。ScZ是一种常见的精神障碍，与一系列投诉有关，包括幻觉和妄想。精神病的这些症状伴随着感知和认知的明显障碍。更好地了解认知缺陷是特别重要的，因为目前的治疗无法改善感知和记忆功能，导致患者难以组织他们的生活和维持就业。我们希望，我们区分不同大脑模式的能力将使我们能够确定患者感知世界困难的原因以及他们组织思想的问题。具体来说，我们将确定ScZ患者的问题是否在于记录进入大脑的信息，或者他们的问题是否更多地在于通过高级大脑区域产生的先前假设来控制他们的思想和感知。因此，我们预计，除了确定ScZ的原因外，这种方法可能与新疗法以及早期检测和诊断相关，因为它可以告知治疗是否应该专注于提高感知听觉和视觉信息的能力，而不是专注于对患者可能拥有的世界的假设和想法。

Understanding how the brain processes and transmits information is one the fundamental challenges for current basic and medical research. Recent evidence suggests two broad classes of processes can be distinguished that seem to support different functions and are characterized by distinct biological correlates: 1) a "feedforward" mode that transmits information based upon the characteristics of the incoming stimulus and 2) a "feedback" mode that is governed by the internal activity of the brain, such as expectations and predictions about events. This distinction may be fundamental for gaining novel insights into how the brain operates under normal circumstances and how changes in these two different modes may contribute to psychiatric disorders, such as schizophrenia (ScZ).Until now, distinguishing these different brain modes using non-invasive brain imaging, such as functional magnetic resonance imaging (fMRI) or Magnetoencephalography (MEG), has been challenging. However, novel evidence from basic anatomy and biology has suggested that distinct brain waves at different frequencies as well as particular brain layers may support these different brain modes. As a result, we will attempt for the first time to identify these brain modes through using state-of-the-art brain imaging and thus gain a new understanding of how the brain transmits information and how these processes might contribute to ScZ.In the first part of the project, we will present healthy volunteers sequences of sounds while they watch a movie. During this task, we measure their brain waves with a MEG-machine. In particular, we are interested in finding out whether changes in rhythms of neural activity, so-called "oscillations", may be influenced by the presence of sounds that deviate in duration. In particular, we aim to show that the flow of these oscillations between brain regions will change depending on whether a sound is different or not. The MEG-recordings will be accompanied by fMRI-measurements at 7 Tesla. In contrast to the majority of fMRI-research which is carried out with a field strength of 3 Tesla, we expect that fMRI-recordings at 7 Tesla reveal novel details about brain activity that cannot be observed with conventional fMRI-machines. In particular, based on our prior work in this area, we expect that we can observe brain activity in different layers which may be crucial for gaining new insights into how the brain uses different channels to communicate. Based on these new insights, we will then apply this framework to understand changes in brain activity in ScZ-patients and young people who are at high-risk for developing the disorder. ScZ is a common mental disorder which is associated with a range of complaints, including hallucinations and delusions. These symptoms of psychosis are accompanied by pronounced impairments in perception and cognition. A better understanding of cognitive deficits is particularly important because current treatments are unable to improve perception and memory functions which result in difficulties of patients' to organize their lives and maintain employment. We expect that our ability to distinguish different brain modes will allow us to identify the cause of patients' difficulties in perceiving the world and their problems in organizing their thoughts. Specifically, we will identify whether the problem for patients with ScZ is to register the information coming into the brain or whether their problems lies more in controlling their thoughts and perceptions through prior assumptions which are generated in higher brain areas. As a result, we expect that in addition to identifying the causes of ScZ, this approach may be relevant for novel therapies and early detection and diagnosis as it could inform whether therapies should focus on improving the ability to perceive auditory and visual information as opposed to focussing on the assumptions and thoughts about the world a patient may have.