Real-time fMRI for insular cortex brain state-triggered experience sampling

项目总结/摘要 对于许多患有精神疾病的患者来说，日常生活痛苦的主要来源是内在的 这些经验似乎经常“自行”发生（自我生成的经验）。这些无法控制的 经验可以采取各种形式，包括沉思，担心，幻觉或妄想。鉴于 严重的全球精神疾病负担，以及对目前的药物有抵抗力的患者的高患病率， 治疗，迫切需要开发新的治疗方法，旨在直接针对大脑系统 产生不适应的自我生成体验。作为治疗发展的先驱， 必须在我们对大脑如何产生自我生成的基本理解方面取得进展。 经验为了满足这一需求，我们将开发一种新的方法，称为“实时功能磁共振成像（fMRI）- 触发的经验采样”，以有效地对自发神经事件（预定义类型的）进行采样， 将这些事件映射到自我生成体验的特定品质。在32名健康成年人中，我们将使用 在线（实时）功能磁共振成像分析，以检测大脑激活，并触发视觉评级量表的出现， 参与者可以在感兴趣的神经事件发生后立即报告他们的经历。 这种方法旨在最大限度地提高每次试验的数据信息量，并提供严格的调查 特定神经事件的心理学意义我们将开发和验证我们的方法， 重点是对背侧前岛叶皮层（daIC）的实时功能磁共振成像分析，这是一个与脑内信号传导有关的脑区。 显著性检测，其被一致地识别为具有异常的结构、功能和连接性， 精神疾病的诊断水平。我们的目的1是确定自发的daIC激活是否 事件被时间锁定在显著的、高唤醒的自我生成体验的实例上。我们将自我采样- 在daIC激活实例和基线（中间daIC）期间生成的经验 活动）事件。我们假设daIC激活，相对于基线事件，将时间锁定到自我， 产生的经验具有更高的主观评级的唤醒和生动性（无论情感效价）。 我们将进一步测试DAIC和自我生成体验之间的关系是否由以下因素介导： 自主觉醒，如基于瞳孔扩张和蓝斑（皮质下的 觉醒相关神经调节的发生器）。我们的目标2是确定自我的特定品质是否 产生的经验取决于daIC和全脑活动之间的耦合。我们将研究 daIC激活的不同实例是否与多个不同的全脑共激活模式共同发生。 我们将进一步测试不同的daIC共激活模式是否与情绪波动有关。 （正面与负面的经验）。如果成功的话，我们的方案以后可以应用于精神病患者， 疾病并潜在地指导干预措施的发展（例如，神经刺激），旨在针对 产生自我生成体验的神经过程是精神疾病的核心。

PROJECT SUMMARY/ABSTRACT For many patients suffering from psychiatric illness, the primary source of daily-life distress is inner experiences that often seem to occur ‘on their own’ (self-generated experiences). These uncontrollable experiences can take various forms, including rumination, worry, hallucination or delusional thinking. Given the severe global burden of mental illness, and the high prevalence of patients who are resistant to current treatments, there is a pressing need to develop new therapies designed to directly target the brain’s systems that produce maladaptive self-generated experiences. As a precursor to therapy development, significant progress must be made in our fundamental understanding of how the brain gives rise to self-generated experiences. To address this need, we will develop a new approach called “real-time functional MRI (fMRI)- triggered experience-sampling” to efficiently sample spontaneous neural events (of a predefined type) and to map those events to specific qualities of self-generated experiences. Within 32 healthy adults, we will use online (real-time) fMRI analysis to detect brain activations and trigger the appearance of visual rating scales so that participants can report their experiences immediately after the occurrence of a neural event of interest. This approach aims to maximize how informative the data are on each trial and to offer rigorous investigation of the psychological significance of specific neural events. We will develop and validate our approach with a focus on real-time fMRI analysis of the dorsal anterior insular cortex (daIC), a brain region implicated in salience detection that is consistently identified as having aberrant structure, function, and connectivity in psychiatric illness at a transdiagnostic level. Our Aim 1 is to determine whether spontaneous daIC activation events are time-locked to instances of salient, high-arousal self-generated experience. We will sample self- generated experiences both during instances of daIC activation and during baseline (intermediate daIC activity) events. We hypothesize that daIC activation, relative to baseline events, will be time-locked to self- generated experiences with higher subjective ratings of arousal and vividness (regardless of affective valence). We will further test whether relationships between the daIC and self-generated experiences are mediated by autonomic arousal, as assessed based on pupil dilation and activation within the locus coeruleus (a subcortical generator of arousal-related neuromodulation). Our Aim 2 is to determine whether specific qualities of self- generated experience depend on coupling between the daIC and whole-brain activity. We will examine whether different instances of daIC activation co-occur with multiple, distinct whole-brain co-activation patterns. We will further test whether distinct daIC co-activation patterns are associated with fluctuations in affect (positive vs. negative experiences). If successful, our protocols can later be applied in patients with psychiatric illness and to potentially guide the development of interventions (e.g., neurostimulation) that aim to target the neural processes that produce self-generated experiences that are core to mental illness.