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

项目摘要/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心 通常看起来是“自己”发生的体验(自我生成的体验)。这些无法控制的东西 体验可以有多种形式，包括沉思、担忧、幻觉或妄想。给定 严重的全球精神疾病负担，以及对当前疾病有抵抗力的患者的高流行率 治疗，迫切需要开发新的治疗方法，旨在直接针对大脑系统 会产生不适应的自我产生的体验。作为治疗发展的先驱，意义重大 我们必须在对大脑如何产生自我生成的基本理解上取得进展 经历。为了满足这一需求，我们将开发一种名为实时功能磁共振(FMRI)的新方法。 触发体验-采样“，以有效地采样(预定义类型的)自发神经事件并 将这些事件与自我创造的体验的特定品质对应起来。在32名健康的成年人中，我们将使用 在线(实时)功能磁共振分析，以检测大脑激活并触发视觉评级量表的出现，因此 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意义。我们将开发和验证我们的方法 重点是实时fMRI分析背侧前岛叶皮质(DAIC)，这是一个涉及到 被一致识别为具有异常结构、功能和连接性的显著检测 跨诊断水平的精神疾病。我们的目标1是确定DAIC的自发激活 活动被时间锁定在显著的、高度唤醒的自我生成体验的实例中。我们将为您提供以下样本： 在DAIC激活实例和基准(中级DAIC)期间生成的体验 活动)事件。我们假设，相对于基线事件，DAIC的激活将被时间锁定到自身 产生的体验具有更高的唤醒和生动的主观评分(不考虑情感价位)。 我们将进一步测试DAIC和自我生成体验之间的关系是否由 自主神经唤醒，根据蓝斑(皮质下)内的瞳孔扩张和激活来评估 觉醒相关神经调节的生成器)。我们的目标2是确定自我的特定品质是否 产生的经验依赖于DAIC和全脑活动之间的耦合。我们将研究 不同的DAIC激活实例是否与多个不同的全脑共同激活模式共存。 我们将进一步测试不同的DAIC共激活模式是否与影响的波动相关 (积极和消极的经历)。如果成功，我们的方案稍后可以应用于精神病患者 并可能指导制定干预措施(例如，神经刺激)，目的是针对 产生自我产生的体验的神经过程，这些体验是精神疾病的核心。

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.