Decoding Prior Bias in Psychosis Using Population Receptive Fields

项目摘要 精神分裂症是一种非常普遍和负担沉重的疾病，影响约2600万人 全球范围内，每年约有1600万年的生命因残疾而丧失。典型的症状 精神分裂症是一种幻听，约80%的患者会出现幻听，约30%的患者对幻听没有反应。 可用的治疗。尽管它们的影响，幻听的神经机制是差 明白幻听被认为是由于对先前知识的更大偏见， 形成感知（先验偏见）。先验偏见是指将先验知识纳入感知中， 感知更可能的感官事件。先前的研究使用知觉过程中的单单位记录 决策任务探索了先验偏见的神经表现。这项工作的主要发现是， 刺激特征的行为偏差（例如，反向运动与反向运动）与更大的 感受野与刺激特征一致的神经元的活动。为了探索神经机制， 因此，确定感受野的调谐和设计实验是至关重要的， 利用这种调谐（目标1）。群体感受野（pRF）成像是一种新的功能磁共振成像方法， 允许在听觉和视觉区域中定义具有色调和视网膜组织的神经调谐， 分别例如，音调拓扑pRF映射可以定义宏观组织的区域， 一群神经元被调谐到一个特定的音调频率。通过将音调定位的pRF与行为 任务，以探测感知偏差的音调频率的神经机制的直接测量， 可以产生幻听的先验偏差（目标2）。 在目标1中，我们将使用pRF音调定位映射来定义听觉皮层的音调定位组织， 未用药的精神分裂症患者（N=30），并研究与匹配的健康人相比的差异 对照组（N=30）。我们假设幻听的严重程度与更广泛的pRF相关 协调联合听觉皮层。在目标2中，我们将确定先验偏差的神经表示， 在同一个人的双音频率辨别任务中，通过获得fMRI来观察幻听。 未服药的精神分裂症患者和匹配的健康对照组。这项任务消除了先前的偏见， 将通过使用在目标1中获得的音调定位图直接测量，以将激活定位到特定的 频率.我们假设先前的偏见将表现在fMRI信号作为一个过度激活的pRF的 调谐到先前的信息，并且过度激活的程度将与听觉的严重程度相关。 幻觉

PROJECT SUMMARY Schizophrenia is an exceedingly prevalent and burdensome illness that affects ~26 million individuals world-wide and accounts for ~16 million years of life lost due to disability per year. A characteristic symptom of schizophrenia is auditory hallucinations, occurring in ~80% of patients with ~30% of sufferers unresponsive to available treatments. Despite their impact, the neural mechanisms of auditory hallucinations are poorly understood. Auditory hallucinations are thought to arise from greater bias towards prior knowledge when forming perceptions (prior bias). Prior bias is the incorporation of prior knowledge into percepts that biases perception towards more likely sensory events. Previous studies using single-unit recordings during perceptual decision-making tasks have probed the neural manifestation of prior bias. A major finding of this work is that behavioral bias for a stimulus feature (e.g. leftward motion vs rightward motion) is associated with greater activity in neurons with receptive fields tuned to that stimulus feature. To probe the neural mechanisms of prior bias it is thus critical to define the tuning of receptive fields and design experiments that capitalize on this tuning (Aim 1). Population receptive field (pRF) mapping is a novel fMRI method that allows definition of neural tuning in auditory and visual regions with tonotopic and retinotopic organization, respectively. For example, tonotopic pRF mapping can define regions that are macroscopically organized with ensembles of neurons tuned to a specific tone frequency. By combining tonotopic pRF with a behavioral task to probe perceptual biases in tone frequency a direct measurement of the neural mechanisms of prior bias in auditory hallucinations can be developed (Aim 2). In Aim 1 we will use pRF tonotopic mapping to define the tonotopic organization of the auditory cortex in unmedicated patients with schizophrenia (N=30) and investigate differences compared to matched healthy controls (N=30). We hypothesize that the severity of auditory hallucinations will be correlated with broader pRF tuning in the associative auditory cortex. In Aim 2 we will determine the neural representation of prior bias in auditory hallucinations by acquiring fMRI during a two-tone frequency discrimination task in the same unmedicated schizophrenia patients and matched healthy controls from Aim 1. This task elicits prior bias that will be directly measured by using the tonotopic maps acquired in Aim 1 to localize activation to specific frequencies. We hypothesize that prior bias will manifest in the fMRI signal as an over-activation of the pRF's tuned to the prior information and that the degree of over-activation will correlate with the severity of auditory hallucinations.