A Neural Biomarker for Hallucinations: Medial Prefrontal Aberrations in Neural Connectivity Predict Self-Agency Deficits and Hallucination Severity in Schizophrenia.

Journal of brain research Pub Date : 2021-01-01 Epub Date: 2021-05-18
Shalaila S Haas, Leighton B N Hinkley, Melissa Fisher, Sophia Vinogradov, Srikantan Nagarajan, Karuna Subramaniam
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Abstract

Prior studies have shown that the medial prefrontal cortex (mPFC) represents one neural substrate that mediates judgments of self-agency (i.e., the awareness that 'I am the originator of my actions'). Patients with schizophrenia (SZ) manifest cardinal self-agency deficits that contribute to debilitating psychotic symptoms (e.g. hallucinations) and distort reality monitoring. This is the first study in which we examine across 2 SZ samples, the mPFC site that underlies self-agency deficits during an explicit reality-monitoring task (i.e., while subjects distinguish self-generated information from externally-derived information) in one SZ sample, and link intrinsic functional connectivity (iFC) during rest within this a priori task-evoked self-agency seed with hallucination symptoms in a different SZ sample. In particular, we examined the iFC between the mPFC site that underlies self-agency deficits with all other brain regions in SZ using resting-state functional magnetic resonance imaging (fMRI). Resting-state fMRI data were collected from 32 SZ and 28 age, gender, and education-matched healthy control (HC) subjects. Functional connectivity maps were computed for each subject and compared between the HC and SZ groups. Within-group and between-group analyses revealed that aberrant iFC in this a priori-defined mPFC 'self-agency seed' predicted hallucination severity. The present findings reveal that the neural aberrations in this mPFC site represents one cardinal biomarker that underlies explicit self-agency deficits during a reality-monitoring task in one SZ sample that generalized to aberrant iFC differences in a different SZ sample and predicted worsening psychotic hallucinatory experiences. This region may represent a key neurobiological target for treatment avenues to improve hallucinatory symptoms.

幻觉的神经生物标记:内侧前额叶神经连接畸变可预测精神分裂症患者的自我行为缺陷和幻觉严重程度。
先前的研究表明,内侧前额叶皮层(mPFC)是介导自我代理判断(即 "我是我行为的始作俑者 "的意识)的神经基质之一。精神分裂症(SZ)患者表现出明显的自我代理缺陷,这导致了令人衰弱的精神症状(如幻觉)并扭曲了对现实的监控。这是我们首次在两个 SZ 样本中研究一个 SZ 样本在明确的现实监控任务中(即当受试者区分自我产生的信息和外部来源的信息时)导致自我一致性缺陷的 mPFC 位点,并在另一个 SZ 样本中将这种先验任务诱发的自我一致性种子在休息时的内在功能连接(iFC)与幻觉症状联系起来。特别是,我们使用静息态功能磁共振成像(fMRI)检查了自认能力缺陷的 mPFC 位点与 SZ 所有其他脑区之间的 iFC。研究人员收集了 32 名 SZ 受试者和 28 名与年龄、性别和教育程度相匹配的健康对照组(HC)受试者的静息态 fMRI 数据。计算了每个受试者的功能连接图,并对 HC 组和 SZ 组进行了比较。组内和组间分析表明,先验定义的 mPFC "自我代理种子 "的异常 iFC 预测了幻觉的严重程度。目前的研究结果表明,在一个 SZ 样本的现实监控任务中,mPFC 这一部位的神经异常代表了一种主要的生物标志物,它是明确的自我代理能力缺陷的基础,这种缺陷在不同的 SZ 样本中泛化为异常的 iFC 差异,并预示着精神病性幻觉体验的恶化。该区域可能是改善幻觉症状治疗途径的关键神经生物学靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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