Thalamocortical Networks in Psychosis

精神病中的丘脑皮质网络

• 批准号: 9119628
• 负责人: Neil D. Woodward
• 金额: $ 46.37万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-01 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9119628
• 关键词: Address; Affect; Animal Model; Attention; Biological Markers; Bipolar Disorder; Brain; Caregiver Burden; Chronic; Chronic Schizophrenia; Cognition; Cognitive; Cognitive deficits; Conflict (Psychology); Development; Differential Diagnosis; Diffusion Magnetic Resonance Imaging; Disease; Disease model; Exhibits; Functional Magnetic Resonance Imaging; Health; Image; Impaired cognition; Impairment; Investigation; Knowledge; Life; Link; Maintenance; Maps; Medial Dorsal Nucleus; Memory impairment; Modeling; Outcome; Pathology; Pathway interactions; Patients; Prefrontal Cortex; Psychotic Disorders; Rest; Schizophrenia; Short-Term Memory; Specificity; Staging; Structure; Testing; Thalamic structure; Work; base; cognitive function; differential expression; economic cost; network dysfunction; neurodevelopment; neuroimaging; neuropsychiatry; psychosocial; relating to nervous system

DESCRIPTION (provided by applicant): This project will investigate thalamocortical networks in schizophrenia (SZ) and psychotic bipolar disorder (BD). Despite considerable evidence that the thalamus is abnormal in psychosis, several knowledge gaps must be addressed before thalamic pathology can be established as a biomarker. First, although attention has focused on the mediodorsal (MD) nucleus, conflicting findings from post-mortem studies and limitations of conventional imaging approaches has made it difficult to establish the anatomical specificity of thalamic pathology. Second, it is not known if thalamocortical dysconnectivity extends to psychotic BD. Overlapping deficits in cognitive functions supported by the thalamic circuitry, including working memory (WM), suggests this may be the case. However, differences in the pathways leading to cognitive impairment also predict there will be differences. In SZ, cognitive impairment is superimposed on a background of compromised pre-morbid functioning and remains stable across illness stages. In BD, pre-morbid functioning is intact and cognitive impairment is relatively modest in the early stage of the illness; whereas chronic patients are virtually indistinguishable from SZ. This has led to different etiological models of psychosis: SZ is conceptualized as a neurodevelopment disorder and BD a neuroprogressive illness. These models predict overlapping abnormalities in thalamocortical circuitry in chronic patients, but differential impairment in the early stage of psychosis. Finally, despite compelling evidence from animal models linking thalamocortical dysconnectivity to WM, the functional consequences of thalamocortical network dysfunction are poorly understood. In separate studies of chronic (Aim 1) and early stage psychosis (Aim 2), we will determine if thalamocortical network pathology varies in accordance with the different trajectories of cognitive impairment in psychotic disorders, and is related to WM impairment (Aim 3). We will test the following specific hypotheses: 1) in chronic psychosis, both SZ and psychotic BP patients will exhibit reduced connectivity between the PFC and MD thalamus; and 2) in early stage psychosis, SZ, but not psychotic BP, will exhibit reduced PFC-MD thalamus connectivity. Additionally, we will test the hypothesis that somatomotor hyper-connectivity observed in prior studies of chronic SZ, which we proposed is due to atypical pre-morbid brain maturation, is present in early stage SZ, but not early stage or chronic psychotic BP. If confirmed, these hypotheses will provide a powerful approach to differentiating psychotic disorders at both early and chronic stages of the illness, and further support the different etiological models of SZ and BD. Alternatively, the results might indicate there is greater overlap in thalamocortical pathology between SZ and BD than appreciated and challenge the different etiological models of these disorders. Moreover, examining functional connectivity during WM may provide translational evidence supporting a mechanistic thalamocortical dysconnectivity model of WM impairment and identify potential treatment targets for ameliorating cognitive impairment.

描述(申请人提供)：这个项目将研究精神分裂症(SZ)和精神病性双相情感障碍(BD)的丘脑皮质网络。尽管有相当多的证据表明丘脑在精神病中是异常的，但在丘脑病理学被确定为生物标志物之前，必须解决几个知识差距。首先，虽然人们的注意力集中在内侧背核(MD)，但尸检研究中相互矛盾的发现和传统成像方法的局限性使得建立丘脑病理的解剖学特异性变得困难。其次，尚不清楚丘脑皮质连接障碍是否延伸到精神病性BD。丘脑回路支持的认知功能的重叠缺陷，包括工作记忆(WM)，表明情况可能是这样的。然而，导致认知障碍的途径的不同也预示着将会有不同。在深圳，认知障碍叠加在病前功能受损的背景上，并在疾病阶段保持稳定。在BD中，发病前的功能是完整的，认知障碍在疾病的早期阶段相对较轻；而慢性患者实际上与SZ无法区分。这导致了不同的精神病病因模型：SZ被概念化为神经发育障碍，而BD被概念化为神经进行性疾病。这些模型预测慢性患者丘脑皮质环路的重叠异常，但在精神病的早期阶段有不同的损害。最后，尽管来自动物模型的令人信服的证据将丘脑皮质连接障碍与WM联系起来，但丘脑皮质网络功能障碍的功能后果却知之甚少。在对慢性精神病(目标1)和早期精神病(目标2)的单独研究中，我们将确定丘脑皮质网络病理是否根据精神病患者认知障碍的不同轨迹而变化，并与WM损害(目标3)有关。我们将测试以下特定假设：1)在慢性精神病中，SZ和精神病BP患者都会表现出PFC和MD丘脑之间的连接减少；以及2)在早期精神病中，SZ，但不是精神病BP，将显示PFC-MD丘脑连接减少。此外，我们将检验先前慢性SZ研究中观察到的躯体运动高连接性的假设，该假说是由于非典型的病前脑成熟所致，存在于早期SZ，而不是早期或慢性精神病性BP。如果得到证实，这些假说将提供一种有效的方法来区分疾病早期和慢性阶段的精神障碍，并进一步支持SZ和BD的不同病因模式。或者，结果可能是 提示SZ和BD在丘脑皮质病理上存在比人们所认识的更大的重叠，并对这些疾病的不同病因模型提出了挑战。此外，检测WM期间的功能连接可能提供支持WM损害的机械性丘脑皮质连接障碍模型的翻译证据，并确定改善认知损害的潜在治疗靶点。