Visual Network Connectivity and Perceptual Modulation in Early Psychosis

早期精神病中的视觉网络连接和知觉调节

• 批准号: 10438086
• 负责人: Alfredo Luis Sklar
• 金额: $ 18.81万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10438086
• 关键词: Activities of Daily Living; Address; Adult; Age; Attention; Biological Models; Brain; Chronic; Chronic Disease; Chronic Schizophrenia; Clinical; Clinical assessments; Cognitive; Cognitive deficits; Communication; Communities; Conflict (Psychology); Cues; Data; Detection; Development; Disease; Dorsal; Economic Burden; Electroencephalography; Evoked Potentials; Exhibits; Frequencies; Functional disorder; Future; Goals; Human; Impaired cognition; Impairment; Individual; Intervention; Left; Link; Literature; Magnetoencephalography; Mediating; Morbidity - disease rate; Neurobehavioral Manifestations; Occupational; Onset of illness; Operating System; Outcome; Patients; Perception; Performance; Pharmaceutical Preparations; Phase; Population; Prevalence; Primates; Process; Psychoses; Psychotic Disorders; Research; Scalp structure; Sensory; Societies; Source; Stimulus; Symptoms; System; Therapeutic Intervention; Variant; Vision; Visual; Visual Cortex; Visual Perception; Visual attention; Visual impairment; Work; attentional modulation; cognitive system; critical period; early psychosis; experience; first episode psychosis; first episode schizophrenia; functional decline; functional disability; improved; information processing; instrument; neural correlate; noninvasive brain stimulation; relating to nervous system; response; selective attention; social; stimulus processing; targeted treatment; therapy development; visual processing

Abstract Psychosis is a debilitating chronic illness associated with marked impairments of functional capacity in individuals and a significant economic burden for society. Despite various treatment options to address the positive symptoms of the illness, relatively few have been successfully developed to target cognitive symptoms that account for significant deficits in social and occupational functioning. Recent work suggests that deficits in bottom-up visual perceptual processes contribute to these more established cognitive impairments and their associated functional decline. Furthermore, distortions in visual perception have a significant clinical impact, particularly during early stages of the illness, despite being underappreciated in traditional clinical settings. Unfortunately, our limited understanding of the relationship between perceptual and cognitive systems in psychosis hinders our ability to isolate targets for therapeutic interventions. The proposed study will examine disruptions in bottom-up perceptual responses emerging from local cortical processes in addition to their modulation by coordinated activity across a distributed attentional network and ascertain the impact of each on clinical outcomes in first-episode psychosis. Response amplification in visual contrast perception, a well- documented disruption in chronic psychosis with implications for treatment of the disorder, remains understudied at disease onset. Moreover, the top-down modulation of this fundamental perceptual mechanism remains unexplored in psychotic illness despite significant literature detailing the facilitation of contrast perception via attention in healthy populations. I hypothesize that this modulation, mediated by long-range cortical communication across a distributed visual attention network, will exhibit marked disruption and be more closely associated with cognitive and functional deficits in early psychosis compared to disruptions in local perceptual responses. I will use simultaneously recorded M/EEG data to localize regions of visual cortex exhibiting altered stimulus contrast processing. This approach will also be used to isolate sources of impaired connectivity across regions of the dorsal attention network underlying the modulation of contrast perception by attention in healthy adults. Finally, symptoms and functional impairments will be assessed using validated clinical instruments to quantify the clinical impact of these visual processing deficits in first-episode patients. Identifying the various levels of information processing at which dysfunctions arise in psychosis is key to elucidating the mechanisms underlying its least well treated yet most devastating symptoms. Results from this study will inform interventional approaches targeting specific disruptions in visual processing associated with negative clinical outcomes. Examining disruptions at an early illness stage will help disambiguate the effects of primary disease processes from confounds such as age and medication usage and inform longitudinal trajectories of these disease impairments to identify vulnerable developmental timepoints and maximize the benefits of our interventions.

摘要 精神病是一种使人衰弱的慢性疾病，与个体的功能能力显著受损有关。 也给社会带来了巨大的经济负担。尽管有不同的治疗选择来解决阳性 在疾病的症状中，相对较少成功地发展成针对认知症状的 造成社会和职业功能严重缺陷的原因。最近的研究表明， 自下而上的视觉感知过程有助于这些更成熟的认知障碍及其 相关的功能衰退。此外，视觉知觉的扭曲具有显著的临床影响， 特别是在疾病的早期阶段，尽管在传统的临床环境中被低估。 不幸的是，我们对知觉和认知系统之间关系的有限理解 精神病阻碍了我们隔离治疗干预目标的能力。拟议的研究将审查 局部皮质过程中出现的自下而上知觉反应的中断 通过分布式注意网络上的协调活动进行调制，并确定每个活动对 首发精神病的临床结局。视觉对比度知觉中的反应放大 记录在案的慢性精神病的中断及其对疾病治疗的影响，仍未得到研究 在疾病发作时。此外，这一基本知觉机制的自上而下的调制仍然存在 尽管有大量文献详细描述了对比知觉的易化作用，但在精神病方面仍未被研究。 关注健康人群。我推测这种调节是由远程大脑皮层 跨分布式视觉注意力网络的通信将表现出明显的中断，并更加紧密 与局部知觉障碍相比，早期精神病患者存在认知和功能障碍 回应。我将使用同步记录的M/EEG数据来定位显示改变的视觉皮质区域 刺激对比度处理。此方法还将用于隔离连接受损的来源 健康人注意调节对比知觉的背侧注意网络区域 成年人。最后，将使用经过验证的临床仪器来评估症状和功能损害 量化这些视觉处理缺陷对首发患者的临床影响。确定不同的 精神病患者产生功能障碍的信息处理水平是阐明其机制的关键 其最不好的治疗却是最具破坏性的症状。这项研究的结果将为干预提供信息 针对与阴性临床结果相关的视觉处理特定干扰的方法。 在早期疾病阶段检查中断将有助于消除原发疾病过程的影响 从年龄和药物使用等方面的混淆，并提供这些疾病的纵向轨迹 我们的目标是确定脆弱的发展时间点，并最大限度地发挥我们干预措施的益处。