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: 10623217
• 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/10623217
• 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; Outcome; Patients; Perception; Performance; Pharmaceutical Preparations; Phase; Population; Prevalence; Primates; Process; Psychoses; Psychotic Disorders; Research; Scalp structure; Schizophrenia; Sensory; Societies; Source; Stimulus; Symptoms; System; Therapeutic Intervention; Variant; Vision; Visual; Visual Cortex; Visual Perception; Visual System; Visual attention; Visual impairment; Work; attentional modulation; cognitive system; critical period; early psychosis; effective intervention; experience; first episode psychosis; first episode schizophrenia; functional decline; functional disability; improved; information processing; instrument; neural; neural correlate; noninvasive brain stimulation; psychotic; 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，与个体的功能能力的显著损害有关 对社会造成巨大的经济负担。尽管有各种治疗方案来解决积极的问题， 虽然这种疾病的症状，相对较少已经成功地开发出针对认知症状， 造成社会和职业功能的严重缺陷。最近的研究表明， 自下而上的视觉感知过程有助于这些更确定的认知障碍及其 相关功能下降。此外，视觉感知的失真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了。 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 自下而上的知觉反应中断，除了他们的局部皮层过程出现， 通过跨分布式注意力网络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果。在视觉对比知觉中的反应放大，一个很好的- 慢性精神病中有记录的中断与疾病治疗的影响，仍然没有得到充分研究 在疾病发作时。此外，这种基本感知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通过以下方式促进对比感知，但在精神病中尚未探索 注意健康人群。我假设这种调节，由长距离皮层介导， 通过分布式视觉注意力网络的通信，将表现出显着的中断， 与早期精神病的认知和功能缺陷相关，与局部知觉障碍相比， 应答我将使用同时记录的M/EEG数据来定位视觉皮层的区域， 刺激对比处理这种方法还将用于隔离连接受损的来源， 背侧注意网络的区域是注意对健康人对比度知觉的调制的基础。 成年人了最后，将使用经验证的临床工具评估症状和功能障碍， 量化这些视觉处理缺陷在首次发作患者中的临床影响。识别各种 在精神病中出现功能障碍的信息处理水平是阐明机制的关键 隐藏着治疗最不好但最具破坏性的症状。本研究的结果将告知干预性研究 针对与负面临床结果相关的视觉处理中的特定中断的方法。 在疾病的早期阶段检查干扰将有助于消除原发性疾病过程的影响 从混淆，如年龄和药物使用，并告知这些疾病的纵向轨迹 损伤，以确定脆弱的发育时间点并最大限度地发挥我们干预措施的效益。