Effects of Psychopathology on Prefrontal Cortical Functioning During Goal-Directe

精神病理学对目标导向期间前额皮质功能的影响

• 批准号: 7903421
• 负责人: SHARON L THOMPSONSCHILL
• 金额: $ 19.69万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-30 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7903421
• 关键词: Achievement; Activities of Daily Living; Affect; Anterior; Area; Attention; Basal Ganglia; Basic Science; Behavioral; Behavioral Research; Brain; Brain Pathology; Clinical; Clinical Psychology; Clinical Research; Cognitive; Communities; Data; Decision Making; Depressed mood; Development; Diagnosis; Disease; Effectiveness; Emission-Computed Tomography; Event; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Image; Impulsivity; Individual; Individual Differences; Interdisciplinary Study; Lateral; Lead; Lesion; Life; Limbic System; Link; Major Depressive Disorder; Measures; Memory; Mental Depression; Methodology; Moods; Motor; Neurocognitive; Neurosciences; Neurosciences Research; Outcome; Pathology; Patients; Pennsylvania; Performance; Perfusion; Photons; Physiological; Population; Positron-Emission Tomography; Prefrontal Cortex; Procedures; Process; Psychometrics; Psychopathology; Research; Subgroup; Symptoms; Therapeutic; Transcranial magnetic stimulation; Translational Research; Treatment Effectiveness; Treatment outcome; Universities; base; cingulate cortex; clinical practice; frontal lobe; improved; innovation; insight; neuroimaging; neuropsychological; novel; patient population; programs; treatment planning

DESCRIPTION (provided by applicant): Basic research on prefrontal cortex (PFC) functioning has established a specific cognitive and behavioral profile of patients afflicted by lesions in this region, that is characterized by a decline in performance in tasks that require focused attention, inhibition, or action sequencing in goal achievement. Research in clinical psychology has revealed a similarly suboptimal cognitive style in the majority of patients diagnosed with depression, as indicated by pronounced difficulties in decision-making, perseverations on, particularly negative, interpretations of life events, and ineffectiveness in task completion. Recent developments in clinical neuroscience have suggested that neurodevelopmental abnormalities in prefrontal regions are critically associated with major depression. Specifically, different types of abnormalities in the dorsolateral prefrontal (DLPFC) and orbitofrontal (OBC) cortices, anterior cingulate cortex (ACC), and basal ganglia are hypothesized to underlie the brain circuit pathophysiology linked to the disorder. Despite recent research on the identification of such PFC anomalies, few studies have investigated individual differences among patients on how abnormalities in these areas affect performance on a variety of cognitive tasks and how they are associated with treatment effectiveness and therapeutic outcomes. The primary aim of the present project is to establish a strong partnership between the clinical and neuroscience communities of the University of Pennsylvania that will focus on the development of translational research between basic behavioral/neuroscience research on PFC function and clinical research on depression. We aim to initiate a research program that will explore the relationships between the deficient cognitive profile in depression (i.e., disruptions in normal cognitive and motor inhibition, attentional disturbances, and impulsivity) and a certain physiological profile as characterized by PFC-limbic system abnormalities. The focus of this project is to develop a set of new methodologies that will provide more detailed neurocognitive assessments of hypofrontal functioning in depression that will allow for better characterization of different patient subgroups. The present research program incorporates diverse and novel methodologies including behavioral, perfusion fMRI, transcranial magnetic stimulation (TMS), and neuropsychological/clinical studies, and introduces a novel set of tasks that will allow for a better characterization of hypofrontal cognitive profile in normal subjects, as well as its manifestation in different populations of depressed patients. Through the development of a comprehensive set of neurocognitive assessment procedures we will be able to better characterize different populations of patients diagnosed with depression based on lateral PFC hypo- functioning and to make specific predictions on the effectiveness and outcome of different treatment plans. Finally, we aim to collect exploratory data in support of the development of a larger-scale, long-term research plan promoting interdisciplinary research on the diagnosis and treatment of depression based on the relationship between PFC functioning and specific cognitive and mood profiles of different patient subgroups that can be used to guide optimal clinical practice. Research on the frontal lobes has established a specific cognitive and behavioral profile of patients afflicted by lesions in this region, which is characterized by a decline in performance in tasks that require focused attention and memory. Research in clinical psychology has revealed similar problems in patients diagnosed with depression, as indicated by their difficulties in decision-making and their negative interpretations of life events. Different types of abnormalities in regions of the prefrontal cortex are hypothesized to underlie the behavioral and cognitive problems linked to this disorder. Despite recent research on the brain pathology of depression, few studies have investigated individual differences among patients on how this pathology affects performance on a variety of cognitive tasks and how it is associated with treatment effectiveness and therapeutic outcomes. The goal of this project is to improve our understanding of basic behavioral processes and brain involvement in cognitive tasks in depression, which will lead to more accurate diagnoses and to the selection of the most suitable treatment approaches for individual patients. RELEVANCE: Research on the frontal lobes has established a specific cognitive and behavioral profile of patients afflicted by lesions in this region, which is characterized by a decline in performance in tasks that require focused attention and memory. Research in clinical psychology has revealed similar problems in patients diagnosed with depression, as indicated by their difficulties in decision-making and their negative interpretations of life events. Different types of abnormalities in regions of the prefrontal cortex are hypothesized to underlie the behavioral and cognitive problems linked to this disorder. Despite recent research on the brain pathology of depression, few studies have investigated individual differences among patients on how this pathology affects performance on a variety of cognitive tasks and how it is associated with treatment effectiveness and therapeutic outcomes. The goal of this project is to improve our understanding of basic behavioral processes and brain involvement in cognitive tasks in depression, which will lead to more accurate diagnoses and to the selection of the most suitable treatment approaches for individual patients.

描述（由申请人提供）：关于前额叶皮层（PFC）功能的基础研究，已经建立了受病变折磨的患者的特定认知和行为特征，其特征是在需要集中注意力，抑制，抑制或行动测序的目标方面的绩效下降。临床心理学的研究表明，大多数被诊断出患有抑郁症的患者的认知方式类似，这表明，决策困难，持续的持续性，尤其是负面的解释，对生活事件的解释以及任务完成的无效性。临床神经科学的最新发展表明，前额叶区域的神经发育异常与严重抑郁症密切相关。具体而言，假设背侧外侧前额叶（DLPFC）和眶额（OBC）皮质，前扣带回皮层（ACC）和基底神经节的不同类型的异常，以此为基础，以与与该疾病相关的脑电路病理学。尽管最近对这种PFC异常的鉴定研究了，但很少有研究研究了患者之间关于这些领域异常如何影响各种认知任务的表现以及它们与治疗效率和治疗结果如何相关的表现。本项目的主要目的是在宾夕法尼亚大学的临床和神经科学群落之间建立牢固的伙伴关系，该伙伴将着重于基本行为/神经科学研究对PFC功能与抑郁症临床研究之间的转化研究的发展。我们旨在启动一项研究计划，该计划将探讨抑郁症中不良认知概况之间的关系（即正常认知和运动抑制作用，注意力障碍和冲动性的破坏），以及以PFC-LIMBIC系统异常为特征的某些生理特征。该项目的重点是开发一系列新方法，这些方法将对抑郁症中的额外功能进行更详细的神经认知评估，从而可以更好地表征不同的患者亚组。本研究计划涵盖了各种各样和新颖的方法，包括行为，灌注FMRI，经颅磁刺激（TMS）和神经心理学/临床研究，并介绍了一套新的任务，可以更好地表现出正常受试者的低胸腔认知概况，以及其在不同人群中的表现。通过开发一组全面的神经认知评估程序，我们将能够更好地表征基于侧向PFC功能低下的抑郁症患者的不同人群，并对不同治疗计划的有效性和结果做出具体预测。最后，我们旨在根据PFC功能与可用于指导最佳临床实践的不同患者子组的特定认知和不同患者子组的特定认知和情绪谱之间的关系，收集探索性数据，以支持大规模的长期研究计划的发展，促进有关抑郁症诊断和治疗的跨学科研究。对额叶的研究已经建立了受病变折磨的患者的特定认知和行为特征，其特征是任务的表现下降，需要集中注意力和记忆力。临床心理学的研究揭示了被诊断出患有抑郁症的患者的类似问题，这表明他们在决策中的困难及其对生活事件的负面解释。假设前额叶皮层区域中不同类型的异常是与该疾病有关的行为和认知问题的基础。尽管最近对抑郁症的脑病理学进行了研究，但很少有研究研究了患者之间关于这种病理如何影响各种认知任务的表现以及与治疗效果和治疗结果如何相关的患者的个体差异。该项目的目的是提高我们对抑郁症认知任务的基本行为过程和大脑参与的理解，这将导致更准确的诊断，并为个别患者选择最合适的治疗方法。 相关性：对额叶的研究已经建立了受病变折磨的患者的特定认知和行为概况，其特征是任务的绩效下降，需要集中注意力和记忆力。临床心理学的研究揭示了被诊断出患有抑郁症的患者的类似问题，这表明他们在决策中的困难及其对生活事件的负面解释。假设前额叶皮层区域中不同类型的异常是与该疾病有关的行为和认知问题的基础。尽管最近对抑郁症的脑病理学进行了研究，但很少有研究研究了患者之间关于这种病理如何影响各种认知任务的表现以及与治疗效果和治疗结果如何相关的患者的个体差异。该项目的目的是提高我们对抑郁症认知任务的基本行为过程和大脑参与的理解，这将导致更准确的诊断，并为个别患者选择最合适的治疗方法。