Visual pathway abnormalities and self-organisation of the visual system

视觉通路异常和视觉系统的自组织

• 批准号: 149341228
• 负责人: Professor Dr. Michael Hoffmann
• 金额: --
• 依托单位: Universitätsaugenklinik
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/149341228?language=en
• 关键词: Visual; pathway; abnormalities; self; organisation

Congenital malformations of the optic chiasm cause large scale abnormal input to the visual cortex. They therefore provide a valuable key to understand the framework guiding human visual pathway development and plasticity for the benefit of basic neuroscience and clinical applications. In the work leading up to this project we identified the visual cortex as a site of critical importance (a) for plastic mechanisms to make abnormal input available for visual function and (b) for action and failure of visual maturation. Remarkably, a potential cortical MRI-biomarker for such amblyopia-like processes appears to be generalizable beyond chiasma abnormalities, as indicated by our companion research on achromatopsia in an independent DFG-project. Based on these foundations, the proposed project aims to decipher how developmental mechanisms operate in the human visual brain at the level of brain function, connectivity, and anatomy. For this purpose, we will apply an interdisciplinary approach of ophthalmology, psychophysics, highest-standard anatomical/diffusion-weighted/functional MRI (a/d/fMRI) and artificial-intelligence based neuro-computations (deep-learning). Specifically, we will investigate (1) reorganisation of top-down attentional modulation with 7T fMRI, (2) intra-cortical connectivity and fine-structure via 7T a/dMRI, (3) altered visual development via deep-learning based analyses of MRI-brain-anatomies for individualized diagnostics. To make a significant, neuro-scientifically and clinically meaningful contribution to the understanding of visual pathway developments in congenital vision disorders, we will extend our investigations beyond our previous target group (chiasma abnormalities) by integrating groups with congenital cone-dysfunction (achromatopsia) and early blindness. This integration of our related, but previously independent research activities, paves the way for a generalization of our insights that will significantly increase the impact of our research. This is further supported by the use of highest-standard a/d/fMRI that is possible due to our proven expertise, our strong collaborations with leaders in the field, and the recent extension of the local infra-structure by the novel 7T connectome scanner (Siemens 7T Terra.X Impulse Edition). It is expected that this integrated approach of functional and structural analyses in congenital visual pathway disorders will provide significant insights into neural development and reorganisation that will have a lasting impact on our view of visual system plasticity and ultimately on clinical applications. Specifically, we aim to set a general precedent for the MRI-based identification of changes of intra-cortical and cortico-cortical connectivity, and of visual cortex maturation, including amblyopia correlates, that will spur the development of novel diagnostics and therapeutic approaches.

先天性视交叉畸形会导致视觉皮层的大规模异常输入。因此，它们为理解指导人类视觉通路发育和可塑性的框架提供了宝贵的钥匙，以利于基础神经科学和临床应用。在该项目的前期工作中，我们确定视觉皮层是一个至关重要的部位（a）为视觉功能提供异常输入的可塑性机制，以及（b）视觉成熟的行动和失败。值得注意的是，这种弱视样过程的潜在皮质 MRI 生物标志物似乎可以推广到交叉异常之外，正如我们在一个独立 DFG 项目中对全色盲的伴随研究所表明的那样。基于这些基础，拟议的项目旨在破译人类视觉大脑在大脑功能、连接性和解剖学层面上的发育机制如何运作。为此，我们将采用眼科、心理物理学、最高标准的解剖/扩散加权/功能 MRI (a/d/fMRI) 和基于人工智能的神经计算（深度学习）的跨学科方法。具体来说，我们将研究（1）通过 7T fMRI 自上而下的注意力调节重组，（2）通过 7T a/dMRI 进行皮质内连接和精细结构，（3）通过基于深度学习的 MRI 脑解剖分析来改变视觉发育，以进行个性化诊断。为了对理解先天性视力障碍的视觉通路发育做出重大的、神经科学和临床上有意义的贡献，我们将通过整合患有先天性视锥细胞功能障碍（全色盲）和早期失明的群体，将我们的研究扩展到之前的目标群体（交叉异常）之外。这种对我们相关但以前独立的研究活动的整合，为我们的见解的概括铺平了道路，这将显着提高我们研究的影响力。最高标准的 a/d/fMRI 的使用进一步支持了这一点，这得益于我们经过验证的专业知识、与该领域领导者的密切合作，以及最近通过新型 7T 连接组扫描仪（西门子 7T Terra.X 脉冲版）对本地基础设施的扩展。预计这种先天性视觉通路疾病的功能和结构分析的综合方法将为神经发育和重组提供重要的见解，这将对我们对视觉系统可塑性的看法并最终对临床应用产生持久影响。具体来说，我们的目标是为基于 MRI 识别皮质内和皮质-皮质连接的变化以及视觉皮层成熟（包括弱视相关性）的变化树立一个普遍的先例，这将刺激新的诊断和治疗方法的发展。