New metrics of brain network breakdown in the progressive aphasias

开发有效的痴呆症治疗方法可能取决于对脑损伤如何发展和引起症状的更好理解。一些痴呆症会产生高度特异性的脑损伤模式，这些模式可能是这些疾病中大脑功能障碍的重要线索。我的项目将专注于选择性痴呆疾病的一个重要类别：原发性进行性失语症（PPA），这导致语言丧失和行为变化与大脑额叶和颞叶的萎缩。在这个项目中，我将建立在罕见痴呆症的国家转诊基础上，并集中在伦敦大学学院神经病学研究所的专业科学资源。使用专门的心理学测试，我将测量PPA患者对非语言声音的大脑反应，并与另一种痴呆症（阿尔茨海默病）患者和健康人的反应进行比较;我将使用结构和功能MRI扫描评估与这些反应相关的大脑结构和功能的变化。这些测量将使我能够确定PPA中的大脑功能障碍在多大程度上是特定于语音或更普遍地影响声音信号的; PPA中的大脑功能障碍是否特定于特定类型的痴呆症;以及PPA中的大脑功能障碍如何扩展到影响对语音以外的有意义信号的理解。这些发现可能对我们理解PPA、准确诊断以及最终评估治疗方法具有重要意义。在短期内，这项研究可能有助于通过指导认知，行为和沟通策略的应用来改善PPA患者的症状。从长远来看，识别支持这些症状的大脑改变可能会提供新的疾病活动措施，使我们能够跟踪药物和其他干预措施的影响，并可能使我们能够预测脑组织病理学，以针对特定的药物治疗。

Development of effective treatments for dementia may depend on improved understanding of how brain damage develops and causes symptoms. Some dementias produce highly specific patterns of brain damage that are likely to hold important clues about the brain malfunction in these diseases. My project will focus on one important category of selective dementia diseases: the primary progressive aphasias (PPA), which lead to language loss and behavioural changes associated with shrinkage of the frontal and temporal lobes of the brain. In this project I will build on the national referral base in uncommon dementias and the specialised scientific resources concentrated at the Institute of Neurology, University College London. Using specialised psychology tests, I will measure brain responses to nonverbal sounds in patients with PPA compared with responses in patients with another dementia (Alzheimer's disease) and in healthy people; and I will assess the changes in brain structure and function linked to these responses using structural and functional MRI scans. These measurements will allow me to determine the extent to which brain malfunction in PPA is specific for speech or affects sound signals more generally; whether brain malfunction in PPA is specific for a particular kind of dementia; and how brain malfunction in PPA extends to affect understanding of meaningful signals beyond speech. These findings would potentially have important implications for our understanding of PPA, for accurate diagnosis, and ultimately, for assessing treatments. In the short term this research may help to improve the symptoms experienced by patients with PPA by guiding the application of cognitive, behavioural and communication strategies. In the longer term, the identification of brain alterations underpinning these symptoms may provide new measures of disease activity that will allow us to track the effects of drugs and other interventions, and may allow us to predict brain tissue pathology for targeting particular drug treatments.