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更好地了解脑损伤是如何发展和引起症状的。一些痴呆症会产生高度特定的脑损伤模式，这可能是这些疾病中大脑功能障碍的重要线索。我的项目将集中在选择性痴呆疾病的一个重要类别：原发性进行性失语症（PPA），它导致语言丧失和与大脑额叶和颞叶萎缩相关的行为改变。在这个项目中，我将建立在罕见痴呆症的国家转诊基地和集中在伦敦大学学院神经病学研究所的专业科学资源。通过专门的心理学测试，我将测量PPA患者对非语言声音的大脑反应，并将其与另一种痴呆症患者（阿尔茨海默病）和健康人的反应进行比较；我将通过结构和功能核磁共振扫描来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的大脑功能障碍在多大程度上是针对言语的，还是更普遍地影响声音信号；PPA中的脑功能障碍是否对特定类型的痴呆症具有特异性；以及PPA中的大脑功能障碍如何扩展到影响对言语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具有重要意义。在短期内，本研究可以通过指导认知、行为和沟通策略的应用，帮助改善PPA患者的症状。从长远来看，识别这些症状背后的大脑变化可能为疾病活动提供新的测量方法，这将使我们能够追踪药物和其他干预措施的效果，并可能使我们能够预测针对特定药物治疗的脑组织病理。

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.