New metrics of brain network breakdown in the progressive aphasias

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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.