Title: The impact of neurodegeneration on neuronal coding – 7T fMRI in frontal and temporal aphasia
Funder: The Academy of Medical Sciences

Abstract: With this award I will: a) Use 7-Tesla functional MRI I aim to identify the neural basis of the language presentations of Frontotemporal Lobar Degeneration (FTD). b) In turn to understand the neural basis of language and prediction. Specifically, I will: a) Use the aphasic forms of FTD as demonstrator conditions for network-effects of neurodegeneration, because of their stereotyped patterns of neurodegeneration, the psychophysical precision of language as a probe, and the fragility of human language networks to synaptic disruption. b) Apply multivariate pattern analysis to brain regions that are not themselves affected by neurodegeneration, directly observing the effect of diaschisis on the pattern of neural activation. I will apply two well understood paradigms to drive neural activity during imaging in 20 patients and at least 20 controls - a perceptual prediction task based on Cope 2017, and a representational similarity task based on Kriegeskorte 2008. These will answer focussed questions across two research strands, with the overall hypotheses: 1) The core problem in non-fluent variant primary progressive aphasia is inflexible motor speech predictions due to delayed processing in inferior frontal gyrus (‘Broca’s area’). This will be reflected in increased stability of single word representations in temporal lobe. 2) Semantic dementia results from a failure of anterior temporal lobe to bind neural activity in the rest of cortex into complex percepts. If this is true, the consequence is not a reversion to random object coding, but rather a visual-feature representation, which we can observe in behavioural and neural representational similarity.

Lay abstract: Language is one of the most fundamentally human abilities. It allows us to communicate our needs, understand the desires of others, and to think abstractly about the world around us. It is extremely complicated and fragile, requiring many brain areas to work together. To understand a sentence, we need to arrange sounds into the building blocks of words, and convert those words into understanding. Patients with semantic dementia (SD) can hear and repeat speech normally, but they do not understand it. In fact, they lack factual knowledge about objects, animals and the world. If presented with a model of a lion and asked what it is, they are likely to say that it is a much more commonly encountered animal: a cat. But they aren't just getting muddled up - they are actually seeing the lion as a cat, and understanding it to be a cat. We will show patients with SD pictures of rare and common animals, while using a very powerful brain scanner to look at the pattern of activity in their brain. In this way, we can observe the brain's code for understanding, and how it goes wrong if a small but crucial brain area is damaged. Similarly, patients with non-fluent variant primary progressive aphasia (nfvPPA) get confused when what they hear is not what they expected to hear. They can't cope with the unexpected. We will use the same techniques to observe the brain's predictions, and how it corrects itself when we hear an unexpected word.

Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: NEUROLOGICAL