UnaWireD

Why is the diseased human brain able to produce false beliefs that persist despite evidence to the contrary? Unawareness of neurological disturbances (anosognosia) and Delusions are examples of such false beliefs. Both have productive, narrative features. Both have been independently linked to processes involved in self-reflection, metamemory, and error-monitoring. Despite their phenomenological similarities, the research investigating their mechanisms has progressed independently. UnaWireD will provide the first in-depth investigation of anosognosia and delusions in combination to test the hypothesis that they share common brain mechanisms. Although these symptoms impact significantly on a range of brain disorders, the proposal focuses on Alzheimer’s Disease (AD), in which the difference between patients who show the most severe form of these symptoms and patients who never present them is striking yet largely unexplained. In particular, it is not known whether these symptoms represent a response of the spared brain to the damage (depending on pre-existing vulnerability or resilience) or are a consequence of the damage itself (depending on type, localisation and severity of pathology). By combining advanced imaging with experimental paradigms and extended clinical and biomarker characterisation, UnaWireD will: 1. Establish whether anosognosia and delusions define a specific clinical subtype in AD; 2. Determine if they are associated with premorbid personality and cognitive abilities; 3. Identify the brain networks specifically altered in the anosognosia/delusion AD subtype; 4.Test if anosognosia is associated with an imbalance in the brain neurotransmitter dopamine. UnaWireD will deliver a new framework to study the interplay between the spared and damaged brain in the origin of productive symptoms across neurological diseases. By doing so, it will open a window towards a better understanding of the uniquely human abilities of self-reflection and consciousness