Synaptic loss and its impact on predictive language processing

Disorganised thinking may be more than just a symptom and could reflect deeper changes in how the brain is wired. Research suggests that people with disorganised speech often show reduced grey matter in language-related brain regions, possibly due to excessive loss of synapses, the tiny connections that allow brain cells to communicate. These changes may be linked to genetic risk factors for psychosis, many of which affect how synapses form and are maintained.

To explore this, we are using a cutting-edge brain imaging technique called SV2A-PET (using the tracer [11C]-UCB-J) to directly measure synaptic density in the brain’s language network. We will compare these brain measures with speech patterns analyzed by Large Language Models (LLMs) to see how changes in brain connectivity relate to disorganised thinking. By including both individuals with severe mental illness and their high-risk siblings, this work could reveal whether protecting synapses might help reduce persistent disorganisation and guide future treatments.