Neural correlates of delusions and hallucinations in dementia Lead Investigator: Ryan Darby Institution : BIDMC/MGH Massachusetts ADRC E-Mail : darby.ryan@gmail.com Proposal ID : 772 Proposal Description: Delusions and hallucinations are common in patients with dementia, occurring in up to 60 of patients. Moreover, the presence of hallucinations and delusions is associated with worse caregiver burden, lower quality of life for both patients and caregivers, and more rapid clinical progression. Yet despite the prevalence and severity of these symptoms, therapies aimed at treating hallucinations and delusions in patients with neurological diseases are often ineffective. One reason for this is that while delusion and hallucinations are often grouped together as psychotic symptoms, there is increasing evidence that hallucinations and delusions are dissociable. The goal of the proposed research will be to determine the unique neuroimaging correlates occurring in dementia patients with delusions vs. hallucinations, providing useful biomarkers and potential therapeutic targets for future studies. Both delusions and hallucinations are thought to result from the combination of (1) abnormal bottom-up processing leading to perceptual abnormalities, and (2) abnormal top-down processing resulting in abnormal monitoring of perception. We hypothesize that monitoring systems disrupted in delusions vs. hallucinations are different. Specifically, we hypothesize that belief monitoring deficits leading to delusions will involve the neuropsychological process of expectation violation and localize the right lateral prefrontal cortex, while reality monitoring deficits leading to hallucinations will involve the neuropsychological process of source monitoring and localize to the medial prefrontal and anterior cingulate cortices. Finally, we hypothesize that dysfunction in perceptual regions will relate to the specific content of a delusion or hallucination. Specific Aims