To better understand the structural neuroanatomic substrate of psychotic symptoms in neurodegenerative disease (NDG) patients.

Psychosis in NDG is a major source of stress, anxiety, and depression both for patients and their caregivers and is associated with earlier institutionalization and a higher cost of care. Symptoms are often treated pharmacologically, presuming a neurochemical origin, but few large-scale studies have determined whether particular patterns of regional degeneration are more likely to engender psychotic symptoms. Furthering our understanding of the root causes of this important clinical feature could lead to more tailored prognostic and therapeutic approaches.

Numerous regions in the bilateral frontal lobes and right temporal lobe predicted psychosis at pFWE<0.05, including peaks at the right nucleus accumbens (T=4.54), right anterior insula (T= 4.60), and right thalamus (T=4.41).

These preliminary results further support past studies finding psychosis related to frontal lobe dysfunction and lend more support to the interesting observation that right hemisphere dysfunction is often correlated with psychosis. They are also notable for confirming the contribution of the right thalamus to psychosis, which has been implicated in schizophrenia and in FTD patients who are C9orf72 carriers. The right anterior insula has been seen to play a role in emotions and processing of external stimuli, and similarly the nucleus accumbens is involved with emotion, salience and reward, suggesting emotions may play a key role in reality testing.