Large-scale brain networks coordinate human behavior, and their anatomy helps explain how neurodegenerative diseases progress. Alzheimer's disease targets the default mode network, while behavioral variant frontotemporal dementia targets the salience network. The default mode network is active when healthy people consider personal moral dilemmas, yet Alzheimer's patients respond normally to these dilemmas, whereas frontotemporal dementia patients give abnormally utilitarian responses. This discrepancy may arise because the salience network modulates default mode network activity.
Psychosis is a common and burdensome symptom in neurodegenerative diseases. Analyzing 283 autopsy-confirmed cases, delusions were linked to atrophy in the right temporal lobe and bilateral frontal lobes, especially when persecutory or paranoid, implicating circuits for reward, emotion, self-awareness, and executive function. Misidentification delusions correlated with right ventral temporal-occipital atrophy, disrupting visual stream processing. No consistent atrophy patterns emerged with hallucinations. Damage to these brain regions predisposes individuals to delusions across different syndromes and pathologies, suggesting shared mechanisms between neurologic and psychiatric disorders.