Patient-specific functional networks track early cognitive alterations and minor hallucinations in Parkinson’s disease

Abstract Minor hallucinations (MHs) affect up to 40% of patients with Parkinson’s disease (PD) and are early indicators of cognitive decline. Unlike previous group-level studies, connectome-based brain fingerprinting enables the capture of individualized neural features. Leveraging this framework in a cross-sectional cohort of patients with Parkinson’s disease with and without MHs using resting-state functional magnetic resonance imaging, here we show that each patient exhibits a unique brain fingerprint, irrespective of MH status. The most individualized features were associated with clinically relevant measures such as motor-symptom severity and cognitive performance. Patients with MHs showed a loss of individual-specific features in brain networks linked to cognitive health, whereas the cerebellar-to-cortex connectivity—typically less distinctive—became more prominent, emphasizing the role of somatosensory and motor integration in MH pathogenesis. Moreover, MH-related fingerprint regions mapped onto cortical territories with lower densities of neurotransmitter systems implicated in hallucinations. Overall, our fully data-driven findings reveal a distinct, patient-specific signature that differentiates patients with Parkinson’s disease and MHs.