A Systematic Review on Resting State Functional Connectivity in Patients with Neurodegenerative Disease and Hallucinations

Hallucinations are a complex and multidimensional phenomenon which can differ based on the involved pathology, typology and sensory modality. Hallucinations are common in patients with neurodegenerative diseases. Recent sparse evidence from resting state functional magnetic resonance imaging (rs-fMRI) studies has identified altered functional connectivity in those patients within several brain networks, such as the default mode, attentional and sensory ones, without, however, providing an organized picture of the mechanisms involved. This systematic review, following PRISMA guidelines, aims at critically analyzing the current literature on the brain networks associated with the phenomenon of hallucinations in patients with neurodegenerative diseases. Ten rs-fMRI studies fulfilled our selection criteria. All these studies focused on synucleinopathies, and most of them focused on visual hallucinations and were characterized by a heterogeneous methodology. Thus, instead of offering a definite picture of the mechanisms underlying hallucinations in neurodegeneration, this systematic review encourages further research especially concerning tauopathies. Notwithstanding, the findings overall suggest a disruption in the top-down (associated with memory intrusion and difficulty of inhibition) and in the bottom-up processes (associated with the sensory areas involved in the hallucinations). Further investigations are needed in order to disentangle the brain mechanisms involved in hallucinations and to overcome possible limitations characterizing the current literature.