Premotor and fronto-striatal mechanisms associated with presence hallucinations in dementia with Lewy bodies

Introduction: presence hallucinations (PH) are frequent in dementia with Lewy bodies (DLB), but their cortico-subcortical origin is unknown. Recent studies have defined key frontal and temporal areas contributing to the occurrence of PH (PH-network) and tested their relevance in subjects with Parkinson's disease (PD). With the present study, we aimed at disentangling the metabolic and dopaminergic correlates of pH as well as their relation to a recently defined PH brain network in DLB.

Methods: for the present study, we included 34 DLB subjects (10 with PH (PH + ); 24 without PH (PH-)), who underwent ¹⁸F-FDG PET and ¹²³I-FP-CIT SPECT imaging. We performed ¹⁸F-FDG PET group comparisons, as well as interregional correlation analyses using ¹⁸F-FDG PH-network regions as a seed.

Results: PH + versus PH- had reduced ¹⁸F-FDG uptake in precentral, superior frontal and parietal gyri, involving ventral premotor cortex (vPMC) of the PH-network that showed strongly reduced functional connectivity with bilateral cortical regions. ¹⁸F-FDG vPMC uptake was negatively correlated with caudate ¹²³I-FP-CIT uptake in PH+ (p = 0.028) and interregional correlation analysis seeding from the vPMC showed widespread fronto-parietal ¹⁸F-FDG decreases in PH + .

Discussion: these findings uncover the pivotal role of vPMC (involved in a PH-network) and its cortico-striatal connections in association with PH in DLB, improving our understanding of psychosis in neurodegeneration.