The role of the visual thalamus in hallucinations in dementia with Lewy bodies

Background: Complex visual hallucinations occur in 70% of dementia with Lewy bodies (DLB) cases and significantly affect patient wellbeing. Visual cortical and retinal abnormalities have been recorded in DLB cases and may contribute to visual hallucinations. The visual thalamus plays a vital role in relaying and modulating sensory input. In particular, the lateral geniculate nucleus (LGN) and pulvinar nucleus play important roles in relaying optical input and visual attention, respectively. This study therefore determined whether pathological and molecular changes occur in the LGN and pulvinar nucleus in post-mortem tissue taken from DLB patients. Methods: The LGN from six DLB, seven AD and seven control cases was serially sectioned for quantitative analyses of cellular populations using stereology and neuropathological lesions using densitometric analysis. Frozen pulvinar tissue from 12 DLB cases was compared with tissue from 12 control cases using a range of protein expression assays. Results: In DLB, the LGN was found to be relatively intact, while greater cell loss and neuropathological lesions were found in AD cases. However, substantial, significant reductions have been found in an array of synaptic proteins, including synaptophysin, gephyrin and PSD-95 in the pulvinar nucleus in DLB cases. Conclusions: These results suggest that the pre-cortical primary visual pathway is structurally intact in DLB cases but that the secondary visual pathway, routed through the pulvinar, may be impaired. Damage to the pulvinar nucleus may lead to attentional issues either directly or through alterations in interplay between top-down and bottom-up processing, both of which have been postulated to underlie visual hallucinations in DLB.