Limbic thalamus atrophy is associated with visual hallucinations in Lewy body disorders

Recent models of hallucinations in Lewy body disorders implicate dysfunction in ‘higher order’ thalamic regions involved in perceptual integration and cognitive processing. However, the degree of pathology and degeneration in these regions has not been assessed. We sought to assess atrophy, neuronal size, and neuronal numbers in the Mediodorsal (MDn) and Anterior Principal (APn) nuclei of the thalamus across Lewy body disorders comparing between patients with and without hallucinations. Postmortem tissue was acquired from 24 patients with Lewy body disease and 10 age-matched controls and analyzed using standard stereological and quantitative neuropathological techniques. Atrophy in MDn was significantly greater in patients with well-formed visual hallucinations and did not correlate significantly with neuronal size or number. Atrophy in APn was seen across all Lewy body disorders but was not significantly associated with hallucinations. α-synuclein immunoreactivity was found to be low in both the APn and MDn across all groups. These results suggest that MDn atrophy may be a marker of hallucinations and plays a role in their pathophysiology.