Changes in both top-down and bottom-up effective connectivity drive visual hallucinations in Parkinson's disease

Abstract

Visual hallucinations are common in Parkinsons disease and are associated with poorer quality of life and higher risk of dementia. An important and influential model that is widely accepted as an explanation for the mechanism of visual hallucinations in Parkinsons disease and other Lewy-body diseases is that these arise due to aberrant hierarchical processing, with impaired bottom-up integration of sensory information and overweighting of top-down perceptual priors within the visual system. This hypothesis has been driven by behavioural data and supported indirectly by observations derived from regional activation and correlational measures using neuroimaging. However, until now, there was no evidence from neuroimaging for differences in causal influences between brain regions measured in patients with Parkinsons hallucinations. This is in part because previous resting-state studies focus on functional connectivity, which is inherently undirected in nature and cannot test hypotheses about directionality of connectivity. Spectral dynamic causal modelling is a Bayesian framework that allows the inference of effective connectivity - defined as the directed (causal) influence that one region exerts on another region - from resting-state functional MRI data. In the current study, we utilise spectral dynamic causal modelling to estimate effective connectivity within the resting-state visual network in our cohort of 15 Parkinsons disease visual hallucinators, and 75 Parkinsons disease non-hallucinators. We find that visual hallucinators display decreased bottom-up effective connectivity from the lateral geniculate nucleus to primary visual cortex and increased top-down effective connectivity from left prefrontal cortex to primary visual cortex and medial thalamus, as compared to non-hallucinators. Importantly, we find that the pattern of effective connectivity is predictive of the presence of visual hallucinations and associated with their severity within the hallucinating group. This is the first study to provide evidence, using resting state effective connectivity, to support a model of aberrant hierarchical predictive processing as the mechanism for visual hallucinations in Parkinsons disease.