Understanding the temporal dynamics of visual hallucinations in Parkinson's Disease with dementia

Abstract

Background Integrative models of visual hallucinations (VH) posit that the symptom requires disruptions to both bottom-up and top-down visual processing. Although many lines of evidence point to a mixture of aberrant processing and disconnection between key nodes in the visual system, in particular the dorsal and ventral attention networks, there have been no attempts to understand the dynamic behaviour of these systems in Parkinson’s disease with dementia (PDD) with VH. Aims The primary aim of this thesis was to explore the correlates of synaptic communication in the visual system and how spatio-temporal dynamics of the early visual system are altered in relation to the severity of VH. The secondary aim was to help understand the balance between the contributions of bottom-up and top-down processing for the experience of VH in PDD. Methods An assortment of investigative approaches, including resting state electroencephalography (EEG), visual evoked potentials (VEPs), and concurrent EEG and transcranial magnetic stimulation (TMS) were applied in a group of PDD patients with a range of VH severities (n = 26) and contrasted with a group of age matched healthy controls (n = 17). Results Latency of the N1 component was similar between groups, suggesting intact transfer between the retina and the cortex. However, PDD patients had an inherent reduction in the amplitude of the VEP components and displayed a pattern of declining P1 latencies in association with more frequent and severe VH. Evoked potentials arising from TMS of the striate cortex were similar in amplitude and latency for each of the components between PDD and controls. However, inter-component activity at several stages was altered in the PDD group, whilst the frequency and severity of VH was positively associated with the amplitudes of several components in the occipital and parietal regions. Finally, attentional modulation as measured by the alpha-band reactivity was also compromised in PDD patients. iv Conclusions These data provide neurophysiological evidence that both early bottom-up and top-down dysfunctions of the visual system occur in PDD patients who hallucinate, thus supporting integrative models of VH.