GESTIÓN AMBIENTAL

Early electrophysiological studies of perception in PD and PDD used the presentation of different dynamic visual stimuli, such as patterns and flashing lights, to investigate the integrity of visual input (e.g. Nightingale, et al, 1986; Bodis-Wolner et al, 1978). Much like various cognitive paradigms these methods also produce an ERP which can be recorded directly from the retina (electroretinography, ERG) or from the primary visual cortex (visual evoked potential, VEP). Both the ERG and VEP have been widely studied in PD, and whilst there exists some contention between findings (Tagliati et al, 1996; Erskine et al, 2015), there is enough evidence to suggest that LRP is associated with some level of deficient function within the retina (Nightingale et al, 1986; Onofrj et al, 2006; Diederich et al, 1998; Pieri et al, 2000; Archibald et al, 2009; Nowacka et al, 2015) and the transfer of the visual signal to the primary visual cortex (Matsui et al, 2005; Okuda et al, 1995; Bodis-Wolner et al, 1978; Bodis-Wolner & Antal, 2005; Bandini et al, 2001).

In both the ERG and the VEP the waveform components are typically shown to have reduced amplitudes when compared with those of the control group, which is believed to stem from the depletion of dopaminergic cells in the retina exerting a negative influence upon the activity of photoreceptors at multiple retinal layers (Archibald et al, 2009; Maurage et al, 2003; Nowacka et al, 2015; Shulman & Fox, 1996; Krizaj et al, 1998). The consequences of this for perception are poor visual acuity, difficulties with the control of image contrast, and reduced sensitivity to colour and motion (Archibald et al, 2009). Urwyler et al, described a positive relationship between the presence of visual complaints and the experience of simple VH in PD (Urwyler et al, 2014), which might partly be explained by the pathophysiology of PD at the level of the retina. For example the depletion of retinal dopamine leads to poor control of surround inhibition, and as a result the flexible control of contrast for efficient separation of image features is affected (Dowling et al, 1986; Archibald et al, 2009; Nowacka

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et al, 2015). The degraded image sent to the visual cortex could thus manifest as a feeling of presence, or a simple misperception (Diederich et al, 2004; Onofrj et al, 2006). The

improvement of these measurements in response to levodopa treatment (Starkstein et al, 1989; Oishi et al, 1995; Amabile et al, 1986) supports that there is some role of the pre-striate

dopaminergic system in the VH experienced in PDD. However, it is necessary to contrast this against the observation that dopaminergic medications can exacerbate the experience of VH, suggesting that the distribution and impact of dopamine depletion within the visual system as a whole is a complex issue.

As well as the control of cellular communication within the retina the structural integrity of the pre-striate pathways between the retina and the primary visual cortex is considered to exert some influence over the generation of VH. Studies using the pattern reversal VEP have previously made inferences about this based on the latency of the P1 (or P100) component, finding that it is elongated in patients with PD and it has been suggested that the conduction of the signal is slowed by some factor related to PD pathology (Matsui et al, 2005; Bodis- Wolner et al, 1978). In PD patients, Matsui et al, found that increasing latency of the P1 was a strong predictor for the experience of VH, suggesting that inefficiencies in the transmission of information from the eye associates with the development of VH (Matsui et al, 2005). Source localisation of the VEP P1 component in healthy controls shows that its origins are in V2 and the extra-striate cortices (Di Russo et al, 2002; Di Russo et al, 2005), meaning that the P1 is representative of higher level visual processing. Instead of the P1 it would be more appropriate to consider the N1 (or N75) component of the VEP as a marker of conduction velocity due to it being generated by thalamo-cortical projections between the lateral geniculate nucleus (LGN) and V1 (Di Russo et al, 2005). However there is a paucity of research surrounding the involvement of the N1 component in LBD research, and also in VH research. Nevertheless, under the traditional interpretation of P1 latency the extended latency of the P1 component has previously been demonstrated as a predictor of VH in patients with PD (Matsui et al, 2005), supporting the involvement of visual input/early bottom-up visual processing in the experience of VH. Other investigative approaches have sought to determine if there are any effects of LRP on the lateral geniculate nucleus (LGN) and found that

compared with controls, in the LGN pathology is still only relatively low in LBD patients; further both groups had shown similar levels of BOLD activation during fMRI prior to death (Erskine et al, 2015). Interestingly, although the LGN is relatively spared in LBD thinning of the optic nerve fibre layer has been related to the experience of VH in PD without dementia (Lee et al, 2014). It is beyond the scope of this text to comment on how this might influence

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the transmission delay of the visual signal, however, the combination of poor quality retinal output and an intact LGN might be a pre-requisite state for the development of VH (Erskine et al, 2015). In this case whilst the LGN transfers information to the cortex effectively,

pregeniculate input remains compromised. Also whilst this provides some basis for bottom- up contributions to VH generation in LBD, it falls short of describing a complete mechanism.