By and large the history of clinical VEP recordings in PD paints a picture of delays in conduction velocity from the retina to V1 (Bodis-Wollner, 1978; Kupersmith et al, 1982; Bandini et al, 2001), in tandem with impaired clarity of the visual input (e.g. lowered visual acuity; Archibald et al, 2009). In these cases the P1 component is much more latent when compared to typical control scores, and thus interpreted as a marker of impaired visual information transfer. However, estimates of the P1 source suggest that this potential is generated by a number of inputs in the posterior visual cortex, possibly as a result of rapid cross-talk between V1 and V2 (Barnikol et al, 2006; DiRusso et al, 2005). For example, Pins and ffytche (2003) found that the combination V1, the lateral occipital cortex, and the medial occipital cortex, all contributed to the generation of the visual P1 response (Pins & ffytche, 2003). On the other hand the N1 is estimated to be generated by thalamocortical projections from the LGN to V1 (DiRusso et al, 2005). Based on the estimated population of neurons contributing to the N1 source it is thus likely to be a more temporally accurate marker of information arriving at V1. However, due to its less obvious nature this component is often unreported in clinical cases. In the current study the N1 latency was not significantly different between the groups, and did not demonstrate a trend related to VH severity. Although it is not possible to directly estimate the activity of LGN projections using EEG the lack of group
90
latency differences in the N1 component indirectly supports the notion that conduction delays in the pre-striate pathways in PDD are limited regardless of VH severity. Although there are known differences at the level of the retina (Nightingale et al, 1986; Archibald et al, 2009), and in the gating properties of the primary visual cortex (Perry et al, 1990; McKeith et al, 2004), relatively little is understood about how visual information is transferred to V1 in Lewy body dementias. Several recent pathological examinations have described a lack of Lewy body pathology in the LGN and the primary visual pathway (Erskine et al, 2015; Yamamoto et al, 2006), the implication of which is that there are no structural or
neurochemical changes occurring which alter the conduction velocity along the optic nerves towards V1 (save for changes in the retinal nerve fibre layer thickness (Lee et al, 2014), although this has not been considered in the context of the VEP in PDD). One interpretation is that the findings in the present study of similar N1 latency measurements between the groups may imply that intact conduction could be one part of a set of pre-requisites for the experience of VH.
In contrast the amplitude of the N1 and P1 components were significantly reduced in the PDD group relative to controls, as were their visual acuity scores. Previous interpretations of reductions in pattern reversal amplitudes have implicated diminishing visual acuity (Chen et al, 2012). In PD a number of visual abnormalities have been reported, accounting for age related retinal changes (Archibald et al, 2009) such as poor visual acuity (Jones et al, 1992; Holroyd et al, 2001), low contrast sensitivity (Regan & Neima, 1984; Bodis-Wollner et al, 1987), and reduced sensitivity to colours (Price et al, 1992; Pieri et al, 2000). Although alterations in cortical processing are likely to play a role, studies of the neurochemical and psychophysical mechanisms of these impairments strongly support changes within the retinal cells (Bulens et al, 1987; Hutton et al, 1993; Rodnitzky, 1997; Büttner et al, 2000; Nguyen- Legros et al, 1994; Nguyen-Legros et al, 1988; Inzelberg et al, 2004; Nowacka et al, 2015). Recently Nowacka and colleagues (Nowacka et al, 2015) contrasted electroretinogram (ERG) amplitudes with measures of retinal thickness, and patient reports on dopamine-dependent visual functions, in early stage PD. Although their findings did not reach significance for visual acuity, or retinal thickness, there was a reduction in the amplitudes of the scotopic α and β-waves of the ERG, which is thought to be regulated by dopaminergic signalling (Shulman & Fox, 1996; Krizaj et al, 1998). Further, as the peak time of the ERG oscillatory potentials increased PD patients were more likely to report difficulties in light adaptation and contrast sensitivity. The reduction in amplitude of the α and β-waves points to a disturbance
91
of photoreceptors at multiple layers of the retina, which would create problems with adaptation to different light states. Due to the reduced level of information reaching the primary visual cortex there would follow a reduction in the density of neurons required to process the incoming signal (N1). This would then be reflected in subsequent cortical processing (P1, N2). Conversely, compensatory models are gaining increasing traction to explain cortical processing changes in dementia (Coyle et al, 2015; Rowan, 2011); thus despite the physical decline of the early visual system significant compensatory changes may also be occurring in an attempt to normalise conduction times as the stability of these are essential for normal cortical processing. However, clarifying this would require a
longitudinal study of the VEP contrasted between those patients who would go on to develop VH versus those who would not.
An alternative proposal is that the changes in contrast sensitivity act to alter the thresholds required for access to conscious perception (Pins & ffytche, 2003). Here the amplitude change would reflect a downshift in the extent of resources applied for processing, as a result of changes to the psychophysical mechanisms governing early visual attention, scaled by the input’s relation to the visual threshold (Pins & ffytche, 2003; Lu & Dosher, 1998). Although this alternative explanation is perfectly plausible for explaining mechanisms of visual
attention and access to conscious experience the paradigms used by these studies are more finely tailored towards the study of higher visual cognition than the methods used in the current study. The pattern reversal paradigm used in the current study also presents a high luminance, and balanced contrast stimulus to the participant, with no active attention required to perceive the pattern. Here the potentials measured reflect processing in response to the onset and offset of light emitted from the display. The possibility remains that with a more nuanced design than the one presented here it would be feasible to measure the consequences of poor photoreceptor activation for conscious perception (e.g. Pins & ffytche, 2003),
although the choice of a simplistic passive stimulus has significant advantages in cognitively impaired participants as it avoids the confound of potential task dependent performance effects.
In the current study the visual acuity, N1 and P1 amplitudes were unrelated to disease
duration, motor severity, or age, implying that retinal changes were driven primarily by PDD pathology. In addition they were not related to VH occurrence or severity. However, the pairing of bottom-up impairments with compromises in the quality of the information being presented to higher cortical visual areas might place an individual with PDD in an “at risk”
92
state for VH. The co-presence of other factors such as dysfunctions in attention/executive control may then be required for the manifestation of VH – at least in PDD. This integrative interpretation contrasts with the visual deprivation/release models which are believed to underpin the generation of VH in conditions such as Charles Bonnet syndrome (e.g. Siatkowski et al, 1990; Burke, 2002).