Specific impairment of visual spatial covert attention mechanisms in Parkinson's disease
Research highlights
▶ Specific loss of attentional mechanisms in Parkinson's disease, independently of sensory deficits. ▶ Pathological redistribution of spatial mechanisms of covert attention in Parkinson disease. ▶ Loss of right hemispheric dominance of visual attention in Parkinson's disease.
Introduction
There is substantial evidence for non-motor manifestations in Parkinson's disease (Archibald et al., 2009, Bodis-Wollner, 1990, Bodis-Wollner, 2003, Bodis-Wollner et al., 1987, Bodis-Wollner and Tzelepi, 1998, Bodis-Wollner and Yahr, 1978, Castelo-Branco et al., 2009, Mosimann et al., 2004, Silva et al., 2005, Uc et al., 2005, Uc et al., 2007, Van Asselen and Castelo-Branco, 2009). Patient studies clearly separating low level sensory and visual spatial attention deficits within the same task are however still lacking. Recent covert attention studies in normal subjects have allowed for the separation of low level sensory processing from the performance enhancement effects of spatial attention (Carrasco, 2006, Pestilli and Carrasco, 2005). These studies provide a novel methodological opportunity to isolate and distinguish such sources of impairment in patients.
The neural basis of visual deficits in PD (Archibald et al., 2009, Bodis-Wollner, 2003, Silva et al., 2005) and the elucidation of which particular processing mechanisms are impaired (e.g., low level contrast detection and/or high level visual attention mechanisms) are crucial issues that can only be addressed if one measures at the same time contrast sensitivity (CS – reciprocal of Threshold measures) with and without manipulation of spatial bias of attention. We have previously demonstrated the advantages of simultaneously studying low and high level visual functions as a way to disentangle the neural origins of visual sensory, perceptual and cognitive deficits (Castelo-Branco et al., 2006, Castelo-Branco et al., 2007, Castelo-Branco et al., 2009, Kozak and Castelo-Branco, 2009). Also, we have previously developed visual CS tasks under conditions that control the spatial distribution of attention (Silva et al., 2008). Adding a cue leads to an asymmetric redistribution of spatial attention. Experimental control is further enhanced by running randomly interleaved psychophysical staircases in space and time, which helps exploring low and high level mechanisms underlying anisotropies in spatial vision (Silva et al., 2008, Silva et al., 2010).
Visual orienting is related to mechanisms of spatial attention in parietal cortex and is often associated with right hemispheric dominance (Davidson and Hugdahl, 2004, Ivry and Robertson, 1998). The main mechanisms of automatic “exogenous” orienting of spatial attention can be related to inhibition of return (IOR) and automatic orienting. Visual spatial attention can be covertly dissociated from the direction of gaze in a voluntarily driven way, via a mechanism known as “endogenous” attention. This mechanism is in contrast with the above mentioned automatic, stimulus-driven orienting termed “exogenous” attention (Posner & Cohen, 1984). Cueing paradigms are frequently used to study endogenous and exogenous orienting of attention (Posner & Cohen, 1984). An important distinguishing factor between the two is the difference in their time-courses. Whereas the effects of endogenous attention require a few hundred milliseconds to fully develop and can be maintained with effort, exogenous attention peaks within 100–120 ms and diminishes rapidly thereafter (Cheal and Lyon, 1991, Nakayama and Mackeben, 1989).
To explicitly tackle the question of how attention modulates visual performance, we have focused on paradigms where cueing is known to be facilitatory and not to induce inhibition of return, which refers to the slowing of a response to a target stimulus presented in the same location as a previous stimulus (Klein, 2000). Accordingly, at relatively short (e.g., 150-ms) cue–target stimulus onset asynchronies (SOAs), attentional orienting to targets at cued vs. uncued locations is facilitated, whereas at relatively long SOAs (e.g., beyond 300 ms), it is inhibited (Klein, 2000). Reductions in IOR have been argued to reflect impaired inhibitory processes in PD (Poliakoff et al., 2003, but see Grande et al., 2006). Here we were not focused on IOR, which reflects higher level late attentional processing, but rather on cueing with short cue-target SOA to measure early attentional facilitatory/inhibitory effects on visual performance of valid vs. invalid cues (Pestilli & Carrasco, 2005).
Putative deficits in visual orienting are also relevant in terms of visual performance asymmetries. Sources of performance asymmetries have been documented at different levels of the visual system (nasotemporal at the level of the retina, up–down at level of the retina, lateral geniculate nucleus and early visual cortex and left–right spatial cortical hemispheric asymmetries). Although some of these asymmetries may cancel out, as is the case of monocular nasotemporal asymmetries, in general a physiological/behavioral consequence can be identified (Silva et al., 2010). This is clearly the case concerning binocular left–right asymmetries (Silva et al., 2008). The relation of these functional asymmetries to cell density across retinotopic representations at different levels of the visual system have been addressed in our previous work (Silva et al., 2008, Silva et al., 2010). In brief, sources of spatial asymmetries in performance within the visual field (VF) can be ascribed to lower levels of visual processing, such as occipital cortex or even the retina (Carrasco et al., 2004, Maia-Lopes et al., 2008, Silva et al., 2008). A pattern of up/down visual field asymmetry has been shown to be also present at the level of striate/extrastriate cortices (Maunsell & Van Essen, 1987).
Probing such anatomic and physiological substrates of attentional and sensory performance may help provide tools to dissect the different visual processing steps that are affected in PD, including visual attention (Kingstone et al., 2002).
In this paper we have followed the seminal work of Carrasco and colleagues that were to first to show a way to separate sensory perception from attentional enhancement of such performance. We have now extended this innovative strategy to patient work on the non-motor cognitive processes that are often impaired in Parkinson disease (Van Asselen et al., 2009, Van Asselen and Castelo-Branco, 2009). It has indeed been hypothesized that attentional processes are more active in PD patients (Briand, Hening, Poizner, & Sereno, 2001), raising the question whether this is due to increased facilitation or reduced inhibition.
There is widespread evidence on the relation between spatial hemispheric dominance and the overlap between the attentional and spatial orienting network (Davidson and Hugdahl, 2004, Ivry and Robertson, 1998). Orienting of spatial attention can be related to anisotropic patterns of psychophysical performance (Nakayama and Mackeben, 1989, Silva et al., 2008) but it is important to recognize that cortical contribution to asymmetric visual performance independently of attentional biases has also been recently considered (Carrasco et al., 2004, Carrasco et al., 2001, Fuller et al., 2008). This is the case in terms of dorso/ventral (up/down) asymmetries in letter identification (Mackeben, 1999), visual acuity (Altpeter, Mackeben, & Trauzettel-Klosinski, 2000) and attentional conjunctive visual search tasks (He, Cavanagh, & Intrilligator, 1996). Furthermore, performance on orientation discrimination tasks depends on the up/down target location (Carrasco et al., 2001). The relevance of the functional superiority of the inferior field in primates and humans is also documented by the over-representation of the lower visual field in area MT (Maunsell & Van Essen, 1987) and in area V6A (Galletti et al., 1999).
Most of the current evidence for functional anisotropies does nevertheless relate to the right hemispheric dominance of spatial attention and to the beneficial effect of covert spatial attention and valid cues in normal subjects (for a review see Carrasco, 2006). Contrast sensitivity represents a basic visual performance dimension where substantial evidence for the role of focused spatial attention on performance improvement has been achieved. Covert attention may be understood as a neural process that enhances the signal (and thereby contrast sensitivity) from a particular part of the sensory scenario. Indeed, in normal subjects, transient covert attention increases contrast sensitivity at the target location with an informative spatial cue (Pestilli & Carrasco, 2005). Transient covert attention implies visual scanning in the absence of eye movements (prior to planning a saccade or not) and may have both benefits and costs. Accordingly, it may enhance contrast sensitivity at cued locations and impair contrast sensitivity at uncued (neutral) or invalid locations.
Here, we have dissected sensory (using baseline contrast sensitivity), early (superior/inferior) visual patterns of performance and parietal visual attention networks (by assessing left/right performance and validity effects under covert attention conditions) in early stage PD.
Performance was assessed using an achromatic contrast sensitivity task that probed a parvocellular-biased spatiotemporal frequency channel using stationary sinusoidal gratings of intermediate spatial frequency (ISF, Silva et al., 2005, Silva et al., 2008). These patterns were previously shown to also yield hemifield patterns of cortical physiological asymmetry in normal subjects, thereby proving to be adequate for the present study (Silva et al., 2008). Right/left asymmetries are a direct reflection of the hemispheric dominance of the right hemisphere in visuospatial attention, and their study thereby provides, in addition to the effect of peripheral valid, invalid and neutral cues, further clues to the study of attentional deficits in Parkinson's disease. These concepts relate visual transient attention (and orienting) mechanisms with the notion of limited resources and thereby provide an interesting additional paradigm to probe deficits in PD.
In sum, we expected PD patients to show distinct spatial patterns of performance as compared to controls and in particular to show impairment on early facilitation of valid cues. Testing at two distinct eccentricities helped probing the prediction whether more peripheral locations (where attentional demands are higher) show a validity effect as compared to central ones, where attentional demands are lower. We have mainly tested exogenous attention and facilitation, by using a 100 ms cue-target onset asynchrony.
Section snippets
Participants selection
35 PD patients (18 males, 17 females) were initially included for this study. The control group comprised 24 demographically matched subjects. Seven patients were excluded due to neuropthalmological exclusion criteria (see below). Given that the main goal of the study was focused on covert attention mechanisms we have further excluded PD patients that were not able to maintain fixation and/or to inhibit reflexive saccades in the presence of exogenous cues (n = 11). We discuss below this
Methodological exclusion of patients unable to keep covert attention
A substantial proportion of our PD patients showed a surprisingly high tendency to move their eyes towards attentional cues. Our data indicated that pre-selected PD patients have significantly impaired ability to inhibit reflexive saccades when an additional visual pre-cue is added, as compared to controls (Chi-square test, p < 0.01). This difference justified our strict exclusion criteria.
A signature of the loss of inhibitory control typically seen in our PD patients can be observed in Fig. 2.
Baseline sensory performance in PD
Concerning central Zone 1 (Fig. 3), we have found a dissociation in performance between controls and PD patients: the pooled contrast sensitivity in Zone 1 was significantly different between groups (p = 0.01, ANOVA). Given that the study of main effects “collapses” variables across “post hoc” levels we have also tested whether this difference held true across regions (Fig. 3). Interestingly, this difference was still significant even when the analysis was confined to spatial subregions (left, p =
Discussion
In this work we were able to identify a specific attentional deficit in PD that could be isolated by explicitly controlling for baseline performance in contrast sensitivity tasks. Our paradigm represents an advantage over traditional paradigms because it does not merely rely on reaction time or percent correct measures which are prone to bias (Fuller et al., 2008). We focused on true psychophysical sensitivity and staircases provide in this respect a great advantage when comparing performance
Acknowledgements
This research was funded by grants from the Portuguese Science and Technology Foundation (FCT): PTDC_SAU_NEU_68483_2006, PTDC_PSI_67381_2006 and PIC_IC_82986_2007, as well as by the National Brain Imaging Network of Portugal (BIN).
References (45)
- et al.
The importance of sustained attention for patients with maculopathies
Vision Research
(2000) Visual deficits related to dopamine deficiency in experimental animals and Parkinson's disease patients
Trends in Neuroscience
(1990)Neuropsychological and perceptual defects in Parkinson's disease
Parkinsonism and Related Disorders
(2003)- et al.
The push–pull action of dopamine on spatial tuning of the monkey retina: The effects of dopaminergic deficiency and selective D1 and D2 receptor ligands on the pattern electroretinogram
Vision Research
(1998) - et al.
Automatic orienting of visuospatial attention in Parkinson's disease
Neuropsychologia
(2001) Covert attention increases contrast sensitivity: Psychophysical, neurophysiological and neuroimaging studies
Progress in Brain Research
(2006)- et al.
Temporal performance fields: Visual and attentional factors
Vision Research
(2004) - et al.
Specific retinotopically based magnocellular impairment in a patient with medial visual dorsal stream damage
Neuropsychologia
(2006) - et al.
Motion integration deficits are independent of magnocellular impairment in Parkinson's disease
Neuropsychologia
(2009, January) Inhibition of return
Trends in Cognitive Sciences
(2000, April)
Visual magnocellular and structure from motion perceptual deficits in neurodevelopmental model of dorsal stream function
Brain Research Cognitive Brain Research
Attention enhances contrast sensitivity at cued and impairs it at uncued locations
Vision Research
Retinal and cortical patterns of spatial anisotropy in contrast sensitivity tasks
Vision Research
The retina in Parkinson's disease
Brain
Covert visuospatial attentional mechanisms in Parkinson's disease
Brain
Visual dysfunction in Parkinson's disease. Loss in spatiotemporal contrast sensitivity
Brain
Measurements of visual evoked potentials in Parkinson's disease
Brain
A large-sample study of sex differences in functional cerebral lateralization
Journal of Clinical and Experimental Neuropsychology
Orienting of visual attention in Alzheimer's disease: Its implication in favor of the interhemispheric balance
Neuropsychiatry and Neuropsychology Behavioral Neurology
Characterizing visual performance fields: Effects of transient covert attention, spatial frequency, eccentricity, task and set size
Spatial Vision
Visual phenotype in Williams-Beuren syndrome challenges magnocellular theories explaining human neurodevelopmental visual cortical disorders
The Journal of Clinical Investigation
Central and peripheral precuing of forced-choice discrimination
Quarterly Journal of Experimental Psychology A: Human Experimental Psychology
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