J Neurol (2010) 257:383–391 DOI 10.1007/s00415-009-5328-7
ORIGINAL COMMUNICATION
REM sleep behaviour disorder and visuoperceptive dysfunction: a disorder of the ventral visual stream? Ana Marques • Kathy Dujardin • Muriel Boucart Delphine Pins • Marie Delliaux • Luc Defebvre • Philippe Derambure • Christelle Monaca
•
Received: 24 August 2009 / Accepted: 11 September 2009 / Published online: 30 September 2009 Ó Springer-Verlag 2009
Abstract In idiopathic rapid eye movement sleep behaviour disorder (RBD), an association with visuoperceptive disorders has been described. However, such an association has not been clearly established in RBD secondary to Parkinson’s disease (PD). We compared visuoperceptive function in four groups of non-demented patients (parkinsonian patients with or without RBD, patients with idiopathic RBD and control participants) via a procedure enabling the analysis of the various components of visual information processing and in order to answer the following question: is RBD associated with visuoperceptive and/or attentional disorders in PD and, if so, where is the dysfunction located along the visual pathway? Sensorial aspects of visual information were evaluated using a contrast sensitivity test, perceptual aspects were assessed using a contour-based object identification test and visual attention was measured in an attentional capture paradigm. The diagnosis of RBD was confirmed by polysomnography. We
A. Marques P. Derambure C. Monaca (&) Service de Neurophysiologie Clinique, Unite´ des troubles de la veille et du sommeil, EA 2683, IFR 114, Hoˆpital Roger Salengro, CHRU de Lille, Lille cedex 59037, France e-mail:
[email protected] A. Marques e-mail:
[email protected] K. Dujardin M. Delliaux L. Defebvre Service de Pathologie du Mouvement, EA 2683, IFR 114, Hoˆpital Roger Salengro, CHRU Lille, Lille cedex 59037, France M. Boucart D. Pins Laboratoire Neurosciences Fonctionnelles et Pathologies, CNRS UMR 8160, IFR 114, Universite´ Lille 2, CHRU Lille, Lille cedex 59037, France
observed a higher object identification threshold (OIT) (1) in PD patients with RBD compared with PD patients without RBD and with controls and (2) in idiopathic RBD patients compared with controls. There were no significant OIT differences between PD patients with RBD and idiopathic RBD patients or between PD patients without RBD and controls. We did not find any significant inter-group differences in any of the other visuoperceptive tests. RBD, idiopathic or secondary to PD, is associated with perceptual closure dysfunction. Our results suggest that this perceptual dysfunction is specifically associated with RBD and may be related to a non-dopaminergic impairment. Keywords REM sleep behaviour disorder Parkinson’s disease Visuoperception Perceptual closure
Introduction Rapid eye movement (REM) sleep behaviour disorder (RBD) is a parasomnia characterised by loss of normal skeletal muscle atonia during REM sleep, which then enables dream mentation to be acted out. Behaviour is frequently elaborate, violent (screaming, punching, grasping, kicking, etc.) and potentially harmful for the patient him/ herself and/or their bedpartner [1]. Polysomnographic recording reveals loss of muscle atonia during more than 20% of the periods of REM sleep and is required to confirm the diagnosis [2]. RBD affects mainly men (sex ratio: 8/1) over 50 and its prevalence in the general population is about 0.5% [3, 4]. RBD may be either idiopathic or secondary to neurodegenerative diseases (particularly alpha-synucleinopathies) [5, 6]. In its idiopathic form, RBD is frequently associated with cognitive impairment in general and visuoperceptive disorders in particular [7–11]. Ferini-Strambi
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et al. [10] described impaired visuospatial constructional abilities and altered visuospatial learning in patients with idiopathic RBD. In RBD associated with Parkinson’s disease (PD), cognitive disorders have been described recently: specific deficits were found in episodic verbal memory, executive function and visuospatial and visuoperceptual processing in PD patients with RBD, compared with PD patients without RBD and to controls [12]. This parasomnia may thus herald cognitive decline. However, the precise relationship between RBD and cognitive impairment has not yet been established. Given the close relationship between RBD and visual dysfunction, we sought to determine the visual information processing level or component that might be specifically impaired in RBD. More specifically, the present study set out to investigate the link between RBD (confirmed by polysomnography), PD and visual disorders by assessing visuoperceptive function in four groups of non-demented patients: PD patients with or without RBD, patients with idiopathic RBD and control subjects. We used a procedure that enabled analysis of the sensory, perceptual and attentional components of visual information processing. We hypothesized that visuoperceptive disorders are more frequent in patients with RBD, whether idiopathic or associated with PD.
comorbidities, no severe apnoea syndrome (apnoea/hypopnoea index [ 30). Patients participating in another study, having been treated with psychotropic drugs in the previous 3 months, with an unstable posology for at least 3 months or taking acetylcholinesterase inhibitors were excluded. Individuals with motor fluctuations, undergoing deep brain stimulation or suffering from other neurological comorbidities were also excluded. 1.
2.
3. Methods Population All the study patients were consecutively recruited at the Sleep Consultation and the Movement Disorders departments at Lille University Hospital. Participants were over18 males or females with no visual acuity disorders, no dementia (according to the DSM-IV [13]), no psychiatric
Twenty PD patients participated in the study and were divided into two groups, according to the presence (n = 10) or absence (n = 10) of RBD after polysomnographic analysis. All patients fulfilled the clinical criteria for probable idiopathic PD [14] and were assessed after receiving their usual antiparkinsonian medication. Motor disability was rated using the motor part of the Unified Parkinson’s Disease Rating Scale (UPDRS-III) [15]. The levodopa equivalent dose (LED) was defined as described elsewhere [16]. The two groups were matched with respect to the disease characteristics and their antiparkinsonian treatment. Ten patients with idiopathic, polysomnography-confirmed RBD were included. All displayed normal brain magnetic resonance imaging (MRI) results and none suffered from neurological disorders or were undergoing treatment for RBD at the time of the study. Eight healthy controls also participated in the study. None had a personal history of neurological or psychiatric illness.
This study was approved by the local institutional review board and all participants gave their informed consent to participation in the study. The participants’ demographic and clinical characteristics are shown in Table 1. All four groups were matched with respect to age. The sex ratio (M/F) was higher in the idiopathic RBD group than in the other groups and the
Table 1 Demographic and clinical characteristics of study participants P-RBD
P-NRBD
RBDI
Controls
Gender ratio (M/W)
3/7
3/7
8/2
5/3
Age
64 ± 2.9
59 ± 2.6
59 ± 2.4
64 ± 2
p Value
0.681 a,b,c
Education duration (years)
10 ± 0.6
10.9 ± 0.9
11.3 ± 1.4
15.7 ± 1.7
Duration of RBD
8.4 ± 2.4
–
4.5 ± 1.7
–
0.503
Duration of disease
7.6 ± 1.7
8.1 ± 3.7
–
–
0.912
0.013
Age at onset
56.7 ± 2.1
52.1 ± 4.7
–
–
0.28
Dopasensitivity
49.7 ± 5.3
44.8 ± 3.8
–
–
0.083
LED
703 ± 157
435.5 ± 132.7
–
–
0.604
P-RBD Parkinsonian patients with RBD, P-NRBD parkinsonian patients without RBD, RBDI patients with idiopathic RBD, LED levodopa equivalent dose a
Controls/P-RBD: p = 0.005
b
Controls/P-NRBD: p = 0.003
c
Controls/RBDI: p = 0.015
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educational level was higher for controls than for the other groups. Procedure Sleep and arousal evaluation Patients underwent a subjective evaluation of sleep and vigilance on the Parkinson Disease Sleep Scale (PDSS) [17] and the Epworth Sleepiness Scale (ESS) [18]. Two all-night polysomnographic recordings with continuous audiovisual monitoring were performed. Polysomnographic investigation consisted of a standard montage, including an electroencephalogram, electro-oculograms, submental and bilateral anterior tibialis electromyography (EMG), an electrocardiogram and nasal and oral air-flow, oxygen saturation and thoracic and abdominal movement monitoring. Sleep stages were scored according to a modified version [19] of the standard criteria [20] without the submental EMG criterion, allowing the presence of muscle tone for REM sleep. During REM sleep, we measured tonic and phasic electromyographic activity in the submental region and legs, as described elsewhere [19]. The REM density during REM sleep was also measured visually, according to a previously described method [21]. Healthy control subjects did not undergo this polysomnographic evaluation, although they were screened using a questionnaire to rule out a history of sleep disorders such as insomnia, periodic limb movements, restless legs syndrome, excessive daily somnolence or symptoms suggesting apnoea syndrome or RBD. Cognitive functions were assessed in all participants with a standard procedure, including the Mini Mental State Examination, the Mattis Dementia Rating Scale, forward and backward digit span, a verbal version of the Symbol Digit Modalities Test (the subjects had to verbally associate digits with abstract symbols during 90 s), the Stroop word colour test, a letter and number sequencing task corresponding to a verbal version of the Trail Making Test (the procedure has been described fully elsewhere [22]; performance was evaluated in terms of an alternation cost index), the French version of the Grober and Buschke word list learning and recall test [23] performed according to the procedure described by Pillon et al. [24] and a verbal fluency task (performed in 60 s and under phonemic, semantic and alternate conditions). Evaluation of visuoperceptive functions This evaluation was performed according to an analytical approach, allowing assessment of the sensory, perceptive and attentional aspects of visual information processing.
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The sensorial component: the contrast sensitivity function [25] This test aimed to determine contrast thresholds for different spatial frequencies using a VSG system (Cambridge Research System). The stimulus consisted of a rectangular, sinusoidal grating (15° of visual angle) of a given spatial frequency, appearing on a grey background. Background luminance was equal to the mean luminance of the stimulus (5 cd/m2). Five spatial frequencies were tested (0.5, 1.5, 3.5, 9 and 14 cycle/deg.) on each patient, in a predetermined random order. Participants sat at 50 cm from the screen. Before the test, patients were first dark adapted and performed a brief threshold estimate. For each spatial frequency, the grating was presented continuously with an increasing contrast. The patient had to press a response key as soon as he saw the stimulus. The contrast value so obtained was then used to set the initial contrast of the grating in the real threshold estimate. Thresholds were obtained for each spatial frequency using an estimation procedure described by Levitt [26], varying the contrast of the grating from trial to trial based on the subject’s response. At each trial, stimulus was displayed on the screen until the subject responded. Two descending staircases were run, randomly interleaved. Within each staircase, the contrast of the grating decreased between trials for a ‘Yes (I saw something)’ response and increased for a ‘No (I did not see something)’ response. Stimulus contrast was changed in steps of 1% at the start of each assessment until the first response inversion, then steps were reduced to 0.1%, to allow patients to reach the threshold region in fewer trials. The advantage of the method was that subjects would quickly reach a 50% detection rate. Threshold estimate stopped after ten response inversions (threshold was defined as the mean contrast of the last ten trials). The sensitivity to contrast (defined as the opposite of contrast threshold) was reported on a diagram in logarithmic units (log) according to spatial frequencies, corresponding to the contrast sensitivity function (CSF). The perceptive component: contour-based object identification [27] This test investigated perceptual closure through identification thresholds of incomplete outline drawings of common objects (i.e. a bottle, a boat, a T-shirt, etc.). Ten objects with fragmented contours were presented to the subject in random order. The participants had to say the name of the object presented as soon as they could. An ascending method of limits was used. Each trial started with the high level of fragmentation (5% of the contour present) for each of the ten objects. The percentage of contour was progressively increased in 5% steps per key press by the participant until identification was possible. The next object was then displayed. We evaluated the mean identification threshold for the ten objects, corresponding to the mean percentage of contour needed by the subject for correct object identification.
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The attentional component: an attentional capture paradigm [28] The participant had to detect a black square subtending 3° of visual angle and at a viewing distance of 35 cm, which served as a target. It appeared either above or below (with 4° of eccentricity) a permanent central fixation cross. The subject was instructed to locate the target square (above or below the fixation cross) by pressing one of the two response keys placed vertically in front of him/her. The interval between two targets varied randomly from 1,500 to 2,000 ms. Two lateral discs subtending 3° and centred 4° left and right of the fixation cross served as distractors and were always present. Each block comprised 100 trials. In half of them (baseline), the distractors did not move. For the other 50 trials (attentional capture), one of the lateral distractor discs moved suddenly (with a 35-pixel horizontal jitter movement) for 34 ms (speed: 14.7°/sec). Within each block, the baseline and the capture conditions were randomly presented. Participants were informed that one of the discs might move but were told to focus their attention on the target, to respond as fast as possible concerning its spatial location and to ignore the discs (i.e. the distractors). The target remained on the screen until a response was given. Performance was compared in two conditions determined by the probability of the side of motion. In one condition, the motion signal could occur with an equal probability (50%) on the left or the right of the fixation cross. In the other, the motion signal occurred only on the right (100%). In the 50% condition, the motion signal was unpredictable and thus involved attentional capture and slower response times (RTs) when designating the location of the target. In the 100% condition, the motion signal was predictable and irrelevant for the task; normally, the subjects rapidly resisted the interference and neglected the distractor. The two probability conditions (50, 100%) were presented in separate blocks of 100 trials each. Within each block, the baseline and the capture conditions were Table 2 Evaluation of vigilance and sleep: REM sleep efficacy, architecture and motor characteristics
PDSS Epworth Sleep Scale Sleep latency (min) REM sleep latency (min)
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Statistical analysis Considering the small sample size and the non-homogeneity of the variances, non-parametric Kruskall–Wallis tests were performed to analyse the effect of group (PD with RBD/PD without RBD/idiopathic RBD/controls) on cognitive and clinical parameters. When justified, post hoc comparisons were performed using non-parametric Mann– Whitney tests. The significance threshold was set at p \ 0.05.
Results Sleep The mean (SD) results are shown in Table 2. The group comparisons did not reveal any significant differences concerning the subjective evaluation of vigilance (ESS score) and sleep (PDSS score). There was no significant effect of group on sleep efficiency and architecture. Concerning the motor characteristics of REM sleep, patients with RBD and those without RBD differed significantly in terms of loss of atonia, since it was the criteria used to define RBD. However, PD patients with RBD and patients with idiopathic RBD did not significantly differ in terms of loss of atonia. There were no significant inter-group differences in the phasic motor characteristics of REM sleep.
P-RBD
TST (min)
PDSS Parkinson Disease Sleep Scale, TST total sleep time, SWS slow wave sleep, TA tibialis anterior
randomly presented. The order of the two blocks was randomized between participants. Response times and the cost of distraction for the RTs (moving trials–baseline trials) were computed. The whole session lasted about 10 min. All tests were administered by a neuropsychologist or a neurologist blinded to the diagnosis of RBD.
102.4 ± 4 7.2 ± 1.4 418.3 ± 21 20.8 ± 6 157.9 ± 25.2
P-NRBD 87.4 ± 9.8 10.7 ± 2. 400 ± 27.1 9.9 ± 2.3 114.1 ± 19
RBDI – 8 ± 2.8 364.8 ± 22.1 33 ± 10.9 155.6 ± 35
p Value 0.387 0.279 0.147 0.055 0.294
Deep SWS (%)
28.4 ± 3.1
26.6 ± 4.10
17.5 ± 2.6
0.074
REM sleep (%)
19.6 ± 2
20.3 ± 16.3
16.3 ± 3.1
0.113
Efficacity (%)
72.6 ± 3.6
72.6 ± 5.2
68.2 ± 2.9
0.27
Maintenance (%)
82.6 ± 3.3
81.3 ± 5.8
77 ± 3.2
0.27
Atonia loss (%)
36.1 ± 7.8
4.2 ± 1.5
35.1 ± 5.9
REM density (%)
13.2 ± 2.2
12.8 ± 2.5
10 ± 2.1
0.675
4 ± 0.8
2.6 ± 0.6
4.4 ± 0.9
0.149
4.4 ± 0.72
2.7 ± 0.4
4.3 ± 0.8
0.209
Phasic TA activity (%) Phasic submental activity (%)
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Table 3 Mean (±SD) results of the cognitive assessments P-RBD
P-NRBD
RBDI
Controls
p Value
MMSE (/30)
28.2 ± 0.4
28.2 ± 0.8
27.8 ± 0.4
29.5 ± 0.2
0.232
MDRS (/144)
137.2 ± 1.8
138.9 ± 1.2
139.2 ± 1.2
142.7 ± 0.6
0.131
Forward digit span
5.6 ± 0.3
5.7 ± 0.4
4.9 ± 0.3
6.4 ± 0.5
0.142
Backward digit span
4.6 ± 0.4
4.1 ± 0.5
3.9 ± 0.1
4.2 ± 0.4
0.8
Symbol digit modalities test (nb of symbols correctly transcoded/90 s)
40 ± 4
48.8 ± 3.2
45.1 ± 3.6
53 ± 1.3
0.152
Stroop word-colour task (interference cost index)
0.9 ± 0.16
0.73 ± 0.09
0.73 ± 0.15
0.69 ± 0.11
Letter and number sequencing task (alternation cost index)
2.6 ± 0.5
2.1 ± 0.4
3.4 ± 0.9
0.977
2 ± 0.5
0.61
16
0.064
Word list learning and recall test Number of words correctly encoded (/16)
15.4 ± 0.4
15.1 ± 0.2
15.1 ± 0.4
Number of words correctly free recalled (/48)
33.1 ± 1.5
32.3 ± 1.6
25.4 ± 1.9a,b,c
32.1 ± 0.6
0.012*
47.3 ± 0.4
46.3 ± 0.8
44.8 ± 0.8
47.1 ± 0.4
0.087
15.7 ± 2.2
15.7 ± 1.8
11.1 ± 1.8
17.7 ± 1.1d,e 0.037**
21 ± 1.3
20 ± 1.7
18.4 ± 1.5
24.7 ± 1.7
Number of words recalled (free ? reminded) (/48) Word fluency task (60 s) Number of words beginning with ‘‘P’’ Number of animal names
0.112
Number of words beginning with ‘‘T’’/’’V’’
11.7 ± 0.9
12.2 ± 1.8
10.7 ± 0.9
13.8 ± 1
0.397
Number of words beginning with ‘‘R’’/professions
10.3 ± 1.4
11.4 ± 1.4
10.1 ± 1
12.7 ± 1
0.518
Motor sequences Crossed taping test (/3)
2.9 ± 0.1
2.8 ± 0.1
Go No Go (/3)
2.2 ± 0.3
2.1 ± 0.3
2.8 ± 0.1 3
0.825 0.104
MMSE Mini Mental Status Examination, MDRS Mattis Dementia Rating Scale a
RBDI/P-RBD: p = 0.005
b
RBDI/P-NRBD: p = 0.003
c
RBDI/controls: p = 0.013 Controls/P-RBD: p = 0.043
d e
Controls/RBDI: p = 0.014
Cognitive function
Perceptual aspects
Cognitive assessment confirmed the absence of global cognitive decline in the four groups of participants (see Table 3). We observed a significant effect of group only on the Grober and Buschke free recall of names: patients with idiopathic RBD showed poorer free recall, compared with the three other groups. There was also a significant effect of group on the number of words generated in 60 s during the verbal fluency task in the phonemic condition: performance was higher in the control group than in either of the two RBD groups (idiopathic or associated with PD).
A significant effect of group was observed for the OIT (p = 0.022). Post hoc comparisons revealed a lower OIT for (1) PD patients with RBD, compared with PD patients without RBD and with healthy controls (p = 0.026 and p = 0.011, respectively) and (2) for idiopathic RBD patients, compared with healthy controls (p = 0.034). There was no significant OIT difference between (1) PD patients with RBD and patients with idiopathic RBD or (2) between PD patients without RBD and controls (Fig. 2a). PD patients (whether with or without RBD) showed more false identifications than controls did (p = 0.001 and p = 0.009, respectively) (Fig. 2b).
Visuoperceptive function Sensorial aspects
Attentional aspects The contrast sensitivity function had the usual dome shape, with lower sensitivities for higher and lower spatial frequencies [29] (Fig. 1). We did not observe a significant effect of group on any of the spatial frequencies tested.
In the attentional capture evaluation, there was no significant effect of group on any of the task parameters (see Table 4).
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4
Contrast sensitivity function P-NRBD P-RBD
Contrast sensitivity median (log)
4
RBDI Controls
3 3 2 2 1 1 0 0,5
1,5
3,5
9
14
Spatial frequency (c/d) Fig. 1 Contrast sensitivity function
Discussion The present study provides the first analytical assessment of visuoperceptive disorders in patients with RBD by addressing the sensorial, perceptual and attentional components of visual information processing in four groups of non-demented patients: PD patients with and without RBD, idiopathic RBD patients and healthy controls. Our results confirm the association between RBD (whether idiopathic or secondary to PD) and visual disorders. Moreover, our data show that this impairment specifically concerns visual perception. We observed an impairment in contour-based object identification in patients with RBD (compared with those without RBD), independently of the association with PD. Visuoperceptive disorders have frequently been described in RBD (mostly in the idiopathic form). Indeed, patients with idiopathic RBD were shown to have visuoconstructive and visuospatial impairment (compared with controls) and, more generally, their cognitive profile has
Fig. 2 Mean (±SD) performance in contour-based object identification a a P-RBD versus P-NRBD: p = 0.026, b P-RBD versus controls: p = 0.011, c RBDI versus controls: p = 0.034. b d P-RBD versus controls: p = 0.001, e P-NRBD versus controls: p = 0.009
a 20 18 16 14 12 10 8 6 4 2 0
Object identification threshold (%)
b 60
ab
c
False identifications (%)
d
50
e
40 30 20 10 0
P-RBD
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some similarities with that of patients with Lewy body dementia (LBD) [8–10]. Despite the relatively large number of studies investigating visuoperceptive functions in idiopathic RBD, there have been fewer published studies of visuoperceptive function in RBD associated with PD. Sinforiani et al. [30] reported impairment of executive functions in PD patients with RBD (compared with PD patients without RBD) but no significant difference concerning visuoperceptive function. However, in Sinforiani et al.’s study, the diagnosis of RBD was not confirmed by polysomnography and the visuoperceptive tests used were quite non-specific; for example, Corsi’s block tapping test involves working memory as well as visuospatial perception. More recently, an impairment of visuospatial and visuoperceptual processing has been shown in nondemented PD patients with RBD (confirmed by polysomnography), compared with both non-demented PD patients without RBD and control subjects [12] and in line with our present findings. However, in this latter study, the visuoperceptive tests were not specific; visuospatial abilities were assessed with the Rey-Osterrieth complex figure test and the block design subtest from the Wechsler Adult Intelligence Scale III, and visuoperceptual abilities were assessed with the Bells test. According to our results, it seems that the visual information processing impairment in RBD (whether idiopathic or in PD) specifically concerns visual perception, which corresponds to recomposition of the picture’s elementary properties in order to obtain an overall, elaborate representation enabling the object and its location to be identified. Object identification is mainly performed by the ventral visual pathway (the ‘‘what’’ stream), whereas the processing of motion and spatial location is assumed by the dorsal visual stream (the ‘‘where’’ stream) [31]. Our results thus suggest an impairment of the ventral visual pathway in RBD. Indeed, contour-based object identification (which was specifically impaired here in RBD patients) requires the ability to identify an object with partially fragmented contours. It corresponds to a ‘‘perceptual closure’’ phenomenon, mainly performed by the lateral occipital
P-NRBD
RBDI
Controls
P-RBD
P-NRBD
RBDI
Controls
J Neurol (2010) 257:383–391 Table 4 Mean performance (±SD) in an attentional capture test
389
P-RBD
P-NRBD
RBDI
Controls
p Value
Attentional capture 50% distractors on the right Total RT (ms)
386.2 ± 28.7
340.8 ± 13.0
354.7 ± 25.2
325.7 ± 16.3
0.514
Right distractor cost (%)
-3.1 ± 2.3
-7.8 ± 8.5
-1.2 ± 2.2
-0.5 ± 2.1
0.730
Left distractor cost (%)
-4.7 ± 1.9
0.1 ± 1.3
-2 ± 1.9
-0.4 ± 2.2
0.257
Total RT (ms)
371.6 ± 22.5
342.5 ± 12.5
357.3 ± 27.1
328.7 ± 17.2
0.524
Right distractor cost (%)
-1.4 ± 1.6
0.5 ± 1.2
-4.6 ± 1.6
-1.2 ± 1.6
0.109
100% distractors on the right
RT response time
complex (LOC), one of the components of the ventral visual stream) [32]. Fragmented object identification also requires unimpaired retrieval of images stored in memory. It has been suggested that the perirhinal cortex (PRh), a cholinergic structure located in the medial temporal lobe (MTL), contributes to both object memory and perception [33]. Consequently, the impairment in object identification observed in RBD patients might not be related to perceptual impairment alone but could also reflect dysfunction in retrieval processing of mental images, particularly in the PRh. Further studies are needed to investigate these points more specifically. Our results also suggest that the sensory and attentional aspects of visual information processing are unaffected in RBD patients. Concerning sensory processes, we did not observe any difference between RBD and non-RBD patients in terms of contrast sensitivity. The absence of a difference in contrast sensitivity between PD and non-PD patients might appear surprising, since contrast sensitivity impairment has been well described in PD and is considered to be related to dopaminergic depletion [34, 35]. The lack of a difference in our study is probably explained by the fact that our PD patients were receiving optimal dopaminergic treatment at the time of assessment. Indeed, it has been shown that levodopa therapy can restore contrast sensitivity in PD to near-normal levels [35, 36]. Concerning attention, our results are in agreement with those of Raggi et al. [37] who studied active and passive auditory oddball paradigms and an attentional test in idiopathic RBD and controls. They did not report any significant between-group difference for event-related potential latency or amplitude. As RBD is frequently associated with parkinsonism, the involvement of dopaminergic versus non-dopaminergic pathways has regularly been addressed. Most data argue against a dopaminergic origin: (1) some PD patients never develop RBD or only do so after the appearance of parkinsonism or cognitive impairment, and RBD can occur in both treated and untreated PD patients [38]; (2) even though levodopa [39] and pramipexole [40] show some efficacy in RBD, this is mainly due to a decrease in REM
sleep time, without modifying muscle tone during REM sleep and (3) a recent study reported a preferential association of RBD with non-tremor-predominant PD [41]. In the present study, the fact that we did not observed any significant difference in visual perception between PD patients with RBD and idiopathic RBD patients or between PD patients without RBD and controls argues in favour of a non-dopaminergic cause of the disorder. It is well known that motor control during REM sleep is mainly performed by cholinergic nuclei in the brainstem, namely the sublocus coeruleus and the pedunculopontine and laterodorsal tegmental nuclei [42]. Cholinergic systems may thus be involved in the physiopathology of RBD. The question of the involvement of cholinergic systems in the visual perception impairment associated with RBD needs to be addressed in further studies. The results of the present study suggest that RBD is specifically associated with a perceptual closure impairment which does not depend on the presence of PD, suggesting a non-dopaminergic substrate for this visual disorder. However, certain limitations of the present study need to be considered. The fact that the PD patients were receiving treatment might act as a bias by enhancing their contrast sensitivity and their attentional abilities. However, the PD patients with and without RBD were matched with respect to their LED, disease duration and clinical characteristics. The likelihood that dopaminergic treatment had an influence on our results is thus quite low. The healthy control group had a longer mean educational duration than the three other groups, which limits the interpretation of our results. However, as there were no significant differences between the PD patients without RBD and the healthy controls in any of the cognitive tests, it is likely that our results are not explained by a difference in academic level.
Conclusion Our results suggest that RBD is associated with an impairment of the ventral visual pathway, irrespective of concomitant PD. Doubt can be cast on the reality of
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‘‘idiopathic’’ RBD, as this condition is always associated with subtle cognitive dysfunction (i.e. object identification impairment) that involves the occipital–temporal visual stream in particular. This object identification impairment might explain the frequent occurrence of hallucinations in RBD—particularly in LBD, where RBD and hallucinations are diagnostic criteria. Acknowledgments The authors would like to thank A. Deste´e, F. Durif, J. M. Jacquesson, P. Despretz, D. Devos, A. Degardin, A. Kreisler, E. Lerhun, C. Moreau, I. Poirot, C. Simonin, and M. Tir for their help in this study.
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