- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03137238
Self-motion Perception in Parkinson's Disease (SMP_PD)
Optic Flow and Vestibular Sensory Integration in Self-motion Perception in Parkinson's Disease
Parkinson's Disease as well as being a disorder of motor function also causes a wide range of non-motor disturbances many of which are involved in the prodromal stage prior to the onset of motor symptoms. Abnormal perception in the visual and in other domains is increasingly being recognized. Control of the movement of our bodies in space involves perception of self-motion which is dependent on the processing and integration of multimodality information from the kinesthetic, proprioceptive, visual (mostly optic flow) and vestibular systems. Dysfunction in this process may contribute to disturbed postural control and thus result in gait abnormalities and falls which are common as Parkinson's disease progresses, is difficult to treat and causes disability and a loss of independence.
The integration of information from different modalities ("multisensory integration") is vital for intact perception of the world. Theoretical studies, based on Bayesian statistics, have provided a framework to study multisensory-integration with predictions for an 'optimal' strategy.
Many human and animal studies have demonstrated near optimal cue-integration. Yet, while multisensory integration is an active topic of research in normal brain function, with well-established tools, it has not been studied in PD. The investigators hypothesize, based on the apparent over-dependence in PD on visual cues that PD patients will demonstrate defective multisensory integration. This can have profound effects on basic motor functions. Furthermore, based on both visual and vestibular abnormalities (described above) the basic (uni-sensory) performance may also be degraded in PD.
In this study the investigators will observe the basic (uni-sensory) and the multisensory integration of visual and vestibular perception of self-motion within the same experiment.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Parkinson's disease (PD) is classically characterized by a decline in motor function, marked by the hallmark symptoms of akinesia, bradykinesia, rigidity and tremor as well as impaired posture and balance. However, non-motor symptoms are also recently becoming recognized as a major part of the disease. Non-motor symptoms may include sleep disorders, mood disturbances, hallucinations, cognitive impairment, and various sensory and perceptual deficits. In contrast to the motor symptoms, non-motor symptoms are less observable by nature, and can therefore go unnoticed if not tested directly.
Already, early studies revealed broad visual dysfunction in PD. This includes delays in visual evoked responses and abnormalities in contrast, spatiotemporal and color sensitivity. PD patients also have altered perception of visual orientation as well as complex visual impairments. Yet, despite their visual deficits, PD patients seem to be functionally more dependent on vision, versus controls. This seems to contradict established principles of optimal sensory integration, according to which, impaired cues should be less relied upon. However, this can only be gauged within a principled framework that measures, quantifies and compares the precision of relevant perceptual cues. Namely, it is the relative reliabilities of sensory cues that should, according to schemes of optimal (Bayesian) integration, set the extent to which the cues are relied upon (related to further below).
Research has demonstrated impairments in sensory systems, other than vision, such as proprioceptive and vestibular function. Interestingly, many sensory deficits in PD may be closely associated with "classic" motor symptoms. For example: : i) dysfunctional vestibular signals may lead to impaired balance control in PD, (ii) proprioceptive deficits impair voluntary and reflexive motor commands, (iii) impairments in spatial perception may contribute to freezing of gait (FOG), and (iv) PD patients overestimate the volume of their own speech, likely reflecting perceptual deficits either by impaired sensorimotor integration or by impaired self-awareness of motor deficits. Also, higher perceptual functions, such as perception of emotion from facial expression, is impaired in parkinsonian patients. Perception of self-motion arises primarily from inertial motion (vestibular) and optic flow (visual) cues. When presented with radial expanding optic flow patterns, PD patients demonstrate altered navigational veering and altered perception of the egocentric midline as well as reduced activation in visual brain areas versus controls. However, thresholds of self-motion perception from optic flow have not yet been investigated, and will thus be measured in this study.
Vestibular abnormalities might also affect perception of self-motion in PD. Recently, Bertolini et al. (2015) found impaired tilt perception in PD, but here too, vestibular thresholds of linear self-motion perception have not been researched directly. Hence, the first aim of this study is to determine the thresholds of unisensory (visual and vestibular) perception of self-motion in PD, using a rigorous and well used paradigm of heading discrimination.
However, in addition to deficits in visual and vestibular perception of self-motion, PD patients may suffer from sub-optimal integration of these cues. Hence, the second major aim is to specifically investigate the integration of visual and vestibular cues for self-motion perception. This will be done in the Bayesian framework of multisensory integration.
The integration of information from different modalities ("multisensory integration") is vital for intact perception of the world. Theoretical studies, based on Bayesian statistics, have provided a framework to study multisensory-integration with predictions for an 'optimal' strategy. Assuming Gaussian distribution and a flat prior, optimal integration of multiple cues reduces to straight forward linear equation, according to which the multisensory percept is a weighted combination of the underlying cues. Many human and animal studies have indeed demonstrated near optimal cue-integration. Yet, while multisensory integration is an active topic of research in normal brain function, with well-established tools, it has not been studied in PD.The investigators hypothesize, based on the apparent over-dependence in PD on visual cues. PD patients might demonstrate non-optimal multisensory integration (namely overweighting of visual cues). This can have profound effects on basic function.
Adding sensory noise to a stimulus reduces its reliability. In the optic flow stimuli of self-motion through a 3D cloud of dots, reliability can be controlled by manipulating the coherence of the moving dots. For 100% coherence (no added noise), all the dots move coherently according to the direction of simulated self-motion. When noise is added, e.g. to 75% coherence, 75% of the dots move coherently according to the direction of self-motion, whereas the remaining 25% move in a random direction As coherence is decreased the visual stimulus reliability reduces. Recently the investigators showed that different clinical groups (e.g. autism) can respond differently to the addition of visual noise. Hence, as part of these experiments, the investigators will also compare visual perception in the absence and presence of added visual noise. The pathophysiology of PD is often understood to reflect increased neuronal noise (e.g. beta oscillations) hence the investigators hypothesize that external sensory noise might have a stronger effect on PD patients vs. controls (perhaps by the stimulus aggravating, rather than reducing, neuronal fluctuations in PD).
Hence, in this study the investigators have 3 main aims: i) to observe the basic (unisensory) visual and vestibular perception of self-motion in PD, ii) to observe the multisensory integration in PD patients, within the framework of Bayesian inference, and iii) to observe the effects of reducing visual reliability (the addition of visual stimulus noise) on performance in PD. All three aims will be addressed with the same experiment. All participants will come for two visits. PD patients will perform the same procedure once "on" medication and once "off" medication (the order of which will be counterbalanced between patients; determined randomly in advance). For the "off" medication condition, patients will stop taking their PD medication 12 hours before the experiments (until after the experiment). The control group will also perform the experiment twice in order to control the possible artifact of learning effects.
Study Type
Enrollment (Anticipated)
Contacts and Locations
Study Contact
- Name: Simon Israeli-Korn, Dr
- Phone Number: +972545262014
- Email: Simon.Israeli-korn@sheba.health.gov.il
Study Contact Backup
- Name: Adam Zaidel, Ph.D
- Phone Number: +972558876884
- Email: ajzaidel@gmail.com
Study Locations
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Ramat Gan, Israel, 52621
- Recruiting
- Sheba Medical Center
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Contact:
- Simon D Israeli-Korn, MD PhD
- Phone Number: 05452620014
- Email: simon.korn@gmail.com
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Ramat Gan, Israel, 5290002
- Recruiting
- Bar Ilan University
-
Contact:
- Adam J Zaidel, PhD
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- Both groups will be screened using the Montreal Cognitive Assessment (MoCA) test, and only individuals with normal cognitive function will be included in the study (above 22)
Exclusion Criteria:
- PD patients determined clinically to be at high risk of falling, indicated by scores of 3 or more on items 2.12, 2.13, 3.10, 3.11 and 3.12 of the Movement Disorder Society- Unified Parkinson's Disease Rating Scale (MDS- UPDRS).
- Participants under 18 years old
- Participants with vertigo or other active vestibular disease
Study Plan
How is the study designed?
Design Details
- Observational Models: Case-Control
- Time Perspectives: Cross-Sectional
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
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Early_PD
People with Parkinson's disease in the early stages with low doses of antiparkinsonian medication and no motor fluctuations.
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There is no therapeutic intervention.
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Advanced_PD
People with advanced Parkinson's disease with motor fluctuations.
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There is no therapeutic intervention.
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Early_controls
Healthy participants matched for age and gender to the 'Early_PD' group.
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There is no therapeutic intervention.
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Advanced_controls
Healthy participants matched for age and gender to the 'Advanced_PD' group.
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There is no therapeutic intervention.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in multisensory integration
Time Frame: All participants will come for two visits, each visit will take 1.5 - 2 hours 4 days and two weeks apart. Measurements will be taken in a continuous fashion during these visits only.
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Psychometric plot will be defined as the proportion of rightward choices as a function of heading angle and calculated by fitting the data with a cumulative Gaussian distribution function.
Separate psychometric functions will construct for visual, vestibular, and combined cues.
The psychophysical threshold and point of subjective equality will be the SD (σ) and mean (μ), respectively, deduced from the fitted distribution function.
We will compare the actual weights patients gave to each cue to the predicted one, and thus will be able to study if their integration was optimal, compere to healthy participants.
No change is expected to occur for control group.
For the PD group, there may be an effect of antiparkinsonian medications, hence PD participants will be tested once after taking the regular antiparkinsonian medications and once after a 12 hour period of not taking any antiparkinsonian medication.
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All participants will come for two visits, each visit will take 1.5 - 2 hours 4 days and two weeks apart. Measurements will be taken in a continuous fashion during these visits only.
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Simon Israeli-Korn, Dr, Institute of Movement Disorders, Sheba medical center, Tel-Hashomer
- Principal Investigator: Adam Zaidel, PhD, Gonda Multidisciplinary Brain Research Center at Bar-Ilan University, Ramat-Gan
Publications and helpful links
General Publications
- Postuma RB, Berg D, Stern M, Poewe W, Olanow CW, Oertel W, Obeso J, Marek K, Litvan I, Lang AE, Halliday G, Goetz CG, Gasser T, Dubois B, Chan P, Bloem BR, Adler CH, Deuschl G. MDS clinical diagnostic criteria for Parkinson's disease. Mov Disord. 2015 Oct;30(12):1591-601. doi: 10.1002/mds.26424.
- Almeida QJ, Lebold CA. Freezing of gait in Parkinson's disease: a perceptual cause for a motor impairment? J Neurol Neurosurg Psychiatry. 2010 May;81(5):513-8. doi: 10.1136/jnnp.2008.160580. Epub 2009 Sep 15.
- Azulay JP, Mesure S, Amblard B, Pouget J. Increased visual dependence in Parkinson's disease. Percept Mot Skills. 2002 Dec;95(3 Pt 2):1106-14. doi: 10.2466/pms.2002.95.3f.1106.
- Ho AK, Bradshaw JL, Iansek T. Volume perception in parkinsonian speech. Mov Disord. 2000 Nov;15(6):1125-31. doi: 10.1002/1531-8257(200011)15:63.0.co;2-r.
- Davidsdottir S, Wagenaar R, Young D, Cronin-Golomb A. Impact of optic flow perception and egocentric coordinates on veering in Parkinson's disease. Brain. 2008 Nov;131(Pt 11):2882-93. doi: 10.1093/brain/awn237. Epub 2008 Oct 28.
- Fetsch CR, Turner AH, DeAngelis GC, Angelaki DE. Dynamic reweighting of visual and vestibular cues during self-motion perception. J Neurosci. 2009 Dec 9;29(49):15601-12. doi: 10.1523/JNEUROSCI.2574-09.2009.
- Gu Y, Angelaki DE, Deangelis GC. Neural correlates of multisensory cue integration in macaque MSTd. Nat Neurosci. 2008 Oct;11(10):1201-10. doi: 10.1038/nn.2191. Epub 2008 Sep 7.
- Gullett JM, Price CC, Nguyen P, Okun MS, Bauer RM, Bowers D. Reliability of three Benton Judgment of Line Orientation short forms in idiopathic Parkinson's disease. Clin Neuropsychol. 2013;27(7):1167-78. doi: 10.1080/13854046.2013.827744. Epub 2013 Aug 19.
- Zaidel A, Goin-Kochel RP, Angelaki DE. Self-motion perception in autism is compromised by visual noise but integrated optimally across multiple senses. Proc Natl Acad Sci U S A. 2015 May 19;112(20):6461-6. doi: 10.1073/pnas.1506582112. Epub 2015 May 4.
- Zaidel A, Spivak A, Grieb B, Bergman H, Israel Z. Subthalamic span of beta oscillations predicts deep brain stimulation efficacy for patients with Parkinson's disease. Brain. 2010 Jul;133(Pt 7):2007-21. doi: 10.1093/brain/awq144. Epub 2010 Jun 9.
- Weil RS, Schrag AE, Warren JD, Crutch SJ, Lees AJ, Morris HR. Visual dysfunction in Parkinson's disease. Brain. 2016 Nov 1;139(11):2827-2843. doi: 10.1093/brain/aww175.
- Montse A, Pere V, Carme J, Francesc V, Eduardo T. Visuospatial deficits in Parkinson's disease assessed by judgment of line orientation test: error analyses and practice effects. J Clin Exp Neuropsychol. 2001 Oct;23(5):592-8. doi: 10.1076/jcen.23.5.592.1248.
- Morgan ML, Deangelis GC, Angelaki DE. Multisensory integration in macaque visual cortex depends on cue reliability. Neuron. 2008 Aug 28;59(4):662-73. doi: 10.1016/j.neuron.2008.06.024.
- Stein BE, Stanford TR. Multisensory integration: current issues from the perspective of the single neuron. Nat Rev Neurosci. 2008 Apr;9(4):255-66. doi: 10.1038/nrn2331. Erratum In: Nat Rev Neurosci.2008 May;9(5):406.
- Revonsuo A, Portin R, Koivikko L, Rinne JO, Rinne UK. Slowing of information processing in Parkinson's disease. Brain Cogn. 1993 Jan;21(1):87-110. doi: 10.1006/brcg.1993.1007.
- Sprengelmeyer R, Young AW, Mahn K, Schroeder U, Woitalla D, Buttner T, Kuhn W, Przuntek H. Facial expression recognition in people with medicated and unmedicated Parkinson's disease. Neuropsychologia. 2003;41(8):1047-57. doi: 10.1016/s0028-3932(02)00295-6. Erratum In: Neuropsychologia. 2003;41(12):1712-3.
- van der Hoorn A, Renken RJ, Leenders KL, de Jong BM. Parkinson-related changes of activation in visuomotor brain regions during perceived forward self-motion. PLoS One. 2014 Apr 22;9(4):e95861. doi: 10.1371/journal.pone.0095861. eCollection 2014.
- Ricciardi L, Visco-Comandini F, Erro R, Morgante F, Bologna M, Fasano A, Ricciardi D, Edwards MJ, Kilner J. Facial Emotion Recognition and Expression in Parkinson's Disease: An Emotional Mirror Mechanism? PLoS One. 2017 Jan 9;12(1):e0169110. doi: 10.1371/journal.pone.0169110. eCollection 2017.
- Knill DC, Pouget A. The Bayesian brain: the role of uncertainty in neural coding and computation. Trends Neurosci. 2004 Dec;27(12):712-9. doi: 10.1016/j.tins.2004.10.007.
- Konczak J, Corcos DM, Horak F, Poizner H, Shapiro M, Tuite P, Volkmann J, Maschke M. Proprioception and motor control in Parkinson's disease. J Mot Behav. 2009 Nov;41(6):543-52. doi: 10.3200/35-09-002.
- Bertolini G, Wicki A, Baumann CR, Straumann D, Palla A. Impaired tilt perception in Parkinson's disease: a central vestibular integration failure. PLoS One. 2015 Apr 15;10(4):e0124253. doi: 10.1371/journal.pone.0124253. eCollection 2015.
- Bodis-Wollner I, Yahr MD. Measurements of visual evoked potentials in Parkinson's disease. Brain. 1978 Dec;101(4):661-71. doi: 10.1093/brain/101.4.661.
- Bodis-Wollner I, Marx MS, Mitra S, Bobak P, Mylin L, Yahr M. Visual dysfunction in Parkinson's disease. Loss in spatiotemporal contrast sensitivity. Brain. 1987 Dec;110 ( Pt 6):1675-98. doi: 10.1093/brain/110.6.1675.
- Fushiki H, Kobayashi K, Asai M, Watanabe Y. Influence of visually induced self-motion on postural stability. Acta Otolaryngol. 2005 Jan;125(1):60-4. doi: 10.1080/00016480410015794.
- Maier F, Prigatano GP, Kalbe E, Barbe MT, Eggers C, Lewis CJ, Burns RS, Morrone-Strupinsky J, Moguel-Cobos G, Fink GR, Timmermann L. Impaired self-awareness of motor deficits in Parkinson's disease: association with motor asymmetry and motor phenotypes. Mov Disord. 2012 Sep 15;27(11):1443-7. doi: 10.1002/mds.25079. Epub 2012 Jun 18.
- Clark JP, Adams SG, Dykstra AD, Moodie S, Jog M. Loudness perception and speech intensity control in Parkinson's disease. J Commun Disord. 2014 Sep-Oct;51:1-12. doi: 10.1016/j.jcomdis.2014.08.001. Epub 2014 Aug 23.
- Carandini M, Churchland AK. Probing perceptual decisions in rodents. Nat Neurosci. 2013 Jul;16(7):824-31. doi: 10.1038/nn.3410. Epub 2013 Jun 25.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- SHEBA-16-3707-SDIK-CTIL
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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