Clinical trial NCT03137238: Self-motion Perception in Parkinson's Disease
Official title: Optic Flow and Vestibular Sensory Integration in Self-motion Perception in Parkinson's Disease
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Parkinson Disease
Keywords: Self-motion perception
Optic flow
Vestibular system
Multisensory integration
Parkinson's disease
Lead sponsor: Sheba Medical Center
Sponsor class: OTHER_GOV
Collaborators: name: Bar-Ilan University, Israel
First posted: 2017-05-02
Enrollment: 100
Sex: ALL
Minimum age (years): 50
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: PD patients and healthy subjects.

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in multisensory integration
timeFrame: 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.
Secondary outcomes:
Other outcomes:
Locations:
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
city: Ramat Gan
country: Israel
facility: Bar Ilan University
Study officials:
affiliation: Institute of Movement Disorders, Sheba medical center, Tel-Hashomer
name: Simon Israeli-Korn, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Gonda Multidisciplinary Brain Research Center at Bar-Ilan University, Ramat-Gan
name: Adam Zaidel, PhD
role: PRINCIPAL_INVESTIGATOR
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