Presence Hallucination in Parkinson's Disease

Unravelling Dysfunctional Brain Networks in Patients With Parkinson's Disease Suffering From Presence Hallucination

Investigation on how robotically mediated sensorimotor stimulation induces and triggers presence hallucinations in patients with Parkinson disease

Study Overview

• Status: Unknown
• Conditions: Parkinson Disease Psychosis
• Intervention / Treatment: Other: Brain changes triggered by PH induction in Parkinson's disease patients with presence hallucinations

Detailed Description

Parkinson's Disease (PD) is primarily known and characterized by motor symptoms such as tremor, rigidity and bradykinesia. However, a significant number of non-motor symptoms also accompany the unfolding of this disease. In fact, hallucinations are experienced by approximately 60% of the patients. The most common and amongst one of the earliest hallucinations in Parkinson's Disease, is the Presence Hallucination (PH), i.e., the strange sensation of perceiving someone behind when no one is actually there. In the present study the researchers aim at investigating the behavioural and neural mechanisms underlying symptomatic PH in PD. To do so the researchers intend to induce the PH in a repeated and controlled manner in the MRI scanner, with an extensively verified paradigm which gives rise to this sensation by means of robotically-mediated sensorimotor stimulation. This setup has in fact been shown to trigger the occurrence of symptomatic PH in these patients. The possibility to induce PH while the patient is in the MRI will allow the researchers to investigate online the brain networks associated with it.

With analysis on the fine brain connectivity changes during PH-induction, the investigators intend to pinpoint the exact mechanism behind the appearance of this hallucination in these patients, in a similar fashion to previous work with the PH-induction in healthy individuals.

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Bern, Switzerland, 3010
    • Recruiting
    • Inselspital
    • Contact: Paul Krack; Phone Number: +41 21 664 03 71; Email: paul.krack@insel.ch
    • Principal Investigator: Paul Krack
  • Geneva, Switzerland, 1202
    • Active, not recruiting
    • Campus Biotech
  • Geneva, Switzerland, 1205
    • Recruiting
    • HUG
    • Contact: Pierre Burkhard; Phone Number: +41 22 372 83 18; Email: pierre.burkhard@hcuge.ch
    • Principal Investigator: Pierre Burkhard
  • Sion, Switzerland, 1951
    • Recruiting
    • Hôpital du Valais
    • Contact: Joseph-André Ghika; Phone Number: +41 27 603 40 89; Email: joseph-andre.ghika@hopitalvs.ch
    • Principal Investigator: Joseph-André Ghika

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosed with Parkinson's disease
• Able to understand instructions and provide informed consent.
• Native speaking language of experimental site (or acquisition of language of experimental site before 6 years old).
• Montreal Cognitive Assessment (Nasreddine & Patel, 2016) with score ≥ 22.
• Able to manipulate the robotic device.

Exclusion Criteria:

• Neurological comorbidities other than Parkinson's disease (e.g. Alzheimer's disease, vascular dementia, multiple sclerosis, stroke, traumatic brain injury, epilepsy, chronic migraine, etc.)
• History or current condition of substance abuse and/or dependence (e.g., alcohol, drugs).
• Suffering from or diagnosed with psychiatric illnesses according to DSM-V criteria (e.g., schizophrenia, bipolar disorders, autism, personality disorders, phobia etc.).
• Family history (1st and 2nd degree) of psychiatric disorders (e.g., schizophrenia or bipolar disorders).
• Severe somatic illnesses (e.g., cancer).
• Severe tremors or physical disability preventing optimal use of robotic device.
• Participating in a pharmacological study.
• Local or general anaesthesia 30 days prior experiment
• Inability to provide informed consent (legal guardianship)
• The following are due to the MRI scanner: body weight exceeding 160kg, implanted metallic devices, foreign metallic objects, unstable angina, cardio-vascular diseases, tattoos with metallic components, external metallic objects, claustrophobia, pregnancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Brain changes triggered by PH induction in Parkinson's disease; Clinical and neuropsychological evaluations + Sensorimotor task for PH-induction

Other: Brain changes triggered by PH induction in Parkinson's disease patients with presence hallucinations; Parkinsonian patients will undergo a two distinct experimental sessions, conducted in two separate days. In day 1, they will complete a series of validated and lab-tailored clinical evaluations, alongside with semi-structured interviews. These tests are designed to assess, the extent of the movement disorder, the predominance of positive symptoms and presence hallucination, potential cognitive impairment, amongst other relevant measures, for sleep assessment, loneliness, apathy and depression. In day 2 patients will perform the described robotic manipulation task in the MRI.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
fMRI bold signal response during robotic manipulation	Analysis of changes of BOLD activity during the asynchronous condition as compared to the synchronous condition	Approximately 45 minutes during each participant's experimental session in arm 1
Sensitivity to the induction bodily illusions of Presence Hallucination, Passivity experiences, loss of agency, and control questions, through lab-tailored questionnaires (7-point Likert-scale)	Note that for the assessment of the sensitivity of each patient to the induction of the presence hallucination, passivity sensations, loss of agency, and control questions, the patients will perform two manipulations with the robotic system described in the introduction, in both the synchronous and asynchronous conditions	Approximately 5 minutes at the end of each participant's experimental session in arm 1

Collaborators and Investigators

• Sponsor: Olaf Blanke
• Collaborators: University Hospital, Geneva; University Hospital Inselspital, Berne; Centre Hospitalier Universitaire Vaudois; Hôpital du Valais
• Investigators: Principal Investigator: Olaf Blanke, Ecole Polytechnique Fédérale de Lausanne

Publications and helpful links

General Publications

• Kalia LV, Lang AE. Parkinson's disease. Lancet. 2015 Aug 29;386(9996):896-912. doi: 10.1016/S0140-6736(14)61393-3. Epub 2015 Apr 19.
• Postuma RB, Berg D. Advances in markers of prodromal Parkinson disease. Nat Rev Neurol. 2016 Oct 27;12(11):622-634. doi: 10.1038/nrneurol.2016.152.
• Wood RA, Hopkins SA, Moodley KK, Chan D. Fifty Percent Prevalence of Extracampine Hallucinations in Parkinson's Disease Patients. Front Neurol. 2015 Dec 21;6:263. doi: 10.3389/fneur.2015.00263. eCollection 2015.
• Diederich NJ, Fenelon G, Stebbins G, Goetz CG. Hallucinations in Parkinson disease. Nat Rev Neurol. 2009 Jun;5(6):331-42. doi: 10.1038/nrneurol.2009.62.
• Fenelon G, Soulas T, Cleret de Langavant L, Trinkler I, Bachoud-Levi AC. Feeling of presence in Parkinson's disease. J Neurol Neurosurg Psychiatry. 2011 Nov;82(11):1219-24. doi: 10.1136/jnnp.2010.234799. Epub 2011 May 7.
• Blanke O, Pozeg P, Hara M, Heydrich L, Serino A, Yamamoto A, Higuchi T, Salomon R, Seeck M, Landis T, Arzy S, Herbelin B, Bleuler H, Rognini G. Neurological and robot-controlled induction of an apparition. Curr Biol. 2014 Nov 17;24(22):2681-6. doi: 10.1016/j.cub.2014.09.049. Epub 2014 Nov 6.

Helpful Links

• Bernasconi F, Blondiaux E, Potheegadoo J, Stripeikyte G, ..., Blanke O (2020) sensorimotor hallucinations in Parkinson's disease

Study record dates

Study Major Dates

• Study Start (Actual): August 17, 2020
• Primary Completion (Anticipated): June 30, 2021
• Study Completion (Anticipated): June 30, 2021

Study Registration Dates

• First Submitted: July 15, 2020
• First Submitted That Met QC Criteria: October 1, 2020
• First Posted (Actual): October 8, 2020

Study Record Updates

• Last Update Posted (Actual): October 8, 2020
• Last Update Submitted That Met QC Criteria: October 1, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Parkinson; psychosis; fMRI; connectivity; hallucinations; presence hallucination
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Schizophrenia Spectrum and Other Psychotic Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Perceptual Disorders; Psychotic Disorders; Parkinson Disease; Mental Disorders; Hallucinations
• Other Study ID Numbers: PD_PH

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No