Digital-robotic markers for hallucinations in Parkinson’s disease

Hallucinations are frequent non-motor symptoms in Parkinson’s disease (PD) associated with dementia and higher mortality. Despite their high clinical relevance, current assessments of hallucinations are based on verbal self-reports and interviews that are limited by important biases. Here, we used virtual reality (VR), robotics, and digital online technology to quantify presence hallucination (PH) in laboratory and home-based settings. We establish that elevated numerosity estimation of digital humans in VR is a digital marker for experimentally induced PH in healthy participants, as confirmed across several control conditions and analyses. We translated the digital marker (numerosity estimation) to an online procedure that 170 PD patients carried out remotely at their homes, revealing that PD patients with disease-related PH (but not control PD patients) showed higher numerosity estimation. Numerosity estimation enables quantitative monitoring of hallucinations, is an easy-to-use unobtrusive online method, reaching people far away from medical centers, translating neuroscientific findings using robotics and VR, to patients’ homes without specific equipment or trained staff.

[1]  S. Meuth,et al.  Evidence from ClinicalTrials.gov on the growth of Digital Health Technologies in neurology trials , 2023, npj Digital Medicine.

[2]  Sungmin Han,et al.  Perspective: Present and Future of Virtual Reality for Neurological Disorders , 2022, Brain sciences.

[3]  O. Blanke,et al.  Theta oscillations and minor hallucinations in Parkinson’s disease reveal decrease in frontal lobe functions and later cognitive decline , 2022, bioRxiv.

[4]  G. Rognini,et al.  Neuroscience robotics for controlled induction and real-time assessment of hallucinations , 2022, Nature Protocols.

[5]  Houeto Jean-Luc [Parkinson's disease]. , 2022, La Revue du praticien.

[6]  Francisco Macía Varela,et al.  A Separate Reality: An Update on Place Illusion and Plausibility in Virtual Reality , 2022, Frontiers in Virtual Reality.

[7]  King Chung Ho,et al.  Virtual exam for Parkinson’s disease enables frequent and reliable remote measurements of motor function , 2022, npj Digital Medicine.

[8]  R. Arrighi,et al.  Unimpaired groupitizing in children and adolescents with dyscalculia , 2022, Scientific Reports.

[9]  Olaf Blanke,et al.  Virtual Reality platform for functional magnetic resonance imaging in ecologically valid conditions , 2021, VRST.

[10]  D. Nyholm,et al.  An updated calculator for determining levodopa-equivalent dose , 2021, Neurological Research and Practice.

[11]  Masayuki Hara,et al.  Robot-induced hallucinations in Parkinson’s disease depend on altered sensorimotor processing in fronto-temporal network , 2021, Science Translational Medicine.

[12]  Danko D. Georgiev,et al.  Virtual Reality for Neurorehabilitation and Cognitive Enhancement , 2021, Brain sciences.

[13]  Masayuki Hara,et al.  Thought consciousness and source monitoring depend on robotically controlled sensorimotor conflicts and illusory states , 2020, iScience.

[14]  J. Pearson,et al.  Hallucinations on demand: the utility of experimentally induced phenomena in hallucination research , 2020, Philosophical Transactions of the Royal Society B.

[15]  J. Kulisevsky,et al.  Minor hallucinations reflect early gray matter loss and predict subjective cognitive decline in Parkinson's disease , 2020, European journal of neurology.

[16]  David C. Burr,et al.  “Groupitizing”: a strategy for numerosity estimation , 2020, Scientific Reports.

[17]  B. Lenggenhager,et al.  Measuring perceived self-location in virtual reality , 2020, Scientific Reports.

[18]  B. Mollenhauer,et al.  Levodopa Equivalent Dose Conversion Factors: An Updated Proposal Including Opicapone and Safinamide , 2020, Movement disorders clinical practice.

[19]  Oliver Alan Kannape,et al.  Sensorimotor conflicts induce somatic passivity and louden quiet voices in healthy listeners , 2020, Schizophrenia Research.

[20]  Joonkoo Park,et al.  Attractive serial dependence between memorized stimuli , 2020, Cognition.

[21]  A. Griffa,et al.  Sensorimotor Induction of Auditory Misattribution in Early Psychosis. , 2020, Schizophrenia bulletin.

[22]  C. Demanuele,et al.  Development of digital biomarkers for resting tremor and bradykinesia using a wrist-worn wearable device , 2020, npj Digital Medicine.

[23]  Christian Herff,et al.  Monitoring Parkinson’s disease symptoms during daily life: a feasibility study , 2019, npj Parkinson's Disease.

[24]  C. Herff,et al.  Monitoring Parkinson’s disease symptoms during daily life: a feasibility study , 2019, npj Parkinson's Disease.

[25]  J. Onnela,et al.  Harnessing digital technology to predict, diagnose, monitor, and develop treatments for brain disorders , 2019, npj Digital Medicine.

[26]  Jeffrey M. Hausdorff,et al.  Is every-day walking in older adults more analogous to dual-task walking or to usual walking? Elucidating the gaps between gait performance in the lab and during 24/7 monitoring , 2019, European Review of Aging and Physical Activity.

[27]  H. Shimada,et al.  Relationship between Daily and In-laboratory Gait Speed among Healthy Community-dwelling Older Adults , 2019, Scientific Reports.

[28]  J. Kulisevsky,et al.  Disruption of the default mode network and its intrinsic functional connectivity underlies minor hallucinations in Parkinson's disease , 2018, Movement disorders : official journal of the Movement Disorder Society.

[29]  Daniel Ansari,et al.  A New Method for Calculating Individual Subitizing Ranges , 2018, J. Numer. Cogn..

[30]  A. Rizzo,et al.  Recommendations for Methodology of Virtual Reality Clinical Trials in Health Care by an International Working Group: Iterative Study , 2019, JMIR mental health.

[31]  D. Aarsland,et al.  Risk factors for non-motor symptoms in Parkinson's disease , 2018, The Lancet Neurology.

[32]  Luke E. Miller,et al.  Assessing cognitive dysfunction in Parkinson's disease: An online tool to detect visuo‐perceptual deficits , 2018, Movement disorders : official journal of the Movement Disorder Society.

[33]  Per B. Brockhoff,et al.  lmerTest Package: Tests in Linear Mixed Effects Models , 2017 .

[34]  B. Rothbaum,et al.  The Use of Virtual Reality Technology in the Treatment of Anxiety and Other Psychiatric Disorders , 2017, Harvard review of psychiatry.

[35]  M. Slater,et al.  Virtual reality in the assessment, understanding, and treatment of mental health disorders , 2017, Psychological Medicine.

[36]  Daniela Berg,et al.  Advances in markers of prodromal Parkinson disease , 2016, Nature Reviews Neurology.

[37]  Gerard Llorach,et al.  Web-Based Live Speech-Driven Lip-Sync , 2016, 2016 8th International Conference on Games and Virtual Worlds for Serious Applications (VS-GAMES).

[38]  Sabarish V. Babu,et al.  A virtual experimenter to increase standardization for the investigation of placebo effects , 2016, BMC Medical Research Methodology.

[39]  Michael B. Del Rosario,et al.  Wearable pendant device monitoring using new wavelet-based methods shows daily life and laboratory gaits are different , 2016, Medical & Biological Engineering & Computing.

[40]  J. Kulisevsky,et al.  Minor hallucinations occur in drug‐naive Parkinson's disease patients, even from the premotor phase , 2016, Movement disorders : official journal of the Movement Disorder Society.

[41]  S. Ueno,et al.  Predictable Risk Factors for the Feeling of Presence in Patients with Parkinson's Disease , 2015, Movement disorders clinical practice.

[42]  T. Kawada Predictors of dementia in Parkinson disease: A prospective cohort study , 2015, Neurology.

[43]  Joshua de Leeuw,et al.  jsPsych: A JavaScript library for creating behavioral experiments in a Web browser , 2014, Behavior Research Methods.

[44]  Juan Wisnivesky,et al.  Geographic accessibility to clinical trials for advanced cancer in the United States. , 2015, JAMA internal medicine.

[45]  David C. Burr,et al.  A generalized sense of number , 2014, Proceedings of the Royal Society B: Biological Sciences.

[46]  Akio Yamamoto,et al.  Neurological and Robot-Controlled Induction of an Apparition , 2014, Current Biology.

[47]  D. Bates,et al.  Fitting Linear Mixed-Effects Models Using lme4 , 2014, 1406.5823.

[48]  D. Burr,et al.  Compressive mapping of number to space reflects dynamic encoding mechanisms, not static logarithmic transform , 2014, Proceedings of the National Academy of Sciences.

[49]  M. Lana-Peixoto Complex visual hallucinations in mentally healthy people. , 2014, Arquivos de neuro-psiquiatria.

[50]  J. Kulisevsky,et al.  Neural correlates of minor hallucinations in non-demented patients with Parkinson's disease. , 2014, Parkinsonism & related disorders.

[51]  Sukhvinder S. Obhi,et al.  Intentional binding and the sense of agency: A review , 2012, Consciousness and Cognition.

[52]  Axel Cleeremans,et al.  Behavioral Priming: It's All in the Mind, but Whose Mind? , 2012, PloS one.

[53]  Akio Yamamoto,et al.  A novel approach to the manipulation of body-parts ownership using a bilateral master-slave system , 2011, 2011 IEEE/RSJ International Conference on Intelligent Robots and Systems.

[54]  G. Fénelon,et al.  Feeling of presence in Parkinson's disease , 2011, Journal of Neurology, Neurosurgery & Psychiatry.

[55]  J. Hoffman,et al.  Small subitizing range in people with Williams syndrome , 2011, Visual cognition.

[56]  C. Clarke,et al.  Systematic review of levodopa dose equivalency reporting in Parkinson's disease , 2010, Movement disorders : official journal of the Movement Disorder Society.

[57]  G. Alves,et al.  What predicts mortality in Parkinson disease? , 2010, Neurology.

[58]  S. Chaudhury Hallucinations: Clinical aspects and management , 2010, Industrial psychiatry journal.

[59]  S. Anderson,et al.  Incidence of and risk factors for cognitive impairment in an early Parkinson disease clinical trial cohort , 2009, Neurology.

[60]  G. Stebbins,et al.  Hallucinations in Parkinson disease , 2009, Nature Reviews Neurology.

[61]  O. Blanke,et al.  Spatial aspects of bodily self-consciousness , 2009, Consciousness and Cognition.

[62]  K. Gwinn‐Hardy,et al.  Diagnostic criteria for psychosis in Parkinson's disease: Report of an NINDS, NIMH work group , 2007, Movement disorders : official journal of the Movement Disorder Society.

[63]  M. Guha APA Dictionary of Psychology , 2007 .

[64]  J. Morris,et al.  Clinical phenotype of Parkinson disease dementia , 2006, Neurology.

[65]  Olaf Blanke,et al.  Induction of an illusory shadow person , 2006, Nature.

[66]  D. Aarsland,et al.  Prevalence and characteristics of dementia in Parkinson disease: an 8-year prospective study. , 2003, Archives of neurology.

[67]  D. Wegner The mind's best trick: how we experience conscious will , 2003, Trends in Cognitive Sciences.

[68]  P. Haggard,et al.  Voluntary action and conscious awareness , 2002, Nature Neuroscience.

[69]  A. David,et al.  Visual hallucinations in Parkinson's disease: a review and phenomenological survey , 2001, Journal of neurology, neurosurgery, and psychiatry.

[70]  J. Culpepper Academic Press Dictionary of Science and Technology , 2000 .

[71]  G. Fénelon,et al.  Hallucinations in Parkinson's disease: prevalence, phenomenology and risk factors. , 2000, Brain : a journal of neurology.

[72]  L M Parsons,et al.  Imagined spatial transformation of one's body. , 1987, Journal of experimental psychology. General.

[73]  L E Krueger,et al.  Perceived numerosity: A comparison of magnitude production, magnitude estimation, and discrimination judgments , 1984, Perception & psychophysics.

[74]  E. Poulton Models for biases in judging sensory magnitude. , 1979, Psychological bulletin.

[75]  Timothy D. Wilson,et al.  Telling more than we can know: Verbal reports on mental processes. , 1977 .

[76]  S M Anstis,et al.  Letter: A chart demonstrating variations in acuity with retinal position. , 1974, Vision research.

[77]  R. C. Oldfield The assessment and analysis of handedness: the Edinburgh inventory. , 1971, Neuropsychologia.

[78]  R. Shepard,et al.  Mental Rotation of Three-Dimensional Objects , 1971, Science.

[79]  J. Botwinick,et al.  Speed response as a function of perceptual difficulty and age. , 1955, Journal of gerontology.

[80]  T. Reese,et al.  The Effect of Differential Reinforcement on the Discrimination of Visual Number , 1951 .

[81]  E. L. Kaufman,et al.  The discrimination of visual number. , 1949, The American journal of psychology.

[82]  R Core Team,et al.  R: A language and environment for statistical computing. , 2014 .

[83]  Robert Rosenthal,et al.  Experimenter effects in behavioral research, Enlarged ed. , 1976 .

[84]  J. B.,et al.  The Power of Numerical Discrimination , 1871, Nature.