Neuroscience robotics for controlled induction and real-time assessment of hallucinations

ABSTRACT Although hallucinations are important and frequent symptoms in major psychiatric and neurological diseases, little is known about their brain mechanisms. Hallucinations are

unpredictable and private experiences, making their investigation, quantification and assessment highly challenging. A major shortcoming in hallucination research is the absence of methods

able to induce specific and short-lasting hallucinations, which resemble clinical hallucinations, can be elicited repeatedly and vary across experimental conditions. By integrating clinical

observations and recent advances in cognitive neuroscience with robotics, we have designed a novel device and sensorimotor method able to repeatedly induce a specific, clinically relevant

hallucination: presence hallucination. Presence hallucinations are induced by applying specific conflicting (spatiotemporal) sensorimotor stimulation including an upper extremity and the

torso of the participant. Another, MRI-compatible, robotic device using similar sensorimotor stimulation permitted the identification of the brain mechanisms of these hallucinations.

Enabling the identification of behavioral and a frontotemporal neural biomarkers of hallucinations, under fully controlled experimental conditions and in real-time, this method can be

applied in healthy participants as well as patients with schizophrenia, neurodegenerative disease or other hallucinations. The execution of these protocols requires intermediate-level skills

in cognitive neuroscience and MRI processing, as well as minimal coding experience to control the robotic device. These protocols take ~3 h to be completed. Access through your institution

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MODULATES INDUCED HALLUCINATIONS AND UNDERLYING BRAIN MECHANISMS Article Open access 11 September 2024 NUMEROSITY ESTIMATION OF VIRTUAL HUMANS AS A DIGITAL-ROBOTIC MARKER FOR HALLUCINATIONS

IN PARKINSON’S DISEASE Article Open access 12 March 2024 PREDICTING THE BODILY SELF IN SPACE AND TIME Article Open access 27 June 2024 DATA AVAILABILITY MRI data are available on zenodo.org

(https://zenodo.org/record/4423384#.YkKyHDWxVmN). Behavioral data can be found on GitLab (https://gitlab.epfl.ch/fbernasc/np-p210507a.git). CODE AVAILABILITY The codes to control the robots

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_Neuroimage_ 59, 2142–2154 (2012). Article  PubMed  Google Scholar  Download references ACKNOWLEDGEMENTS This research was supported by two generous donors advised by CARIGEST SA (Fondazione

Teofilo Rossi di Montelera e di Premuda and a second one wishing to remain anonymous) to O.B., Parkinson Suisse to O.B, Bertarelli Novartis Foundation for Medical-Biological Research

Foundation to O.B., Empiris Foundation to O.B., Swiss National Science Foundation to O.B. Grant-in-Aid for Scientific Research (B) (19H04187) of the Japan Society for the Promotion of

Science to M.H. Grant-in-Aid for Scientific Research (A) (22H00526) of the Japan Society for the Promotion of Science to M.H. E.B. is supported by The National Center of Competence in

Research (NCCR) ‘Synapsy—The Synaptic Bases of Mental Diseases’ (# 51AU40–125759) to O.B. We thank P. Pozeg, A. Serino, S. Giedre, R. Salomon and P. Progin for their contribution to the

development of the different experimental paradigms. The authors thank the MRI Facility, Human Neuroscience Platform, Fondation Campus Biotech Geneva for providing the MRI check-list

questionnaire. AUTHOR INFORMATION Author notes * These authors contributed equally: Fosco Bernasconi, Eva Blondiaux. AUTHORS AND AFFILIATIONS * Laboratory of Cognitive Neuroscience, Center

for Neuroprosthetics & Brain Mind Institute, Faculty of Life Sciences, Swiss Federal Institute of Technology (EPFL), Geneva, Switzerland Fosco Bernasconi, Eva Blondiaux, Giulio Rognini, 

Herberto Dhanis, Laurent Jenni, Jevita Potheegadoo & Olaf Blanke * Graduate School of Science and Engineering, Saitama University, Saitama, Japan Masayuki Hara * Department of Clinical

Neurosciences, Geneva University Hospital, Geneva, Switzerland Olaf Blanke Authors * Fosco Bernasconi View author publications You can also search for this author inPubMed Google Scholar *

Eva Blondiaux View author publications You can also search for this author inPubMed Google Scholar * Giulio Rognini View author publications You can also search for this author inPubMed 

Google Scholar * Herberto Dhanis View author publications You can also search for this author inPubMed Google Scholar * Laurent Jenni View author publications You can also search for this

author inPubMed Google Scholar * Jevita Potheegadoo View author publications You can also search for this author inPubMed Google Scholar * Masayuki Hara View author publications You can also

search for this author inPubMed Google Scholar * Olaf Blanke View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS The study and the protocol

were designed by F.B., E.B., G.R. and O.B. The robotic system and codes for controlling it were designed by M.H and J.L. H.D. developed the code for the GUI allowing to adapt the behavior of

the robots depending on the experimental conditions. J.P. adapted the questionnaire for the assessment of the illusions induced by the robotic device. The manuscript was written by F.B.,

E.B. and O.B. All authors approved the final version of the manuscript. CORRESPONDING AUTHOR Correspondence to Olaf Blanke. ETHICS DECLARATIONS COMPETING INTERESTS O.B., G.R. and M.H. are

inventors on patent US 10,286,555 B2 held by the Swiss Federal Institute (EPFL) that covers the robot-controlled induction of the feeling of a presence (presence hallucination). O.B. and

G.R. are inventors on patent US 10,349,899 B2 held by the Swiss Federal Institute (EPFL) that covers a robotic system for the prediction of hallucinations for diagnostic and therapeutic

purposes. O.B. and G.R. are co-founders and shareholders of Metaphysiks Engineering SA, a company that develops immersive technologies, including applications of the robotic induction of

presence hallucinations that are not related to the diagnosis, prognosis or treatment of Parkinson’s disease. O.B. is a member of the board and shareholder of Mindmaze SA. PEER REVIEW PEER

REVIEW INFORMATION _Nature Protocols_ thanks the anonymous reviewers for their contribution to the peer review of this work. ADDITIONAL INFORMATION PUBLISHER’S NOTE Springer Nature remains

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(2014): https://doi.org/10.1016/j.cub.2014.09.049 Serino, A. et al. _iScience_ 24, 101955 (2021): https://doi.org/10.1016/j.isci.2020.101955 Bernasconi, F. et al. _Sci. Transl. Med_. 13,

(2021): https://doi.org/10.1126/scitranslmed.abc8362 Stripeikyte, G. et al. _Schizophr. Bull_. (2021): https://doi.org/10.1093/schbul/sbab031 SUPPLEMENTARY INFORMATION SUPPLEMENTARY

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