Using robotics and brain imaging, researchers have discovered an abnormality in the brains of patients with Parkinson's disease that may explain why some experience "presence hallucinations," sensing the shadowy presence of another person when nobody is there.

The study, published Wednesday in Science Translational Medicine, advances our understanding of Parkinson's disease and identifies a potential biomarker and diagnostic tool for predicting the severity of its progression, Eva Blondiaux, a cognitive neuroprosthetics researcher at the Swiss Federal Institute of Technology Lausanne in Switzerland and co-lead author of the study, told The Academic Times. "[Patients] have hallucinations that occur quite frequently, and they can be predictive of the most severe cognitive form of the disease," she explained. 

Parkinson's disease is a neurodegenerative illness that can severely impair motor and cognitive function and eventually lead to dementia. The second-leading neurodegenerative condition worldwide after Alzheimer's disease, Parkinson's is often accompanied by a number of psychiatric symptoms. About half of all Parkinson's patients experience "presence hallucinations," said Jaime Kulisevsky, scientific director at Sant Pau Hospital in Barcelona, Spain, and a co-author of the study. 

"It is very characteristic to have visual hallucinations in the sense that the person sees something that is not real," he said. "It can either be a true vision of a phenomenon — for instance, a person or animal — or a feeling of presence, that someone is at your back or passing by your side. These are two different types of hallucinations known to occur in Parkinson's disease."

Minor hallucinations can emerge during the pre-diagnostic phase of Parkinson's disease, before the onset of typical motor-function symptoms such as tremors, muscle rigidity and slow movement. The hallucinations become more severe and structured as the disease progresses, often causing patients to "lose sight of the hallucinations — they feel like this phenomenon is real and interact with their visions, like, 'Why is this boy in my room?'" Kulisevsky explained. 

The phenomenon remains poorly understood, according to the study's authors. Patients may not report hallucinations for a variety of reasons, including embarrassment, and even if they do, they aren't likely to be present with a clinician during an episode. "It's hard to study because clinicians don't always ask those questions to patients, like whether they're having hallucinations," Blondiaux said. "There's really no tool to quantify them and say how strong [hallucinations] are and how much they affect the patients." 

Seeking to objectively measure presence hallucinations in Parkinson's patients, the researchers used robotics to artificially induce the sensation of an outside presence in both a control group of healthy people and 56 patients with Parkinson's disease. Olaf Blanke, another Swiss Federal Institute of Technology researcher and co-lead author of the paper, pioneered this technique of tricking the brain into sensing "ghosts" in a 2014 study. Participants were asked to complete a task in front of themselves using their dominant hand while a robot arm traced the same movement on the back of their body a few seconds later. This technique convincingly mimics the hair-raising sense of another person's presence.  

"For the brain, it's a bit strange because, usually, what you do in your front space has consequences in front of you," Blondiaux said. "Here, the consequence is behind you — you're moving in front but getting touched on your back. What we did to induce presence hallucinations is introduce a delay between what you're doing in the front and what happens on your back. During this strange condition is where you get the impression that there is a presence behind you." 

Participants also went through the same test while their brains were scanned using magnetic resonance. This allowed the researchers to pinpoint the regions of the brain involved in presence hallucinations. The researchers found that patients who experienced hallucinations had a loss of connectivity in the frontal-temporal network of the brain. "We were able to identify a circuit that implies some frontal-temporal disconnection in the brain, explaining this phenomenon of presence hallucinations," Kulisevsky said. "This has very important implications for understanding what is happening in the brains of patients and how we can develop treatments to control or avoid patients suffering these hallucinations." 

Perhaps most significantly, this abnormality in the frontal-temporal region could predict which patients will experience the greatest cognitive decline. "There is strong evidence that hallucinations are linked to cognitive deterioration in Parkinson's disease," Kulisevsky said. "That is, the more you have them, and the more severe the hallucinations, the more cognitive impairment you're going to have." 

In the future, it's possible that severe, structured hallucinations will be identified as the main risk factor for progression from Parkinson's disease into dementia. But that is a broad conclusion that demands a far larger sample size, Blondiaux said: "This is what our lab is trying to reconfirm with a larger cohort involving many more patients, to really see the evolution of this [disease]." 

The study, "Robot-induced hallucinations in Parkinson's disease depend on altered sensoriomotor processing in fronto-temporal network," published April 28 in Science Translational Medicine, was authored by Fosco Bernasconi, Eva Blondiaux, Jevita Potheegadoo, Giedre Stripeikyte, Michela Bassolino, Matteo Franza and Giulio Rognini, Swiss Federal Institute of Technology Lausanne (EPFL); Javier Pagonabarraga, Helena Bejr-Kasem, Saul Martinez-Horta, Frederic Sampedro and Jaime Kulisevsky, Sant Pau Hospital, Autonomous University of Barcelona, Centro de Investigación en Red-Enfermedades Neurodegenerativas and Biomedical Research Institute, Spain; Michel Akselrod, EPFL and University Hospital of Lausanne; Masayuki Hara, Saitama University, Japan; Judit Horvath and Pierre R. Burkhard, Geneva University Hospitals; Stéphanie Konik, EPFL and University Hospital of Lausanne; Matthieu Bereau, Geneva University Hospitals and Besançon University Hospital; Joseph-André Ghika, Hôpital du Valais; Dimitri Van De Ville, EPFL and University of Geneva; Nathan Faivre, EPFL and Université Grenoble Alpes; Paul Krack, University Hospital and University of Bern; and Olaf Blanke, EPFL and Geneva University Hospitals.