Presence Hallucinations Research Articles

Exploring the Spectrum of Visual Illusions and Other Minor Hallucinations in Patients with Parkinson's Disease in Lithuania.

Background and Objectives: Parkinson's disease (PD) is associated with various non-motor symptoms, including minor hallucinations, comprising visual illusions and presence and passage hallucinations. Despite their occurrence, even in newly diagnosed PD patients, data regarding the prevalence and characteristics of minor hallucinations, visual illusions in particular, remain limited. The aim of this study was to address this knowledge gap by assessing the prevalence of minor hallucinations in PD patients, with a focus on visual illusions. Materials and Methods: In this prospective pilot study, we enrolled 35 PD patients without dementia and 35 age- and gender-matched PD-unaffected individuals. Cognitive function was assessed using the Montreal Cognitive Assessment, clinical data were collected, and all subjects were assessed via questionnaires regarding 20 types of visual illusions and other minor hallucinations. Results: The prevalence of minor hallucinations was significantly higher among PD patients compared to controls (45.7% vs. 11.4%, p = 0.003). PD patients reported visual illusions and presence hallucinations more frequently than the controls (37.1% vs. 8.6% and 22.9% vs. 2.9%, p = 0.009 and p = 0.028, respectively), with no significant difference in passage hallucinations (20% vs. 8.6%, p = 0.306). In the PD group, the most frequently observed visual illusions were complex visual illusions, kinetopsia, and pelopsia; the latter was also the most common visual illusion in the control group. PD patients experiencing visual illusions were more likely to report presence hallucinations compared to patients without visual illusions (53.8% vs. 4.5%, p = 0.002); no significant differences in other clinical characteristics were found. Conclusions: Minor hallucinations are a common phenomenon among PD patients without dementia, with a higher prevalence than among healthy controls. Visual illusions are the most prevalent type of minor hallucinations, affecting more than a third of PD patients, with complex visual illusions, kinetopsia, and pelopsia being the most frequently reported types.

Numerosity estimation of virtual humans as a digital-robotic marker 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 (vivid sensations that another person is nearby when no one is actually present and can neither be seen nor heard) in laboratory and home-based settings. We establish that elevated numerosity estimation of virtual human agents in VR is a digital marker for experimentally induced presence hallucinations 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 presence hallucinations (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.

Minor hallucinations in Parkinson's disease with probable rapid eye movement sleep behavior disorder.

Rapid eye movement sleep behavior disorder (RBD) and minor hallucinations (MHs) are prevalent nonmotor symptoms in Parkinson's disease (PD). The purpose of this study was to explore the association of MHs in PD patients with probable RBD (pRBD). This cross-sectional study included 291 patients diagnosed with PD. Patients who scored 6 or higher on the Rapid Eye Movement Behavior Disorder (RBD) Screening Questionnaire were defined as pRBD. A comprehensive evaluation was performed for all patients, including the collection of demographic information, clinical assessment, and MH features. Among the 291 PD patients, 69 (23.7%) had pRBD. MHs were observed in 35 (50.7%) patients with pRBD, significantly higher than 29.7% in patients without RBD (p = 0.015). The main type of MHs in pRBD was presence hallucinations with variable content. Patients with pRBD and MHs tended to be older, had a longer disease duration, and were more likely to take levodopa or dopamine-receptor agonists. Besides, the pRBD with MHs group had higher scores on the Nonmotor Symptoms Questionnaire (NMS-Quest) and Hamilton Anxiety Scale (HAMA). Binary logistic regression analysis revealed that longer disease duration and higher NMS-Quest scores were associated with MHs in PD patients with pRBD. A high prevalence of MHs was observed in PD patients with pRBD. The main type of MHs in pRBD was presence hallucinations. MHs in PD with RBD are mainly associated with disease duration and severity of nonmotor symptoms. These findings provide new insights into the interaction between MHs and RBD.

Psychosis in Parkinson’s Disease and Current Management Trends- an Updated Review of Literature

As a neurodegenerative disorder, Parkinson’s disease (PD) is characterized by a combination of premotor, motor, and nonmotor symptoms. PD is commonly accompanied by psychosis, which is one of the commonest symptoms in the long run. As a result of Parkinson’s disease psychosis (PDP), symptoms can range from minor consequences of the disease (illusions, passage hallucinations, and presence hallucinations), to visual and nonvisual hallucinations and delusions. PDP is associated with a reduction in function and a reduction in quality of life as well. It is commonly believed that PDP is related to economic burden, and it has a significant impact on the utilization of long-term care services. The main focus should be on diagnosing, classifying, and managing PDP in an appropriate manner. As a first step in the management of PDP patients, the emphasis should be on identifying and treating any contributing medical factors, reducing or discontinuing medications that could cause or worsen psychosis, as well as nonpharmacological strategies and considering acetylcholinesterase inhibitors for treatment when dementia is present. A number of medications are being considered for use in PDP, including pimavanserin, quetiapine, and clozapine. The purpose of the current review is to provide a comprehensive understanding of the disorder in the general population with PD, including epidemiology, psychotic symptoms, risk factors, triggers, neuro-signaling pathways, diagnosis, and treatment of PDP.

Psychosis in Parkinson’s disease: a clinical biomarker of disease stage and prognosis

IntroductionParkinson’s disease (PD) is a neurodegenerative disorder characterized by motor and nonmotor symptoms, the latter contributing significantly to morbidity, mortality, nursing home placement and quality of life.ObjectivesWe present a literature review about the impact of psychosis on PD’s prognosis.MethodsA literature review is performed on PUBMED, using the next keywords: "Parkinson’s disease”, “psychosis” and “prognosis”. We focused on data from systematic reviews, clinical trials and meta-analysis published in English on last 10 years.ResultsPsychosis is a common feature of Parkinson’s disease, occurring in up to 30% of PD patients treated chronically with antiparkinsonian drugs. Visual hallucinations are the most common psychotic symptom observed, delusions being considerably less common and affecting only 5% of treated patients.Positive symptoms in PD vary across its course: early in the disease, passage hallucinations, illusions and presence hallucinations occur; later, complete visual hallucinations, initially with good insight, then without insight.Psychosis spectrum symptoms in early PD predict a decline in cognitive function at 2 years, especially visual hallucinations. There is an association between visual hallucinations and the subsequent emergence of dementia.ConclusionsCurrent evidence highlights the role of PD psychosis as a clinical biomarker of disease stage, distribution and future progression. Early recognition and treatment of psychotic symptoms improves disease’s outcomes.Disclosure of InterestNone Declared

Phantom Boarder Relates to Experimentally-Induced Presence Hallucinations in Parkinson's Disease.

Phantom boarder (PB) is the sensation that someone uninvited is in the patient's home despite evidence to the contrary. It is mostly reported by patients with neurodegenerative disorders such as Alzheimer's disease, dementia with Lewy bodies or Parkinson's disease (PD). Presence hallucination (PH) is frequent in neurodegenerative disease, shares several aspects with PB, and is the sensation that someone is nearby, behind or next to the patient (when nobody is actually there). Recent work developed a sensorimotor method to robotically induce PH (robot-induced PH, riPH) and demonstrated that a subgroup of PD patients showed abnormal sensitivity for riPH. We investigated if PD patients with PB (PD-PB) would (1) show elevated sensitivity for riPH that (2) is comparable to that of patients reporting PH, but not PB (PD-PH). We studied the sensitivity of non-demented PD patients in a sensorimotor stimulation paradigm, during which three groups of patients (PD-PB; PD-PH; PD patients without hallucinations, PD-nPH) were exposed to different conditions of conflicting sensorimotor stimulation. We show that PD-PB and PD-PH groups had a higher sensitivity to riPH (compared to PD-nPH). PD-PB and PD-PH groups did not differ in riPH sensitivity. Together with interview data, these behavioral data on riPH show that PB is associated with PH, suggesting that both share some underlying brain mechanisms, although interview data also revealed phenomenological differences. Because PD-PB patients did not suffer from dementia nor delusions, we argue that these shared mechanisms are of perceptual-hallucinatory nature, involving sensorimotor signals and their integration.

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

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.

Cogno-Vest: A Torso-Worn, Force Display to Experimentally Induce Specific Hallucinations and Related Bodily Sensations

Recent advances in virtual reality and robotic technologies have allowed researchers to explore the mechanisms underlying bodily aspects of self-consciousness which are largely attributed to the multisensory and sensorimotor processing of bodily signals (bodily self-consciousness, BSC). One key contribution to BSC, that is, currently poorly addressed due to the lack of a wearable solution, concerns realistic collision sensations on the torso. Here, we introduce and validate a proof-of-concept prototype of the torso-worn force display, the Cogno-vest, that provides mechanical touch on the user’s back in a sensorimotor perception experiment. In a first empirical study, we characterized human finger poking ( <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$N=28$ </tex-math></inline-formula> ). In order to match these poking characteristics and meet the wearability criteria, we used bidirectional, push–pull solenoids as a force actuator in the Cogno-vest. Subsequently, and based on an iterative design procedure, a body-conforming, unisex, torso-worn force display was prototyped. Finally, we conducted a behavioral study that investigated BSC in 25 healthy participants by introducing conflicting sensorimotor signals between their hands and torso (back). Using the final reiteration of the Cogno-vest, we successfully replicated previous findings on illusory states of BSC, characterized by presence hallucinations (PH) and passivity symptoms, and achieved higher illusion ratings compared to static conditions used in prior studies.

Minor hallucinations in isolated rapid eye movement sleep behavior disorder indicative of early phenoconversion: A preliminary study.

Minor hallucinations (MH) are psychotic symptoms that can occur anywhere between prodromal to early Parkinson's disease and after onset of motor problems. MH include visual illusions, presence hallucinations, and passage hallucinations. Isolated rapid eye movement sleep behavior disorder (RBD) is a harbinger of neurodegenerative diseases. We conducted a retrospective cohort study to investigate the clinical characteristics of isolated RBD with MH and the risk of phenoconversion. We retrospectively analyzed the data of 36 patients with isolated RBD (four females; median age, 75.0years). We defined cases reporting at least one minor hallucination as RBD with MH. Demographic data and cognitive function were compared between patients with and without MH, and Cox proportional hazards models estimated the risk of phenoconversion. We included 10 (27.8%) patients with MH and 26 (72.2%) without MH. Patients with MH were older, had less dopamine transporter accumulation, more severe autonomic dysfunction, more depressive symptoms, and lower verbal fluency and symbol coding test scores than patients without MH. After follow-up (median, 2.50years), 13.9% (5/36) of all patients developed phenoconversion (Parkinson's disease, two patients; dementia with Lewy bodies, three patients). The rate of phenoconversion was significantly higher in patients with MH (40.0% vs. 3.8%, p=.005). The Cox proportional hazards model adjusted for age, sex, and disease duration revealed that MH was a significant risk factor for phenoconversion (hazard ratio, 14.72; 95% confidence interval, 1.35-160.5). Minor hallucinations may be utilized as early clinical markers for prodromal estimation of neurodegenerative diseases.

Presence Hallucinations during Locomotion in Patients with Parkinson's Disease.

The presence hallucination (PH) is the sensation that somebody is nearby when no one is actually there. Affecting up to 60% of patients with Parkinson's disease (PD) and occurring early, PHs are clinically relevant for indicating potential negative clinical outcome.1-3 Recently, we have induced PHs safely in patients with PD by generating sensorimotor conflicts while patients repeatedly actuated a robotic device providing tactile feedback.4 Patients with symptomatic PHs were more sensitive to such sensorimotor stimulation than those without. We also identified abnormal sensorimotor processes predictive for the occurrence of PHs. Here, we describe the case of two patients with PD who reported PHs after PD onset only when they were involved in repetitive locomotor activities in daily life—clinical evidence in favor of the importance of sensorimotor signals in PHs in PD, compatible with repetitive robotic sensorimotor stimulation inducing PH in PD.4 A 73-year old patient experienced PHs repeatedly, but only when walking outside his home. PHs are frequent and enduring, occurring several times per week: “I'm walking, then I feel that someone is just behind me, a bit on my right, wanting to overtake me, bending over my shoulder. This person seems to walk faster than me, just two steps behind. I stop quickly, and move sideways for this person to pass, but when I look behind, there's no one”. The patient also described passage hallucinations2 and somatosensory hallucinations, but all as occurring outside locomotion periods. Another 79-year old patient experienced two distinct PHs, one positive (guardian angel) and one negative PH, occurring independently from each other several times per month, only during walking. The patient has the impression of someone behind her, close (1 m), on the right side, next to her shoulder, as if someone is “catching up” with her. The positive PH lasts for a few seconds only, the negative PH somewhat longer. The patient would step sideways to let the “person” pass but there is no one. Passage hallucinations and visual illusions occur occasionally, but always outside locomotion periods. The repeated occurrence of PHs during locomotion in these two patients, and not in other situations, suggests that sensorimotor processing related to gait plays a functional role in PH. We argue that for some patients with PD, locomotion—a highly procedural motor activity associated with tactile and proprioceptive feedback—facilitates PHs by interfering with sensorimotor processes.4 A widespread network including cerebellum, cortical and sub-cortical structures is involved in locomotion and integration of related sensorimotor signals, for which the role of the basal ganglia has particularly been emphasized.5 Partly similar brain regions were recruited in robot-induced PHs,4 suggesting a neural overlap between gait control and PHs. We note that both patients did not suffer from dementia, nor delusions (Table 1). PHs were unrelated to recent changes in medication. Future research in patients with PD investigating the impact of ongoing locomotor activity on altered sensory perceptions is needed and may reveal that PHs during locomotion are more frequent than commonly thought. The authors are grateful to the two patients for their time and for sharing their subjective experience of hallucinations with us. We also thank Prof. Paul Krack, Prof. Ghika, Dr. Benoît Wicki, Dr. Fosco Bernasconi and Dr. Oliver A. Kannape for their review and critique of the manuscript. (1) Research project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript Preparation: A. Writing of the first draft, B. Review and Critique. J.P: 1A, 1B, 1C, 3A. H.D: 1B, 2C, 3B. J.H: 1C, 3B. P.B: 1C, 3B. O.B: 1A, 3A, 3B. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. The two patients were recruited in Switzerland from La Tour Hospital (Geneva) and Geneva University Hospital and were identified in the setting of an ongoing study on hallucinations in PD. The patients gave written informed consent prior to participating in the study approved by the local ethics committee of the Commission cantonale d'éthique de la recherche (CCER) of Geneva (protocol n° 2019–02275). The present observational report is part of a larger research project investigating hallucinations in Parkinson's disease. This project was supported by two generous donors advised by CARIGEST SA, the first one wishing to remain anonymous and second one being Fondazione Teofilo Rossi di Montelera e di Premuda; Bertarelli Foundation; Swiss National Science Foundation [grant number FNS 320030_188798], Parkinson Schweiz Foundation ; Empiris foundation (grant number 532305) and Novartis Foundation [grant number 20A054]. The authors report no conflict of interest. The authors declare that there are no additional disclosures to report.

Robot-induced hallucinations in Parkinson's disease depend on altered sensorimotor processing in fronto-temporal network.

Hallucinations in Parkinson's disease (PD) are disturbing and frequent non-motor symptoms and constitute a major risk factor for psychosis and dementia. We report a robotics-based approach applying conflicting sensorimotor stimulation, enabling the induction of presence hallucinations (PHs) and the characterization of a subgroup of patients with PD with enhanced sensitivity for conflicting sensorimotor stimulation and robot-induced PH. We next identify the fronto-temporal network of PH by combining MR-compatible robotics (and sensorimotor stimulation in healthy participants) and lesion network mapping (neurological patients without PD). This PH-network was selectively disrupted in an additional and independent cohort of patients with PD, predicted the presence of symptomatic PH, and associated with cognitive decline. These robotics-neuroimaging findings extend existing sensorimotor hallucination models to PD and reveal the pathological cortical sensorimotor processes of PH in PD, potentially indicating a more severe form of PD that has been associated with psychosis and cognitive decline.

Fronto-Temporal Disconnection Within the Presence Hallucination Network in Psychotic Patients With Passivity Experiences.

Psychosis, characterized by hallucinations and delusions, is a common feature of psychiatric disease, especially schizophrenia. One prominent theory posits that psychosis is driven by abnormal sensorimotor predictions leading to the misattribution of self-related events. This misattribution has been linked to passivity experiences (PE), such as loss of agency and, more recently, to presence hallucinations (PH), defined as the conscious experience of the presence of an alien agent while no person is actually present. PH has been observed in schizophrenia, Parkinson’s disease, and neurological patients with brain lesions and, recently, the brain mechanisms of PH (PH-network) have been determined comprising bilateral posterior middle temporal gyrus (pMTG), inferior frontal gyrus (IFG), and ventral premotor cortex (vPMC). Given that the experience of an alien agent is a common feature of PE, we here analyzed the functional connectivity within the PH-network in psychotic patients with (N = 39) vs without PE (N = 26). We observed reduced fronto-temporal functional connectivity in patients with PE compared to patients without PE between the right pMTG and the right and left IFG of the PH-network. Moreover, when seeding from these altered regions, we observed specific alterations with brain regions commonly linked to auditory-verbal hallucinations (such as Heschl’s gyrus). The present connectivity findings within the PH-network extend the disconnection hypothesis for hallucinations to the specific case of PH and associates the PH-network with key brain regions for frequent psychotic symptoms such as auditory-verbal hallucinations, showing that PH are relevant to the study of the brain mechanisms of psychosis and PE.

“Men Fear Most What They Cannot See.” sleep paralysis “Ghost Intruders” and faceless “Shadow-People”—The role of the right hemisphere and economizing nature of vision

Sleep paralysis is a curious condition where the paralyzed person may hallucinate terrifying ghosts. These hypnogogic and hypnopompic visions are common worldwide. They often entail seeing and sensing shadow beings; although hallucinating full-fledged figures (e.g., cat-like creatures and witches) are not uncommon. In this paper, I propose a neuroscientific account (building on previous work) for why people see ghosts during sleep paralysis and why these tend to manifest as faceless shadows. This novel venture considers the distinct computational styles of the right and left hemisphere and their functional specializations vis-à-vis florid intruder hallucinations and out-of-body experiences (OBEs) during these dream-like states. Additionally, I provide a brain-based explanation for dissociative phenomena common during sleep paralysis. Specifically, I posit that these ghost hallucinations and OBEs are chiefly mediated by activity in key regions in the right hemisphere; and outline how the functional organization of the visual system (evoking concepts like surface interpolation) and its economizing nature (i.e., proclivity to minimize computational load and take short-cuts) can explain faceless humanoid-shadows and sensed presence hallucinations during sleep paralysis; and how the hypothalamus and anterior cingulate may be implicated during related dissociative states. Ultimately empirical research must shed light on the validity of this account. If this hypothesis is correct, patients with right hemisphere damage (i.e., in implicated areas) should be less likely to hallucinate ghosts during sleep paralysis; i.e., compared to those with intact hemispheres or damage to the left only. It may also be possible to temporarily disable right hemisphere functions during sleep paralysis using transcranial magnetic stimulation. Accordingly, this procedure should eradicate sleep paralysis ghost hallucinations.

Premotor and fronto-striatal mechanisms associated with presence hallucinations in dementia with Lewy bodies

Introductionpresence hallucinations (PH) are frequent in dementia with Lewy bodies (DLB), but their cortico-subcortical origin is unknown. Recent studies have defined key frontal and temporal areas contributing to the occurrence of PH (PH-network) and tested their relevance in subjects with Parkinson’s disease (PD). With the present study, we aimed at disentangling the metabolic and dopaminergic correlates of pH as well as their relation to a recently defined PH brain network in DLB. Methodsfor the present study, we included 34 DLB subjects (10 with PH (PH + ); 24 without PH (PH-)), who underwent 18F-FDG PET and 123I-FP-CIT SPECT imaging. We performed 18F-FDG PET group comparisons, as well as interregional correlation analyses using 18F-FDG PH-network regions as a seed. ResultsPH + versus PH- had reduced 18F-FDG uptake in precentral, superior frontal and parietal gyri, involving ventral premotor cortex (vPMC) of the PH-network that showed strongly reduced functional connectivity with bilateral cortical regions. 18F-FDG vPMC uptake was negatively correlated with caudate 123I-FP-CIT uptake in PH+ (p = 0.028) and interregional correlation analysis seeding from the vPMC showed widespread fronto-parietal 18F-FDG decreases in PH + . Discussionthese findings uncover the pivotal role of vPMC (involved in a PH-network) and its cortico-striatal connections in association with PH in DLB, improving our understanding of psychosis in neurodegeneration.

Factor structure and age invariance of the Cardiff Anomalous Perceptions Scale (CAPS) in healthy older and younger adults.

Although anomalous perceptual experiences are common in healthy older adults, they remain poorly characterized. In particular, it is unclear whether the phenomenology of these experiences differs between healthy older and younger adults. The current study examined similarities and differences in the factor structure of the Cardiff Anomalous Perceptions Scale (CAPS) in healthy, community-dwelling older (n = 194; Mage = 71.89, SD = 7.74, range = 52-91; 69.1% female) and younger adults (n = 421, Mage = 19.40, SD = 2.44, range = 17-34; 69.6% female; N = 615), using exploratory and confirmatory factor analysis, together with measurement invariance testing. The results found that a 2-factor correlated model comprising 23 of the original 32 CAPS items provided the best fit to the data. Further, scalar invariance was found between the two samples, indicating equivalence of the factor structure, factor loadings, and thresholds by age group. Compared with younger adults, the latent group means of older adults were also found to be equal on Factor 1, but significantly lower on Factor 2. Evidence of scalar age invariance on the CAPS suggests that this tool is valid for making comparisons between older and younger adults on two dimensions of anomalous perceptual experiences. Further, the results suggest that anomalous perceptions in the general community may be characterized by two components: anomalous body-centered self-experiences (e.g., alterations in body, touch, smell, and taste perception) and anomalous external experiences (e.g., auditory, visual, and sensed presence hallucinations); each of which may have different causes, correlates, and consequences for healthy ageing. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

S143. NEURAL MECHANISMS OF ROBOT-INDUCED HALLUCINATIONS IN HEALTHY PARTICIPANTS AND SYMPTOMATIC HALLUCINATIONS OF NEUROLOGICAL AND PSYCHIATRIC ORIGIN

BackgroundThe ability to recognize whether sensory consequences have been self-generated or externally produced is an important element of motor control and self-monitoring. Deficits in self-monitoring have been proposed to cause abnormal bodily experiences and psychotic symptoms such as hallucinations. A recent study designed a robotic system that applies sensorimotor stimulation in healthy subjects and safely induces mild presence hallucinations (PH) and passivity experiences (Blanke et al., 2014). PH are defined as the sensation that someone is close by when actually no one is present and passivity experiences are characterized by perceptions or beliefs that an external agent is controlling one’s actions, perceptions, and/or thoughts. Although, both symptoms occur in schizophrenia and Parkinson’s disease, their neural mechanisms are unknown.MethodsHere, we first investigated the neural mechanisms of PH and passivity experiences in 25 healthy subjects. We developed a new MR-compatible robotic system able to generate the aforementioned sensorimotor conflicts, while recording subjects’ brain activity using fMRI. In addition, we applied lesion network mapping to 11 neurological patients with symptomatic PH and compared both populations to find a common PH network. In a final step, we investigated the relevance of the PH network by analyzing the connectivity of the PH network in resting state fMRI data from 58 psychotic patients.ResultsWe first evaluated the regions associated with the general sensorimotor conflict, which revealed the left sensorimotor area, the left putamen, the right inferior parietal lobule and the right cerebellum. Then, we analyzed the regions that were more activated during the condition eliciting PH and passivity experiences and found the inferior frontal gyrus (IFG), the insula, the superior medial gyrus and the middle temporal gyrus (MTG). Comparison of these two networks with the symptomatic PH network in neurological patients highlighted the IFG, the MTG and the vPMc. The resting state analysis within those regions in psychotic patients revealed no global differences between the groups but a functional connectivity decrease between MTG and IFG (bilaterally) specific for psychotic patients experiencing passivity experiences.DiscussionCollectively, we showed that through the use of a robotic system generating sensorimotor conflicts, the neural correlates of induced-PH and passivity experiences can be studied in healthy subjects in a controlled manner. In addition, we found two networks associated with induced-PH and passivity experience. Of these regions, three were also recruited in patients with PH of neurological origin, forming the PH network. MTG-IFG connectivity in the PH network was altered selectively in psychotic patients with passivity experiences, revealing the relevance of the neural mechanisms of PH and passivity experiences in psychosis.

O3.2. ROBOT-INDUCED MILD HALLUCINATIONS AND PASSIVITY EXPERIENCES IN INDIVIDUALS WITH THE 22Q11.2 DELETION SYNDROME

BackgroundThe 22q11.2 deletion syndrome (22q11DS) represents one of the highest genetic risk factors for developing schizophrenia. About 30% of individuals develop symptoms like hallucinations, thought disorders, passivity symptoms or loss of agency. These symptoms could be driven by abnormal sensorimotor predictions associated with the misattribution of self-related events to external sources (Frith, 2005). We developed a robotic device altering sensorimotor processing in healthy subjects and inducing mild to moderate hallucinations (presence hallucinations - PH) and passivity experiences (Blanke et al., 2014). Using this new device and procedure, we tested the sensitivity of individuals with 22q11DS to sensorimotor conflicts provided by the robot and their proneness in experiencing robot-induced PH and related passivity experiences as compared to healthy controls.MethodsThirty-eight individuals with 22q11DS and 21 controls moved, with the hand, a robotic device placed in front of them. A second robot placed behind them reproduced their movements, thus delivering tactile feedback on their back either synchronously (0ms between the movement and the touch, sync) or asynchronously (delay of 500ms, async) (Blanke et al., 2014). Participants rated the strength of robot-induced PH, passivity experiences that they felt during robot manipulation, and control items. Occurrence and severity of clinical symptoms were assessed.ResultsSubjective ratings following robot manipulation were analysed, and age was used as covariate. In the asynch condition, participants reported significantly stronger loss of agency over their hand movements and there was a trend towards a significant interaction between group and conditions for loss of agency with control subjects experiencing more loss of agency in the asynchronous condition than 22q11DS participants. A trend for significance was also observed whereby all subjects reported stronger PH in the asynchronous condition than in the synchronous condition. No significant group effect was observed for the subjective ratings associated with the robot manipulation. For the 22q11DS group, severity scores for items of unusual thought content/delusional ideas of the Structured Interview for Prodromal Syndromes positively and significantly correlated with ratings of robot-induced PH and loss of agency in the async condition. Passivity experiences during the async condition (i.e., the subjective impression that someone else was touching their back) significantly correlated with severity scores for perceptual abnormalities/hallucinations items.DiscussionExperimental induction of sensorimotor conflicts caused mild altered mental states in individuals with 22q11DS as reported for controls. Both 22q11DS and control groups showed more sensitivity to the asynchronous condition during which they perceived loss of agency and passivity over their own actions, suggesting that the robotic stimulations disrupted self-other demarcation. In 22q11DS individuals, induced-PH, passivity experiences and loss of agency felt during the robot manipulation was associated to unusual thought content and abnormal perception. Taken together, our results suggest that 22q11DS is an interesting model to study the development of prodromal signs of psychosis at a very early stage before the onset of schizophrenia.

Minor Hallucinations in Alzheimer's Disease.

Hallucinations may have a broad spectrum and include so-called minor hallucinations (MHs). MHs include passage hallucinations (PHs), visual illusions, and presence hallucinations (PrHs). To determine the prevalence and characteristics of MHs in Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) patients, and to describe their potential relationship with cognition, behavioral symptoms, and use of psychoactive drugs. We have recruited prospectively and consecutively 268 subjects (90 AD mild-moderate drug-naïve patients, 78 aMCI, and 100 controls). All patients responded to a semi-structured questionnaire in order to rate psychotic phenomena. Clinical, neuropsychological, and demographic data of patients with and without MH were compared with those of age, sex, and education-matched controls. The prevalence of MHs was 21.1% (19) in AD, 12.8% (10) in aMCI, and 3% (3) in controls (p < 0.01). The most frequent MH was PrH (9.3%), followed by PH (4.9%) and illusion (0.7%). Eight (27.8%) patients had more than one MH. After adjusting for age and gender, there was a negative correlation between the presence of MHs and MMSE score (r = -0.261; p < 0.01) and a positive correlation between MHs and Neuropsychiatric Inventory score (r = 0.237; p < 0.01). We did not observe a significant relationship between presence of MHs and the consumption of psychoactive drugs (p > 0.05). We have shown that the presence of MHs in patients with newly diagnosed, untreated AD and aMCI is more than controls. MHs were correlated with other behavioral symptoms and a worse cognitive performance. We suggest the specific interrogation for MHs as a clinical feature for this population.

Comprehensive identification of delusions and olfactory, tactile, gustatory, and minor hallucinations in Parkinson's disease psychosis

IntroductionPsychotic symptoms are underdiagnosed in Parkinson's disease (PD), and there is a need for a comprehensive PD psychosis rating scale. MethodsCross-sectional analysis of 199 consecutive PD outpatients. After a routine clinical visit that included the Unified Parkinson's Disease Rating Scale (UPDRS) and Non-Motor Symptoms Questionnaire (NMS-Quest), subjects completed the enhanced Scale for the Assessment of Positive Symptoms in PD (eSAPS-PD), a structured clinical interview that included the standard SAPS-PD with additional prompts for delusions and olfactory, gustatory, and minor hallucinations. Based on the combined results of these assessments, subjects were categorized as having major psychotic symptoms (hallucinations or delusions; PDP-major), isolated minor psychotic symptoms (passage hallucinations, presence hallucinations, or illusions; PDP-minor), or no psychotic symptoms (PD-controls). ResultsWe identified 58 subjects (29%) with psychotic symptoms, including 28 (14%) with major psychotic symptoms and 30 (15%) with isolated minor psychotic symptoms. Hallucinations were present in 56 subjects (28%); most commonly visual (24%, of which 21% were minor only), followed by olfactory (6%), tactile (4%), auditory (2%), and gustatory (1%). The eSAPS-PD detected psychotic symptoms in more subjects (n = 55, 28%) than all other assessments combined (clinical visit, UPDRS part 1, and NMS-Quest) (n = 22, 11%). Compared with PD-controls, PDP-minor subjects had a higher burden of other non-motor symptoms on the Non-Motor Symptoms Scale (37 [27–51] vs. 18 [9–36], p < 0.001) and lower quality of life scores on the PD Quality of Life Questionnaire (138 [125–151] vs. 149 [137–165], p = 0.01). ConclusionThe eSAPS-PD can markedly improve detection of psychotic symptoms in PD.

Parkinson's disease psychosis: presentation, diagnosis and management.

Parkinson's disease is a neurodegenerative disorder characterized by motor and nonmotor symptoms. Psychosis is a common feature of Parkinson's disease. Parkinson's disease psychosis (PDP) encompasses minor phenomena (illusions, passage hallucinations and presence hallucinations), visual and nonvisual hallucinations and delusions. PDP is associated with reduced function and quality of life. The initial management approach should focus on identification and treatment of any contributory medical factors, reduction or discontinuation of medications with potential to induce or worsen psychosis, nonpharmacological strategies and consideration of acetylcholinesterase inhibitor treatment in the setting of dementia. Pimavanserin, quetiapine and clozapine may all be considered for use in PDP. In this review, we discuss the presentation, diagnosis and management of PDP.