Hallucinations In Parkinson's Disease Research Articles

Functional Brain Networks of Minor and Well-Structured Major Hallucinations in Parkinson's Disease.

Minor hallucinations (mHs) and well-structured major hallucinations (MHs) are common symptoms of Parkinson's disease (PD) psychosis. To investigate the resting-state networks (RSNs) in patients with PD without hallucinations (PD-nH), with mH (PD-mH), and with MH (PD-MH). A total of 73 patients with PD were enrolled (27 PD-nH, 23 PD-mH, and 23 PD-MH). Using seed-based functional connectivity analyses, we investigated the RSNs supposedly related to hallucinations in PD: the default mode network (DMN), executive control network (ECN), dorsal attention network (DAN), ventral attention network (VAN), and visual network (VN). We compared the cognitive function and RSN connectivity among the three groups. In addition, we performed a seed-to-seed analysis to examine the inter-network connectivity within each group using the corresponding RSN seeds. PD-MH group had lower test scores for attention and visuospatial functions compared with those in the other groups. The connectivity of the right intracalcarine cortex within the DAN was lower in the PD-MH group than in the others. The PD-mH and PD-MH groups showed higher connectivity in the left orbitofrontal cortex within DMN compared with the PD-nH group, whereas the connectivity was lower in the right middle frontal gyrus (MFG) within ECN, precuneus cortex within VAN, right middle temporal gyrus and precuneus cortex within DAN, and left MFG within VN. The PD-mH and PD-MH groups showed different inter-network connectivity between the five RSNs, especially regarding DAN connectivity. DAN dysfunction may be a key factor in the progression from mH to MH in patients with PD. © 2023 International Parkinson and Movement Disorder Society.

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.

Cerebellar correlates of visual hallucinations in Parkinson's disease and Charles Bonnet Syndrome

Hallucinations, percepts in the absence of external stimuli, are a shared feature of eye-disease (Charles Bonnet Syndrome, CBS) and Parkinson's disease (PD) thought to arise through pathophysiologically distinct mechanisms: deafferentation and attentional network dysfunction respectively. Recent studies have found an association between visual hallucinations and structural changes in the cerebellum without obvious link to either mechanism.Here, we employed Voxel Based Morphometry (VBM), optimised for the cerebellum using the Spatially Unbiased Infratentorial Template (SUIT), to characterise similarities and differences in cerebellar structure associated with visual hallucinations in PD and CBS. Grey and white matter volume (GMV & WMV) from patients with eye-disease (n = 12 hallucinators; n = 9 non-hallucinators) and PD (n = 7 hallucinators; n = 9 non-hallucinators) was examined in a 2-way ANOVA controlling for age, sex, and intracranial volume.Comparing hallucinators to controls across both groups, lower GMV was found bilaterally within cerebellar lobule VIII extending to IX/VII. GMV reductions were also found in Crus 1, greater in PD than eye-disease. Predominantly within PD, hallucination-related lower WMV was found in the medulla. No regions of increased GMV or WMV were found. A correlation was observed between brainstem WMV and lobule VIIIb GMV suggesting a functional association.Lobule VIII comprises a functional node within the Dorsal Attention Network (DAN), linking these findings to current attentional theories of hallucinations, while Crus 1 is linked to cortical visual processing. These findings provide preliminary evidence of a cerebellar contribution to hallucinations that transcends clinical conditions.

423 - Visual Hallucinations in Parkinson Disease and Dementia with Lewy Bodies: a review

Visual Hallucinations (VH) are a common psychiatric symptom of Parkinson’s Disease (PD) and Dementia with Lewy Bodies (DLB). According to the Perception-Attention Deficits Model, VH stem from impaired perceptual (bottom-up), including dorsal (DVS) and ventral visual streams (VVS), and attentional (top-down) processes, with a persistent Default Mode Network (DMN) activity and a dysfunctional imbalance of Dorsal (DAN) and Ventral Attentional Networks (VAN).We review the literature on the neurobiological underpinnings of VH in DLB and PD, concerning overlapping and different mechanisms.In DLB hallucinators, PET-scan findings of disconnection between higher and primary visual areas and dysfunctional recruitment of the VVS, corroborate other imaging and neuropathologic studies which document inferior longitudinal fasciculus damage and increased temporal lobe Lewy body (LB) pathology. The alteration of network topography is more pronounced in the DAN and DMN. The involvement of anterior cortical regions, clustering around attentional networks, is demonstrated in neuropathologic, volumetric and perfusion studies. VH severity closely correlates with anterior cingulate cortex and inferior temporal cortex hypoperfusion, structural changes in the DVS (superior parietal gyrus and precuneus) and increased diffusivity of the right thalamic projections to parieto-occipital cortices. Thalamocortical dysfunction alongside decreased cholinergic activity in reticular nucleus, which receive projections from the nucleus basalis of Meynert, seems to play a crucial role.Both DLB and demented PD hallucinators have more frontal cortical atrophy, yet greater in DLB, supporting top-down mechanisms.Regarding PD hallucinators, findings of cortical atrophy in inferior parietal lobule, cuneus, lingual lobule, and precentral gyrus correlated with hallucination scores. However, some studies did not evidence volumetric cortical differences between hallucinators and non-hallucinators. Moreover, LB are not necessarily present in hallucinators, suggesting other neuropathologic mechanisms in the genesis of VH, namely altered neurochemical circuitry. Volume loss in pedunculopontine nucleus and right-thalamus support the hypothesis of a dysfunctional cholinergic brainstem control of the cortex. PET-scan studies discovered higher 5-HT2A receptor levels in the inferolateral temporal and prefrontal cortices. A greater nigrostriatal impairment is documented in the right-caudate of hallucinators. Therefore, VH may arise from an inability to activate DAN (in which caudate is involved) and consequent faulty visuo-perceptual processing by DMN and VAN.

Genetic risk scores and hallucinations in patients with Parkinson disease.

ObjectiveWe examine the hypothesized overlap of genetic architecture for Alzheimer disease (AD), schizophrenia (SZ), and Parkinson disease (PD) through the use of polygenic risk scores (PRSs) with the occurrence of hallucinations in PD.MethodsWe used 2 population-based studies (ParkWest, Norway, and Parkinson's Environment and Gene, USA) providing us with 399 patients with PD with European ancestry and a PD diagnosis after age 55 years to assess the associations between 4 PRSs and hallucinations after 5 years of mean disease duration. Based on the existing genome-wide association study of other large consortia, 4 PRSs were created: one each using AD, SZ, and PD cohorts and another PRS for height, which served as a negative control.ResultsA higher prevalence of hallucinations was observed with each SD increase of the AD-PRS (odds ratio [OR]: 1.37, 95% confidence interval [CI]: 1.03–1.83). This effect was mainly driven by APOE (OR: 1.92, 95% CI: 1.14–3.22). In addition, a suggestive decrease and increase, respectively, in hallucination prevalence were observed with the SZ-PRS and the PD-PRS (OR: 0.77, 95% CI: 0.59–1.01; and OR: 1.29, 95% CI: 0.95–1.76, respectively). No association was observed with the height PRS.ConclusionsThese results suggest that mechanisms for hallucinations in PD may in part be driven by the same genetic architecture that leads to cognitive decline in AD, especially by APOE.

Effect of Antidepressants on Psychotic Symptoms in Parkinson Disease: A Review of Case Reports and Case Series.

The treatment of Parkinson disease (PD) psychosis remains a challenge. Only a few treatments eliciting significant relief of psychotic symptoms have passed the test of randomized controlled trials. Here, we conducted a review of the literature on the effect of antidepressants on PD psychosis. Because there is no randomized controlled trial that assessed the antipsychotic effects of antidepressants in PD, only case reports, case series, and open-label trials were available to review. Because of the scarce literature, statistical analysis could not be performed. The following antidepressants alleviated hallucinations in PD: amoxapine, citalopram, clomipramine, escitalopram, mianserin, mirtazapine, and venlafaxine. The antidepressants were generally well tolerated, with the exception of amoxapine, which exacerbated parkinsonism. Whereas the conclusions that can be drawn on the efficacy of antidepressants at reducing PD psychosis are limited because of the poor quality of the reported studies, it is encouraging to notice that there are positive anecdotal reports. Further studies are needed to confirm the potential of these drugs and also to determine if a subtype of patients or of psychotic features may be more likely to be improved by antidepressants.

Mind-wandering in Parkinson's disease hallucinations reflects primary visual and default network coupling

Visual hallucinations are an underappreciated symptom affecting the majority of patients during the natural history of Parkinson's disease. Little is known about other forms of abstract and internally generated cognition – such as mind-wandering – in this population, but emerging evidence suggests that an interplay between the brain's primary visual and default networks might play a crucial role in both internally generated imagery and hallucinations. Here, we explored the association between mind-wandering and visual hallucinations in Parkinson's disease, and their relationship with brain network coupling. We administered a validated thought-sampling task to 38 Parkinson's disease patients (18 with hallucinations; 20 without) and 40 controls, to test the hypothesis that individuals with hallucinations experience an increased frequency of mind-wandering. Group differences in the association between mind-wandering frequency and brain network coupling were also examined using resting state functional magnetic resonance imaging. Our results showed that patients with hallucinations exhibited significantly higher mind-wandering frequencies compared to non-hallucinators, who in turn had reduced levels of mind-wandering relative to controls. At the level of brain networks, inter-network connectivity and seed-to-voxel analyses identified that increased mind-wandering in the hallucinating versus non-hallucinating group was associated with greater coupling between the primary visual cortex and dorsal default network. Taken together, our results suggest a relative preservation of mind-wandering in Parkinson's disease patients who experience visual hallucinations, which is associated with increased visual cortex-default network coupling. We propose that the preservation of florid abstract and internally generated cognition in the context of the Parkinson's disease can contribute to visual hallucinations, whereas healthy individuals experience only the vivid images of the mind's eye. These findings refine current models of visual hallucinations by identifying a specific cognitive phenomenon and neural substrate consistent with the top-down influences over perception that have been implicated in hallucinations across neuropsychiatric disorders.

Minor hallucinations in Parkinson disease: A subtle symptom with major clinical implications.

Minor hallucinations in Parkinson disease: A subtle symptom with major clinical implications.

Minor hallucinations in Parkinson disease: A subtle symptom with major clinical implications.

Psychosis is one of the most debilitating complications of Parkinson disease (PD). Although research on PD psychosis has been focused on the study of well-structured visual hallucinations (VH), currently accepted National Institute of Neurological Disorders and Stroke-National Institute of Mental Health diagnostic criteria emphasize minor hallucinations (MH) as the most common psychotic phenomena in PD. The objective of this review is to comprehensively describe the clinical and research advances on the understanding of MH and to provide future directions for obtaining further insights into their potential major implications for PD management and prognosis. A PubMed search was done in November 2018 to identify articles on minor psychotic phenomena in PD. MH often precede the onset of well-structured VH and are associated with other nonmotor symptoms such as REM sleep behavior disorder and depression. The pattern of functional brain connectivity changes associated with MH involve visual-processing areas and attention control networks, which overlap with abnormalities described in patients with well-structured VH. The dysfunction of cortical networks in patients with MH may be an early indicator of a more widespread form of the disease. Although called "minor," MH may have major clinical and prognostic implications. Further research is needed to establish whether MH are associated with a higher risk of disabling psychotic complications, cognitive deterioration, or a more accelerated disease progression. Understanding the early neurobiological underpinnings of MH may provide the background for future studies to identify the progressive dysfunction of neural circuits leading to more severe forms of psychosis in PD.

Informant- and Self-Appraisals on the Psychosis and Hallucinations Questionnaire (PsycH-Q) Enhances Detection of Visual Hallucinations in Parkinson's Disease.

Clinicians vary in their ability to elicit and interpret hallucinatory symptoms in patients with Parkinson's disease (PD). There is limited evidence for informant-report measures of PD hallucinations as adjuncts to clinician-rated scales. To determine the utility of an informant version of the validated Psychosis and Hallucinations Questionnaire (PsycH-Q) for assessing the presence and severity of hallucinations in PD; and, to evaluate accuracy of clinician judgements by comparison with informant report and self-report. One hundred sixty-three PD patient-informant dyads completed self- and informant-report versions of PsycH-Q and three common questionnaire measures: Neuropsychiatric Inventory Questionnaire; Parkinson's Psychosis Questionnaire; and Scales for Outcomes in Parkinson's disease-Psychiatric Complications. We compared self-ratings and informant ratings across analogous subscales for the presence of hallucinations with clinician interview ratings on MDS-UPDRS as a diagnostic standard. There was a low level of agreement between dyads (average κ = 0.39; κ range = 0.32-0.47; P < 0.001), and patients indicated the highest prevalence of hallucinations compared to informant or clinician estimates. Clinician interview missed 32% of PsycH-Q hallucinators identified by dyads. Relative to the sample, 22 patients with exclusively clinician-appraised hallucinations had poorer overall quality of life measured by the Parkinson's Disease Questionnaire. The sole use of clinician-rated scales may underestimate prevalence of PD hallucinations, and there is room for introducing self- and informant-report tools. Nonetheless, clinician appraisals are critical in cases when informant and patient insight might be affected by the impact of illness on quality of life.

Reduced occipital GABA in Parkinson disease with visual hallucinations.

ObjectiveTo investigate the relationship between visual hallucinations in Parkinson disease (PD) and levels of γ-aminobutyric acid (GABA) in the primary visual cortex.MethodsWe utilized magnetic resonance spectroscopy to investigate occipital GABA levels in 36 participants with PD, 19 with and 17 without complex visual hallucinations, together with 20 healthy controls without hallucinations. In addition, we acquired T1-weighted MRI, whole-brain fMRI during a visual task, and diffusion tensor imaging.ResultsWe found lower GABA+/creatine in PD with visual hallucinations (0.091 ± 0.010) vs those without (0.101 ± 0.010) and controls (0.099 ± 0.010) (F2,49 = 4.5; p = 0.016). Reduced gray matter in the hallucinations group was also observed in the anterior temporal lobe. Although there were widespread reductions in white matter integrity in the visual hallucinations group, this was no longer significant after controlling for cognitive function.ConclusionsThe data suggest that reduced levels of GABA are associated with visual hallucinations in PD and implicate changes to the ventral visual stream in the genesis of visual hallucinations. Modulation of visual cortical excitability through, for example, pharmacologic intervention, may be a promising treatment avenue to explore.

Treatment of Visual Disorders in Parkinson Disease.

This article discusses visual disorders in both Parkinson disease (PD) and other Parkinsonian disorders. It is organized largely by the anatomical site of pathology and emphasizes practical treatments. Targeted treatment options include medications, surgery, occupational, and physical therapies as well as optical aids. The causes of visual complaints in Parkinson disease and other similar disorders are being more clearly identified. A new medication approved specifically to treat hallucinations in PD now is available. There is increased understanding of the important role that an ophthalmologist can play in the care of these patients. Finally, research and therapeutic development are unmet needs in accessing and treating visual complaints in PD and Parkinsonian disorders. A better understanding of Parkinson-related visual complaints and of available treatment options is important to optimize patient safety and quality of life. Vision impairment leads to difficulties in many common activities including reading, ambulating, and driving. Falls and injuries, made more likely because of impaired vision, result in an early loss of independence. Awareness of the problem, patient education, ophthalmologic care, selected therapeutics, physical therapy, and occupational therapy are crucial to maximizing quality of life in these patients.

Defining visual illusions in Parkinson's disease: Kinetopsia and object misidentification illusions

ObjectiveTo identify the phenomenological features and neural correlates of visual illusions in Parkinson's disease (PD). MethodsNinety-three patients with PD were assessed via questionnaires regarding visual illusions and behavioral symptoms, and neuropsychological tests, motor assessments and 18-F fluorodeoxyglucose-positron emission tomography (FDG-PET) were performed. The relationship between visual illusions or hallucinations and regional cerebral glucose metabolism was investigated using partial least squares (PLS) correlation and conventional mass-univariate analyses. ResultsKinetopsia, in which stationary objects are perceived as being in motion, and object misidentification illusions, in which objects are misperceived as different objects, were the most common types of visual illusions. Kinetopsia and object misidentification illusions were identified in 24 patients (25.8%) and 17 patients (18.3%), respectively. Eleven patients with kinetopsia and 9 patients with object misidentification illusions had visual hallucinations. Kinetopsia and visual hallucinations were associated with hypometabolism in the temporo-parietal cortices, whereas object misidentification illusions were associated with hypometabolism in the early visual cortex, as well as the temporo-parietal cortices. ConclusionsOur findings suggest that kinetopsia and object misidentification illusions are the most common types of visual illusions in PD. Despite the phenomenological diversity of visual illusions and hallucinations in PD, all of these symptoms are associated with dysfunction of the temporo-parietal cortices, which support visual spatial processing, rather than dysfunction of the ventral temporo-occipital cortices, which supports visual object recognition.

Characterization of diplopia in non-demented patients with Parkinson's disease

IntroductionAlthough diplopia is considered a frequent symptom of Parkinson's disease (PD), little is known about its clinical manifestation, associated mechanisms and treatment. Here we characterized binocular diplopia in non-demented PD patients in an interdisciplinary setting. MethodsPD patients were prospectively screened for diplopia, visual hallucinations, problems with spatial perception, contrast sensitivity, presence of blurred vision, and history of ophthalmological comorbidities via interview. Two groups of PD patients, one with and one without diplopia, underwent clinical and ophthalmological assessment to characterize diplopia in these patients. Clinical features were investigated using the Unified Parkinson's Disease Rating Scale and the Non-Motor Symptoms Scale. ResultsThe frequency of binocular diplopia was 29.6% (n = 37) in our cohort of 125 Parkinson's disease patients. Related mechanisms were heterogeneous including convergence insufficiency, strabismus, and motor fluctuations, as well as symptoms related to visual hallucinations. Diplopia was associated with other visual disturbances like visual hallucinations, blurred vision and problems with spatial perception. Beyond that, diplopia was found to be a predictive factor (3.2, odds ratio) for the occurrence of visual hallucinations in PD. ConclusionBinocular diplopia represents a frequent and relevant symptom in PD patients. Different subtypes should be considered due to different associated mechanisms including ophthalmic pathology and motor fluctuation, as well as intermediate to higher level visual processes. Diplopia seems to be part of a continuous spectrum of positive visual symptoms in Parkinson's disease.

Parkinson's disease alters multisensory perception: Insights from the Rubber Hand Illusion

BackgroundManipulation of multisensory integration induces illusory perceptions of body ownership. Patients with Parkinson's disease (PD), a neurodegenerative disorder characterised by striatal dopamine deficiency, are prone to illusions and hallucinations and have sensory deficits. Dopaminergic treatment also aggravates hallucinations in PD. Whether multisensory integration in body ownership is altered by PD is unexplored. ObjectiveTo study the effect of dopamine neurotransmission on illusory perceptions of body ownership. MethodsWe studied the Rubber Hand Illusion (RHI) in 21 PD patients (on- and off-medication) and 21 controls. In this experimental paradigm, synchronous stroking of a rubber hand and the subject's hidden real hand results in the illusory experience of ‘feeling’ the rubber hand, and proprioceptive mislocalisation of the real hand towards the rubber hand (‘proprioceptive drift’). Asynchronous stroking typically attenuates the RHI. ResultsThe effect of PD on illusory experience depended on the stroking condition (b = −2.15, 95% CI [−3.06, −1.25], p < .0001): patients scored questionnaire items eliciting the RHI experience higher than controls in the illusion-attenuating (asynchronous) condition, but not in the illusion-promoting (synchronous) condition. PD, independent of stroking condition, predicted greater proprioceptive drift (b = 15.05, 95% CI [6.05, 24.05], p = .0022); the longer the disease duration, the greater the proprioceptive drift. However, the RHI did not affect subsequent reaching actions. On-medication patients scored both illusion (critical) and mock (control) questionnaire items higher than when off-medication, an effect that increased with disease severity (log (OR) =.014, 95% CI [.01, .02], p < .0001). ConclusionPD affects illusory perceptions of body ownership in situations that do not typically induce them, implicating dopamine deficit and consequent alterations in cortico-basal ganglia-thalamic circuitry in multisensory integration. Dopaminergic treatment appears to increase suggestibility generally rather than having a specific effect on own-body illusions, a novel finding with clinical and research implications.

Resting activity in visual and corticostriatal pathways in Parkinson's disease with hallucinations

Visual hallucinations are an important non-motor complication of Parkinson's disease (PD) and carry a negative prognosis. Their biological basis is uncertain, but may relate to the activity of resting state networks in brain. We therefore aimed to investigate functional activity of brain in patients with visual hallucinations (PDVH) in resting state compared to patients without hallucinations (PDnonVH) and a healthy control group (HC). Resting state functional MRI was acquired and the primary analysis compared the amplitude of low-frequency fluctuations (ALFF) across groups. This informed a secondary analysis, in the PD groups only, comparing functional connectivity between a 'seed' region in the occipital lobe and the rest of the brain. Individuals with PDVH showed lower ALFF in bilateral lingual gyrus and cuneus and greater ALFF in temporo-parietal regions, medial temporal gyrus and cerebellum than PDnonVH and HC. PDnonVH also had lower ALFF in occipitoparietal region and greater ALFF in medial temporal gyrus, temporo-parietal and cerebellum regions than HC. Functional connectivity analysis revealed that, although both PD groups had lower occipital functional connectivity relative to the HC group, occipital - corticostriatal connectivity was significantly higher in those with PDVH compared with PDnonVH. Our study reveals widespread hemodynamic alterations in PD. However, within a functionally abnormal occipital lobe, those with PDVH have even lower ALFF than non-hallucinators, but have higher occipital functional connectivity with cortical-striatal regions. These findings suggest disruption of pathways underpinning both primary visual perceptual and intrinsic visual integration may contribute to visual hallucinations in PD.

Feasibility of a Web-Based Survey of Hallucinations and Assessment of Visual Function in Patients With Parkinson’s Disease

BackgroundPatients with Parkinson’s disease (PD) experience visual hallucinations, which may be related to decreased contrast sensitivity (ie, the ability to discern shades of grey).ObjectiveThe objective of this study was to investigate if an online research platform can be used to survey patients with Parkinson’s disease regarding visual hallucinations, and also be used to assess visual contrast perception.MethodsFrom the online patient community, PatientsLikeMe, 964 members were invited via email to participate in this study. Participants completed a modified version of the University of Miami Parkinson’s disease hallucinations questionnaire and an online vision test.ResultsThe study was completed by 27.9% (269/964) of those who were invited: 56.9% of this group had PD (153/269) and 43.1% (116/269) were non-Parkinson’s controls. Hallucinations were reported by 18.3% (28/153) of the Parkinson’s group. Although 10 subjects (9%) in the control group reported experiencing hallucinations, only 2 of them actually described formed hallucinations. Participants with Parkinson’s disease with a mean of 1.75 (SD 0.35) and the control group with a mean of 1.85 (SD 0.36) showed relatively good contrast perception as measured with the online letter test (P=.07). People who reported hallucinations showed contrast sensitivity levels that did not differ from levels shown by people without hallucinations (P=.96), although there was a trend towards lower contrast sensitivity in hallucinators.ConclusionsAlthough more Parkinson's responders reported visual hallucinations, a significant number of non-Parkinson's control group responders also reported visual hallucinations. The online survey method may have failed to distinguish between formed hallucinations, which are typical in Parkinson's disease, and non-formed hallucinations that have less diagnostic specificity. Multiple questions outlining the nature of the hallucinations are required. In a clinical interview, the specific nature of the hallucination would be further refined to rule out a vague description that does not indicate a true, formed visual hallucination. Contrary to previous literature, both groups showed relatively good contrast sensitivity, perhaps representing a ceiling effect or limitations of online testing conditions that are difficult to standardize. Steps can be taken in future trials to further standardize online visual function testing, to refine control group parameters and to take steps to rule out confounding variables such as comorbid disease that could be associated with hallucinations. Contacting subjects via an online health social network is a novel, cost-effective method of conducting vision research that allows large numbers of individuals to be contacted quickly, and refinement of questionnaires and visual function testing may allow more robust findings in future research.

Neural correlates of minor hallucinations in non-demented patients with Parkinson's disease

BackgroundHallucinations are a frequent and severe complication in Parkinson's disease (PD). Minor hallucinations are generally not disturbing, but likely progress to well-structured hallucinations with loss of insight and a great impact on quality of life. Knowledge on the neural bases of minor hallucinations may help to describe those systems associated with the early development of psychotic phenomena in PD.In this study, we aimed to identify the pattern of structural brain alterations associated with minor hallucinations in PD by using voxel-based morphometry (VBM). MethodsWe prospectively collected a sample of 46 non-demented PD patients, with (N = 17) and without (n = 29) minor hallucinations (passage and/or presence hallucinations), and 15 healthy controls. Groups were matched for age, education and global cognitive function. Presence and type of minor psychotic phenomena was assessed by the new MDS-UPDRS. Three dimensional T1-weighted MRI images were acquired with a 1.5 T magnet, and analyzed using optimized VBM. ResultsCompared to controls, PD with minor hallucinations (PD-mH) showed reduced gray matter volume bilaterally in different areas of the dorsal visual stream, and in functionally related midbrain and cerebellar structures. Additionally, bilateral gray matter volume increases were observed in the PD-mH group in limbic and paralimbic regions. ConclusionsOur data support a major role of the dorsal visual stream in the genesis of minor hallucinations in PD, reinforcing the importance of posterior cortical regions for the development of cognitive and psychiatric complications in PD.

Risk factors for hallucinations in Parkinson's disease: Results from a large prospective cohort study

The aim of this study was to identify risk factors for the development of hallucinations in patients with Parkinson's disease (PD). A broad range of motor and nonmotor features was assessed at baseline and during the following 5 years in 386 PD patients. Cross-sectional analyses of baseline data and longitudinal analyses of follow-up data were performed to identify risk factors for hallucinations in PD. Twenty-one percent of the patients had hallucinations at baseline, whereas 46% of the patients without hallucinations at baseline developed this feature during follow-up. Univariate survival analysis showed that older age, female sex, less education, higher age at onset, and more severe motor and cognitive impairment, depression, daytimes sleepiness, autonomic dysfunction, and motor fluctuations and dyskinesias, as well as higher daily levodopa dose, were associated with the risk of developing hallucinations. This largely corresponds with the features that were associated with the presence of hallucinations at baseline. In a stepwise regression model, older age at onset, female sex, excessive daytime sleepiness, autonomic dysfunction, and dyskinesias emerged as independent risk factors for developing hallucinations. Female sex, autonomic dysfunction, motor fluctuations, and dyskinesias have not been reported as risk factors in previous studies. These findings lend support to the notion that hallucinations in PD are caused by a combination of risk factors that are associated with (the interaction between) older age and more advanced disease. The identification of female sex as a risk factor for developing of hallucinations in PD is a new finding and should be verified in future studies.

911 – Development of a psycho-sensory hallucinations scale in schizophrenia and parkinson's disease (PSAS scale)

Although visual hallucinations in Parkinson's disease (PD) have been described in several major studies, little is known about over psycho-sensory hallucinations witch are hallmark symptoms of schizophrenia (SCZ). The purpose of this study was to to create and validate a specific tool for the assessment of all sensory modality of hallucinations in PD and SCZ.The Psycho- Sensory hAllucinations Scale (PSAS) was developed with sixteen items to evaluate the core aspect of hallucinations (‘guardian angel’; auditory, visual, olfactory and gustatory, cenesthetic modalities). It was then evaluated in patients with SCZ and idiopathic PD who met the hallucination criteria. Results 86 PD patients and 51 SCZ were evaluated by using the PSAS scale. Data from correlational analyses supported the construct and discriminant validity of the scale in all hallucinatory modalities were related to both gold-standard (PANSS P3 and UPDRS I Item2). Test-retest reliability (33 SCZ and 50 PD) over a 1-week interval determined 2 patients groups :stable : there's no significant (p>.05) differences between before and after measurements in each domainand unstable: all sub-scale and total score significantly (in the range .045 to .002) changed.Inter-rater reliability (18 SCZ and 17 PD) varied by subscale sense hallucinations and domain-specific κs ranged from .56 to .94. Conclusions The results suggest that the usefulness of PSAS as a clinical tool is for initial detailed evaluation and monitoring changes in hallucinations, in SCZ and PD. The next step will be to compare all modality hallucinatory manifestations in PD and schizophrenia.