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Drug-induced neuropsychiatric symptoms are not uncommon, particularly in patients with multiple comorbidities and polypharmacy. Sacubitril/valsartan is a combination medication used in the treatment of heart failure, especially for reducing hospitalizations in patients with heart failure with preserved ejection fraction (HFpEF). However, its neurological side effects, including delirium, hallucinations, and confusion, have been increasingly reported. This case report explores the occurrence of drug-induced delirium, specifically visual hallucinations, in a 79-year-old male with HFpEF and end-stage kidney disease (ESKD) after starting sacubitril/valsartan., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Pena et al.)

Background: Charles Bonnet syndrome (CBS) is a condition in which people with vision loss experience complex visual hallucinations. These complex visual hallucinations may be caused by increased excitability in the visual cortex that are present in some people with vision loss but not others., Objectives: We aimed to evaluate the association between γ-aminobutyric acid (GABA) in the visual cortex and CBS. We also tested the relationship among visually evoked responses, functional connectivity, and CBS., Design: This is a prospective, case-controlled, cross-sectional observational study., Methods: We applied 3-Tesla magnetic resonance spectroscopy, as well as task-based and resting state (RS) connectivity functional magnetic resonance imaging in six participants with CBS and six controls without CBS. GABA+ was measured in the early visual cortex (EVC) and in the lateral occipital cortex (LOC). Participants also completed visual acuity and cognitive tests, and the North-East Visual Hallucinations Interview., Results: The two groups were well-matched for age, gender, visual acuity and cognitive scores. There was no difference in GABA+ levels between groups in the visual cortex. Most participants showed the expected blood oxygenation level dependent (BOLD) activation to images of objects and the phase-scrambled control. Using a fixed effects analysis, we found that BOLD activation was greater in participants with CBS compared to controls. Analysis of RS connectivity with LOC and EVC showed little difference between groups. A fixed effects analysis showed a correlation between the extent of functional connectivity with LOC and hallucination strength., Conclusion: Overall, our results provide no strong evidence for an association between GABAergic inhibition in the visual cortex and CBS. We only found subtle differences in visual function and connectivity between groups. These findings suggest that the neurochemistry and visual connectivity for people with Charles Bonnet hallucinations are comparable to a sight loss population. Differences between groups may emerge when investigating subtle and transient changes that occur at the time of visual hallucinations., (© The Author(s), 2024.)

Background: Perception is frequently impaired in patients with Alzheimer's disease (AD). Several patients exhibit visual or haptic hallucinations., Case Summary: A 71-year-old Chinese man presented with visual and haptic hallucinations he had been experiencing for 2 weeks. The clinical manifestations were the feeling of insects crawling and biting the limbs and geison. He looked for the insects while itching and scratching, which led to skin breakage on the limbs. He was treated with topical and anti-allergic drugs in several dermatology departments without any significant improvement. After admission, the patient was administered risperidone (0.5 mg) and duloxetine (2 mg/day). One week later, the dose of risperidone was increased to 2 mg/day, and that of duloxetine was increased to 60 mg/day. After 2 weeks of treatment, the patient's sensation of insects crawling and biting disappeared, and his mood stabilized., Conclusion: This patient manifested psychiatric behavioral symptoms caused by AD brain atrophy. It was important to re-evaluate the patient's cognitive-psychological status when the patient repeatedly went to the hospital for treatment. Follow-up attention to cognitive function and the consideration of perceptual deficits as early manifestations of AD should be considered., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Occipital lobe epilepsies (OLEs) are a subset of epileptic disorders manifesting predominantly with visual and oculomotor abnormalities that are often misdiagnosed due to similarities with migraines with visual aura and other central nervous system (CNS) pathologies. This case study describes an 88-year-old male with a three-week history of intermittent kaleidoscopic visual phenomena, accompanied by blurring of vision and altered level of consciousness. Neurological examination revealed right homonymous hemianopsia and focal neurological deficits, including forced right gaze preference and nystagmus. Diagnostic modalities, MRI and MRA, ruled out ischemic stroke but indicated mild to moderate cerebral atrophy and chronic microvascular ischemic changes. The patient exhibited a seizure episode characterized by right-sided gaze preference and altered consciousness. Postictally, transient right homonymous hemianopsia was observed, consistent with Todd's phenomenon. Treatment with intravenous levetiracetam and lorazepam led to a reduction in seizure frequency. This case highlights the importance of comprehensive evaluation in distinguishing OLEs from other conditions with similar visual presentations like migraine with aura or occipital lobe stroke being more predominant., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Milosavljevic et al.)

Understandings of how visual hallucinations appear have been highly influenced by generative approaches, in particular Friston's Active Inference conceptualization. Their core proposition is that these phenomena occur when hallucinatory expectations outweigh actual sensory data. This imbalance occurs as the brain seeks to minimize informational free energy, a measure of the distance between predicted and actual sensory data in a stationary open system. We review this approach in the light of old and new information on the role of environmental factors in episodic hallucinations. In particular, we highlight the possible relationship of specific visual triggers to the onset and offset of some episodes. We use an analogy from phase transitions in physics to explore factors which might account for intermittent shifts between veridical and hallucinatory vision. In these triggered forms of hallucinations, we suggest that there is a transient disturbance in the normal one-to-one correspondence between a real object and the counterpart perception such that this correspondence becomes between the real object and a hallucination. Generative models propose that a lack of information transfer from the environment to the brain is one of the key features of hallucinations. In contrast, we submit that specific information transfer is required at onset and offset in these cases. We propose that this transient one-to-one correspondence between environment and hallucination is mediated more by aberrant discriminative than by generative inference. Discriminative inference can be conceptualized as a process for maximizing shared information between the environment and perception within a self-organizing nonstationary system. We suggest that generative inference plays the greater role in established hallucinations and in the persistence of individual hallucinatory episodes. We further explore whether thermodynamic free energy may be an additional factor in why hallucinations are temporary. Future empirical research could productively concentrate on three areas. Firstly, subjective perceptual changes and parallel variations in brain function during specific transitions between veridical and hallucinatory vision to inform models of how episodes occur. Secondly, systematic investigation of the links between environment and hallucination episodes to probe the role of information transfer in triggering transitions between veridical and hallucinatory vision. Finally, changes in hallucinatory episodes over time to elucidate the role of learning on phenomenology. These empirical data will allow the potential roles of different forms of inference in the stages of hallucinatory episodes to be elucidated.

Voriconazole is a second-generation azole used to treat serious fungal infections. Visual hallucinations constitute a representative adverse event caused by voriconazole. However, its mechanism of action remains unclear. In patients with schizophrenia or Parkinson's disease, the frequency of visual hallucinations is associated with brain dopamine levels. This study investigated the frequency of visual hallucinations in patients treated with voriconazole alone or in combination with dopaminergic medicines or dopamine antagonists, using data collected from the Food and Drug Administration Adverse event Reporting System (FAERS). The frequency of visual hallucinations with voriconazole alone and in combination with a dopaminergic medicine (levodopa) or dopamine antagonists (risperidone and chlorpromazine) was compared using data from the FAERS between 2004 and 2023, using the reporting odds ratio (ROR) with relevant 95% confidence intervals (CI). The reference group comprised patients who had been administered voriconazole without dopaminergic medication or dopamine antagonists. Of the patients, 22,839, 90,810, 109,757, 6,435, 20, 83, and 26, respectively were treated with voriconazole, levodopa, risperidone, chlorpromazine, voriconazole plus levodopa, voriconazole plus risperidone, and voriconazole plus chlorpromazine. The occurrence of visual hallucinations increased when used in combination with levodopa (ROR = 12.302, 95% CI = 3.587-42.183). No increase in incidence was associated with the concomitant use of dopamine antagonists (risperidone, ROR = 1.721, 95% CI = 0.421-7.030; chlorpromazine, ROR = none, 95% CI = none). Dopaminergic medicine may increase the risk of visual hallucinations in patients treated with voriconazole. Whether voriconazole positively modulates dopamine production warrants further investigation using a translational research approach., (© 2024. The Author(s).)

Introduction: Pareidolias, or visual misperceptions, are a non-motor symptom of Parkinson's disease (PD) with unclear pathophysiology. The noise pareidolia test (NPT) is a tool for screening pareidolias. The usefulness of the NPT in differentiating PD from atypical parkinsonian syndromes (APS) is also unknown., Methods: We retrospectively investigated 74 patients with PD and 18 patients with APS who took the NPT. Correlations between the number of pareidolic responses, gray matter volume, and cerebral blood flow were also examined in the patients with PD., Results: The median number of pareidolic responses in patients with PD and patients with APS was 0 (interquartile range (IQR): 0-3) and 0 (IQR: 0-1), respectively, and tended to be higher in patients with PD than in those with APS (p = 0.077). It was significantly higher in patients with PD who had hallucinations (2; IQR: 0-9) (p = 0.016). The area under the receiver operating characteristic curve for the number of pareidolic responses in the NPT was 0.62 when used to differentiate PD and APS, and the optimal cutoff number of pareidolic responses was 2/3. Sensitivity and specificity were 25.7% and 100%, respectively. In the PD group, the number of pareidolic responses was correlated with age (r = 0.27; p = 0.021) and the Frontal Assessment Battery (FAB) score (r = -0.34; p = 0.0099). Magnetic resonance imaging showed no significant correlation between the number of pareidolic responses and the volume of focal gray matter. On cerebral hypoperfusion mapping, the left parietal lobe had a significant correlation with the number of pareidolic responses (r = 0.35; p = 0.027)., Conclusion: The number of pareidolic responses in NPT was suggested to be useful as a red flag to rule out APS in differentiating PD from APS. In PD without dementia, the number of pareidolic responses was associated with reduced blood flow in the left parietal lobe., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Matsumoto et al.)

Introduction: Visual hallucinations are often considered to be suggestive of a secondary cause of psychosis, however, this association has never been assessed meta-analytically. We aimed to compare the presence of visual hallucinations in patients with psychosis due to a primary or secondary cause., Method: We conducted a meta-analysis of case-control studies directly comparing primary and secondary psychosis. A random-effects model, following the DerSimonian and Laird method, was used to pool studies and generate overall odds ratios (OR), 95% confidence intervals (CI) and prediction intervals (PI)., Results: Fourteen studies (904 primary and 804 secondary psychosis patients) were included. Visual hallucinations were significantly associated with secondary psychosis (OR = 3.0, 95% CI = 1.7-5.1, p  < 0.001) with moderate between-study heterogeneity (I 2  = 70%). Subgroup analysis by type of secondary psychosis (organic, drug-induced, mixed) was non-significant. Analysis of the content of visual hallucinations (51 primary and 142 secondary psychosis patients) found hallucinations of inanimate objects were significantly more likely to be associated with secondary psychosis (OR = 0.1, 95% CI = 0.01-0.8, p  = 0.03)., Conclusions: Visual hallucinations were strongly associated with a secondary cause of psychosis. The presence of visual hallucinations in a patient presenting with psychosis may serve as a potential "red flag" for a secondary cause and warrant further investigation.

Despite decades of research, we do not definitively know how people sometimes see things that are not there. Eight models of complex visual hallucinations have been published since 2000, including Deafferentation, Reality Monitoring, Perception and Attention Deficit, Activation, Input, and Modulation, Hodological, Attentional Networks, Active Inference, and Thalamocortical Dysrhythmia Default Mode Network Decoupling. Each was derived from different understandings of brain organisation. To reduce this variability, representatives from each research group agreed an integrated Visual Hallucination Framework that is consistent with current theories of veridical and hallucinatory vision. The Framework delineates cognitive systems relevant to hallucinations. It allows a systematic, consistent, investigation of relationships between the phenomenology of visual hallucinations and changes in underpinning cognitive structures. The episodic nature of hallucinations highlights separate factors associated with the onset, persistence, and end of specific hallucinations suggesting a complex relationship between state and trait markers of hallucination risk. In addition to a harmonised interpretation of existing evidence, the Framework highlights new avenues of research, and potentially, new approaches to treating distressing hallucinations., Competing Interests: Conflicts of interest The following authors report no competing interests: James Barnes, Robert Dudley, Nico Diederich, Dominic ffytche, Karl Friston, Simon Lewis, Shigetoshi Nara, Claire O’Callaghan, Javier Pagonabarraga, James M Shine, Ichiro Tsuda. Daniel Collerton has received royalty payments from Wiley publishers. Christopher C Goetz has received faculty stipends from the International Parkinson and Movement Disorder Society, Guest professorship honoraria provided by University of Chicago and Illinois State Neurological Society, and a stipend as Volume Editor from Elsevier Publishers. He has also received royalty payments from Elsevier Publishers and Wolters Kluwer Publishers. Jennifer G Goldman has received grant/research support from Acadia Pharmaceuticals and honoraria from Medscape. Renaud Jardri has been invited to scientific meetings and expert boards by Lundbeck, Janssen and Otsuka. Jaime Kulisevsky has received fees for presentations or advisory boards from: Teva, UCB, Roche, Abbvie, Zambon, Bial, Sanofii and Neuroderm. Marco Onofrj has served on the scientific advisory boards of GlaxoSmithKline, Novartis, Lundbeck, Eisai, Valeant, Medtronic, and Newron; has received speaker honoraria from Zambon, the World Parkinson Congress, the Movement Disorder Society, and the Atypical Dementias congress; publishing royalties from Springer; was an invited guest and lecturer for the Mental Disorders in Parkinson Disease Congress; serves on the editorial board of Medicine (Baltimore) and Frontiers in Neuroscience; has been employed as a speaker for Boehringer Ingelheim, GlaxoSmithKline, UCB, and Zambon; and has received research support from the Italian Ministry of Health and the Italian Ministry of Education. Glenn Stebbins received compensation for consulting and advisory board membership from Acadia Pharmaceuticals, Adamas Pharmaceuticals, Biogen, Ceregene, CHDI Management, Neurocrine Biosciences, Pfizer, Tools-4-Patients, Ultragenyx and the Sunshine Care Foundation. John-Paul Taylor has received speaker fees from GE Healthcare. He has consulted for Kirin Kyowa and Sosei-Heptares. Rimona S Weil has received speaking honoraria from GE Healthcare and writing honoraria from Britannia., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Although differential diagnosis between autoimmune encephalitis and schizophrenia spectrum disorders is crucial for a good outcome, the psychiatric symptoms that distinguish these two conditions have not been identified even though psychiatric symptoms are often the main manifestation of autoimmune encephalitis. Also, there are many situations in clinical psychiatry in which laboratory testing and imaging studies are not available. Because no comparative study of the psychiatric symptoms between these two conditions has been carried out, we explored diagnostically useful psychiatric symptoms in a retrospective case-control study., Methods: We recruited 187 inpatients with first-episode psychosis who were admitted to our psychiatric unit and categorized them into two groups: the autoimmune encephalitis group (n = 10) and the schizophrenia spectrum disorders group (n = 177). Differences in the symptoms and signs between the two groups were investigated., Results: Schneider's first-rank symptoms (e.g., verbal commenting hallucinations and delusional self-experience) were observed only in the schizophrenia spectrum disorders group, whereas altered perception was found more frequently in the autoimmune encephalitis group. Functional status was worse in the autoimmune encephalitis group, and neurological and neuropsychological signs were revealed almost exclusively in this group. A history of mental illness was more frequently reported in the schizophrenia spectrum disorders group than in the autoimmune encephalitis group., Conclusions: The psychiatric symptoms, i.e., Schneider's first-rank symptoms and altered perception, together with neurological and neuropsychological signs, functional status, and past history, may help clinicians accurately differentiate these two conditions among patients with first-episode psychosis., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Visual hallucinations (VH) in Lewy body disease (LBD) have a heterogenous phenomenology classified into minor phenomena (MVH) and complex hallucinations (CVH). Mechanisms underpinning VH and their temporal aspects are largely unknown. According to the hodotopic model, we investigated whether changes in distinct cognitive domains and neural networks in the hallucination trait underpin temporal aspects of MVH and CVH in the hallucination state. 35 LBD patients with VH underwent a complete neuropsychological evaluation and resting-state fMRI. North-East-Visual-Hallucinations-Interview was used to assess their typical VH content, duration, and frequency. We found that MVH was not associated with cognitive impairment, while CVH was associated with impairments in visuoperceptual processes, attention and visual abstract reasoning. In seed-to-seed functional connectivity (FC) analysis we identified functional couplings associated with MVH and CVH temporal severity (duration x frequency), duration and frequency. MVH severity was negatively associated with FC between early visual areas (EVA) and ventral-visual-stream regions, and negatively associated with FC between brainstem and EVA, which may be linked to LBD brainstem neuropathology. CVH duration was positively associated with FC between ventral-visual stream and salience network (SN). CVH frequency was negatively associated with FC between DMN and SN. Functional alterations in distinct visual and attentional networks and their dynamic interaction in trait LBD hallucinators are linked to both the phenomenology of state content and its temporal characteristics. Within a network, VH frequency and duration may be linked to different types of functional alterations: increased connectivity leading to sustained activity prolonging VH (duration) and decreased connectivity increasing dysregulated, spontaneous activity (frequency). These findings support the hodotopic hypothesis of VH and may reflect a link between VH phenomenology, LBD neuropathological progression and the involvement of specific neurotransmitter systems., (© 2022. The Author(s).)

Patients with Parkinson's disease (PD) complicated with rapid eye movement sleep behavior disorder (RBD) present with distinct clinical features. The purpose of this study was to determine the clinical features of sleep and autonomic symptoms in PD patients with probable RBD (pRBD). The study included 126 patients with PD. pRBD was defined as having a history of dream-enacting behavior with a total score of 5 or greater on the Japanese version of the RBD Screening Questionnaire (RBDSQ-J). The Parkinson's Disease Sleep Scale-2 (PDSS-2) was used to evaluate sleep disturbances. Scales for Outcomes in Parkinson's Disease-Autonomic dysfunction (SCOPA-AUT) were used to evaluate autonomic symptoms. Clinical assessments included disease severity, motor symptoms, olfaction, depression, cognitive function, levodopa equivalent dose (LED), and cardiac metaiodobenzylguanidine (MIBG) scintigraphy. Correlations between RBDSQ-J total scores and clinical variables were analyzed. Compared to PD patients without pRBD, PD patients with pRBD showed severe hyposmia, severe sleep-related symptoms, severe dysautonomia, and more reduced cardiac MIBG scintigraphy. Within the PDSS-2, the "PD symptoms at night" domain was significantly more severe in PD patients with pRBD. Within the SCOPA-AUT, the "urinary" and "cardiovascular" domains were significantly higher in PD patients with pRBD. In correlation analyses, RBDSQ-J total scores were positively correlated with PDSS-2 total scores, "PD symptoms at night" and "disturbed sleep" domains, Epworth Sleepiness Scale scores, SCOPA-AUT total scores, "urinary," "cardiovascular," and "thermo" domain scores, and LED. RBDSQ-J total scores were negatively correlated with cardiac MIBG scintigraphy uptake. Binary logistic regression analysis showed that PDSS-2 subitem 7 (distressing hallucinations) and SCOPA-AUT subitem 11 (weak stream of urine) were significant determinants for pRBD. Our study showed that PD patients with pRBD had characteristic sleep and autonomic symptoms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fujita, Shiina, Sakuramoto, Nozawa, Ogaki and Suzuki.)

Oral isotretinoin is an effective treatment for severe acne. However, psychiatric side effects are noted, including a few cases of psychosis and mania triggered by isotretinoin. In this report, we present a case of visual hallucinations due to isotretinoin. In our case, with the discontinuation of isotretinoin, the hallucinations regressed and no other cause was found., (© 2021 Wiley Periodicals LLC.)

Background: Visual hallucination (VH) refers to a spontaneous visual perception without corresponding external stimuli and often occurs in ophthalmological and neuropsychiatric disorders. It is associated with poor quality of life, and increased patient hospitalization and nursing home admission. To date, a scientometric analysis of research on VH is lacking., Aim: To objectively summarize the features of VH research and gain insights into the emerging trends in research on VH., Methods: CiteSpace V was used in this article. Publication outputs, document types, geographic distributions, co-authorship status, research hotspots, and co-citation status were analyzed. A total of 2176 original articles and 465 reviews were included in the database downloaded from the Web of Science Core Collection. We selected the top 50 most cited or occurring articles or items to create a visualized network with a 1-year interval. In the document co-citation analysis stage, we performed clustering analysis on co-cited references, and log likelihood tests were used to name the clusters., Results: The results showed that most publications can be classified into neurology, sports, and ophthalmology studies. In addition, North America, Europe, Asia and Australia published the most documents. Some well-known authors have always had a leading role in this field; meanwhile, new authors keep emerging. A relatively stable cooperation has been formed among many authors. Furthermore, neuropsychiatric symptom and functional connectivity are the top hotspots. Research on VH in dementia with Lewy bodies and Parkinson's disease (PD) have received much attention. Studies on VH in PD are likely to be the new emerging trends in the future, especially the mechanisms of VH., Conclusion: Research on VH has formed a complete system. More large-scale clinical and in-depth basic research are required to better understand the mechanisms underlying VH, which will contribute to our understanding of the pathophysiology and therapeutic options for VH., Competing Interests: Conflict-of-interest statement: Authors declare no conflict of interests for this article., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: Functional alterations of the visual attention networks in a setting of impaired visual information processing have a role in the genesis of visual hallucinations (VH) in dementia with Lewy bodies (DLB). This multimodal MRI study aims at exploring structural and functional basis of VH., Methods: 23 DLB patients (10 with and 13 without VH) and 13 healthy controls were studied. They underwent MRI with T1-w sequences to measure cortical thickness, DTI for whole-brain and single tract microstructural properties and rs-fMRI of the default mode, dorsal and ventral attention, and visual networks., Results: In DLB with VH, whole-brain DTI revealed a lower fractional anisotropy and a greater mean diffusivity in the right frontal and temporo-parietal white matter tracts. Tracts dissection showed lower fractional anisotropy in the right inferior and superior (ventral part) longitudinal fasciculi (ILF and SLF) (p < .05, corrected), and greater mean diffusivity (p < .05). The extent of white matter microstructural alterations involving the right ILF and SLF correlated with the severity of VH (r = .55, p < .01; r = .42, p < .05, respectively), and with performance in the visual attention task (r = -.56 and r = -.61; p < .01, respectively). Cortical thickness in the projection areas of the right SLF was significantly reduced (p < .05). Patients with VH also showed an altered functional connectivity in the ventral attention network, connected by the ventral portion of the SLF (p < .05)., Conclusions: Our findings suggest that a combination of microstructural and functional alterations involving the attention networks in the right hemisphere may be important in the genesis of VH., Competing Interests: Declaration of competing interest The authors have no competing interests to disclose., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: Minor hallucinations (MHs), including sense of presence, passage hallucinations, and visual illusions, have been reported in Parkinson's disease (PD). Here, we investigated the prevalence and associated risk factors for MHs according to appearance time., Methods: Data on the clinical characteristics and the appearance time of MHs for 100 PD patients were collected using a questionnaire and analyzed. MHs were classified into two groups according to the time when MHs appeared: MHs appearing while awake during the daytime (dMHs) and MHs appearing at arousal from sleep during the night or early morning (aMHs)., Results: Thirty-eight patients (38%) experienced MHs. dMHs and aMHs were present in 21 (21%) and 28 patients (28%), respectively. Compared to patients without MHs, patients with dMHs had more severe motor symptoms, longer disease duration, higher levodopa equivalent daily dose (LEDD), and higher rates of cognitive impairment and visual hallucinations during the daytime, whereas patients with aMHs had a higher rate of rapid eye movement sleep behavior disorder (RBD), longer disease duration, higher LEDD, and higher dopamine agonist dosage. Logistic regression analysis showed that cognitive impairment was significantly associated with dMHs (odds ratio (OR) 7.292, p = .001), and that RBD (OR 8.306, p < .001) and LEDD (OR 1.002, p = .049) were significantly associated with aMHs., Conclusions: Patients with MHs have different clinical characteristics according to the time when MHs appear. These findings have important clinical and prognostic implications and suggest appropriate therapeutic options for psychotic symptoms., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Patients with schizophrenia frequently present with visual disturbances including hallucination, and this symptom is particularly prevalent in individuals with comorbid depressive disorders. Currently, little is known about the neurobiological mechanisms of such psychiatric symptoms, and few explanations for the co-occurrence of schizophrenia, depression, and visual disturbances are available., Methods: In this study, we generated a mouse schizophrenia model in which depressive symptoms were also induced. We adopted in vivo two-photon calcium imaging and ex vivo electrophysiological recording of the primary visual cortex to reveal the synaptic transmission and neural activity in the mouse schizophrenia model., Results: In vivo two-photon calcium imaging and ex vivo electrophysiological recording of the primary visual cortex revealed impaired synaptic transmission and abnormal neural activity in the schizophrenia model, but not in the depression model. These functional deficits were most prominent in the combined schizophrenia and depression model., Conclusion: Overall, our data support a mechanism by which the visual cortex plays a role in visual disturbances in schizophrenia., (© 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Visual hallucinations (VH) are a common symptom of Parkinson's disease with dementia (PDD), affecting up to 65% of cases. Integrative models of their etiology posit that a decline in executive control of the visuo-perceptual system is a primary mechanism of VH generation. The role of bottom-up processing in the manifestation of VH in this condition is still not clear although visual evoked potential (VEP) differences have been associated with VH at an earlier stage of PD. Here we compared the amplitude and latency pattern reversal VEPs in healthy controls ( n = 21) and PDD patients ( n = 34) with a range of VH severities. PDD patients showed increased N2 latency relative to controls, but no significant differences in VEP measures were found for patients reporting complex VH (CVH) ( n = 17) compared to those without VH. Our VEP findings support previous reports of declining visual system physiology in PDD and some evidence of visual system differences between patients with and without VH. However, we did not replicate previous findings of a major relationship s between the integrity of the visual pathway and VH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer DF declared past co-authorship and research collaboration with several of the authors DC, J-PT, PU, MF to the handling Editor., (Copyright © 2021 Murphy, Killen, Gupta, Graziadio, Rochester, Firbank, Baker, Allan, Collerton, Taylor and Urwyler.)

Objectives: Charles Bonnet Syndrome (CBS) is a rare clinical condition which has been defined as complex visual hallucinations (CVH) due to visual loss. This study investigated differences in the EEG power spectral density (PSD) and magnitude-squared coherences between patients with eye disease and hallucinations (VH+), and the control subjects with eye disease without hallucinations (VH-)., Methods: 19 scalp channels EEG was recorded in four VH+ (CBS) and four VH- subjects during an eyes-closed resting condition. Artefact-free epochs were analyzed to obtain PSD values in the delta, theta, alpha1, alpha2, beta1, beta2 and gamma frequency bands. Coherence values were calculated through inter-hemispheric and intra-hemispheric electrodes pairs of interest. All subjects were performed with neuropsychological and behavioral assessments to evaluate cognitive functions., Results: The VH + group had increase PSD in theta, beta2 and gamma bands in central, parietal and occipital (O2) areas. The synchronicity was altered particularly in parietal and frontal-parietal regions especially at theta and alpha1 respectively., Conclusions: The aberrant activity in occipital and parietal regions suggest the mechanism of CBS. This is a major electrophysiological study of understanding CBS and visual hallucinations., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: Pareidolias are ilusionary misjudgments and are seen as the result of deliberately or unconsciously caused misinterpretations by the human brain, which tends to complete diffuse and apparently incomplete perceptual images. The psychopathological value of pareidolia in the context of neuropsychiatric diseases has, however, been little researched so far., Methods: In this pilot study, a total of 25 patients (mean age 43.3 years, SD 16.2) with an affective disorder or schizophrenic disease (ICD-10: F3.X or F2.X) and 25 healthy volunteers (mean age 46.1 years, SD 15.4) were compared for sociodemographic factors and psychometric findings, as well as pareidolias and creativity., Results: We found that the patients identified significantly fewer pareidolias than healthy controls (p = 0.002) and that patients with schizophrenia, in particular, had a significantly lower hit rate (p = 0.005). Across the whole group, there were clear positive correlations between pareidolia and high creativity, as well as personality traits such as impulsiveness/spontaneity, extraversion, and conscientiousness., Conclusions: Unexpectedly, having less nosology-specific features than individual specific properties such as creativity and extraversion, and especially openness and verbal intelligence, in patients with affective disorder or schizophrenia promotes the recognition of pareidolia as a specific form of illusionary misperception., (© 2021 S. Karger AG, Basel.)

Introduction: We investigated whether disruption of the inferior longitudinal fasciculus and inferior fronto-occipital fasciculus are associated with visual hallucinations in Parkinson's disease (PD)., Methods: Sixty consecutive right-handed patients with PD with and without visual hallucinations were enrolled in this cross-sectional study. Diffusion tensor imaging was acquired by 3.0 T magnetic resonance imaging. We measured fractional anisotropy and mean diffusivity of the bilateral inferior longitudinal fasciculus and inferior fronto-occipital fasciculus using diffusion tensor tractography analysis software., Results: Seventeen patients with PD had visual hallucinations; these patients tended to have lower fractional anisotropy and higher mean diffusivity values in all fasciculi than did patients without visual hallucinations. A univariate logistic analysis showed that the presence of visual hallucinations was significantly associated with lower fractional anisotropy and higher mean diffusivity of the left inferior longitudinal fasciculus, and lower Mini-Mental State Examination (MMSE) scores. A multivariable logistic analysis adjusted by MMSE scores and disease duration showed a significant association between the presence of visual hallucinations and fractional anisotropy and mean diffusivity values of the left inferior longitudinal fasciculus., Conclusions: Our results suggest that disruption of left inferior longitudinal fasciculus integrity is associated with visual hallucinations in patients with PD, independent of cognitive impairment and disease duration., (© 2020 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Background: In Parkinson's disease (PD) patients, the factors related to weight loss remain unclear., Objective: To investigate determinants of low body mass index (BMI) in PD patients., Methods: We identified factors associated with low BMI in PD patients in a multicenter case-control study. A total of 435 PD patients and 401 controls were included., Results: The mean BMI was significantly lower in PD patients than in controls (22.0±3.4 kg/m2 vs. 25.4±4.3 kg/m2), with an adjusted odds ratio (AOR) of 3.072 (95% CI, 2.103-4.488; p < 0.001) for low BMI (<22 kg/m2) in PD. Compared to the high-BMI PD group (>22 kg/m2), the low-BMI PD group (<22 kg/m2) had more women; a longer disease duration; higher revised Movement Disorder Society Unified PD Rating Scale (MDS-UPDRS) II and IV scores; an increased levodopa equivalent dose (LED); and increased constipation, visual hallucination, dysphagia, dyskinesia and wearing off rates. There were no between-group differences in depression, anhedonia, apathy, sleep problems and daytime sleepiness. Multivariable analysis showed that visual hallucination (AOR, 2.408; 95% CI, 1.074-5.399; p = 0.033) and the MDS-UPDRS IV (AOR, 1.155; 95% CI, 1.058-1.260; p = 0.001) contributed to low BMI after controlling for clinical factors. In a second model, visual hallucination (AOR, 2.481; 95% CI, 1.104-5.576; p = 0.028) and dyskinesia (sum of the MDS-UPDRS 4.3-4.6) (AOR, 1.319; 95% CI, 1.043-1.668; p = 0.021) significantly contributed to low BMI., Conclusion: PD patients were 3 times more likely than healthy controls to have a low BMI. Motor complications, particularly dyskinesia, and visual hallucination were significantly associated with low BMI in PD patients.

Visual hallucinations (VH) are commonly found in the course of synucleinopathies like Parkinson's disease and dementia with Lewy bodies. The incidence of VH in these conditions is so high that the absence of VH in the course of the disease should raise questions about the diagnosis. VH may take the form of early and simple phenomena or appear with late and complex presentations that include hallucinatory production and delusions. VH are an unmet treatment need. The review analyzes the past and recent hypotheses that are related to the underlying mechanisms of VH and then discusses their pharmacological modulation. Recent models for VH have been centered on the role played by the decoupling of the default mode network (DMN) when is released from the control of the fronto-parietal and salience networks. According to the proposed model, the process results in the perception of priors that are stored in the unconscious memory and the uncontrolled emergence of intrinsic narrative produced by the DMN. This DMN activity is triggered by the altered functioning of the thalamus and involves the dysregulated activity of the brain neurotransmitters. Historically, dopamine has been indicated as a major driver for the production of VH in synucleinopathies. In that context, nigrostriatal dysfunctions have been associated with the VH onset. The efficacy of antipsychotic compounds in VH treatment has further supported the notion of major involvement of dopamine in the production of the hallucinatory phenomena. However, more recent studies and growing evidence are also pointing toward an important role played by serotonergic and cholinergic dysfunctions. In that respect, in vivo and post-mortem studies have now proved that serotonergic impairment is often an early event in synucleinopathies. The prominent cholinergic impairment in DLB is also well established. Finally, glutamatergic and gamma aminobutyric acid (GABA)ergic modulations and changes in the overall balance between excitatory and inhibitory signaling are also contributing factors. The review provides an extensive overview of the pharmacology of VH and offers an up to date analysis of treatment options., (Copyright © 2019 Russo, Carrarini, Dono, Rispoli, Di Pietro, Di Stefano, Ferri, Bonanni, Sensi and Onofrj.)

There is a growing recognition in psychosis research of the importance of hallucinations in modalities other than the auditory. This has focused attention on cognitive and neural processes that might be shared by, and which might contribute distinctly to, hallucinations in different modalities. In this article, I address some issues around the modality-generality of cognitive and neural processes in hallucinations, including the role of perceptual and reality-monitoring systems, top-down and bottom-up processes in relation to the psychological and neural substrates of hallucinations, and the phenomenon of simultaneous multimodal hallucinations of the same entity. I suggest that a functional systems approach, inspired by some neglected aspects of the writings of A. R. Luria, can help us to understand patterns of hallucinatory experience across modalities and across clinical and non-clinical groups. Understanding the interplay between modality-general and modality-specific processes may bear fruit for improved diagnosis and therapeutic approaches to dealing with distressing hallucinations.

We have evaluated an 82 years old PD patient who has acutely developed VH secondary to acute visual loss that was associated with increased electroencephalographic activity in the gamma range over the parietal, occipital and frontal regions. In this respect, we have tested the therapeutic effect of occipital lobe oriented rTMS application and its electrophysiological correlates that led to significant improvement in the hallucinatory symptomatology of the patient after two weeks. We have revealed that the improved hallucinatory symptoms after rTMS application resolved completely after switching from the pramipexole treatment to L-Dopa indicating that there could be a combined therapeutic effect of L-Dopa and rTMS. Furthermore, Quantitative-Electroencephalography analysis has shown that the therapeutic effects of rTMS and L-Dopa were seen with the improvement of impaired gamma power spectrum. Although the main limitation of this report is that this a single case study and that these findings need to be replicated in a larger sample, e.g., as part of a controlled trial, our present findings help us to enlighten the unknown pathophysiological overlapping between the visual hallucinations in PD and Charles Bonnet Syndrome. Finally, our study revealed increased gamma coherence and power spectrum which is seen with visual hallucinations and improved after the application of 1 Hz rTMS on the occipital lobe. These findings together suggest that rTMS could be used as a therapeutic tool for parkinsonian complex VH and probably due affecting gamma coherence and power spectrum., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Charles Bonnet Syndrome (CBS) is a condition of the visually impaired, in which hallucinations - or, more appropriately, visions - of geometric patterns, people, and objects appear within the visual field. Most people with CBS are older adults, a function of increased likelihood of visual deterioration in later life, but the condition can occur at any age. Diagnostic criteria vary among professions, but generally includes awareness that the visions are not real, the absence of other accompanying sensory hallucinations, and the absence of dementia or other neurological condition. The mechanism by which the phenomenon occurs is not well understood, although some speculation exists that it is akin to phantom limb syndrome. Although there has recently been increasing awareness about the condition, many in the fields of medicine, optometry, and social work have not heard of it. As front-line providers for clients, it is important that social workers be well informed about the condition to alleviate anxiety our clients may have about expressing their experiences with the condition.

Research into hallucinations typically regards them as single sensory or unimodal experiences leading to a comparative neglect of co-occurring multi-sensory hallucinations (MSH). People with psychosis who have visual hallucinations (VH) report high rates of hallucinations in other senses (auditory, olfactory, tactile). However, it is not known if this is similar to other groups who report VH. Consequently, this study explored MSH in four different patient groups who all had current VH. Archival data from standardised assessments of visual hallucinations in people with psychosis (n = 22), eye disease (ED) (n = 82), Lewy body Dementia (LBD) (n = 41), and Parkinson's disease (PD) (n = 41) determined the presence of MSH. People with psychosis and visual hallucinations reported significantly higher rates of MSH (auditory, 73%; tactile, 82%; olfactory/gustatory hallucinations, 27%) than the LBD group (auditory, 21%; tactile, 28%; olfactory/gustatory, 6%), ED (auditory, 1%; tactile, 11%; olfactory/gustatory, 0%) and PD patients (auditory, 3%; tactile, 8%; olfactory/gustatory, 3%). Regardless of diagnostic grouping, participants with MSH reported greater conviction that the VH were real, and reported greater distress. People with psychosis with VH report high rates of MSH unlike groups of older adults with VH. These between group differences in MSH prevalence have implications for clinical practice and theory., (Copyright © 2018. Published by Elsevier B.V.)

Background: Dementia with Lewy bodies (DLB) is characterized by progressive cognitive decline, fluctuating cognition, visual hallucinations, rapid eye movement sleep behavior disorder, and parkinsonism. DLB is the second most common type of degenerative dementia of all dementia cases. However, DLB, particularly in the early stage, is underdiagnosed and sometimes misdiagnosed with other types of dementia. Thus, it is of great interest investigating neurophysiological markers of DLB., Method: We introduced exact low-resolution brain electromagnetic tomography (eLORETA)-independent component analysis (ICA) to assess activities of 5 electroencephalography (EEG) resting-state networks (RSNs) in 41 drug-free DLB patients., Results: Compared to 80 healthy controls, DLB patients had significantly decreased activities in occipital visual and sensorimotor networks, where DLB patients and healthy controls showed no age dependences in all EEG-RSN activities. Also, we found correlations between all EEG-RSN activities and DLB symptoms. Specifically, decreased occipital α activity showed correlations with worse brain functions related to attention/concentration, visuospatial discrimination, and global cognition. Enhanced visual perception network activity correlated with milder levels of depression and anxiety. Enhanced self-referential network activity correlated with milder levels of depression. Enhanced memory perception network activity correlated with better semantic memory, visuospatial discrimination function, and global cognitive function as well as with severer visual hallucination. In addition, decreased sensorimotor network activity correlated with a better semantic memory., Conclusion: These results indicate that eLORETA-ICA can detect EEG-RSN activity alterations in DLB related to symptoms. Therefore, eLORETA-ICA with EEG data can be a useful noninvasive tool for sensitive detection of EEG-RSN activity changes characteristic of DLB and for understanding the neurophysiological mechanisms underlying this disease., (© 2019 S. Karger AG, Basel.)

Background and Objective: Charles Bonnet Syndrome (CBS) has been defined as complex visual hallucinations (CVH) due to visual loss. The underlying mechanism of CBS is not clear and the underlying pathophysiology of the visual hallucinations in CBS patients and pure visually impaired patients is still not clear., Methods: In our study, we have scanned three patients with eye disease and CBS (VH+) and three patients with eye disease without CBS (VH-) using FDG-PET., Results: Our results showed underactivity in the pons and overactivity in primary right left visual cortex and inferior parietal cortex in VH- patients and underactivity in left Broca, left inf frontal primary visual cortex and anterior and posterior cingulate cortex in VH+ patients relative to the normative 18FFDG PET data that was taken from the database consisting of 50 age-matched healthy adults without neuropsychiatric disorders., Conclusion: From this distributed pattern of activity changes, we conclude that the generation of visual hallucination in CBS is associated with bottom-up and top-down mechanism rather than the generally accepted visual deafferentation-related hyperexcitability theory., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

A 70-year-old right-handed man noticed that the right side of the screen on his television displayed a time lag compared to the other side. For five days before admission, he had characteristic polyopia, visual photopia, and complex hallucination. Upon neurological examination, he showed no abnormal findings except for right homonymous hemianopia. MRI showed acute infarction of the occipital gyri and part of the lingual gyrus in the left occipital lobe. After admission, he experienced various visual hallucinations and visual illusions, including metamorphopsia and micropia, many times. They gradually disappeared after 2 months. Various hallucination was caused by the release of visual information, and illusion was thought to be due to integration failure of visual information. The appearance of complex hallucination in the blind visual field is known due to the damage of the region on the left occipital gyrus. However, the cases with various symptoms such as visual photopia and micropsia are rare.

The aim of this paper was to describe the nursing application of mirror visual feedback in a patient suffering from long-term visual hallucinations. The intervention period was from May 15th to October 19th, 2015. Using the five facets of psychiatric nursing assessment, several health problems were observed, including disturbed sensory perceptions (prominent visual hallucinations) and poor self-care (e.g. limited abilities to self-bathe and put on clothing). Furthermore, "caregiver role strain" due to the related intense care burden was noted. After building up a therapeutic interpersonal relationship, the technique of brain plasticity and mirror visual feedback were performed using multiple nursing care methods in order to help the patient suppress her visual hallucinations by enhancing a different visual stimulus. We also taught her how to cope with visual hallucinations in a proper manner. The frequency and content of visual hallucinations were recorded to evaluate the effects of management. The therapeutic plan was formulated together with the patient in order to boost her self-confidence, and a behavior contract was implemented in order to improve her personal hygiene. In addition, psychoeducation on disease-related topics was provided to the patient's family, and they were encouraged to attend relevant therapeutic activities. As a result, her family became less passive and negative and more engaged in and positive about her future. The crisis of "caregiver role strain" was successfully resolved. The current experience is hoped to serve as a model for enhancing communication and cooperation between family and staff in similar medical settings.

Corticobasal syndrome (CBS) is a typical phenotype of corticobasal degeneration (CBD). However, autopsy series have shown that many CBS cases emerge from various types of non-CBD pathology. We report a 73-year-old Korean man who was clinically diagnosed with CBS whose underlying pathology was Alzheimer's disease (AD) at autopsy (CBS-AD). This case suggests that early developing memory impairment and myoclonus, severe temporoparietal atrophy, and visual hallucinations may support a more specific prediction of CBS-AD.

Objectives: The differential diagnosis of psychotic symptoms is broad and extends beyond primary psychotic and affective disorders. We aim to illustrate that the chronology and phenomenological nature of hallucinatory symptoms may provide clues towards alternative diagnoses, such as hallucinogen persisting perceptual disorder (HPPD). We describe the resurgence of visual pseudo-hallucinations in a young woman in the context of previous substance-induced hallucinatory symptoms and a prior diagnosis of occipital lobe epilepsy. She presented a diagnostic challenge, saw several emergency and specialist doctors and attracted stigmatising diagnoses leading to anxiety and depressive symptoms. Her symptoms were finally recognised as HPPD, and she was treated appropriately with lamotrigine., Conclusions: Patients with perceptual disturbance can present in various clinical settings, and HPPD is an under-recognised diagnostic possibility. Delayed or misdiagnosis prolongs profound functional impairment and social decline, and predisposes the patient to the development of anxiety and depression and related increased risk of suicide.

Derinöz-Güleryüz O. Doxylamine succinate overdose: Slurred speech and visual hallucination. Turk J Pediatr 2018; 60: 439-442. Doxylamine succinate is a commonly used antihistamine for respiratory allergies including allergic rhinitis as well as for the management of insomnia. As it is available over-the-counter like other nonprescription antihistamines and sleep aids, there is a risk of overdose. It is believed that doxylamine succinate has both peripheral and central activity with its anticholinergic properties. Delirium, seizures, and coma are among the central adverse effects that are rare. This case was presented since it is the first case in the literature who developed slurred speech and visual hallucination after high dose doxylamine succinate use and received antidotal therapy for anticholinergic side effects.