The INSPIRE research project explored neuropsychiatric symptoms associated with Systemic Autoimmune Rheumatic Diseases (SARDs), identifying hallucinatory experiences as a lesser known but impactful symptoms. Following consultations with clinicians and patients, areas of focus included the prevalence, sensory modalities, insight, timings, and emotional valence of hallucinations in SARDs. Our previous research shows that hallucinations and related perceptual phenomena often go unreported and unrecognised in clinical settings with SARD patients.

This study analyses and compares hallucination experiences in patients with systemic lupus erythematosus (SLE) and inflammatory arthritis (IA). We evaluated prevalence, modalities, insight, emotional valence, and timings of hallucinations.

Quantitative data from cross-sectional surveys (n=1022) and qualitative data from interviews were integrated using mixed methods. Quantitative data are presented descriptively and comparatively (using Pearson's χ2 tests), and qualitative data were analysed thematically.

SLE patients reported a greater lifetime prevalence of hallucinations compared to IA patients, with significant differences in visual (12% vs 6%), olfactory (11% vs 6%), tactile (11% vs 5%), and presence (10% vs 3%) modalities (all p<0.005). Auditory hallucinations were not significantly more frequent in SLE (8%) compared to IA (5%) (p =0.071). Consistent lack of insight into hallucinations was rare (11% of SLE, and 4% of IA patients). SLE patients were significantly more likely to experience hallucinations in contexts unrelated to periods of sleep transition than IA patients (p =0.020). Recognizing hallucinations as SARD symptoms helped patients develop positive coping mechanisms and reduced distress. However, fear of clinician judgment, stigma, and misdiagnoses discouraged reporting.

The higher prevalence in SLE likely reflects its greater direct impact of SLE (compared to IA) on the brain. Hallucinatory experiences in SARDs aligned more closely with neurological diseases than primary psychotic disorders. Understanding the varying modalities and contexts of hallucinations as potential direct effects of SLE could improve attribution, treatment, and coping strategies, while reducing stigma and fostering open communication between patients and clinicians.

Cortical regions such as parietal area H (PH) and the fundus of the superior temporal sulcus (FST) are involved in higher visual function and may play a role in dementia with Lewy bodies (DLB), which is frequently associated with hallucinations. The authors evaluated functional connectivity between these two regions for distinguishing participants with DLB from those with Alzheimer's disease (AD) or mild cognitive impairment (MCI) and from cognitively normal (CN) individuals to identify a functional connectivity MRI signature for DLB.

Eighteen DLB participants completed cognitive testing and functional MRI scans and were matched to AD or MCI and CN individuals whose data were obtained from the Alzheimer's Disease Neuroimaging Initiative database (https://adni.loni.usc.edu). Images were analyzed with data from Human Connectome Project (HCP) comparison individuals by using a machine learning-based subject-specific HCP atlas based on diffusion tractography.

Bihemispheric functional connectivity of the PH to left FST regions was reduced in the DLB group compared with the AD and CN groups (mean±SD connectivity score=0.307±0.009 vs. 0.456±0.006 and 0.433±0.006, respectively). No significant differences were detected among the groups in connectivity within basal ganglia structures, and no significant correlations were observed between neuropsychological testing results and functional connectivity between the PH and FST regions. Performances on clock-drawing and number-cancelation tests were significantly and negatively correlated with connectivity between the right caudate nucleus and right substantia nigra for DLB participants but not for AD or CN participants.

The functional connectivity between PH and FST regions is uniquely affected by DLB and may help distinguish this condition from AD.

Alzheimer's disease (AD) is neuropathologically defined by deposits of misfolded hyperphosphorylated tau (HP-tau) and amyloid-β. Lewy body (LB) dementia, which includes dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), is characterized pathologically by α-synuclein aggregates. HP-tau and amyloid-β can also occur as co-pathologies in LB dementia, and a diagnosis of mixedAD/DLB can be made if present in sufficient quantities. We hypothesized that the spread of these abnormal proteins selectively affects vulnerable areas, resulting in pathologic regional covariance that differentially associates with pre-mortem clinical characteristics. Our aims were to map regional quantitative pathology (HP-tau, amyloid-β, α-synuclein) and investigate the spatial distributions from tissue microarray post-mortem samples across healthy aging, AD and LB dementia. The study involved 159 clinico-pathologically diagnosed human post-mortem brains (48 controls, 47 AD, 25 DLB, 20 mixedAD/DLB, 19 PDD). The burden of HP-tau, amyloid-β and α-synuclein was quantitatively assessed in cortical and subcortical areas. Principal components (PC) analysis was applied across all cases to determine the pattern nature of HP-tau, amyloid-β and α-synuclein. Further analyses explored the relationships of these pathological patterns with cognitive and symptom variables. Cortical (tauPC1) and temporo-limbic (tauPC2) patterns were observed for HP-tau. For amyloid-β, a cortical-subcortical pattern (amylPC1) was identified. For α-synuclein, four patterns emerged: 'posterior temporal-occipital' (synPC1), 'anterior temporal-frontal' (synPC2), 'parieto-cingulate-insula' (synPC3), and 'frontostriatal-amygdala' (synPC4). Distinct synPC scores were apparent among DLB, mixedAD/DLB and PDD, and may relate to different spreading patterns of α-synuclein pathology. In dementia, cognitive measures correlated with tauPC1,tauPC2 and amylPC1 pattern scores (P ≤ 0.02), whereas such variables did not relate to α-synuclein parameters in these or combined LB dementia cases. Mediation analysis then revealed that in the presence of amylPC1, tauPC1 had a direct effect on global cognition in dementia (n = 65, P = 0.04), while tauPC1 mediated the relationship between amylPC1 and cognition through the indirect pathway (amylPC1 → tauPC1 → global cognition) (P < 0.05). Last, in synucleinopathies, synPC1 and synPC4 pattern scores were associated with visual hallucinations and motor impairment, respectively (P = 0.02). In conclusion, distinct patterns of α-synuclein pathology were apparent in LB dementia, which could explain some of the disease heterogeneity and differing spreading patterns among these conditions. Visual hallucinations and motor severity were associated with specific α-synuclein topographies in LB dementia that may be important to the clinical phenotype and could, after necessary testing/validation, be integrated into semiquantitative routine pathological assessment.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor and non-motor symptoms. The non-motor features may precede the onset of motor symptoms and occur throughout all stages of PD. The non-motor symptoms reflect multisystem involvement of the central and peripheral nervous systems, multiple neurotransmitters, and multiple pathologies. PD management necessitates a comprehensive approach to address non-motor symptoms, including pharmacologic and non-pharmacological interventions and often multiple different disciplines or specialists in the PD care team. This review article discusses symptoms and treatments for the non-motor symptoms of PD including those affecting mood, cognition, behavior, sleep, autonomic function, and sensory systems.

There appears to be a fundamental difference between the two ways of how an object becomes perceptually experienced. One occurs when preconscious object-specifying sensory data processing crosses a certain threshold so that sensory constituents of object depiction become consciously experienced. The other occurs when the already consciously experienced sensory features of the object become interpreted as belonging to a certain visual object category. Surprisingly, experimental facts about neural markers of conscious access gathered so far do not allow us to distinguish mechanisms responsible for these two varieties.

A cortical multicompartment layer-5 pyramidal neuron-based generic processing model is presented in order to conceptualize a possible mechanistic solution for the explanatory cul-de-sac. To support the argument, a review of pertinent research is compiled as associated with data from studies where physically invariant perceptual stimuli have underwent alternative interpretation(s) by the brain.

Recent developments in the newly emerging field of cellular psycho(physio)logy are introduced, offering a hypothetical solution for distinguishing the mechanisms subserving sensory content experience and conscious interpretation.

The multicompartment single cell-based mechanistic approach to brain process correlates of conscious perception appears to have an added value beyond the traditional inter-areal connectivity-based theoretical stances.

Visual hallucinations in individuals following sight loss (Charles Bonnet syndrome; CBS) have been posited to arise because of spontaneous, compensatory, neural activity in the visual cortex following sensory input loss from the eyes-known as deafferentation. However, neurophysiological investigations of CBS remain limited. We performed a multi-modal investigation comparing visual cortical activity in 19 people with eye disease who experience visual hallucinations (CBS) with 18 people with eye disease without hallucinations (ED-Controls; matched for age and visual acuity) utilising functional MRI, EEG, and transcranial magnetic stimulation (TMS). A pattern of altered visual cortical activity in people with CBS was noted across investigations. Reduced BOLD activation in ventral extrastriate and primary visual cortex, and reduced EEG alpha-reactivity in response to visual stimulation was observed in CBS compared to ED-Controls. The CBS group also demonstrated a shift towards lower frequency band oscillations in the EEG, indicative of cortical slowing, with significantly greater occipital theta power compared to ED-controls. Furthermore, a significant association between reduced activation in response to visual stimulation and increased excitability (in the form of reduced TMS phosphene thresholds) was observed in CBS, indicating persistent visual cortical activation consistent with hyperexcitability, which was found to be significantly associated with increased hallucination severity. These results provide converging lines of evidence to support the role of increased visual cortical excitability in the formation of visual hallucinations in some people following sight loss, consistent with the deafferentation hypothesis.

Visual hallucinations are a common non-motor feature of Parkinson's disease and have been associated with accelerated cognitive decline, increased mortality and early institutionalization. Despite their prevalence and negative impact on patient outcomes, the repertoire of treatments aimed at addressing this troubling symptom is limited. Over the past two decades, significant contributions have been made in uncovering the pathological and functional mechanisms of visual hallucinations, bringing us closer to the development of a comprehensive neurobiological framework. Convergent evidence now suggests that degeneration within the central cholinergic system may play a significant role in the genesis and progression of visual hallucinations. Here, we outline how cholinergic dysfunction may serve as a potential unifying neurobiological substrate underlying the multifactorial and dynamic nature of visual hallucinations. Drawing upon previous theoretical models, we explore the impact that alterations in cholinergic neurotransmission has on the core cognitive processes pertinent to abnormal perceptual experiences. We conclude by highlighting that a deeper understanding of cholinergic neurobiology and individual pathophysiology may help to improve established and emerging treatment strategies for the management of visual hallucinations and psychotic symptoms in Parkinson's disease.

Visual hallucinations (VH) are an important neuropsychiatric feature of dementia. The association between VH and cognition remains controversial.

To investigate the differences in clinical correlates of VH and explore the associations between VH and cognitive functional decline in individuals with dementia with Lewy bodies (DLB) and Alzheimer's disease (AD).

Outpatient medical records of 154 patients with DLB and 297 patients with AD between January 2017 and December 2023 were reviewed. We collected demographic characteristics and used neuropsychological assessments and semi-structured detailed interviews to evaluate cognition and VH. Multiple linear regression and mediation analyses were employed to analyze the data, adjusting for confounding variables.

DLB patients had a higher prevalence of VH than AD patients (p < 0.01). The presence of VH predicted lower Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores in both DLB and AD patients (p < 0.01). In DLB patients, VH were associated with lower attention function scores after adjustment (p = 0.027). In AD patients, VH were related to worsened orientation ability after adjustment (p = 0.033). Attention function partially mediated the association between VH and cognition in DLB patients (p < 0.01), whereas orientation function partially mediated this association in AD patients (p < 0.01).

VH may independently correlate with deterioration in global cognitive performance. In DLB patients with VH, attentional function appears to be more impaired, whereas in AD patients, orientation function is the most affected. Different cognitive domains may help distinguish between DLB and AD patients with VH.

Parkinson's Disease (PD) is a multifaceted neurodegenerative disorder characterized, in addition to the well-recognized motor disturbances, by a complex interplay between cognitive and psychiatric manifestations. We dissect the complex landscape of PD-related psychiatric symptoms, taking into account the impact of functional neurological disorders, somatic delusions, impulse control disorders, and conditions within the bipolar spectrum. The newer entities of somatoform and functional neurological disorders, as well as preexisting bipolar spectrum disorders, are analyzed in detail. Moreover, we emphasize the need for a holistic understanding of PD, wherein the cognitive and psychiatric dimensions are valued alongside motor symptoms. Such an approach aims to facilitate early detection and personalized interventions, and enhance the overall quality of life for individuals suffering from this neurodegenerative disorder.

Parkinson's disease psychosis (PDP) is one of the most severe and disabling non-motor symptoms in the progression of Parkinson's disease (PD), significantly impacting the prognosis of PD patients. In recent years, there has been an increase in literature on PDP. However, bibliometrics has rarely been applied to PDP research. This study provides an overview of the current state of PDP research and predicts future trends in this field.

The literature search was conducted using the Web of Science Core Collection, with the search terms (Parkinson* AND (psychotic* OR hallucination* OR illusion* OR delusion* OR misperception* OR psychosis OR psychoses)). VOSviewer and CiteSpace software were employed to perform bibliometric analysis and visual representation of the search results.

A total of 603 articles were effectively included. Since 2017, there has been a significant upward trend in publications related to PDP. The United States, the United Kingdom, and Canada were the top three contributing countries in terms of publication volume, with France also having a strong influence in this field. Movement Disorders and King's College London included and published the most articles on PDP. The paper titled "Hallucinations in Parkinson's Disease: Prevalence, Phenomenology, and Risk Factors" received the highest number of citations and average citations. Cluster analysis results identified brain, prevalence, connectivity, and atypical antipsychotics as key hotspots in this field. High-frequency keywords were grouped into three themes: neurobiology, therapeutic strategies, and symptom research. Among them, pimavanserin, risk, and functional connectivity have been the most studied areas in the past 7 years and are likely to remain key topics in future research.

Research on PDP has garnered increasing attention. This study visualizes PDP research over the past 25 years to analyze global hotspots and trends. It offers researchers a valuable perspective for identifying key topics and understanding research trajectories in this expanding field.

Visual release hallucinations are perceptual disturbances that occur in individuals who have experienced vision loss. Almost 50 million people worldwide are believed to experience visual release hallucinations, yet they are profoundly underdiagnosed. Although first described within the Charles Bonnet syndrome, the paradigm underlying this syndrome precludes their consideration in many populations, such as those with underlying psychiatric illness or dementia. Consequently, visual release hallucinations have rarely been studied in patients presenting with psychosis. We conducted a scoping review to determine whether visual-release hallucinations occur in psychotic patients.

The PubMed research database was searched from inception through April 2023. Cases were collected reporting on psychotic patients experiencing suspected visual release hallucinations. Individual treatment courses and responses were extracted.

Thirteen cases compiled from 11 different studies were summarized to provide baseline characteristics and overall trends in treatment response. Most patients did not remit from pharmacological management alone. All patients who received reafferentation therapy remitted, though many were not candidates. Almost half of the patients did not achieve remission.

Visual release hallucinations can manifest in psychosis and may contribute to treatment-resistant psychosis among psychiatric populations. A shift in our understanding of visual release hallucinations may aid their recognition in psychotic patients by shifting the focus toward visual release features. Recognizing release features among patients with hallucinatory conditions may open new treatment avenues for managing patients with psychosis. A preliminary screening index for visual release features is provided to support this shift.

Neural underpinnings of Parkinson's disease psychosis remain unclear to this day with relatively few studies and reviews available. Using a systematic review approach, here, we aimed to qualitatively synthesize evidence from studies investigating Parkinson's psychosis-specific alterations in brain structure, function or chemistry using different neuroimaging modalities. PubMed, Web of Science and Embase databases were searched for functional MRI (task-based and resting state), diffusion tensor imaging, PET and single-photon emission computed tomography studies comparing Parkinson's disease psychosis patients with Parkinson's patients without psychosis. We report findings from 29 studies (514 Parkinson's psychosis patients, mean age ± SD = 67.92 ± 4.37 years; 51.36% males; 853 Parkinson's patients, mean age ± SD = 66.75 ± 4.19 years; 55.81% males). Qualitative synthesis revealed widespread patterns of altered brain function across task-based and resting-state functional MRI studies in Parkinson's psychosis patients compared with Parkinson's patients without psychosis. Similarly, white matter abnormalities were reported in parietal, temporal and occipital regions. Hypo-metabolism and reduced dopamine transporter binding were also reported whole brain and in sub-cortical areas. This suggests extensive alterations affecting regions involved in high-order visual processing and attentional networks.

Auditory hallucinations are common in people with histories of adversity, possibly indicating a causal relationship. However, hallucinations occur in multiple sensory modalities and the relationship between trauma and hallucinations in other sensory domains is less explored. We examined the occurrence of hallucinatory experiences in different sensory modalities in people with psychosis who also met criteria for Post-Traumatic Stress Disorder (n = 67). Particular attention was paid to the number of modalities reported and whether the experiences were linked to the person's adversity. This linkage was explored in two ways. First, it was predicted that those people reporting more trauma experiences and symptoms of PTSD would report a greater number of hallucination modalities. Second, we examined if there was content or thematic linkage between the trauma and the hallucinatory experiences. There were high levels of reported auditory (89.6 %), visual (58.2 %) and tactile (46.3 %) hallucinations. Hallucinations in two or more modalities were the norm (71.6 % of the participants). The number of hallucination modalities was moderately associated with a greater number of past traumas and PTSD symptoms. There was a high degree of content and thematic linkage between the trauma and the hallucinations. The linkage between trauma and auditory hallucinations extends to other sensory domains.

Visual hallucinations can increase the burden of disease for both patients with Parkinson's disease and their caregivers. Multiple neurotransmitters have been implicated in the neuropathology of visual hallucinations, which provide targets for treatment and prevention. In this study, we assessed the association between cholinergic denervation and visual hallucinations in Parkinson's disease in vivo, using PET imaging of the cholinergic system. A total of 38 patients with Parkinson's disease participated in this study. A group of 10 healthy subjects, matched for age, sex and education, was included for comparison. None of the participants used cholinergic drugs. Thirteen patients who had experienced visual hallucinations in the past month (VH+) were compared with 20 patients who had never experienced visual hallucinations in their lives (VH-). Cholinergic system integrity was assessed with PET imaging using 18F-fluoroethoxybenzovesamicol as the tracer. We assessed the differences in tracer uptake between groups by cluster-based analysis and by analysis of predefined regions of interest consisting of the ventral visual stream, the dorsal attentional network, the ventral attentional network and the lateral geniculate nucleus and mediodorsal nucleus of the thalamus. The Parkinson's disease group (n = 38) showed an extensive pattern of decreased tracer uptake throughout the brain compared with the controls (n = 10). Within the Parkinson's disease group, the VH+ group (n = 13) showed a cluster of decreased tracer uptake compared with the VH- group (n = 20), which covered most of the left ventral visual stream and extended towards superior temporal areas. These results were mirrored in the regions of interest-based analysis, in which the VH+ group showed the strongest deficits in the left inferior temporal gyrus and the left superior temporal gyrus compared with the VH- group. Visual hallucinations in Parkinson's disease are associated with a marked cholinergic deficiency in the left ventral visual stream and the left superior temporal lobe, in addition to an extensive global cholinergic denervation in the general Parkinson's disease population.

Perception is frequently impaired in patients with Alzheimer's disease (AD). Several patients exhibit visual or haptic hallucinations.

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.

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.

Psychosis and visual hallucinations are a prevalent non-motor symptom of Parkinson's disease, negatively affecting patients' quality of life and constituting a greater risk for dementia. Understanding neural mechanisms associated to these symptoms is instrumental for treatment development. The mismatch negativity is an event-related potential evoked by a violation in a sequence of sensory events. It is widely considered an index of sensory change-detection. Reduced mismatch negativity response is one of the most replicated results in schizophrenia and has been suggested to be a superior psychosis marker. To understand whether this event-related potential component could be a similarly robust marker for Parkinson's psychosis, we used electroencephalography with a change-detection task to study the mismatch negativity in the visual modality in 20 participants with Parkinson's and visual hallucinations and 18 matched Parkinson's participants without hallucinations. We find that visual mismatch negativity is clearly present in participants with Parkinson's disease without hallucinations at both parieto-occipital and frontal sites, whereas participants with Parkinson's and visual hallucinations show reduced or no differences in the two waveforms, confirming the sensitivity of mismatch negativity to psychosis, even within the same diagnostic group. We also explored the relationship between hallucination severity and visual mismatch negativity amplitude, finding a negative correlation between visual hallucinations severity scores and visual mismatch negativity amplitude at a central frontal and a parieto-occipital electrodes, whereby the more severe or complex (illusions, formed visual hallucinations) the symptoms the smaller the amplitude. We have also tested the potential role of the serotonergic 5-HT2A cascade in visual hallucinations in Parkinson's with these symptoms, following the receptor trafficking hypothesis. We did so with a pilot study in healthy controls (N = 18) providing support for the role of the Gi/o-dependent pathway in the psychedelic effect and a case series in participants with Parkinson's and visual hallucinations (N = 5) using a double-blind crossover design. Positive results on psychosis scores and mismatch amplitude add further to the potential role of serotonergic modulation of visual hallucinations in Parkinson's disease.

In the last decade, no other branch of clinical pharmacology has been subject to as much criticism of failed innovation and unsatisfactory effectiveness as psychopharmacology. Evolutionary psychiatry can offer original insights on the problems that complicate pharmacological research. Considering that invalid phenotyping is a major obstacle to drug development, an evolutionary perspective suggests targeting clinical phenotypes related to evolved behavior systems because they are more likely to map onto the underlying biology than constructs based on predetermined diagnostic criteria. Because of their emphasis on symptom remission, pharmacological studies of psychiatric populations rarely include functional capacities as the primary outcome measure and neglect the impact of social context on the effects of psychiatric drugs. Evolutionary psychiatry explains why it is appropriate to replace symptoms with functional capacities as the primary target of psychiatric therapies and why social context should be a major focus of studies assessing the effectiveness of drugs currently used and new drugs under development. When the focus of research shifts to those questions that go beyond the "disease-based" concept of drug action, evolutionary psychiatry clearly emerges as a reference framework to assess drug effectiveness and to optimize clinicians' decisions about prescribing, deprescribing, and non-prescribing.

Cognitive deficits are associated with poor quality of life and increased risk of development of dementia in patients with Parkinson's disease (PD) psychosis. The trajectory of cognitive decline in PD psychosis remains however unclear.

We examined this using data from the Parkinson's Progression Markers Initiative study.

We analysed data from patients with drug-naïve PD (n=676) and healthy controls (HC, n=187) over 5 years, and examined all cognitive measures assessed at each time point. We classified patients with PD into those who developed psychosis over the course of the study (PDP) and those without psychosis throughout (PDnP) using the Movement Disorders Society Unified Parkinson's Disease Rating Scale part I hallucinations/psychosis item. We used linear mixed-effect models with restricted maximum likelihood. Age, sex, ethnicity, education and neuropsychiatric and PD-specific symptoms were entered as covariates of interest.

There were no baseline cognitive differences between PD patient groups. There were differences in cognitive performance between PD and HC across the majority of the assessments.Patients with PDP exhibited greater cognitive decline over 5 years compared with PDnP across most domains even after controlling for sociodemographics, depression, sleepiness, rapid eye movement sleep behaviour disorder and motor symptom severity (immediate recall, b=-0.288, p=0.003; delayed recall, b=-0.146, p=0.003; global cognition, Montreal Cognitive Assessment, b=-0.206, p<0.001; visuospatial, b=-0.178, p=0.012; semantic fluency, b=-0.704, p=0.002; processing speed, b=-0.337, p=0.029).

Patients with PD psychosis exhibited decline in semantic aspects of language, processing speed, global cognition, visuospatial abilities and memory, regardless of sociodemographic characteristics, neuropsychiatric and motor symptoms. These cognitive domains, particularly semantic aspects of language may therefore play an important role in PD psychosis and warrant further investigation.

NCT01141023.

Sensory inputs enter a constantly active brain, whose state is always changing from one moment to the next. Currently, little is known about how ongoing, spontaneous brain activity participates in online task processing. We employed 7 Tesla fMRI and a threshold-level visual perception task to probe the effects of prestimulus ongoing brain activity on perceptual decision-making and conscious recognition. Prestimulus activity originating from distributed brain regions, including visual cortices and regions of the default-mode and cingulo-opercular networks, exerted a diverse set of effects on the sensitivity and criterion of conscious recognition, and categorization performance. We further elucidate the mechanisms underlying these behavioral effects, revealing how prestimulus activity modulates multiple aspects of stimulus processing in highly specific and network-dependent manners. These findings reveal heretofore unknown network mechanisms underlying ongoing brain activity's influence on conscious perception, and may hold implications for understanding the precise roles of spontaneous activity in other brain functions.

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.

Visual hallucinations in Lewy body disease (LBD) can be differentiated based on phenomenology into minor phenomena (MVH) and complex hallucinations (CVH). MVH include a variety of phenomena, such as illusions, presence and passage hallucinations occurring at early stages of LBD. The neural mechanisms of visual hallucinations are largely unknown. The hodotopic model posits that the hallucination state is due to abnormal activity in specialized visual areas, that occurs in the context of wider network connectivity alterations and that phenomenology of VH, including content and temporal characteristics, may help identify brain regions underpinning these phenomena. Here we investigated both the topological and hodological neural basis of visual hallucinations integrating grey and white matter imaging analyses. We studied LBD patients with VH and age matched healthy controls (HC). VH were assessed using a North-East-Visual-Hallucinations-Interview that captures phenomenological detail. Then we applied voxel-based morphometry and tract based spatial statistics approaches to identify grey and white matter changes. First, we compared LBD patients and HC. We found a reduced grey matter volume and a widespread damage of white tracts in LBD compared to HC. Then we tested the association between CVH and MVH and grey and white matter indices. We found that CVH duration was associated with decreased grey matter volume in the fusiform gyrus suggesting that LBD neurodegeneration-related abnormal activity in this area is responsible for CVH. An unexpected finding was that MVH severity was associated with a greater integrity of white matter tracts, specifically those connecting dorsal, ventral attention networks and visual areas. Our results suggest that networks underlying MVH need to be partly intact and functional for MVH experiences to occur, while CVH occur when cortical areas are damaged. The findings support the hodotopic view and the hypothesis that MVH and CVH relate to different neural mechanisms, with wider implications for the treatment of these symptoms in a clinical context.

Visual hallucinations (VH) are associated with visual prediction error in patients with dementia with Lewy bodies (DLB). Given this relationship, environmental adjustments have been suggested, but detailed contents for implementing such environmental adjustments and assessments are poorly documented. This case report preliminarily demonstrates methods for improving VH through our experience with two patients with DLB. We conducted familial interviews to assess the phenomenological features of VH and reviewed photographs of patients' homes to identify the environmental triggers of VH, known as photo assessment of the living environment (PA-LE).

Patient 1 was a 78-year-old woman with a Mini-Mental State Examination (MMSE) score of 11/30. She experienced seeing a stranger, children, and cats at home, which frightened her. VH frequently occurred in the living room and bedroom. The PA-LE showed that several environmental features, such as cushions on a sofa, the pattern on a carpet under a table, and clothing on hangers, were suggestive triggers of VH. Patient 2 was an 88-year-old woman with a MMSE score of 5/30. She had seen strangers, children, and animals at home, some of which were linked to a theft delusion. VH frequently occurred in the living room and bedroom. The PA-LE found that several environmental features, such as clothing on hangers and dolls, were suggestive of VH triggers. Non-pharmacological approaches were tailored to the patients' environmental and psychological states using interviews and PA-LE. This included removing environmental triggers, reducing negative mood, and providing coping strategies for VH. This improved their VH and their caregivers' knowledge of VH.

Phenomenological assessments using photographs of the patient's home could identify the environmental triggers associated with VH in patients with DLB and assist in environmental adjustments.

Parkinson disease (PD) psychosis (PDP) is a spectrum of illusions, hallucinations and delusions that are associated with PD throughout its disease course. Psychotic phenomena can manifest from the earliest stages of PD and might follow a continuum from minor hallucinations to structured hallucinations and delusions. Initially, PDP was considered to be a complication associated with dopaminergic drug use. However, subsequent research has provided evidence that PDP arises from the progression of brain alterations caused by PD itself, coupled with the use of dopaminergic drugs. The combined dysfunction of attentional control systems, sensory processing, limbic structures, the default mode network and thalamocortical connections provides a conceptual framework to explain how new incoming stimuli are incorrectly categorized, and how aberrant hierarchical predictive processing can produce false percepts that intrude into the stream of consciousness. The past decade has seen the publication of new data on the phenomenology and neurobiological basis of PDP from the initial stages of the disease, as well as the neurotransmitter systems involved in PDP initiation and progression. In this Review, we discuss the latest clinical, neuroimaging and neurochemical evidence that could aid early identification of psychotic phenomena in PD and inform the discovery of new therapeutic targets and strategies.

Vivid mental imagery has been proposed to increase the likelihood of experiencing hallucinations. Typically, studies have employed a modality general approach to mental imagery which compares imagery across multiple domains (e.g., visual, auditory and tactile) to hallucinations in multiple senses. However, modality specific imagery may be a better predictor of hallucinations in the same domain. The study examined the contribution of imagery to hallucinations in a non-clinical sample and specifically whether imagery best predicted hallucinations at a modality general or modality specific level.

In study one, modality general and modality specific accounts of the imagery-hallucination relationship were contrasted through application of self-report measures in a sample of 434 students. Study two used a subsample (n = 103) to extend exploration of the imagery-hallucinations relationship using a performance-based imagery task.

A small to moderate modality general relationship was observed between self-report imagery and hallucination proneness. There was only evidence of a modality specific relationship in the tactile domain. Performance-based imagery measures were unrelated to hallucinations and self-report imagery.

Mental imagery may act as a modality general process increasing hallucination proneness. The observed distinction between self-report and performance-based imagery highlights the difficulty of accurately measuring internal processes.

Visual snow syndrome (VSS) is a rarely diagnosed neurological phenomenon. It is a visual disorder characterised by the presence of numerous white, black, or translucent dots in the visual field, resembling the 'snow' of an analogue TV set experiencing reception interference. According to The International Classification of Headache Disorders, 3rd edition, visual snow is defined as a pattern of continuous small dots across the visual field lasting >3 months and accompanied by at least two of the following four additional symptoms: palinopsia, increased entoptic phenomena, photophobia, and nyctalopia. These complaints are not consistent with a typical migraine with visual aura and cannot be better explained by another disorder. The authors present the case of a 39-year-old woman who was diagnosed with VSS. The symptoms appeared after a migraine attack and had not alleviated. The patient reported a sensation of constant 'TV screen snow'. A neurological examination found no signs of focal damage to the nervous system. The results of the ophthalmological examination, MRI of the brain with contrast, MRI of the eye sockets, and EEG were normal. VSS is a phenomenon that is still not fully understood, different from migraine aura and associated with a number of additional symptoms. VSS is very difficult to treat. In this case, a lot of drugs were used without improvement. Further research must be conducted to determine the best treatment options for these patients.

Visual hallucinations are a common, potentially distressing experience of people with Lewy body disease (LBD). The underlying brain changes giving rise to visual hallucinations are not fully understood, although previous models have posited that alterations in the connectivity between brain regions involved in attention and visual processing are critical.

Data from 41 people with LBD and visual hallucinations, 48 with LBD without visual hallucinations and 60 similarly aged healthy comparator participants were used. Connections were investigated between regions in the visual cortex and ventral attention, dorsal attention and default mode networks.

Participants with visual hallucinations had worse cognition and motor function than those without visual hallucinations. In those with visual hallucinations, reduced functional connectivity within the ventral attention network and from the visual to default mode network was found. Connectivity strength between the visual and default mode network correlated with the number of correct responses on a pareidolia task, and connectivity within the ventral attention network with visuospatial performance.

Our results add to evidence of dysfunctional connectivity in the visual and attentional networks in those with LBD and visual hallucinations.

Visual hallucination is a prevalent psychiatric disorder characterized by the occurrence of false visual perceptions due to misinterpretation in the brain. Individuals with Parkinson's disease often experience both minor and complex visual hallucinations. The underlying mechanism of complex visual hallucinations in Parkinson's patients is commonly attributed to dysfunction in the visual pathway and attention network. However, there is limited research on the mechanism of minor hallucinations.

To address this gap, we conducted an experiment involving 13 Parkinson's patients with minor hallucinations, 13 Parkinson's patients without hallucinations, and 13 healthy elderly individuals. We collected and analyzed EEG and MRI data. Furthermore, we utilized EEG data from abnormal brain regions to train a machine learning model to determine whether the abnormal EEG data were associated with minor hallucinations.

Our findings revealed that Parkinson's patients with minor hallucinations exhibited excessive activation of cortical excitability, an imbalanced interaction between the attention network and the default network, and disruption in the connection between these networks. These findings is similar to the mechanism observed in complex visual hallucinations. The visual reconstruction of one patient experiencing hallucinations yields results that differ from those observed in subjects without such symptoms.

The visual reconstruction results demonstrated significant differences between Parkinson's patients with hallucinations and healthy subjects. This suggests that visual reconstruction techniques may offer a means of evaluating hallucinations.

Predictive processing models are often ascribed a certain generality in conceptually unifying the relationships between perception, action, and cognition or the potential to posit a 'grand unified theory' of the mind. The limitations of this unification can be seen when these models are applied to specific cognitive phenomena or phenomenal consciousness. Our article discusses these shortcomings for predictive processing models of hallucinations by the example of the Charles-Bonnet-Syndrome. This case study shows that the current predictive processing account omits essential characteristics of stimulus-independent perception in general, which has critical phenomenological implications. We argue that the most popular predictive processing model of hallucinatory conditions - the strong prior hypothesis - fails to fully account for the characteristics of nonveridical perceptual experiences associated with Charles-Bonnet-Syndrome. To fill this explanatory gap, we propose that the strong prior hypothesis needs to include reality monitoring to apply to more than just veridical percepts.

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.

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.

This is a prospective, case-controlled, cross-sectional observational study.

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.

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.

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.

Charles Bonnet syndrome (CBS) is a condition characterised by visual hallucinations of varying complexity on a background of vision loss. CBS research has gained popularity only in recent decades, despite evidence dating back to 1760. Knowledge of CBS among both the patient and professional populations unfortunately remains poor, and little is known of its underlying pathophysiology. CBS parallels two other better-known conditions that occur as a result of sensory loss: phantom limb syndrome (PLS) (aberrant sensation of the presence of a missing limb) and tinnitus (aberrant sensation of sound). As 'phantom' conditions, CBS, PLS and tinnitus share sensory loss as a precipitating factor, and, as subjective perceptual phenomena, face similar challenges to investigations. Thus far, these conditions have been studied separately from each other. This review aims to bridge the conceptual gap between CBS, PLS and tinnitus and seek common lessons between them. It considers the current knowledge base of CBS and explores the extent to which an understanding of PLS and tinnitus could provide valuable insights into the pathology of CBS (including the roles of cortical reorganisation, emotional and cognitive factors), and towards identifying effective potential management for CBS.