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Background: Auditory verbal hallucinations, which frequently involve negative emotions, are reliable symptoms of schizophrenia. Brain asymmetries have also been linked to the condition, but the relevance of asymmetries within the amygdala, which coordinates all emotional signals, to the content of and response to auditory verbal hallucinations has not been explored., Methods: We evaluated the performance of two asymmetry biomarkers that were recently introduced in literature: the distance index, which captures global asymmetries, and a revised version of the laterality index, which captures left-right local asymmetries. We deployed random forest regression models over values computed with the distance index and with the laterality index over amygdala nuclei volumes (lateral, basal, accessory-basal, anterior amygdaloid area, central, medial, cortical, cortico-amygdaloid area, and paralaminar) for 71 patients and 71 age-matched controls., Results: Both biomarkers made successful predictions for the 35 items of the revised version of the Belief About Voices Questionnaire, such that hallucination severity increased with increasing local asymmetries and with decreasing global asymmetries of the amygdala., Conclusions: Our findings highlight a global reorganization of the amygdala, where left and right nuclei volumes differ pairwise but become proportionally more similar as hallucinations increase in severity. Identifying asymmetries in particular brain structures relevant to specific symptoms could help monitor the evolution and outcome of psychopathological conditions., Competing Interests: Declarations Ethics approval and consent to participate All volunteers provided written informed consent before participating in the study, according to the Regional Committee for Medical Research Ethics in Western Norway (REK Vest #2016/800), which approved the study, and the Declaration of Helsinki. Consent for publication Consent for publication has been secured from each participant as part of the informed consent form each of them signed upon enrollment in the study. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Psychotic symptoms (hallucinations and delusions) are a type of neuropsychiatric symptom found during Alzheimer's Disease (AD)., Objective: This systematic review aims to comprehensively capture, analyse, and evaluate the body of evidence that has investigated associations between brain regions/networks and psychotic symptoms in AD., Methods: The protocol, created according to the PRISMA guidelines, was pre-registered on OSF (https://osf.io/tg8xp/). Searches were performed using PubMed, Web of Science and PsycInfo. A partial coordinate-based meta-analysis (CBMA) was performed based on data availability., Results: Eighty-two papers were selected: delusions were found to be associated mainly with right fronto-temporal brain regions and the insula; hallucinations mainly with fronto-occipital areas; both were frequently associated with the anterior cingulate cortex. The CBMA, performed on the findings of fourteen papers on delusions, identified a cluster in the frontal lobe, one in the putamen, and a smaller one in the insula., Conclusions: The available evidence highlights that key brain regions, predominantly in the right frontal lobe, the anterior cingulate cortex, and temporo-occipital areas, appear to underpin the different manifestations of psychotic symptoms in AD and MCI. The fronto-temporal areas identified in relation to delusions may underpin a failure to assimilate correct information and consider alternative possibilities (which might generate and maintain the delusional belief), and dysfunction within the salience network (anterior cingulate cortex and insula) may suggest a contribution for how internal and external stimuli are identified; the fronto-occipital areas linked to hallucinations may indicate diminished sensory processing and non-optimal predictive processing, that together contribute to misinterpretation of stimuli and misperceptions; the fronto-temporal and occipital areas, as well as the anterior cingulate cortex were linked to the psychotic cluster., Competing Interests: Declaration of competing interest The authors declare no potential conflicts of interest with respect to the research, authorship, or publication of this article., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Schizophrenia spectrum disorders (SSD) are debilitating, with auditory verbal hallucinations (AVHs) being a core characteristic. While gray matter volume (GMV) reductions are commonly replicated in SSD populations, the neural basis of AVHs remains unclear. Using previously published data, this study comprises two main analyses, one of GMV dissimilarities between SSD and healthy controls (HC), and one of GMV differences specifically associated with AVHs. Structural brain images from 71 adults with (n = 46) and without (n = 25) SSD were employed. Group differences in GMVs of the cortex, anterior cingulate (ACC), superior temporal gyrus (STG), hippocampi, and thalami were assessed. Additionally, volumes of left Heschl's gyrus (HG) in a subgroup experiencing AVHs (AVH+, n = 23) were compared with those of patients who did not (AVH-, n = 23). SSD patients displayed reduced GMVs of the cortex, ACC, STG, hippocampi, and thalami compared to HC. AVH+ had significantly reduced left HG volume when compared to AVH-. Finally, a right-lateralized ventral prefrontal cluster was found to be uniquely associated with AVH severity. This study corroborates previous findings of GMV reductions in SSD cohorts. Chiefly, our secondary analysis suggests that AVHs are associated with language areas and their contralateral homologues., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Neuropsychiatric symptoms (including anxiety, depression, apathy, impulse-compulsive behaviors and hallucinations) are among the most common non-motor features of Parkinson's disease. Whether these symptoms should be considered as a direct consequence of the pathophysiologic mechanisms of Parkinson's disease is controversial. Morphometric similarity network analysis and epicenter mapping approach were performed on T1-weighted images of 505 patients with Parkinson's disease and 167 age- and sex-matched healthy participants from Parkinson's Progression Markers Initiative database to reveal the commonalities and specificities of distinct neuropsychiatric symptoms. Abnormal cortical co-alteration pattern in patients with neuropsychiatric symptoms was in somatomotor, vision and frontoparietal regions, with epicenters in somatomotor regions. Apathy, impulse-compulsive behaviors and hallucinations shares structural abnormalities in somatomotor and vision regions, with epicenters in somatomotor regions. In contrast, the cortical abnormalities and epicenters of anxiety and depression were prominent in the default mode network regions. By embedding each symptom within their co-alteration space, we observed a cluster composed of apathy, impulse-compulsive behaviors and hallucinations, while anxiety and depression remained separate. Our findings indicate different structural mechanisms underlie the occurrence and progression of different neuropsychiatric symptoms. Based upon these results, we propose that apathy, impulse-compulsive behaviors and hallucinations are directly related to damage of motor circuit, while anxiety and depression may be the combination effects of primary pathophysiology of Parkinson's disease and psychosocial causes., (© 2024. The Author(s).)

Background and Hypothesis: Persistent auditory verbal hallucinations (pAVHs) and olfactory identification impairment are common in schizophrenia (SCZ), but the neuroimaging mechanisms underlying both pAVHs and olfactory identification impairment are unclear. This study aimed to investigate whether pAVHs and olfactory identification impairment in SCZ patients are associated with changes in cortical thickness., Study Design: In this study, cortical thickness was investigated in 78 SCZ patients with pAVHs (pAVH group), 58 SCZ patients without AVHs (non-AVH group), and 83 healthy controls (HC group) using 3T magnetic resonance imaging. The severity of pAVHs was assessed by the Auditory Hallucination Rating Scale. Olfactory identification deficits were assessed using the Odor Stick Identification Test for Japanese (OSIT-J). In addition, the relationship between the severity of pAVHs and olfactory identification disorder and cortical thickness abnormalities was determined., Study Results: Significant reductions in cortical thickness were observed in the right medial orbital sulcus (olfactory sulcus) and right orbital sulcus (H-shaped sulcus) in the pAVH group compared to both the non-AVH and HC groups (P < .003, Bonferroni correction). Furthermore, the severity of pAVHs was found to be negatively correlated with the reduction in cortical thickness in the olfactory sulcus and H-shaped sulcus. Additionally, a decrease in cortical thickness in the olfactory sulcus showed a positive correlation with the OSIT-J scores (P < .05, false discovery rate correction)., Conclusions: Cortical thickness abnormalities in the olfactory sulcus may be a common neuroimaging mechanism for pAVHs and olfactory identification deficits in SCZ patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Although the initial symptoms of corticobasal degeneration (CBD) are varied, psychiatric symptoms are uncommon. Here, we report the autopsy findings of a patient with early CBD who presented with hallucinations. A 68-year-old man developed memory loss and visions of bears and insects. Because of slow vertical eye movement, postural instability, and levodopa-unresponsive parkinsonism, the patient initially was clinically diagnosed with progressive supranuclear palsy. He died of a urinary tract infection 11 months after the onset of the disease. Histopathological examination revealed neuronal loss and gliosis, which were severe in the substantia nigra and moderate in the globus pallidus and subthalamic nucleus. Astrocytic plaques were scattered throughout the amygdala and premotor cortex. The superficial cortical layers lacked ballooned neurons and spongiosis, and tau deposition was greater in glia than in neurons. The amygdala contained a moderate number of argyrophilic grains and pretangles. Western blot analysis showed a 37-kDa band among the low-molecular-weight tau fragments. Because the CBD pathology was mild, we attributed the patient's visual hallucinations to the marked argyrophilic grain pathology. CBD can occur with psychiatric symptoms, including visual hallucinations, and argyrophilic grain pathology may be associated with psychiatric symptoms., (© 2024 Japanese Society of Neuropathology.)

Hallucination is a sensory perception that occurs in the absence of external stimuli during abnormal neurological disturbances and various mental diseases. Hallucination is recognized as a core psychotic symptom and is particularly more prevalent in individuals with schizophrenia. Strikingly, a significant number of subjects with Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and other neurological diseases like cerebral stroke and epileptic seizure also experience hallucination. While aberrant neurotransmission has been linked to the neuropathogenic events of schizophrenia, the precise cellular mechanism accounting for hallucinations remains obscure. Neurogenesis is a cellular process of producing new neurons from the neural stem cells (NSC)-derived neuroblasts in the brain that contribute to the regulation of pattern separation, mood, olfaction, learning, and memory in adulthood. Impaired neurogenesis in the hippocampus of the adult brain has been linked to stress, anxiety, depression, and dementia. Notably, many neurodegenerative disorders are characterized by the mitotic and functional activation of neuroblasts and cell cycle re-entry of mature neurons leading to a drastic alteration in neurogenic process, known as reactive neuroblastosis. Considering their neurophysiological properties, the abnormal integration of neuroblasts into the existing neural network or withdrawal of their connections can lead to abnormal synaptogenesis, and neurotransmission. Eventually, this would be expected to result in altered perception accounting for hallucination. Thus, this article emphasizes a hypothesis that aberrant neurogenic processes at the level of reactive neuroblastosis could be an underlying mechanism of hallucination in schizophrenia and other neurological diseases., Competing Interests: The authors have no conflicts of interest to declare., (© Copyright by the Author(s). Published by Cell Physiol Biochem Press.)

Background: Persistent auditory verbal hallucinations (pAVHs) are a fundamental manifestation of schizophrenia (SCZ), yet the exact connection between pAVHs and brain structure remains contentious. This study aims to explore the potential correlation between pAVHs and alterations in grey matter volume (GMV) within specific brain regions among individuals diagnosed with SCZ., Methods: 76 SCZ patients with pAVHs (pAVH group), 57 SCZ patients without AVHs (non-AVH group), and 83 healthy controls (HC group) were investigated using 3 T magnetic resonance imaging. The P3 hallucination item of the Positive and Negative Syndrome Scale was used to assess the severity of pAVHs. Voxel-based morphometry was used to analyze the GMV profile between the three groups., Results: Compared to the non-AVH and HC groups, the pAVH group exhibited extensive reduction in GMV within the frontotemporal cortex. Conversely, no significant difference in GMV was observed between the non-AVH and HC groups. The severity of pAVHs showed a negative correlation with GMV in several regions, including the right fusiform, right inferior temporal, right medial orbitofrontal, right superior frontal, and right temporal pole (p = 0.0036, Bonferroni correction). Stepwise linear regression analysis revealed that GMV in the right temporal pole (β = -0.29, p = 0.001) and right fusiform (β = -0.21, p = 0.01) were significantly associated with the severity of pAVHs., Conclusions: Widespread reduction in GMV is observed within the frontotemporal cortex, particularly involving the right temporal pole and right fusiform, which potentially contribute to the pathogenesis of pAVHs in individuals with chronic SCZ., Competing Interests: Declaration of competing interest None of the authors have competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Previous longitudinal magnetic resonance imaging studies have shown progressive gray matter (GM) reduction during the earliest phases of schizophrenia. It is unknown whether these progressive processes are homogeneous in all groups of patients. One way to obtain more valid findings is to focus on the symptoms. Auditory hallucinations (AHs) are frequent and reliable symptoms of psychosis. The present study aims to analyze whether longitudinal changes in structural abnormalities in cortical regions are related to the presence of AHs and the intensity of psychotic symptoms in a large sample., Methods: A Magnetic Resonance (MR) voxel-based morphometry analysis was applied to a group of 128 first episodes psychosis (FEP) patients (63 patients with AHs and 65 patients without AHs) and 78 matched healthy controls at baseline and at a 2-year follow-up., Results: At baseline, FEP patients exhibited significant GM volume reductions in the temporal, frontal and precentral regions. At follow-up, FEP patients exhibited GM volume changes in the temporal, Rolandic, frontal, precentral and insula regions. At baseline, no significant differences were found between FEP patients with and without AHs. At follow-up, while FEP patients with AHs showed less GM volume in temporal and frontal lobes, non-AH FEP patients showed reductions in the frontal, precentral and fusiform areas. PANSS scores showed statistically significant correlations with GM volume reductions at baseline and follow-up., Conclusions: Brain cortical loss in the early phases of psychosis is not associated with potentially transitory AHs; however, brain structural changes may emerge as AHs appear in chronic patients., Competing Interests: Declaration of competing interest Anna Mane has served as a speaker and received honoraria to attend conferences from Otsuka, Angelini and Neuraxpharm. Concepción de-la-Cámara received financial support to attend scientific meetings from Janssen, Almirall, Lilly, Lundbeck, Rovi, Esteve, Novartis, Astrazeneca, Pfizer and Casen Recordati. Roberto Rodríguez-Jiménez has been a consultant for, spoken in activities of, or received grants from: Instituto de Salud Carlos III, Fondo de Investigación Sanitaria (FIS), Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid Regional Government (S2010/ BMD-2422 AGES; S2017/BMD-3740), JanssenCilag, Lundbeck, Otsuka, Pfizer, Ferrer, Juste, Takeda, Exeltis, Casen-Recordati, Angelini, Rovi. Angela Ibáñez has received research support from or served as speaker or advisor for Janssen-Cilag, Lundbeck, Otsuka and Casen Recordati. Jerónimo Saiz-Ruiz has been a speaker for and on the advisory boards of Adamed, Lundbeck, Servier, Medtronic, Casen Recordati, Neurofarmagen, Otsuka, Indivior, Lilly, Schwabe, Janssen and Pfizer, outside the submitted work. Leticia González-Blanco has received honoraria for lecturing, research and/or travel grants for attending conferences from the Spanish Foundation of Psychiatry and Mental Health, Instituto de Salud Carlos III, Otsuka-Lundbeck, Janssen-Cilag, Angelini, Casen Recordati and Pfizer. Miquel Bernardo has been a consultant for, received grant/research support and honoraria from, and been on the speakers/advisory board of ABBiotics, Adamed, Angelini, Casen Recordati, Janssen-Cilag, Menarini, Rovi and Takeda. The remaining authors declare no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: Juvenile systemic lupus erythematosus (j-SLE) is a rare chronic auto-immune disease involving several organs. Neuropsychiatric (NP) SLE (NPSLE) is frequent in j-SLE and associated with increased morbidity/mortality. Although NPSLE classification criteria exist, attributing NP features to j-SLE remains a major challenge. The study objective is to thoroughly describe j-NPSLE patients and assist in their diagnosis., Methods: This is a 4-year retrospective monocentric study of j-SLE patients. NP events were attributed to j-SLE using standardised diagnostic criteria and multidisciplinary paediatric clinical expertise. Clinical features, brain magnetic resonance imaging (MRI)s and samples analysis including cerebrospinal fluid were assessed. A risk of j-NPSLE score was developed based on multivariable logistic regression analysis., Results: Of 39 patients included, 44% were identified as having j-NPSLE. J-NPSLE diagnosis was established at the onset of j-SLE in 59% of patients. In addition to frequent kidney involvement (76%) and chilblains (65%), all j-NPSLE patients displayed psychiatric features: cognitive symptoms (82%), hallucinations (76%), depressed mood (35%), acute confused state (18%) and catatonia (12%). Neurological involvement was often mild and nonspecific, with headache (53%) in about half of the patients. The main features reported on brain MRI were nonspecific T2/FLAIR white matter hyperintensities (65%), and cerebral atrophy (88%). Upon immunosuppressive treatment, clinical improvement of NP features was observed in all j-NPSLE patients. The score developed to attribute j-NPSLE probability, guide further investigations and appropriate treatments is based on hallucinations, memory, sleep and renal involvement (Sensitivity: 0.95 Specificity: 0.85). Cerebrospinal fluid (CSF) neopterin assessment increases the score sensitivity and specificity., Conclusion: Physicians should carefully and systematically assess the presence of NP features at diagnosis and early stages of j-SLE. For j-NPSLE patients with predominant psychiatric features, a multidisciplinary collaboration, including psychiatrists, is essential for the diagnosis, management and follow-up., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Abstract: Hallucinations can be caused by biological, psychological, neurological, ophthalmological, and environmental factors. This article discusses a selection of the various conditions that can present with visual disturbances and hallucinations including schizophrenia, HIV, neurosyphilis, hyperammonemia, migraine, substance use, brain tumors, sleep disturbances, thyroid disorders, delirium, ophthalmologic conditions, and Lewy body dementia, providing an overview of the differential diagnosis of visual hallucinations. The mechanisms by which these conditions can lead to hallucinations are also discussed, and insight into the recommended medical workup for each is provided., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Hallucinations are a prominent transdiagnostic psychiatric symptom but are also prevalent in individuals who do not require clinical care. Moreover, persistent psychosis-like experience in otherwise healthy individuals may be related to an increased risk to transition to a psychotic disorder. This suggests a common etiology across clinical and non-clinical individuals along a multidimensional psychosis continuum that may be detectable in structural variations of the brain. The current diffusion tensor imaging study assessed 50 healthy individuals (35 females) to identify possible differences in white matter associated with hallucination proneness (HP). This approach circumvents potential confounds related to medication, hospitalization, and disease progression common in clinical individuals. We determined how HP relates to white matter structure in selected association, commissural, and projection fiber pathways putatively linked to psychosis. Increased HP was associated with enhanced fractional anisotropy (FA) in the right uncinate fasciculus, the right anterior and posterior arcuate fasciculus, and the corpus callosum. These findings support the notion of a psychosis continuum, providing first evidence of structural white matter variability associated with HP in healthy individuals. Furthermore, alterations in the targeted pathways likely indicate an association between HP-related structural variations and the putative salience and attention mechanisms that these pathways subserve., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Abnormal 40 Hz auditory steady-state response (ASSR) has been observed in some psychiatric disorders. Nevertheless, the role of 40 Hz ASSR in persistent auditory verbal hallucinations (pAVHs) schizophrenia (SCZ) is still unknown. This study aims to investigate whether the 40 Hz ASSR impairment is related to pAVHs and can detect pAVHs severity., Methods: We analyzed high-density electroencephalography data that from 43 pAVHs patients (pAVH group), 20 moderate auditory verbal hallucinations patients (mid-AVH group), and 24 without auditory verbal hallucinations patients (non-AVH group). Event-related spectral perturbation and inter-trial phase coherence (ITPC) were calculated to quantify dynamic changes of the 40 Hz ASSR power and ITPC, respectively., Results: Frontal-central, the 40 Hz ASSR power, and ITPC were significantly lower in the pAVH group than in the non-AVH group; There was no significant difference between the pAVH and mid-AVH group. The 40 Hz ASSR was significantly negatively correlated with the severity of pAVHs. The 40 Hz ASSR power, and ITPC could be used as a combinational marker to detect SCZ patients with and without pAVHs., Conclusion: Our findings have shed light on the pathological mechanism of pAVHs in SCZ patients. These results can provide potential avenues for therapeutic intervention of pAVHs., Competing Interests: Declaration of Competing Interest There are no conflicts of interest to declared., (Copyright © 2023. Published by Elsevier B.V.)

Introduction: Neuropsychiatric symptoms (NPS) are common in Lewy body disease (LBD), but their etiology is poorly understood., Methods: In a population-based post mortem study neuropathological data was collected for Lewy body (LB) neuropathology, neurofibrillary tangles (NFT), amyloid beta burden, TDP-43, lacunar infarcts, cerebral amyloid angiopathy (CAA), and hyaline atherosclerosis. Post mortem interviews collected systematic information regarding NPS and cognitive status. A total of 1038 cases were included: no pathology (NP; n = 761), Alzheimer's disease (AD; n = 189), LBD (n = 60), and AD+LBD (n = 28)., Results: Hallucinations were associated with higher LB Braak stages, while higher NFT Braak staging was associated with depression, agitation, and greater number of symptoms in the Neuropsychiatric Inventory. Cases with dual AD+LBD pathology had the highest risk of hallucinations, agitation, apathy, and total symptoms but a multiplicative interaction between these pathologies was not significant., Discussion: LB and AD pathology contribute differentially to NPS likely with an additive process contributing to the increased burden of NPS., (© 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Hallucinations are a complex and multidimensional phenomenon which can differ based on the involved pathology, typology and sensory modality. Hallucinations are common in patients with neurodegenerative diseases. Recent sparse evidence from resting state functional magnetic resonance imaging (rs-fMRI) studies has identified altered functional connectivity in those patients within several brain networks, such as the default mode, attentional and sensory ones, without, however, providing an organized picture of the mechanisms involved. This systematic review, following PRISMA guidelines, aims at critically analyzing the current literature on the brain networks associated with the phenomenon of hallucinations in patients with neurodegenerative diseases. Ten rs-fMRI studies fulfilled our selection criteria. All these studies focused on synucleinopathies, and most of them focused on visual hallucinations and were characterized by a heterogeneous methodology. Thus, instead of offering a definite picture of the mechanisms underlying hallucinations in neurodegeneration, this systematic review encourages further research especially concerning tauopathies. Notwithstanding, the findings overall suggest a disruption in the top-down (associated with memory intrusion and difficulty of inhibition) and in the bottom-up processes (associated with the sensory areas involved in the hallucinations). Further investigations are needed in order to disentangle the brain mechanisms involved in hallucinations and to overcome possible limitations characterizing the current literature., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to explore the effects of atypical antipsychotics (AaPs) on brain white matter (WM) tracts in healthy individuals with auditory verbal hallucinations (Hi-AVHs)., Methods: We analyzed neuroimaging, AVH symptoms, and cognitive assessment data obtained from 39 Hi-AVHs who reported being distressed by persistent AVHs and volunteered to receive AaP treatment. We used tract-based spatial statistics (TBSS) and t tests to explore AaP pharmacotherapy effects on AVH symptoms and brain WM alterations in Hi-AVH subjects., Results: TBSS and t tests revealed WM alterations after AaP treatment, relative to pretreatment observations. Although AaPs alleviated AVH symptoms, WM alterations in these subjects expanded over 8 months of AaP treatment, encompassing most major WM tracts by the end of the observation period, including the corpus callosum, arcuate fasciculus, cortico-spinal tracts, anterior commissure, and posterior commissure., Conclusions: The worsening of AaP-associated WM alterations observed in this study suggest that AaPs may not be a good choice for the treatment of Hi-AVHs despite their ability to alleviate AVHs.

Neurological soft signs (NSS) are well documented in individuals with schizophrenia (SZ), yet so far, the relationship between NSS and specific symptom expression is unclear. We studied 76 SZ patients using magnetic resonance imaging (MRI) to determine associations between NSS, positive symptoms, gray matter volume (GMV), and neural activity at rest. SZ patients were hypothesis-driven stratified according to the presence or absence of auditory verbal hallucinations (AVH; n = 34 without vs 42 with AVH) according to the Brief Psychiatric Rating Scale. Structural MRI data were analyzed using voxel-based morphometry, whereas intrinsic neural activity was investigated using regional homogeneity (ReHo) measures. Using ANCOVA, AVH patients showed significantly higher NSS in motor and integrative functions (IF) compared with non-hallucinating (nAVH) patients. Partial correlation revealed that NSS IF were positively associated with AVH symptom severity in AVH patients. Such associations were not confirmed for delusions. In region-of-interest ANCOVAs comprising the left middle and superior temporal gyri, right paracentral lobule, and right inferior parietal lobule (IPL) structure and function, significant differences between AVH and nAVH subgroups were not detected. In a binary logistic regression model, IF scores and right IPL ReHo were significant predictors of AVH. These data suggest significant interrelationships between sensorimotor integration abilities, brain structure and function, and AVH symptom expression., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Moyamoya disease (MMD) is characterized by the progressive development of stenosis in the distal carotid territory and an abnormal vascular network. It is a rare disease with a higher prevalence in Asian countries compared with other countries. The most common symptoms of MMD vary from stroke to epileptic seizure and headaches. However, individuals with MMD may also experience psychiatric symptoms such as depression, anxiety, and, in rare cases, psychosis. We report the case of a 34-year-old man with MMD who suffered from psychosis accompanied by visual hallucinations. The man was diagnosed with MMD and attends periodic follow-ups in our neurology outpatient clinic. After undergoing programmed neurosurgery, the man's immediate postoperative follow-up neuroimaging showed an extensive right frontotemporal acute ischemic lesion for which he was treated and released. Almost a year later, he presented to an outpatient psychiatric clinic where he complained of visual hallucinations and delusions. This time, there was no change in neuroimaging. Treatment with olanzapine was successful, and the man's symptoms were completely reversed. To our knowledge, this is the first reported case of visual hallucinations in an individual with MMD. This case is especially relevant because the visual hallucinations were not associated with an occipital ischemic lesion or with epileptic activity. We propose a topographic hypothesis to explain such findings., Competing Interests: L.G.-R. has been an advisory board member of, and a speaker for, Janssen-Cilag, Astra-Zeneca, Angelini Recordati, Lundbeck, Otsuka, GSK, and Pfizer. The remaining authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Functional connectivity abnormalities between Broca's and Wernicke's areas and the putamen revealed by functional magnetic resonance imaging (fMRI) are related to auditory hallucinations (AH). In long-term schizophrenia, reduced white matter structural integrity revealed by diffusion imaging in left arcuate fasciculus (connecting Broca's and Wernicke's areas) is likely related to AH. The structural integrity of connections with putamen and their relation to AH are unknown. Little is known about this relationship in first-episode psychosis (FEP), although auditory transcallosal connections were reported to play a role. White matter in the Broca's-Wernicke's-putamen language-related circuit and auditory transcallosal fibers was examined to investigate associations with AH in FEP., Methods: White matter connectivity was measured in 40 FEP and 32 matched HC using generalized fractional anisotropy (gFA) derived from diffusion spectrum imaging (DSI)., Results: FEP and HC did not differ in gFA in any fiber bundle. In FEP, AH severity was significantly inversely related to gFA in auditory transcallosal fibers and left arcuate fasciculus. Although the right hemisphere arcuate fasciculus-AH association did not attain significance, the left and right arcuate fasciculus associations were not significantly different., Conclusions: Despite overall normal gFA in FEP, AH severity was significantly related to gFA in transcallosal auditory fibers and the left hemisphere connection between Broca's and Wernicke's areas. Other bilateral tracts' gFA were weakly associated with AH. At the first psychotic episode, AH are more robustly associated with left hemisphere arcuate fasciculus and interhemispheric auditory fibers microstructural deficits, likely reflecting mistiming of information flow between language-related cortical centers., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The 22q11.2 deletion syndrome (22q11.2 DS), one of the highest genetic risk for the development of schizophrenia, offers a unique opportunity to understand neurobiological and functional changes preceding the onset of the psychotic illness. Reduced auditory mismatch negativity response (MMN) has been proposed as a promising index of abnormal sensory processing and brain pathology in schizophrenia. However, the link between the MMN response and its underlying cerebral mechanisms in 22q11.2 DS remains unexamined. We measured auditory-evoked potentials to frequency deviant stimuli with high-density electroencephalogram and volumetric estimates of cortical and thalamic auditory areas with structural T1-weighted magnetic resonance imaging in a sample of 130 individuals, 70 with 22q11.2 DS and 60 age-matched typically developing (TD) individuals. Compared to TD group, the 22q11.2 deletion carriers reveal reduced MMN response and significant changes in topographical maps and decreased gray matter volumes of cortical and subcortical auditory areas, however, without any correlations between MMN alteration and structural changes. Furthermore, exploratory research on the presence of hallucinations (H+\H-) reveals no change in MMN response in 22q11.2DS (H+ and H-) as compared to TD individuals. Nonetheless, we observe bilateral volume reduction of the superior temporal gyrus and left medial geniculate in 22q11.2DSH+ as compared to 22q11.2DSH- and TD participants. These results suggest that the mismatch response might be a promising neurophysiological marker of functional changes within the auditory pathways that might underlie elevated risk for the development of psychotic symptoms., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

Psychosis is the most common neuropsychiatric side-effect of dopaminergic therapy in Parkinson's disease (PD). It is still unknown which factors determine individual proneness to psychotic symptoms. Schizotypy is a multifaceted personality trait related to psychosis-proneness and dopaminergic neurotransmission in healthy subjects. We investigated whether (1) PD patients exhibit lower schizotypy than controls and (2) dopamine-related neuropsychiatric side-effects can be predicted by higher schizotypy. In this cross-sectional study, we used the Oxford-Liverpool Inventory of Feelings and Experiences in 56 PD patients (12 women, mean ± sd age: 61 ± 11 years) receiving their usual dopaminergic medication and 32 age-matched healthy controls (n = 32; 18 women, mean ± sd age: 57 ± 6 years). We further compared schizotypy scores of patients with (n = 18, 32.1%) and without previously experienced psychosis. We found that patients exhibited lower schizotypy than controls. Further, patients with a history of psychosis exhibited higher schizotypy than patients without these symptoms. Using an information theoretic measure and a machine learning approach, we show that schizotypy yields the greatest predictive value for dopamine-associated hallucinations compared to other patient characteristics and disease related factors. Our results indicate an overlap between neural networks associated with schizotypy and the pathophysiology of PD and a relationship between schizotypy and psychotic side-effects of dopaminergic medication.

Hallucinations-while often considered an indication of mental illness-are commonly experienced by those without a need for clinical care. These nonclinical voice-hearers offer an opportunity to investigate hallucinations in the absence of confounds inherent to the clinical state. Recent work demonstrates an association between auditory verbal hallucinations (AVH) and structural variability in paracingulate sulcus (PCS) of medial prefrontal cortex in a clinical population. However, before PCS length may be considered a biomarker for clinical hallucination risk, it is necessary to investigate PCS structure in a nonclinical population of voice-hearers with AVH phenomenology similar to those of their clinical counterparts. In the current study, PCS length was measured from T1-weighted structural MRI scans of four groups of participants: (1) voice-hearers with a psychotic disorder (n = 15); (2) voice-hearers without a psychotic disorder (n = 15); (3) nonvoice-hearers with a psychotic disorder (n = 14); and (4) nonvoice-hearers without a psychotic disorder (n = 15). There was a main effect of AVH status-but not psychosis-on right PCS length, with no interaction of AVH and psychosis. Participants with AVH exhibited reduced right PCS length compared to participants without AVH (mean reduction = 8.8 mm, P < 0.05). While past studies have demonstrated decreased PCS length in clinical voice-hearers, ours is the first demonstration that shorter right PCS extends to nonclinical voice-hearers. Our findings support the hypothesis that differences in PCS length are related to the propensity to hear voices and not to illness, consistent with a continuum model of voice-hearing., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Combining structural (sMRI) and functional magnetic resonance imaging (fMRI) data in schizophrenia patients with and without auditory hallucinations (9 SZ&#95;AVH, 12 SZ&#95;nAVH), 18 patients with bipolar disorder, and 22 healthy controls, we examined whether cortical thinning was associated with abnormal activity in functional brain networks associated with auditory hallucinations. Language-task fMRI data were combined with mean cortical thickness values from 148 brain regions in a constrained principal component analysis (CPCA) to identify brain structure-function associations predictable from group differences. Two components emerged from the multimodal analysis. The "AVH component" highlighted an association of frontotemporal and cingulate thinning with altered brain activity characteristic of hallucinations among patients with AVH. In contrast, the "Bipolar component" distinguished bipolar patients from healthy controls and linked increased activity in the language network with cortical thinning in the left occipital-temporal lobe. Our findings add to a body of evidence of the biological underpinnings of hallucinations and illustrate a method for multimodal data analysis of structure-function associations in psychiatric illness., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Schizophrenic patients often experience visual hallucinations (VHs) and auditory hallucinations (AHs); however, brain aberrations associated with combined VH and AH in schizophrenic patients remains poorly documented. Changes to the brain and cognition during the first episode of untreated schizophrenic patients (FUSCH) with both VHs and AHs (FUSCHVA) were evaluated. One-hundred and fifty-seven patients were enrolled that had FUSCH (1) with VHs but not AHs (FUSCHV), and (2) with AHs but not VHs (FUSCHA), plus FUSCHVA and healthy controls (n = 30). Gray matter volume (GMV) and MATRICS Consensus Cognitive Battery (MCCB) was measured to reflect impairments to the brain and cognition, respectively. FUSCHVA patients had the severest cognitive impairment for all components of the MCCB, followed by FUSCHV and FUSCHA patients. Compared to healthy patients, FUSCHVA patients had reduced GMV in the occipital, parietal, frontal, and temporal cortex, and increased GMV in the hippocampus and striatum. Compared to FUSCHV patients, FUSCHVA patients had reduced GMV in the occipital cortex and postcentral gyrus, and increased GMV in the posterio-parietal lobe. Compared to patients with FUSCHA, the GMV in patients with FUSCHVV was reduced in the occipital cortex and posterio parietal lobe. In conclusion, visual and auditory hallucinations appear to deteriorate reciprocally in FUSCHVA patients, accompanied with sever cognitive impairments. Compared to AHs, VHs might be accompanied with severe GMV impairment in the brain, especially in the primary visual cortex and higher perception integration cortex (posterio parietal lobe) in patients with FUSCH., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The arcuate fasciculus (AF) has been implicated in the pathology behind schizophrenia and auditory verbal hallucinations (AVHs). White matter tracts forming the arcuate fasciculus can be quantified and visualized using diffusion tensor imaging (DTI) tractography. Although there have been a number of studies on this topic, the results have been conflicting. Studying the underlying white matter structure of the AF could shed light on the constrains for interaction between temporal and frontal language areas in AVHs. The participants were 66 patients with a schizophrenia diagnosis, where AVHs were defined from the Positive and Negative Syndrome Scale (PANSS), and compared with a healthy control group. DTI was performed on a 3T MR scanner, and tensor estimation was done using deterministic streamline tractography. Statistical analysis of the data showed significantly longer reconstructed tracks along the AF in patients with severe and frequent AVHs, as well as an overall significant asymmetry with longer tracks in the left compared to the right side. In addition, there were significant positive correlations between PANSS scores and track length, track volume, and number of track streamlines for the posterior AF segment on the left side. It is concluded that the present DTI results may have implications for interpretations of functional imaging results., Competing Interests: Declaration of Competing Interests Co-authors Kenneth Hugdahl and Lars Ersland owns shares in the company NordicNeurolab Inc. (https://nordicneurolab.com/) that produced add-on equipment for the acquisition of the MR data. Kenneth Hugdahl and Lars Ersland declare no conflict of interest, as do all other co-authors., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

In functional imaging, accumulating evidence suggests that spontaneous activity decreases during the resting state in the core brain regions of the default-mode network [e.g. medial prefrontal cortex (mPFC)] in schizophrenia. However, the significance of this decreased activity has not been clarified in relation to its clinical symptoms. In this study, near-infrared spectroscopy (NIRS), which is a simple imaging modality suitable for resting state paradigm, was used to evaluate the intensity of the spontaneous activity during the resting state in chronic schizophrenia. Consistent with previous findings of fMRI studies, spontaneous activity decreased in the mPFC of patients with schizophrenia. In addition, the decreased spontaneous activity was associated with severe hallucinations in this region where reality monitoring is fundamentally engaged. These results may encourage additional application of NIRS with the resting state paradigm into daily clinical settings for addressing the broad phenotypes and unstable course of schizophrenia.

Aim: Personality Disorders (PD) often share clinical and phenomenological overlap with psychotic disorders, especially at onset. However, there is little research on comorbid PD among people experiencing first episode psychosis. We examined the prevalence of PD recording and its sociodemographic and clinical correlates in people accepted to Early Intervention in Psychosis (EIP) services., Methods: Participants were aged 16-35, accepted into 6 EIP services for suspected psychosis, as part of the Social Epidemiology of Psychoses in East Anglia (SEPEA) study. PD was recorded by clinicians according to ICD-10. Multilevel logistic regression was performed., Results: Of 798 participants, 76 people (9.5%) received a clinical diagnosis of PD, with emotionally unstable PD (75.0%, N = 57) the most common subtype. In multivariable analysis, risk factors for PD included female sex (odds ratio [OR]: 3.4; 95% CI: 2.0-5.7), absence of psychotic disorder after acceptance to EIP (OR: 3.0; 95% CI: 1.6-5.5), more severe hallucinations (OR: 1.6; 95% CI: 1.2-2.1), and lower parental SES (OR: 1.4; 95% CI: 1.1-1.8). Compared with the white British, black and minority ethnic groups were less likely to receive a PD diagnosis (OR: 0.3; 95% CI: 0.1-0.7). There was no association between PD and neighbourhood-level deprivation or population-density., Conclusions: Recording of a PD diagnosis was three times more common amongst participants later found not to meet threshold criteria for psychotic disorder, implying phenomenological overlap at referral which highlights difficulties encountered in accurate diagnostic assessment, treatment and onward referral. People with PD experienced more individual-level, but not neighbourhood-level social disadvantage in an already disadvantaged sample., Competing Interests: No authors have competing interests.

Aims: Our article consists in both analysis and synthesis of contemporary cognitive models of auditory verbal hallucinations (AVHs) in schizophrenia. Our work is based on the analysis of the scientific literature including original articles, literature reviews as well as meta-analysis., Methodology: In order to identify the most pertinent studies in the electronic search, the three following databases were systematically searched: PubMed, PsycINFO and MEDLINE. For both the analysis and synthesis we selected original articles, literature reviews as well as meta-analysis referring to any cognitive explanation of the auditory hallucinatory experience in schizophrenia. A cognitive model of auditory hallucinations refers to any incorporation of cognitive frameworks and explanations in one's conceptualization of the hallucinatory phenomenon in schizophrenia. We also focused our work on past conceptualization of auditory hallucinations in order to explain the development and the contribution of current cognitive models in the understanding of the onset and the maintaining of AVHs. After a brief review of clinical characteristics and historical conceptualization of auditory verbal hallucinations, contemporary explanations were presented in the area of schizophrenia. These explanations referred to researches into cognitive psychopathology including metacognitive as well as neuroimaging studies., Results: The examination of scientific literature highlighted the complexity of AVHs through multifactorial explanations here mostly explained by cognitive and metacognitive deficits. We synthesized former conceptualizations of AVHs, which were sustained on mechanistic or sensory explanations. Esquirol, Baillarger and Briere de Boismont were the first as conceiving AVHs as a perception disorder and introduced the idea that auditory hallucinations resulted from a failure to control one's memories/fantasies. Later, Broca and Wernicke discovered auditory areas in the human brain implicated in language comprehension and production. AVHs began to be conceptualized by the scientific world as being mechanistically brain-related. Sigmund Freud was among the first to study the meaning of AVHs, a domain still being investigated by todays cognitive sciences. More recently, neuroimaging studies allowed the validation of these sensory explanations in considering the onset of AVHs through the deficit of cortical and subcortical areas implicated in the process of languages (e.g. Broca and Wernicke areas) and emotions (e.g. limbic system, amygdala, hippocampus). At a more mechanistic level, contemporary cognitive models of AVHs explained AVHs as an intrusive verbal representation into the awareness which is non-inhibited (i.e. deficit in intentional inhibition) and also non-recognized as one's own experience (i.e. deficit in source monitoring, planning and metacognition), or even attributed to an external source (attribution bias). In terms of inhibitory control, inhibition is a basic cognitive mechanism defined as a collection of processes that allows the suppression of previously activated cognitive contents and the clearing of irrelevant actions or attention from consciousness. Intentional inhibition is effortful and occurs when an individual deliberately suppresses the activation of an item after deciding it is irrelevant. Theoretical support for the suggestion that an inhibitory failure is involved in AVHs in schizophrenia arises from studies that have shown that a failure in inhibition results in intrusive thoughts from long-term memory. Recent findings also found that individuals with AVHs in schizophrenia demonstrated an impaired source monitoring. In episodic memory research, a distinction was made between content (an event) and context (e.g. source or temporal characteristics of an event) information. The context of memories provides cues that allow an individual to differentiate one memory from other memories. AVHs are conceptualized as a failure to access the contextual cues that would allow voice-hearer to form an intact representation of events in memories. Regarding planning, AVHs refer to the intrusion of unwanted memories into the inner speech that are not recognized from one's own representation. Previous cognitive theories highlighted the important role played by metacognitive skills and belief (i.e. thinking about one's thinking) in the explanation of AVHs. Finally, the external attribution bias was extensively studied over the last three decades and refers to the tendency to attribute negative events (situational or cognitive) to an external source. In this framework, AVHs refer to intrusive thoughts externally attributed to a voice., Conclusion: For more than one century, scientific discoveries in (bio)medical science have allowed the validation of former sensory and mechanistic explanations of AVHs. Nevertheless, many explanatory models account for the way AVHs are maintained (source monitoring, deficit in planning, externalizing bias), while they scarcely expose how they are triggered (intrusive thoughts, deficit in inhibition). The relation between AVHs and intrusive thoughts still remain unclear, and further studies are needed for the understanding of a potential causal relationship., (Copyright © 2020 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Objectives: Homonymous hemianopia (HH) is the most frequent visual-field defect after a stroke. Some of these patients also have visual hallucinations, the origin and frequency of which remain largely unknown. The aims of this work were to determine the occurrence of visual hallucinations among poststroke hemianopic patients in function of the location (Brodmann areas) of the brain lesion, as determined by MRI, and to study the neuroanatomic correlates of these hallucinations by nature, frequency, and type., Methods: One hundred sixteen patients with HH who had had a stroke in the posterior region, including the occipital lobe, participated in the study. We evaluated the frequency and nature of visual hallucinations with the Questionnaire for Hallucinations in Homonymous Hemianopia. The volume of each patient's brain lesion was modeled in 3 dimensions., Results: Of 116 patients with an HH from a cortical infarction, 85 were excluded due to confounding factors associated with hallucinations. In the final cohort of 31 patients matched for lesion location and etiology, 58% had experienced hallucinations. A significant inverse correlation between lesion size and the frequency of visual hallucinations emerged. The presence of visual hallucinations in poststroke hemianopic patients requires a relatively small lesion that includes, at the very least, loss of the striate cortex but that spares Brodmann area 19, 20, and 37., Conclusion: Our results suggest that visual hallucinations might be due to complex interactions between damaged areas and intact areas of the visual cortex. We discuss these findings regarding models of perception and of visual recognition. Our results also have implications for the clinical care of patients with HH who have had a stroke., (© 2020 American Academy of Neurology.)

Objective: To investigate the microstructural and macrostructural white matter changes that accompany visual hallucinations and low visual performance in Parkinson disease, a risk factor for Parkinson dementia., Methods: We performed fixel-based analysis, a novel technique that provides metrics of specific fiber-bundle populations within a voxel (or fixel). Diffusion MRI data were acquired from patients with Parkinson disease (n = 105, of whom 34 were low visual performers and 19 were hallucinators) and age-matched controls (n = 35). We used whole-brain fixel-based analysis to compare microstructural differences in fiber density (FD), macrostructural differences in fiber bundle cross section (FC), and the combined FD and FC (FDC) metric across all white matter fixels. We then performed a tract-of-interest analysis comparing the most sensitive FDC metric across 11 tracts within the visual system., Results: Patients with Parkinson disease hallucinations exhibited macrostructural changes (reduced FC) within the splenium of the corpus callosum and the left posterior thalamic radiation compared to patients without hallucinations. While there were no significant changes in FD, we found large reductions in the combined FDC metric in Parkinson hallucinators within the splenium (>50% reduction compared to nonhallucinators). Patients with Parkinson disease and low visual performance showed widespread microstructural and macrostructural changes within the genu and splenium of the corpus callosum, bilateral posterior thalamic radiations, and left inferior fronto-occipital fasciculus., Conclusions: We demonstrate specific white matter tract degeneration affecting posterior thalamic tracts in patients with Parkinson disease with hallucinations and low visual performance, providing direct mechanistic support for attentional models of visual hallucinations., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background: Auditory verbal hallucinations (AVH) are a cardinal feature of schizophrenia, but they can also appear in otherwise healthy individuals. Imaging studies implicate language networks in the generation of AVH; however, it remains unclear if alterations reflect biologic substrates of AVH, irrespective of diagnostic status, age, or illness-related factors. We applied multimodal imaging to identify AVH-specific pathology, evidenced by overlapping gray or white matter deficits between schizophrenia patients and healthy voice-hearers., Methods: Diffusion-weighted and T1-weighted magnetic resonance images were acquired in 35 schizophrenia patients with AVH (SCZ-AVH), 32 healthy voice-hearers (H-AVH), and 40 age- and sex-matched controls without AVH. White matter fractional anisotropy (FA) and gray matter thickness (GMT) were computed for each region comprising ICBM-DTI and Desikan-Killiany atlases, respectively. Regions were tested for significant alterations affecting both SCZ-AVH and H-AVH groups, relative to controls., Results: Compared with controls, the SCZ-AVH showed widespread FA and GMT reductions; but no significant differences emerged between H-AVH and control groups. While no overlapping pathology appeared in the overall study groups, younger (<40 years) H-AVH and SCZ-AVH subjects displayed overlapping FA deficits across four regions (p < 0.05): the genu and splenium of the corpus callosum, as well as the anterior limbs of the internal capsule. Analyzing these regions with free-water imaging ascribed overlapping FA abnormalities to tissue-specific anisotropy changes., Conclusions: We identified white matter pathology associated with the presence of AVH, independent of diagnostic status. However, commonalities were constrained to younger and more homogenous groups, after reducing pathologic variance associated with advancing age and chronicity effects.

Background: Comprehensive clinicopathological studies of neuropsychiatric symptoms (NPS) in dementia are lacking., Objective: To describe the pathological correlations of NPS in a sample of institutionalized people with dementia., Methods: We studied 59 people who were consecutively admitted to a nursing home and donated their brain. Correlations between pathological variables and NPS upon admission (n = 59) and at one-year follow-up assessment (n = 46) were explored and confirmed using bivariate and multivariate statistical methods., Results: Mean (SD) age at admission was 83.2 (6.4) years and mean (SD) age at demise was 85.4 (6.6); 73% of the subjects were female and 98% presented advanced dementia. The most frequent etiological diagnosis was Alzheimer's disease (AD; 74.6% clinical diagnosis, 67.8% pathological diagnosis). The pathological diagnosis of AD was associated with aggression (β est 0.31), depression (β est 0.31), anxiety (β est 0.38), and irritability (β est 0.28). Tau stage correlated with aggressive symptoms (β est 0.32) and anxiety (βest 0.33). Coexistence of AD and Lewy body pathology was associated with depression (β est 0.32), while argyrophilic grains were associated with eating symptoms (β est 0.29). Predictive models were achieved for apathy, including cognitive performance, basal ganglia ischemic lesions, and sex as predictors (R2 0.38) and for sleep disorders, including pathological diagnosis of AD and age at demise (R2 0.18) (all p-values <0.05, unadjusted)., Conclusion: AD was the main pathological substrate of NPS in our sample of very elderly people with advanced dementia. However, correlations were mild, supporting a model of focal/asymmetric rather than diffuse brain damage, along with relevance of environmental and other personal factors, in the genesis of those symptoms.

Around 1 in 5 children under 13 years old experience sub-clinical psychotic experiences (PEs) like hallucinations and delusions. While PEs in childhood are a significant risk factor for adult psychotic disorders, the majority of those experiencing childhood PEs do not develop a psychotic disorder. Individual differences in regional brain maturation rates may be responsible for this age-related and often transient emergence of PEs. Fronto-temporal association tracts undergo extensive maturation and myelination throughout childhood and adolescence, thus we focus on individual differences in one such tract, the arcuate fasciculus. A normative population-based sample of children (aged 11-13) attended a clinical interview and MRI (n = 100), 25 of whom were identified as reporting strong PEs. This group had reduced mean and radial diffusivity in the arcuate fasciculus compared with a group of matched controls (n = 25) who reported no PEs. The group difference was greater in the left hemisphere than the right. Mediation analyses showed that this group difference was driven predominantly by perceptual disturbances and an along-tract analysis showed that the group difference was greatest approximately halfway between the frontal and temporal termination points of the tract (adjacent to the left lateral ventricle). This study is the first to investigate links between arcuate fasciculus diffusivity and psychotic experiences in a population sample of children., Competing Interests: Declaration of competing interest The Authors have declared that there are no conflicts of interest., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Alice in Wonderland syndrome (AIWS) is a paroxysmal, perceptual, visual and somesthetic disorder that can be found in patients with migraine, epilepsy, cerebrovascular disease or infections. The condition is relatively rare and unique in its hallucinatory characteristics. OBJECTIVE To discuss the potential pathways involved in AIWS. Interest in this subject arose from a patient seen at our service, in which dysmetropsia of body image was reported by the patient, when she saw it in her son. METHODS We reviewed and discussed the medical literature on reported patients with AIWS, possible anatomical pathways involved and functional imaging studies. RESULTS A complex neural network including the right temporoparietal junction, secondary somatosensory cortex, premotor cortex, right posterior insula, and primary and extrastriate visual cortical regions seem to be involved in AIWS to varying degrees. CONCLUSIONS AIWS is a very complex condition that typically has been described as isolated cases or series of cases.

Background: Up to 20% of patients with AD experience hallucinations. The pathological substrate is not known. Visual hallucinations (VH) are more common in dementia with Lewy bodies (DLB). In autopsy studies, up to 60% of patients with AD have concomitant Lewy body pathology. Decreased perfusion of the occipital lobe has been implicated in DLB patients with VH, and post-mortem studies point to both decreased cholinergic activity and reduced oxygenation of the occipital cortex in DLB., Methods: We used biochemical methods to assess microvessel density (level of von Willebrand factor, a marker of endothelial cell content), ante-mortem oxygenation (vascular endothelial growth factor, a marker of tissue hypoxia; myelin-associated glycoprotein to proteolipid protein-1 ratio, a measure of tissue oxygenation relative to metabolic demand), cholinergic innervation (acetylcholinesterase and choline acetyltransferase), butyrylcholinesterase and insoluble α-synuclein content in the BA18 and BA19 occipital cortex obtained post-mortem from 23 AD patients who had experienced visual hallucinations, 19 AD patients without hallucinations, 19 DLB patients, and 36 controls. The cohorts were matched for age, gender and post-mortem interval., Results: There was no evidence of reduced microvessel density, hypoperfusion or reduction in ChAT activity in AD with visual hallucinations. Acetylcholinesterase activity was reduced in both BA18 and BA19, in all 3 dementia groups, and the concentration was also reduced in BA19 in the DLB and AD without visual hallucinations groups. Insoluble α-synuclein was raised in the DLB group in both areas but not in AD either with or without visual hallucinations., Conclusions: Our results suggest that visual hallucinations in AD are associated with cholinergic denervation rather than chronic hypoperfusion or α-synuclein accumulation in visual processing areas of the occipital cortex.

There is emerging evidence indicating that color discrimination impairments can predict the development of Lewy body dementia in patients with rapid eye movement sleep behavior disorder, Parkinson disease, and in patients with mild cognitive impairment. Despite this clear relationship, color vision deficits are not seen uniformly in patients with dementia with Lewy bodies (DLB), suggesting a more nuanced association with the underlying neuropathology. Visual hallucinations represent a discriminating feature of DLB, and recent evidence implicates visual pathway dysfunction as a significant contributor to this phenomenon. In this study, we examined the relationship between color vision impairment and visual hallucinations, along with other clinical and neuropsychological features in 24 well-characterized patients with DLB alongside 25 healthy controls. Color discrimination impairment was seen in 16 (67%) of 24 DLB participants with a higher error score relative to controls ( P = .001). We demonstrate for the first time a strong association between color discrimination errors on the Farnsworth-Munsell 100 hue test and both the presence and severity of hallucinatory symptoms in DLB based on clinician-derived ( P = .008) and questionnaire-derived ( P = .03) measures. Correlation with clinical and neuropsychological variables revealed that color discrimination is significantly related to visuospatial difficulties measured by the clock-drawing task ( P = .02) but not to global measures of cognition, motor severity, age, or disease duration in our cohort. Factor analysis confirmed a unique relationship between color discrimination, visual hallucinations, and visuospatial function. Our results suggest that color discrimination does not simply relate to dementia but rather indexes higher order perceptual deficits that may predict visual hallucinations in Lewy body disorders and share a common pathophysiological substrate.

Aims and Objectives: The study aimed to assess and compare fractional anisotropy (FA) in bilateral superior longitudinal fasciculi (SLF) and arcuate fasciculi (AF) across schizophrenia with auditory hallucinations(AH), without AH, and healthy controls using diffusion tensor imaging (DTI) tractography., Methodology: Right-handed adult (18-50 years) individuals with DSM-5 diagnosis of schizophrenia with AH (group-I; n=30) were compared to those without lifetime AH (group-II; n=32) and healthy controls (group-III; n=30). Severity of psychosis in groups-I and II was assessed using SAPS, SANS, and CGI-SCH, and psychopathology was assessed using PSYRATS. The FA was calculated for all images on DTI studio-version 3.0 using tractography technique., Results: All three groups were comparable for age, gender, education and illness-severity. Schizophrenia subjects with AH had significantly lower FA values in bilateral SLF and AF compared to those without AH and healthy controls. No difference was observed in corresponding FA values between schizophrenia without AH and healthy controls., Conclusion: White matter disruptions in bilateral SLF and AF appear to be specific to schizophrenia with AH and must be explored further as potential marker of AH, pending replication in other studies., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Auditory verbal hallucinations (AVH) are one of the cardinal symptoms of schizophrenia, and are proposed to be associated with altered integrity of the left perisylvian language pathways. There is considerable heterogeneity in the pattern of white matter abnormalities across previous studies. We investigated the white matter integrity of the perisylvian language pathways in schizophrenia patients with AVH based on a relatively large sample dataset from four different sites. 113 schizophrenia patients with AVH, 96 patients without AVH (nAVH), and 269 healthy controls (HC) underwent diffusion-weighted imaging. Between-group comparisons were performed on the fractional anisotropy (FA) values of the anterior, posterior, and long segment fasciculi within the perisylvian language network. Analysis of covariance among the 3 groups revealed the long segment of the left perisylvian language pathways was significantly different in FA value. Post hoc analysis showed that compared with the HC group, the AVH group had significantly higher FA measurements in the left long segment. The nAVH group showed intermediate FA values for this segment compared to the AVH and HC group but did not differ significantly from either group. Furthermore, the prospective meta-analyses also revealed that FA value of the left long segment was significantly higher in the AVH group compared to the HC group. Our findings suggest the hyperconnectivity pattern of the left perisylvian language pathways in the presence of AVH in schizophrenia and support the self-monitoring of inner speech model., (Copyright © 2018 Elsevier B.V. All rights reserved.)

There is accumulating neuroimaging evidence for both structural and functional abnormalities in schizophrenia patients with persistent auditory verbal hallucinations (AVH). So far, the direct interrelationships between altered structural and functional changes underlying AVH are unknown. Recently, it has become possible to reveal hidden patterns of neural dysfunction not sufficiently captured by separate analysis of these two modalities. A data-driven fusion method called parallel independent component analysis (p-ICA) is able to identify maximally independent components of each imaging modality as well as the link between them. In the present study, we utilized p-ICA to study covarying components among gray matter volume maps computed from structural MRI (sMRI) and fractional amplitude of low-frequency fluctuations (fALFF) maps computed from resting-state functional MRI (rs-fMRI) data of 15 schizophrenia patients with AVH, 16 non-hallucinating schizophrenia patients (nAVH), and 19 healthy controls (HC). We found a significant correlation (r = 0.548, n = 50, p < .001) between a sMRI component and a rs-fMRI component, which was significantly different between the AVH and non AVH group (nAVH). The rs-fMRI component comprised temporal cortex and cortical midline regions, the sMRI component included predominantly fronto-temporo-parietal regions. Distinct clinical features, as measured by the Psychotic Symptoms Rating Scale (PSYRATS), were associated with two different modality specific rs-fMRI components. There was a significant correlation between a predominantly parietal resting-state network and the physical dimension of PSYRATS and the posterior cingulate/temporal cortex network and the emotional dimension of PSYRATS. These data suggest AVH-specific interrelationships between intrinsic network activity and GMV, together with modality-specific associations with distinct symptom dimensions of AVH., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Auditory hallucinations (AH) are a core symptom of psychosis. The brain abnormalities responsible for AH remain controversial due to inconsistent and conflicting findings across studies, with substantial confounding factors, such as chronicity. Few studies have examined the pathological changes that occur in the gray matter (GM) of patients with first-episode psychosis (FEP) and AH. The present study aims to validate the presence and characteristics of these structural abnormalities in relation to the intensity of psychotic symptoms and AH in a larger homogeneous sample than those of previous studies., Methods: A magnetic resonance voxel-based morphometric analysis was applied to a group of 215 patients with FEP (93 patients with AH and 122 patients without AH) and 177 healthy controls. The patients were evaluated using the PANSS scale., Results: Patients with FEP exhibited greater reductions in GM concentrations in the temporal, frontal, cingulate and insular areas than the healthy controls did. No specific differences were found between the patients with FEP and AH and the patients without AH. In addition, total scores on the PANSS were negatively correlated with GM reductions in the FEP group. No correlations were found between the severity of the AH and the GM volumes., Conclusions: As in previous studies, reductions in the GM concentrations in patients with FEP suggest that alterations are present in the early stages of psychosis, and these alterations are correlated with the severity of the illness. The GM reductions were not found to be related to the presence or severity of AH., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Hallucinations are a characteristic symptom of psychotic mental health conditions that are also experienced by many individuals without a clinical diagnosis. Hallucinations in schizophrenia have been linked to differences in the length of the paracingulate sulcus (PCS), a structure in the medial prefrontal cortex which has previously been associated with the ability to differentiate perceived and imagined information. We investigated whether this putative morphological basis for hallucinations extends to individuals without a clinical diagnosis, by examining whether nonclinical individuals with hallucinations have shorter PCS than nonclinical individuals without hallucinations. Structural MRI scans were examined from 3 demographically matched groups of individuals: 50 patients with psychotic diagnoses who experienced auditory verbal hallucinations (AVHs), 50 nonclinical individuals with AVHs, and 50 healthy control subjects with no life-time history of hallucinations. Results were verified using automated data-driven gyrification analyses. Patients with hallucinations had shorter PCS than both healthy controls and nonclinical individuals with hallucinations, with no difference between nonclinical individuals with hallucinations and healthy controls. These findings suggest that the association of shorter PCS length with hallucinations is specific to patients with a psychotic disorder. This presents challenges for full-continuum models of psychosis and suggests possible differences in the mechanisms underlying hallucinations in clinical and nonclinical groups., (© The Author(s) 2018. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

Peduncular hallucinosis (PH) is a rare clinical syndrome with dream-like visual hallucinations intruding normal consciousness. It was initially reported in a 72-year-old woman by Jean Lhermitte in 1992. We uncovered the medical file of this patient with handwritten notes by Lhermitte and commented on it in the light of neurological knowledge that was common at that time. All along his career, Lhermitte has always been fascinated by consciousness disturbances, dreams and hallucinations. He had here the brilliant intuition of linking PH to awareness mechanisms located in the mesencephalic area. This PH case represented a good opportunity to him to emphasize the close relationships between neurology and psychiatry., (Copyright © 2019. Published by Elsevier Masson SAS.)

Multimodal fusion has been regarded as a promising tool to discover covarying patterns of multiple imaging types impaired in brain diseases, such as schizophrenia (SZ). In this article, we aim to investigate the covarying abnormalities underlying SZ in a large Chinese Han population (307 SZs, 298 healthy controls [HCs]). Four types of magnetic resonance imaging (MRI) features, including regional homogeneity (ReHo) from resting-state functional MRI, gray matter volume (GM) from structural MRI, fractional anisotropy (FA) from diffusion MRI, and functional network connectivity (FNC) resulted from group independent component analysis, were jointly analyzed by a data-driven multivariate fusion method. Results suggest that a widely distributed network disruption appears in SZ patients, with synchronous changes in both functional and structural regions, especially the basal ganglia network, salience network (SAN), and the frontoparietal network. Such a multimodal coalteration was also replicated in another independent Chinese sample (40 SZs, 66 HCs). Our results on auditory verbal hallucination (AVH) also provide evidence for the hypothesis that prefrontal hypoactivation and temporal hyperactivation in SZ may lead to failure of executive control and inhibition, which is relevant to AVH. In addition, impaired working memory performance was found associated with GM reduction and FA decrease in SZ in prefrontal and superior temporal area, in both discovery and replication datasets. In summary, by leveraging multiple imaging and clinical information into one framework to observe brain in multiple views, we can integrate multiple inferences about SZ from large-scale population and offer unique perspectives regarding the missing links between the brain function and structure that may not be achieved by separate unimodal analyses., (© The Author(s) 2018. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Vascular endothelial growth factor A (VEGFA) dysfunction may contribute to a number of pathological processes that characterize psychotic disorders. However, the influence of VEGFA gene variants on clinical and neuroimaging phenotypes in psychotic disorders has yet to be shown. In the present study, we examined whether different VEGFA gene variants influence psychosis risk, symptom severity, cognition, and brain volume. The study group included 480 probands (Bipolar I disorder with psychosis, n = 205; Schizoaffective disorder, n = 112; Schizophrenia, n = 163) and 126 healthy controls that were recruited across six sites in the B-SNIP consortium. VEGFA variants identified for analysis (rs699947, rs833070, and rs2146323) were quantified via SNP chip array. We assessed symptoms and cognition using standardized clinical and neuropsychological batteries. The dorsolateral prefrontal cortex (DLPFC), medial temporal lobe, and hippocampal volumes were quantified using FreeSurfer. In our sample, VEGFA rs2146323 A- carriers showed reduced odds of being a proband (p = 0.037, OR = 0.65, 95% CI = 0.43-0.98) compared to noncarriers, but not for rs699947 or rs833070. In probands, rs2146323 A- carriers demonstrated fewer hallucinations (p = 0.035, Cohen's d = 0.194), as well as significantly greater DLPFC (p < 0.05, Cohen's d = -0.21) and parahippocampal volumes (p < 0.01, Cohen's d = -0.27). No clinical or neuroimaging associations were identified for rs699947 or rs833070. In general, we found that the three SNPs exhibited several significant negative relationships between psychosis symptoms and brain structure. In the probands and control groups, positive relationships were identified between several cognitive and brain volume measures. The findings suggest VEGFA effects in the DLPFC and hippocampus found in animals may also extend to humans. VEGFA variations may have important implications in identifying dimensional moderators of function that could be targeted through VEGFA-mediated interventions.

Psychosis, manifested through formed visual hallucinations or minor hallucinations, is a common non-motor symptom of Parkinson's disease (PD). The pathogenesis of psychosis in PD remains unclear; however, is possibly linked to structural and functional alterations in the hippocampus. To explore the role of hippocampus in psychosis, a detailed hippocampal subfield analysis was performed on PD patients with (PD-P) and without psychosis (PD-NP), and healthy controls (HC). An automated subfield parcellation was performed on T1 MRI images of 141 subjects (PD-P:42, PD-NP:51, and HC:48). The volumes of 12 subfields on each side were estimated and analyzed between the three groups and were corrected for multiple comparisons using false discovery rates. The volumes were also correlated to psychosis severity and specific neuropsychological tests and finally were employed to predict the psychosis severity in PD-P using a support vector regression (SVR) model. Compared to controls, PD-NP group did not demonstrate any significant differences; however, the PD-P group had significantly lower total hippocampal volume. Bilateral molecular layer, granule cell-dentate gyrus, left subiculum, and hippocampal tail and right CA3, CA4, and HATA illustrated significantly lower volumes, while bilateral hippocampal fissure demonstrated a significant widening. Compared to PD-NP, the PD-P group had higher volume of the bilateral hippocampal fissures. Finally, SVR could significantly predict the psychosis severity from all the subfield volumes. Our findings indicate a higher degeneration of specific hippocampal subfields in PD-P compared to controls and a trend of higher volume of hippocampal fissures in PD-P group than in PD-NP.