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Background: Despite the high clinical role of delusions as a transnosological psychopathological phenomenon, the number of experimental studies on the different types of delusions across schizophrenia spectrum is still relatively small, and their results are somehow inconsistent. We aimed to understand the current state of knowledge regarding the structural and functional brain alterations in delusions to determine whether particular types of delusions are associated with specific brain changes and to identify common alterations underlying the formation and persistence of delusions regardless of their content., Methods: For this systematic review, we followed PRISMA guidelines to search in PubMed for English papers published between 1953 and September 30, 2023. The initial inclusion criteria for screening purposes were articles that investigated delusions or subclinical delusional beliefs in schizophrenia spectrum disorders, high clinical or genetic risk for schizophrenia using fMRI, sMRI or/and dwMRI methods. Exclusion criteria during the screening phase were articles that investigated lesion-induced or substance-induced delusions, delusions in Alzheimer's disease and other neurocognitive disorders, single case studies and non-human studies. The publication metadata were uploaded to the web-tool for working on systematic reviews, Rayyan. For each of the studies, a table was filled out with detailed information., Results: We found 1752 records, of which 95 full-text documents were reviewed and included in the current paper. Both nonspecific and particular types of delusions were associated with widespread structural and functional alterations. The most prominent areas affected across all types of delusions were the superior temporal cortex (predominantly left language processing areas), anterior cingulate/medial prefrontal cortex and insula. The most reproducible findings in paranoia may be alterations in the functioning of the amygdala and its interactions with other regions. Somatic delusions and delusional infestation were mostly characterized by alterations in the insula and thalamus., Discussion: The data are ambiguous; however, in general the predictive processing framework seems to be the most widely accepted approach to explaining different types of delusions. Aberrant prediction errors signaling during processing of social, self-generated and sensory information may lead to inaccuracies in assessing the intentions of others, self-relevancy of ambiguous stimuli, misattribution of self-generated actions and unusual sensations, which could provoke delusional ideation with persecutory, reference, control and somatic content correspondingly. However, currently available data are still insufficient to draw conclusions about the specific biological mechanisms of predictive coding account of delusions. Thus, further studies exploring more homogeneous groups and interaction of diagnoses by types of delusions are needed. There are also some limitations in this review. Studies that investigate delusions induced by lesions, substance abuse or neurodegeneration and studies using modalities other than fMRI, sMRI or dwMRI were not included in the review. Due to the relatively small number of publications, we systematized them based on a certain type of delusions, while the results could also be affected by the diagnosis of patients, the presence and type of therapy, illness duration etc., 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 article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Previous studies on neuroimaging findings in Alzheimer's disease (AD) patients with hallucinations and delusions have yielded inconsistent results. We aimed to systematically review neuroimaging findings of delusions and hallucinations in AD patients to describe the most prominent neuroimaging features., Methods: We performed a comprehensive search in three online databases, including PubMed, Scopus, and Web of Science in June 2023. We included studies that reported neuroimaging features of AD patients with delusion, hallucination, or psychosis., Results: After the screening, 34 studies with 2241 AD patients were eligible to be included in our qualitative synthesis. On the basis of the included studies, there are significant changes in the volume and perfusion levels of broad brain areas, including the hippocampus, amygdala, insula, cingulate, occipital, frontal, prefrontal, orbitofrontal, temporal, and parietal cortices in these patients. Moreover, AD patients with psychosis, hallucinations, or delusions reflected different EEG waves compared to AD patients without these disorders., Conclusion: The results of our review provided evidence about the neuroimaging alterations in AD patients suffering from psychosis, hallucinations, and delusions using different imaging methods. AD patients with psychosis, hallucinations, or delusions have significant differences in the volume and perfusion levels of various brain regions along with alterations in EEG waves and biological molecules compared to patients with only AD., (© 2024 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)

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.)

Delusion is an important feature of schizophrenia, which may stem from cognitive biases. Working memory (WM) is the core foundation of cognition, closely related to delusion. However, the knowledge of neural mechanisms underlying the relationship between WM and delusion in schizophrenia is poorly investigated. Two hundred and thirty patients with schizophrenia (dataset 1: n = 130; dataset 2: n = 100) were enrolled and scanned for an N-back WM task. We constructed the WM-related whole-brain functional connectome and conducted Connectome-based Predictive Modelling (CPM) to detect the delusion-related networks and built the correlation model in dataset 1. The correlation between identified networks and delusion severity was tested in a separate, heterogeneous sample of dataset 2 that mainly includes early-onset schizophrenia. The identified delusion-related network has a strong correlation with delusion severity measured by the NO.20 item of SAPS in dataset 1 (r = 0.433, p = 2.7 × 10 -7 , permutation-p = 0.035), and can be validated in the same dataset by using another delusion measurement, that is, the P1 item of PANSS (r = 0.362, p = 0.0005). It can be validated in another independent dataset 2 (NO.20 item of SAPS for r = 0.31, p = 0.0024, P1 item of PANSS for r = 0.27, p = 0.0074). The delusion-related network comprises the connections between the default mode network (DMN), cingulo-opercular network (CON), salience network (SN), subcortical, sensory-somatomotor network (SMN), and visual networks. We successfully established correlation models of individualized delusion based on the WM-related functional connectome and showed a strong correlation between delusion severity and connections within the DMN, CON, SMN, and subcortical network., Competing Interests: Declaration of competing interest All other authors report no relevant conflicts., (Copyright © 2024. Published by Elsevier Ltd.)

Objectives: Psychosis, especially in delusions, greatly impairs the quality of life of patients with Parkinson's disease (PD) and their caregivers. Few objective risk indicators of the association between psychosis and clinical features has been reported. It is unclear whether the reduction in DAT binding represents the underlying mechanism of delusion or its association. There are no long-term data on the objective prognostic value of DAT binding for delusions. We investigated whether DAT binding at baseline can be a prognostic risk factor for future development of PD delusions., Materials and Methods: We reviewed the detailed clinical chart of patients with PD without a history of psychosis who underwent [ 123 I]FP-CIT SPECT during the disease. The endpoint was defined as when the delusions occurred during the 5 years after the examination of [ 123 I]FP-CIT SPECT. Specific binding ratio (SBR) values were calculated., Results: Sixty-one patients with PD were included in the analysis, and 11 patients had delusions within 5 years of [ 123 I] FP-CIT SPECT. The average (p = 0.004), minimum (p = 0.004), maximum (p = 0.001), right-sided (p = 0.002), and left-sided (p = 0.003) SBRs in the striatum were significantly smaller in patients with delusions than in patients without delusions. Each difference of each SBR was significantly smaller than those without delusions after adjusting after controlling for age, gender, disease severity, timing of [ 123 I]FP-CIT SPECT, anti-parkinsonian medications, hospitalization, administering more or newly anti-parkinsonian drugs, and receiving DBS or LCIG., Conclusions: PD delusions is still problematic, and lowering DAT binding may be helpful for predicting future delusions, regardless of the timing of [ 123 I]FP-CIT SPECT., Competing Interests: Declaration of Competing Interest The authors reported no conflict of interest. There was no funding related to our paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aim: While conservatism bias refers to the human need for more evidence for decision-making than rational thinking expects, the jumping to conclusions (JTC) bias refers to the need for less evidence among individuals with schizophrenia/delusion compared to healthy people. Although the hippocampus-midbrain-striatal aberrant salience system and the salience, default mode (DMN), and frontoparietal networks ("triple networks") are implicated in delusion/schizophrenia pathophysiology, the associations between conservatism/JTC and these systems/networks are unclear., Methods: Thirty-seven patients with schizophrenia and 33 healthy controls performed the beads task, with large and small numbers of bead draws to decision (DTD) indicating conservatism and JTC, respectively. We performed independent component analysis (ICA) of resting functional magnetic resonance imaging (fMRI) data. For systems/networks above, we investigated interactions between diagnosis and DTD, and main effects of DTD. We similarly applied ICA to structural and diffusion MRI to explore the associations between DTD and gray/white matter., Results: We identified a significant main effect of DTD with functional connectivity between the striatum and DMN, which was negatively correlated with delusion severity in patients, indicating that the greater the anti-correlation between these networks, the stronger the JTC and delusion. We further observed the main effects of DTD on a gray matter network resembling the DMN, and a white matter network connecting the functional and gray matter networks (all P < 0.05, family-wise error [FWE] correction). Function and gray/white matter showed no significant interactions., Conclusion: Our results support the novel association of conservatism and JTC biases with aberrant salience and default brain mode., (© 2024 The Authors. Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

Depressive state is a common complication of spinocerebellar ataxia type 3 (SCA3). To the best of our knowledge, cases of SCA3 presenting with cenesthopathy have not been described. Here, we present a case of a severe depressive state with cenesthopathy and delusion in a young Japanese man with SCA3. A 43-year-old Japanese man with SCA3 developed a severe depressive state with associated cenesthopathy and delusion. He was treated with escitalopram (10 mg/day) and olanzapine (2.5 mg/day). Computed tomography showed atrophy of the cerebellum, bilateral superior cerebellar peduncle, and tegmentum of the pons. Single-photon emission computed tomography demonstrated reduced blood flow in the cerebellum, vermis, and brainstem. After 8 weeks, his depressive state and delusion improved; however, his cenesthopathy persisted. We encountered a case of a severe depressive state with cenesthopathy and delusion in a young Japanese man with SCA3. This case supports previous studies that the cerebellum could have a role beyond motor functions., (© 2021. The Author(s).)

Delusions in schizophrenia are false beliefs that are assigned certainty and not afforded the scrutiny that normally gives rise to doubt, even under conditions of weak evidence. The goal of the current functional magnetic resonance imaging (fMRI) study is to identify the brain network(s) involved in gathering information under conditions of weak evidence, in people with schizophrenia experiencing delusions. fMRI activity during probabilistic reasoning in people with schizophrenia experiencing delusions (n = 29) compared to people with schizophrenia not experiencing delusions (n = 41) and healthy controls (n = 41) was observed when participants made judgments based on evidence that weakly or strongly matched (or mismatched) with the focal hypothesis. A brain network involved in visual attention was strongly elicited for conditions of weak evidence for healthy controls and patients not experiencing delusions, but this increase was absent for patients experiencing delusions. This suggests that the state associated with delusions manifests in fMRI as reduced activity in an early visual attentional process whereby weak evidence is incorrectly stamped as conclusive, manifestating as a feeling of fluency and misplaced certainty, short-circuiting the search for evidence, and providing a candidate neural process for 'seeding' delusions., (Copyright © 2022. Published by Elsevier B.V.)

Background and Hypothesis: Delusions are characteristic of psychotic disorders; however, the brain correlates of delusions remain poorly known. Imaging studies on delusions typically compare images across individuals. Related confounding of inter-individual differences beyond delusions may be avoided by comparing delusional and non-delusional states within individuals., Study Design: We studied correlations of delusions using intra-subject correlation (intra-SC) and inter-subject correlation of functional magnetic resonance imaging (fMRI) signal time series, obtained during a movie stimulus at baseline and follow-up. We included 27 control subjects and 24 first-episode psychosis patients, who were free of delusions at follow-up, to calculate intra-SC between fMRI signals obtained during the two time points. In addition, we studied changes in functional connectivity at baseline and during the one-year follow-up using regions where delusion severity correlated with intra-SC as seeds., Results: The intra-SC correlated negatively with the baseline delusion severity in the bilateral anterior insula. In addition, we observed a subthreshold cluster in the anterior cingulate. These three regions constitute the cortical salience network (SN). Functional connectivity between the bilateral insula and the precuneus was weaker in the patients at baseline than in patients at follow-up or in control subjects at any time point., Conclusions: The results suggest that intra-SC is a powerful tool to study brain correlates of symptoms and highlight the role of the SN and internetwork dysconnectivity between the SN and the default mode network in delusions., 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 © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Knowing explicitly where we are is an interpretation of our spatial representations. Reduplicative paramnesia is a disrupting syndrome in which patients present a firm belief of spatial mislocation. Here, we studied the largest sample of patients with delusional misidentifications of space (ie, reduplicative paramnesia) after stroke to shed light on their neurobiology., Methods: In a prospective, cumulative, case-control study, we screened 400 patients with acute right-hemispheric stroke. We included 64 cases and 233 controls. First, lesions were delimited and normalized. Then, we computed structural and functional disconnection maps using methods of lesion-track and network-mapping. The maps were compared, controlling for confounders. Second, we built a multivariate logistic model, including clinical, behavioral, and neuroimaging data. Finally, we performed a nested cross-validation of the model with a support-vector machine analysis., Results: The most frequent misidentification subtype was confabulatory mislocation (56%), followed by place reduplication (19%), and chimeric assimilation (13%). Our results indicate that structural disconnection is the strongest predictor of the syndrome and included 2 distinct streams, connecting right fronto-thalamic and right occipitotemporal structures. In the multivariate model, the independent predictors of reduplicative paramnesia were the structural disconnection map, lesion sparing of right dorsal fronto-parietal regions, age, and anosognosia. Good discrimination accuracy was demonstrated (area under the curve = 0.80 [0.75-0.85])., Interpretation: Our results localize the anatomic circuits that may have a role in the abnormal spatial-emotional binding and in the defective updating of spatial representations underlying reduplicative paramnesia. This novel data may contribute to better understand the pathophysiology of delusional syndromes after stroke. ANN NEUROL 2021;89:1181-1194., (© 2021 American Neurological Association.)

Background: Obsession and delusion are theoretically distinct from each other in terms of reality testing. Despite such phenomenological distinction, no extant studies have examined the identification of common and distinct neural correlates of obsession and delusion by employing biologically grounded methods. Here, we investigated dimensional effects of obsession and delusion spanning across the traditional diagnostic boundaries reflected upon the resting-state functional connectivity (RSFC) using connectome-wide association studies (CWAS)., Methods: Our study sample comprised of 96 patients with obsessive-compulsive disorder, 75 patients with schizophrenia, and 65 healthy controls. A connectome-wide analysis was conducted to examine the relationship between obsession and delusion severity and RFSC using multivariate distance-based matrix regression., Results: Obsession was associated with the supplementary motor area, precentral gyrus, and superior parietal lobule, while delusion was associated with the precuneus. Follow-up seed-based RSFC and modularity analyses revealed that obsession was related to aberrant inter-network connectivity strength. Additional inter-network analyses demonstrated the association between obsession severity and inter-network connectivity between the frontoparietal control network and the dorsal attention network., Conclusions: Our CWAS study based on the Research Domain Criteria (RDoC) provides novel evidence for the circuit-level functional dysconnectivity associated with obsession and delusion severity across diagnostic boundaries. Further refinement and accumulation of biomarkers from studies embedded within the RDoC framework would provide useful information in treating individuals who have some obsession or delusion symptoms but cannot be identified by the category of clinical symptoms alone.

Delusions are irrational, tenacious, and incorrigible false beliefs that are the most common symptom of a range of brain disorders including schizophrenia, Alzheimer's, and Parkinson's disease. In the case of schizophrenia and other primary delusional disorders, their appearance is often how the disorder is first detected and can be sufficient for diagnosis. At this time, not much is known about the brain dysfunctions leading to delusions, and hindering our understanding is that the complexity of the nature of delusions, and their very unique relevance to the human experience has hampered elucidation of their underlying neurobiology using either patients or animal models. Advances in neuroimaging along with improved psychiatric and cognitive modeling offers us a new opportunity to look with more investigative power into the deluded brain. In this article, based on data obtained from neuroimaging studies, we have attempted to draw a picture of the neural networks involved when delusion is present and evaluate whether different manifestations of delusions engage different regions of the brain.

The dopamine D1 receptor (D1R) is thought to play a role in psychosis and schizophrenia, however positron emission tomography studies comparing patients and controls have been inconsistent. To circumvent some of the limitations of clinical studies, such as antipsychotic exposure, an alternative approach is to examine subclinical psychotic symptoms within the general population, i.e. psychosis proneness traits. In this study, we investigated whether D1R availability is associated with delusional ideation in healthy controls, in four experiments, using [ 11 C]SCH23390 PET (n = 76) and psychometric questionnaires (n = 217). We performed exploratory analyses, direct self-replication, and confirmatory analyses using Bayesian statistical modelling. Collectively, we found strong evidence that there is little to no linear association between delusional ideation and D1R. If hypothesised changes in D1R in drug-naive psychosis patients can be confirmed, our results suggest that they may either occur at disease onset, or that they are associated with specific aspects of psychosis other than delusional ideation., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest. SC has received grant support from AstraZeneca as co-investigator, and has served as speaker for Roche and Otsuka Pharmaceuticals. L.F. was, during the study, employed at the Precision Medicine and Genomics, IMED Biotech Unit at Karolinska Institutet., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Integrating evidence that contradicts a belief is a fundamental aspect of belief revision and is closely linked to delusions in schizophrenia. In a previous functional magnetic resonance imaging (fMRI) study on healthy individuals, we identified functional brain networks underlying evidence integration as visual attention network (VsAN; dorsal anterior cingulate cortex, insula, occipital regions), default-mode network (DMN), and cognitive evaluation network (CEN; orbitofrontal cortex, inferior frontal gyrus, parietal cortex). In the current clinical fMRI study, we compared network-based activity during evidence integration between healthy controls (n = 41), nondelusional (n = 37), and delusional (n = 33) patients with schizophrenia, and related this activity to cognitive processing involved in evidence integration measured outside the scanner. Task-induced coordinated activation was measured using group-constrained principal component analysis for fMRI. Increased VsAN activation, reduced DMN deactivation, and reduced CEN activation were observed for schizophrenia, with this pattern being most pronounced for the delusional group. Importantly, poor evidence integration comprehensively measured outside the scanner was significantly associated with increased VsAN activation and reduced DMN deactivation when processing confirmatory evidence, and with reduced CEN activation when processing disconfirmatory evidence. This is the first comprehensive study of the functional brain networks associated with evidence integration in schizophrenia and highlights how an imbalance of functional brain networks responding to confirmatory and disconfirmatory evidence may underlie delusions in schizophrenia., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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.)

Background: The structural integrity of the anterior cingulum has been repeatedly observed to be abnormal in patients with schizophrenia. More recently, aberrant myelination of frontal fasciculi, especially, cingulum has been proposed to underlie delayed corollary discharges that can affect sense of agency and contribute to delusions of control (Schneiderian delusions). Using the magnetization transfer phenomenon at an ultra-high field 7T MRI, we investigated the putative myelin content of cingulum bundle in patients with schizophrenia., Methods: Seventeen clinically stable patients with schizophrenia and 20 controls were recruited for this 7T MRI study. We used a region-of-interest method and extracted magnetization transfer ratio (MTR) from left and right dorsal cingulum bundles and estimated patients v. controls differences. We also related the cingulum MTR values to the severity of Schneiderian delusions., Results: Patients had a significant reduction in the MTR, indicating reduced myelin content, in the cingulum bundle (right cingulum Hedges' g = 0.91; left cingulum g = 0.03). The reduced MTR of left cingulum was associated with higher severity of Schneiderian delusions (τ = -0.45, p = 0.026) but no such relationship was seen for the right cingulum MTR (τ = -0.136, p = 0.50) among patients. The association between the left cingulum MTR and Schneiderian delusions was not explained by the presence of other delusions, hallucinations, disorganization or negative symptoms., Conclusions: Dysmyelination of the cingulum bundle is seen in a subgroup of patients with schizophrenia and may be involved in the mechanism of Schneiderian delusions.

Delusion is a belief about yourself, people, or events that has no accordance with reality. Although it is known that stroke could cause various psychiatric and psychological effects, including depression, anxiety, and aggressiveness, psychotic symptoms, especially delusions, are rather uncommon. The most investigated poststroke delusions are paranoid type, nihilistic, and Fregoli syndrome. We will describe two patients showing delusion symptoms (Cotard-like and erotomanic ones) that occurred after a stroke involving the right temporal lobe, the basal ganglia and insular region, persisting for a long period after the stroke onset. We have, therefore, supposed that the simultaneous involvement of these brain areas could be involved in the neuroanatomical basis of delusions, as also demonstrated by the neurofunctional evaluation.

Objective: Delusions affect approximately a third of Alzheimer disease (AD) patients and are associated with poor outcomes. Previous studies investigating the neuroanatomic correlates of delusions have yet to reach a consensus, with findings of reduced volume across all lobes, particularly in frontal regions. The current study examined the gray matter (GM) differences associated with delusions in AD., Methods: Using voxel-based morphometry, we assessed GM in 23 AD patients who developed delusions (AD+D) and 36 comparable AD patients who did not (AD-D) at baseline and follow-up. Analysis of variance was used to identify consistent differences between AD+D and AD-D patients across time points (main effect of group), consistent changes from baseline to follow-up (main effect of time), and differential changes between AD+D and AD-D over time (interaction of group and time). All data were obtained from the National Alzheimer's Coordinating Center database., Results: The AD+D group had consistently lower frontal GM volume, although both groups showed decreased GM in frontotemporal brain regions over time. An interaction was observed between delusions and longitudinal change, with AD+D patients having significantly elevated GM in predominantly temporal areas at baseline assessment, becoming significantly lower than the AD-D group at follow-up., Conclusion: These findings suggest that, there are specific volumetric markers that distinguish patients with delusions from those without, before, and after the onset of delusions. Specifically, the decline of GM in temporal areas that had elevated levels prior to the onset of delusions may be involved in the manifestation of delusions., (Copyright © 2018 American Association for Geriatric Psychiatry. All rights reserved.)

Background: Working-memory impairment is a core cognitive dysfunction in people with schizophrenia and people at mental high risk. Recent imaging studies on working memory have suggested that abnormalities in prefrontal activation and in connectivity between the frontal and parietal regions could be neural underpinnings of the different stages of psychosis. However, it remains to be explored whether comparable alterations are present in people with subclinical levels of psychosis, as experienced by a small proportion of the general population who neither seek help nor show constraints in daily functioning., Methods: We compared 24 people with subclinical high delusional ideation and 24 people with low delusional ideation. Both groups performed an n-back working-memory task during functional magnetic resonance imaging. We characterized frontoparietal effective connectivity using dynamic causal modelling., Results: Compared to people who had low delusional ideation, people with high delusional ideation showed a significant increase in dorsolateral prefrontal activation during the working-memory task, as well as reduced working-memory-dependent parietofrontal effective connectivity in the left hemisphere. Group differences were not evident at the behavioural level., Limitations: The current experimental design did not distinguish among the working-memory subprocesses; it remains unexplored whether differences in connectivity exist at that level., Conclusion: These findings suggest that alterations in the working-memory network are also present in a nonclinical population with psychotic experiences who do not display cognitive deficits. They also suggest that alterations in working-memory-dependent connectivity show a putative continuity along the spectrum of psychotic symptoms., Competing Interests: None declared., (© 2019 Joule Inc. or its licensors)

Introduction: Although important to cognitive neuropsychiatry and theories of delusions, Capgras delusion has largely been reported in single case studies. Bell et al. [2017. Uncovering Capgras delusion using a large scale medical records database. British Journal of Psychiatry Open, 3(4), 179-185] previously deployed computational and clinical case identification on a large-scale medical records database to report a case series of 84 individuals with Capgras delusion. We replicated this approach on a new database from a different mental health service provider while additionally examining instances of violence, given previous claims that Capgras is a forensic risk., Methods: We identified 34 additional cases of Capgras. Delusion phenomenology, clinical characteristics, and presence of lesions detected by neuroimaging were extracted., Results: Although most cases involved misidentification of family members or partners, a notable minority (20.6%) included the misidentification of others. Capgras typically did not present as a monothematic delusion. Few cases had identifiable lesions with no evidence of right-hemisphere bias. There was no evidence of physical violence associated with Capgras., Conclusions: Findings closely replicate Bell et al. (2017). The majority of Capgras delusion phenomenology conforms to the "dual route" model although a significant minority of cases cannot be explained by this framework.

Structural brain abnormalities, including decreased gray matter (GM) and white matter (WM) volume, have been observed in patients with schizophrenia. These decrements were found to be associated with positive and negative symptoms, but affective symptoms (depression and anxiety) were poorly explored. We hypothesized that abnormalities in GM and WM volume might also be related to affective symptoms. GM and WM volumes were calculated from high-resolution T1 structural images acquired from 24 patients with schizophrenia and 26 healthy controls, and the associations of positive, negative, and affective symptoms with the brain volumes that showed significant reduction in patients were investigated. Patients demonstrated GM volume reductions in the bilateral prefrontal cortex, and WM volume reductions in the right frontal and left corpus callosum. Prefrontal cortex volume was significantly and inversely associated with both auditory-verbal hallucinations and depression severity. WM volume alterations, in contrast, were related to alogia, anhedonia, and delusions. The combined impact of auditory-verbal hallucinations and depression on similar sub-regions of the prefrontal cortex suggests that depression is involved in hearing voices. Further, this adverse impact of depression on prefrontal GM volume may underlie the impairment demonstrated by these patients in cognitive tasks that rely on executive processes., (Copyright © 2018. Published by Elsevier B.V.)

In many cases delusions in schizophrenia spectrum disorders (SSD) are driven by strong emotions such as feelings of paranoia or grandiosity. We refer to these extreme emotional experiences as psychotic affectivity. We hypothesized that increased structural connectivity of the supero-lateral medial forebrain bundle (slMFB), a major tract of the reward system, is associated with delusional psychotic affectivity. Forty-six patients with SSD and 44 healthy controls (HC) underwent diffusion weighted magnetic resonance imaging (DW-MRI)-scans. The slMFB and a comparison tract (corticospinal tract) were reconstructed using diffusion tensor imaging (DTI)-based tractography. Fractional anisotropy (FA) was sampled across the tracts. We used a mixed-model analyses of variance controlling for age and gender to compare FA of bilateral slMFB between SSD-patients and HC. Correlations of FA of bilateral slMFB and the PANSS-positive item delusions were calculated. In addition, FA was compared between three clinically homogeneous SSD-subgroups in terms of psychotic affectivity (severe, mild and no PA, sPA, mPA, nPA) and HC. FA of the slMFB did not differ between all SSD-patients and HC. In SSD-patients there was a positive correlation between delusions and FA in bilateral slMFB. Likewise, SSD-subgroups of psychotic affectivity and HC differed significantly in FA of the slMFB. Results were driven by higher FA in the right slMFB in sPA as compared to nPA and to HC. There was no significant effect for the comparison tract. In conclusion, increased structural connectivity of the slMFB may underlie delusional experiences of paranoia and grandiosity in SSD., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Reasoning biases such as the jumping-to-conclusions bias (JTC) are thought to contribute to delusions. Interventions targeting these biases such as metacognitive training (MCT) may improve delusions. So far, it is not clear whether JTC depends on dopaminergic reward areas that constitute the main action locus of antipsychotic drugs, or on additional cortical areas. The present study aimed to investigate fMRI activation and functional connectivity patterns underlying JTC, and their changes following MCT, in patients with delusions., Methods: Participants were 25 healthy individuals and 26 patients with current delusions who were either medication-free or on stable medication without sufficient response. We assessed (1) BOLD activity in the task-positive (TPN), task-negative (TNN), and subcortical reward network (RN); (2) Psychophysiological interactions (PPI) of peak activation areas., Results: Presence of JTC (irrespective of group) was associated with lower RN activity during conclusion events, and with increased effective connectivity between TPN and TNN during draw events. Following MCT, changes were observed in TPN activity and in effective connectivity of inferior parietal cortex (part of the TPN) with all three target networks., Conclusion: JTC is associated not only with reward system areas that constitute the main target of antipsychotic drugs, but also with cortical areas, particularly of the TPN.

Background: Monothematic delusional disorders are characterized by a single tenacious belief. They provide a great opportunity to study underlying brain structures in the absence of confounding symptoms that accompany delusions in schizophrenia. Delusional beliefs include persecution, jealousy or somatic delusions including infestation. It is unclear whether specific delusional content is associated with distinct neural substrates., Methods: We used magnetic resonance imaging in patients presenting with somatic vs. non-somatic delusional disorders. Patients with delusional infestation (DI, n=18), and individuals with non-somatic delusional disorders (n=19) were included, together with healthy volunteers (n=20). Uni- and multivariate techniques for structural data analysis were applied to provide a comprehensive characterization of abnormal brain volume at both the regional and neural network level., Results: Patients with DI showed lower gray matter volume in thalamic, striatal (putamen), insular and medial prefrontal brain regions in contrast to non-somatic delusional disorders and healthy controls. Importantly, these differences were consistently detected at regional and network level. Compared to healthy controls, patients with delusional disorders other than DI showed lower gray matter volume in temporal cortical regions., Conclusion: The data support the notion that dysfunctional somatosensory and peripersonal networks could mediate somatic delusions in patients with DI in contrast to delusional disorders without somatic content. The data also suggest putative content-specific neural signatures in delusional disorders and in delusion formation per se., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Schizophrenia is characterized by social interaction deficits contributing to poor functional outcome. Hand gesture use is particularly impaired, linked to frontal lobe dysfunction and frontal grey matter deficits. The functional neural correlates of impaired gesturing are currently unclear. We therefore investigated aberrant brain activity during impaired gesturing in schizophrenia. We included 22 patients with schizophrenia and 25 healthy control participants matched for age, gender, and education level. We obtained functional magnetic resonance imaging data using an event-related paradigm to assess brain activation during gesture planning and execution. Group differences in whole brain effects were calculated using factorial designs. Gesture ratings were performed by a single rater, blind to diagnoses and clinical presentation. During gesture planning and execution both groups activated brain areas of the praxis network. However, patients had reduced dorsolateral prefrontal cortex (DLPFC) and increased inferior parietal lobe (IPL) activity. Performance accuracy was associated with IPL activity in patients. Furthermore, patients activated temporal poles, amygdala and hippocampus during gesture planning, which was associated with delusion severity. Finally, patients demonstrated increased dorsomedial prefrontal cortex activity during planning of novel gestures. We demonstrate less prefrontal, but more IPL and limbic activity during gesturing in schizophrenia. IPL activity was associated with performance accuracy, whereas limbic activity was linked to delusion severity. These findings may reflect impaired social action planning and a limbic interference with gestures in schizophrenia contributing to poor gesture performance and consequently poor social functioning in schizophrenia.

Delusions of reference in schizophrenia are thought to result from misattributions of self-relevance to neutral events. Activation of regions within the cortical midline structures (CMS; e.g., medial prefrontal cortex, cingulate cortex, and precuneus) have been previously associated with self-referential processing in schizophrenia patients; however, the specificity of this pattern to individuals with current delusions of reference has yet to be determined. In the present study, we identified functional brain networks that underlie self-referential processing using task-based multivariate functional connectivity. Healthy control subjects (n=15) and schizophrenia patients with (n=14) and without (n=13) current delusions of reference were shown ambiguous statements while undergoing functional magnetic resonance imaging, and evaluated whether these statements were thought to be specifically about them. Our results revealed two functionally distinct CMS networks that differed between patients and controls during self-referential processing: a posterior CMS network, which showed muted deactivity in non-delusional patients; and an anterior CMS network, in which delusional patients demonstrated hyperactivity. Furthermore, activity within the anterior CMS network across the three groups showed a linear pattern of increasing activity associated with greater intensity of delusions of reference, suggesting that hyperactivity in this network may underlie delusions of reference., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Erotomania arising from a central nervous system (CNS) neoplasm has not been previously described. Here, we present the first known case, to our knowledge, of erotomania with associated persecutory delusions arising following diagnosis and treatment of a left frontal lobe brain tumor.

Background: Delusion is the most characteristic symptom of psychosis. While researchers suggested an association between changes of the cortical salience network (CSN) and delusion, whether these CSN findings are a cause or a consequence of delusion remains unknown., Method: To assess the effect of CSN functioning to forthcoming changes in delusion scores, we measured brain activation with 3-T functional magnetic resonance imaging in two independent samples of first-episode psychosis patients (total of 27 patients and 23 healthy controls). During scanning, the patients evaluated statements about whether an individual's psychosis-related experiences should be described as a mental illness, and control statements that were also evaluated by healthy controls. Symptoms were assessed at the baseline and at 2 months follow-up with Brief Psychiatric Rating Scale., Results: Both tasks activated the CSN in comparison with rest. Activation of CSN ('illness evaluation v. control task' contrast) in patients positively correlated with worsening of or less improvement in delusions at the 2-month follow-up assessment. This finding was independent of delusion and clinical insight scores at the baseline evaluation., Conclusions: Our findings link symptom-evaluation-related CSN functioning to severity of delusion and, importantly, add a new layer of evidence for the contribution of CSN functioning to the longitudinal course of delusions.

Assessing morphological, perfusion and metabolic brain changes preceding or associated with neuropsychiatric symptoms (NPSs) will help in the understanding of pathophysiological underlying processes in Alzheimer's disease (AD). This review aimed to highlight the main findings on significant associations between neuroimaging and NPSs, the pathophysiology to elucidate possible underlying mechanisms, and methodological issues to aid future research. Research papers published from January 1990 to October 2015 were identified in the databases PsycInfo, Embase, PubMed and Medline, using key words related to NPSs and imaging techniques. In addition to a semi-systematic search in the databases, we also performed hand searches based on reported citations identified to be of interest. Delusions, apathy and depression symptoms were particularly associated with brain changes in AD. The majority of studies disclosed an association between frontal lobe structural and/or metabolic changes and NPSs, implicating, interestingly, for all 12 NPSs studied, the anterior cingulate cortex although temporal, subcortical and parietal regions, and insula were also involved. Given the high degree of connectivity of these brain areas, frontal change correlates of NPSs may help in the understanding of neural network participation. This review also highlights crucial methodological issues that may reduce the heterogeneity of results to enable progress on the pathophysiological mechanisms and aid research on NPS treatments in AD. Based on a broad review of the current literature, a global brain pattern to support the huge heterogeneity of neuroimaging correlates of NPSs in AD and methodological strategies are suggested to help direct future research., (© 2016 EAN.)

Delusions are cardinal positive symptoms in schizophrenia; however, the neural substrates of delusions remain unknown. In the present study, we investigated the neural correlates of delusions in schizophrenia using multi-modal magnetic resonance imaging (MRI) techniques. Diffusion, structural and perfusion MRIs were performed in 19 schizophrenia patients with severe delusions, 30 patients without delusions and 30 healthy controls. Fractional anisotropy (FA), gray matter volume (GMV) and cerebral blood flow (CBF) were voxel-wisely compared among the three groups. Although patients without delusions exhibited decreased FA in white matter regions and decreased GMV in gray matter regions relative to controls, patients with severe delusions demonstrated comparable FA in all of these white matter regions and similar GMV in most of these gray matter regions. Both patient subgroups had less GMV in the amygdala and anterior cingulate cortex than controls. Although two patient subgroups showed consistent CBF changes relative to controls, only CBF in the anterior cingulate cortex was lower in patients with severe delusions than in patients without delusions. These findings suggest that schizophrenia patients with severe delusions have relatively normal structural integrity. Importantly, the excessively reduced perfusion in the anterior cingulate cortex may be associated with the development of delusions in schizophrenia.

Background: There is growing evidence to suggest that delusions associated with schizophrenia arise from altered structural brain connectivity. The present study investigated whether structural changes in three major fasciculi that interconnect the limbic system - the cingulum bundle, uncinate fasciculus and fornix - are associated with delusions in chronic schizophrenia patients., Methods: Free-water corrected Diffusion Tensor Imaging was used to investigate the association between delusions and both microstructural changes within these three fasciculi and extracellular changes in the surrounding free-water. Clinical data and diffusion MRI scans were obtained from 28 healthy controls and 86 schizophrenia patients, of whom 34 had present state delusions, 35 had a lifetime history but currently remitted delusions, and 17 had never experienced delusions., Results: While present state and remitted delusions were found to be associated with reduced free-water corrected fractional anisotropy (FAT) and increased free-water corrected radial diffusivity (RDT) in the cingulum bundle bilaterally, extracellular free-water (FW) in the left cingulum bundle was found to be specifically associated with present state delusions in chronic schizophrenia. No changes were observed in the remaining tracts., Conclusions: These findings suggest that state and trait delusions in chronic schizophrenia are associated with microstructural processes, such as myelin abnormalities (as indicated by decreased FAT and increased RDT) in the cingulum bundle and that state delusions are additionally associated with extracellular processes such as neuroinflammation or atrophy (as indicated by increased FW) in the left cingulum bundle.

SEE STEPHAN ET AL DOI101093/AWW120 FOR A SCIENTIFIC COMMENTARY ON THIS WORK: Real world information is often abstract, dynamic and imprecise. Deciding if changes represent random fluctuations, or alterations in underlying contexts involve challenging probability estimations. Dysfunction may contribute to erroneous beliefs, such as delusions. Here we examined brain function during inferences about context change from noisy information. We examined cortical-subcortical circuitry engaging anterior and dorsolateral prefrontal cortex, and midbrain. We hypothesized that schizophrenia-related deficits in prefrontal function might overestimate context change probabilities, and that this more chaotic worldview may subsequently gain familiarity and be over-reinforced, with implications for delusions. We then examined these opposing information processing biases against less expected versus familiar information patterns in relation to genetic risk for schizophrenia in unaffected siblings. In one experiment, 17 patients with schizophrenia and 24 normal control subjects were presented in 3 T magnetic resonance imaging with numerical information varying noisily about a context integer, which occasionally shifted up or down. Subjects were to indicate when the inferred numerical context had changed. We fitted Bayesian models to estimate probabilities associated with change inferences. Dynamic causal models examined cortical-subcortical circuitry interactions at context change inference, and at subsequent reduced uncertainty. In a second experiment, genetic risk for schizophrenia associated with similar cortical-subcortical findings were explored in an independent sample of 36 normal control subjects and 35 unaffected siblings during processing of intuitive number sequences along the number line, or during the inverse, less familiar, sequence. In the first experiment, reduced Bayesian models fitting subject behaviour suggest that patients with schizophrenia overestimated context change probabilities. Here, patients engaged anterior prefrontal cortex relatively less than healthy controls, in part driven by reduced effective connectivity from dorsolateral prefrontal cortex to anterior prefrontal cortex. In processing subsequent information indicating reduced uncertainty of their predictions, patients engaged relatively increased mid-brain activation, driven in part by increased dorsolateral prefrontal cortex to midbrain connectivity. These dissociable reduced and exaggerated prefrontal and subcortical circuit functions were accentuated in patients with delusions. In the second experiment, analogous dissociable reduced anterior prefrontal cortex and exaggerated midbrain engagement occurred in unaffected siblings when processing less expected versus more familiar number sequences. In conclusion, patients overestimated ambiguous context change probabilities with relatively reduced anterior frontal engagement. Subsequent reduced uncertainty about contextual state appeared over-reinforced, potentially contributing to confirmation bias and a cascade of aberrant belief processing about a more chaotic world relevant to delusions. These opposing cortical-subcortical effects relate in part to genetic risk for schizophrenia, with analogous imbalances in neural processing of less expected versus familiar information patterns., (© The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The purpose of this study was to investigate the association between brain regional gray matter volume and two subtypes of psychotic symptoms, namely paranoid and misidentification subtypes, in antipsychotic-naïve mild or moderate Alzheimer's disease (AD) patients. Forty AD patients with psychotic symptoms and 25 AD patients without psychotic symptoms were assessed for cognitive and functional impairment. Presence and subtype of psychotic symptoms were assessed by using the delusion and hallucination subscale of the Korean Neuropsychiatric Inventory (K-NPI). Structural MRI images were acquired on a 3 T scanner, and were analyzed using voxel-based morphometry (VBM) for automated analysis. The misidentification subtype is associated with more severe gray matter atrophy, and paranoid subtype is associated with less severe gray matter atrophy compared to non-psychosis group. These results suggest that the misidentification, the paranoid subtype and the non-psychosis group have a distinct neural correlation., (Copyright © 2016. Published by Elsevier Ireland Ltd.)

Background: A consensus on the brain dysfunction(s) underlying the delusions of Alzheimer's Dementia (AD) remains to be achieved. The aim of the present study was to test the hypothesis that content-based categorization of delusional ideas manifests as dysfunction of category-specific brain regions., Methods: Fifty-nine consecutive first-visit AD outpatients underwent Single Photon Emission Computed Tomography (SPECT), Mini-Mental State Examination, and Behavioral Pathology in Alzheimer's Disease Frequency-Weighted Severity scale (BEHAVE-AD-FW) to assess cerebral blood flow (CBF), cognitive function, and delusion, respectively. SPECT images were analyzed by SPM5., Results: CBF decreased at the temporal poles and right inferior temporal gyrus in "delusion of theft," at the temporal poles in "suspiciousness/paranoia," at the right parahippocampal gyrus and insula in "abandonment," and at the right amygdala in "Residence is not home.", Conclusions: Our findings offer a perspective on the discrete categories of the pathological thoughts of AD patients that have previously been lumped together as "delusions." Dysfunction of the temporal poles may be associated with a socioemotional deterioration that may include pathological suspiciousness. Delusion of theft may be a manifestation of socioemotional deterioration and poor insight. Emotional factors may be essential for delusions of abandonment and "not home."

Oral cenesthopathy is a somatic delusion or hallucination involving the oral area and is categorized as a delusional disorder, somatic type. The pathophysiology of this intractable condition remains obscure. In this study, we clarified the pathophysiology of oral cenesthopathy by evaluating regional brain perfusion. We performed single photon emission computed tomography (SPECT) using (99m)Tc-ethylcysteinate dimer in 16 subjects (cenesthopathy:control = 8:8). The SPECT images were visually assessed qualitatively, and quantitative analyses were also performed using a three-dimensional stereotactic region-of-interest template. The visual assessment revealed a right > left perfusion asymmetry in broad areas of the brain among the patients. The quantitative analysis confirmed that the regional cerebral blood flow values on the right side were significantly larger than those on the left side for most areas of the brain in the patients. A comparison of the R/(R + L) ratios in both groups confirmed the significant brain perfusion asymmetry between the two sides in the callosomarginal, precentral, and temporal regions in the patients. Qualitative evaluation of the SPECT images revealed right > left brain perfusion asymmetry in broad regions of the brain. Moreover, the quantitative analyses confirmed the perfusion asymmetry between the two sides in the frontal and temporal areas. Those may provide the key for elucidation of the pathophysiology of oral cenesthopathy.

Objectives: Asomatognosia is broadly defined as unawareness of ownership of one's arm, while somatoparaphrenia is a subtype in which patients also display delusional misidentification and confabulation. Studies differ with regard to the underlying neuroanatomy of these syndromes., Methods: Three groups of patients with right-hemisphere strokes and left hemiplegia were analysed: G1, asomatognosia+neglect; G2, non-asomatognosia+neglect; G3, hemiplegia only. The asomatognosic group was further subdivided into somatoparaphrenia (G1-SP: asomatognosia+delusions/confabulation) and simple asomatognosia (G1-SA; asomatognosia without delusions/confabulation)., Results: Patients with all forms of asomatognosia (G1) had larger lesions than non-asomatognosic patients in all sectors. While patients with or without asomatognosia had significant temporoparietal involvement, we found that the subset of patients with somatoparaphrenia had the largest lesions overall, and somatoparaphrenia cases had significantly more frontal involvement than patients with simple asomatognosia. All patients with asomotognosia (G1-SP and G1-SA) had significant medial frontal damage, suggesting that this region may play a role in the development of asomatognosia in general. Somatoparaphrenia cases also had greater orbitofrontal damage than simple asomatognosia cases, suggesting that the orbitofrontal lesion was critical in the development of somatoparaphrenia., Conclusions: Asomatognosia results from large lesions involving multiple--including temporoparietal--sectors, but the addition of medial frontal involvement appears important. The addition of orbitofrontal dysfunction distinguishes somatoparaphrenia from simple asomatognosia. The data indicate roles for the right medial and orbitofrontal regions in confabulation and self-related systems.

Neuropsychiatric symptoms are frequent in dementia with Lewy bodies (DLB). Dopamine transporter (DAT) imaging with (123)I-labeled ligand N-delta-(fluoropropyl)-2 beta-carbomethoxy-3beta-(4-iodophenyl)tropene ((123)I-FP-CIT), which reliably measures midbrain dopaminergic dysfunction, has provided important evidence on the neurobiological substrate of some of these symptoms including apathy and depression. However, little is known on DAT levels and other distressing symptoms such as delusions and hallucinations. Therefore, (123)I-FP-CIT imaging was performed in 18 well-characterized patients with DLB, and striatal DAT levels were correlated with the frequency/severity ratings of several neuropsychiatric symptoms. A wide range of neuropsychiatric symptoms could be observed in the sample. Significant correlations were observed between decreased striatal DAT levels and visual hallucinations. Although there were no correlations between striatal DAT levels and other neuropsychiatric symptoms, when considering the putamen and the caudate nucleus separately, delusions, depression, and apathy were inversely correlated to decreased caudate DAT levels. The seresults provide intriguing evidence on the involvement of the mesocortical dopaminergic pathways in neuropsychiatric symptoms in DLB., ((c) 2009 Movement Disorder Society.)

Delusions (DEL) are frequent in dementia with Lewy bodies (DLB); however, the neural equivalent is poorly understood. The present study therefore aimed to identify the cerebral metabolic pattern of glucose of a DLB group suffering from DEL (DLB+DEL) as compared to a non-delusional group (DLB-DEL) and a control group (NL); and to determine the predictive value of the regional metabolic deficit for DEL symptomatology in comparison to other clinical variables significantly associated with DEL. Voxel-wise comparisons were conducted between the patient and control groups in SPM2. The most significant regional metabolic deficit of the DLB+DEL group was used a predictor for DEL symptomatology in a logistic regression analysis along with other variables significantly associated with DEL, such as visual hallucinations (VH), and overall cognitive impairment. A significant relative hypometabolism of the right prefrontal cortex was found in the DLB+DEL group, which predicted DEL symptomatology in the regression analysis. VH and overall cognitive dysfunction were no significant predictors. These results underline the significance of right prefrontal damage for DEL in DLB.

Objective: Dysfunction within corticostriatal dopaminergic neurocircuitry has been implicated in neuropsychiatric symptoms associated with Alzheimer disease (AD). This study aimed to test the hypothesis that the symptom domains delusions and apathy would be associated with striatal dopamine (D2) receptor function in AD., Methods: In vivo dopamine (D2/D3) receptor availability was determined with [(11)C]raclopride (RAC) PET in 23 patients with mild and moderate probable AD. Behavioral symptoms were measured using the Neuropsychiatric Inventory and the Apathy Inventory. Imaging data were analyzed using a region-of-interest approach. The potential confounding effects of age, sex, and disease stage were explored using a linear mixed model. Correlational and independent samples comparisons were used to examine the relationship between behavioral and binding potential (BP(ND)) measures., Results: Mean [(11)C]RAC BP(ND) was higher in patients with delusions (n = 7; 5 men) than in patients without delusions (n = 16; 6 men) (p = 0.006). When women were excluded from the analysis, [(11)C]RAC BP(ND) was higher in men with delusions than in men without delusions (p = 0.05). Apathy measures showed no association with [(11)C]RAC BP(ND)., Conclusions: Striatal dopamine (D2/D3) receptor availability is increased in Alzheimer disease patients with delusions, to an extent comparable to that observed in drug-naive patients with schizophrenia. Whether this represents up-regulation of dopamine (D2) or possibly dopamine (D3) receptors and how this relates to responsivity of the striatal dopaminergic system merit further exploration.

Unlabelled: To investigate the association between delusions and cerebral functional deficits in Alzheimer's disease (AD), we evaluated probable AD patients with and without delusions., Methods: Functional brain imaging was performed by single photon emission computed tomography with technetium-99m-labeled ethyl cysteinate dimer (99mTc-ECD) in 64 AD patients and 76 age-matched normal healthy volunteers. SPECT data were analyzed by statistical parametric mapping., Results: In AD patients, no differences were found in age and cognitive activities between those with (n = 25) and without (n = 39) delusions. Compared with normal healthy volunteers, AD patients had significantly decreased perfusion in the posterior cingulate gyri, precunei, and parietal association cortex. Moreover, in the patients with delusions, perfusion was significantly decreased in the frontal lobe with right side dominance. In the comparison between the patients with and without delusions, the patients with delusions had significantly decreased perfusion in the prefrontal cortex, anterior cingulate gyri, inferior to middle temporal cortices, and parietal cortex of the right hemisphere (p < 0.01)., Conclusion: The functional deficits in the right hemisphere may be the cause of delusions in AD., (Copyright 2006 S. Karger AG, Basel.)

Patients with first-rank symptoms (FRS) of schizophrenia do not experience all of their actions and personal states as their own. FRS may be associated with an impaired ability to correctly attribute an action to its origin. In the present study, we examined regional cerebral blood flow (rCBF) with positron emission tomography during an action-attribution task in a group of patients with FRS. We used a device previously used with healthy subjects that allows the experimenter to modulate the subject's degree of movement control (and thus action attribution) of a virtual hand presented on a screen. In healthy subjects, the activity of the right angular gyrus and the insula cortex appeared to be modulated by the subject's degree of movement control of the virtual hand. In the present study, the schizophrenic patients did not show this pattern. We found an aberrant relationship between the subject's degree of control of the movements and rCBF in the right angular gyrus and no modulation in the insular cortex. The implications of these results for understanding pathological conditions such as schizophrenia are discussed.

Objective: We explore a case of a forensic patient with severe personality disorder, borderline type, and additional psychotic symptoms. Furthermore, she showed parietal lobe abnormalities., Method: We describe a case report and the relevant theoretical deliberations., Conclusions: Attempts to categorize patients with severe borderline personality disorder and psychotic symptoms have been made since the beginning of the 20th century. We show that in our patient neuroimaging such as SPECT scan can prove parietal lobe abnormalities. We describe possible links between these findings and her symptoms.

Positron emission tomography was used to examine the mechanisms of the psychotic phenomenon in Alzheimer's disease (AD). Data from 2 patients with delusions and 2 with hallucinations were compared with those of 5 AD patients without psychosis. The patients with paranoid delusions had diminished relative regional cerebral blood flow (rel-CBF) in the left dorsolateral prefrontal and left medial temporal cortices. The patients with visual hallucinations showed diminished rel-CBF in the right parietal, left medial temporal, and left dorsolateral prefrontal cortices. These findings support the hypothesis that a frontal-temporal abnormality is associated with paranoid delusions in AD. By contrast, visual hallucinations are associated with parietal as well as frontal and temporal lobe dysfunction. In these patients, a left prefrontal-temporal cortex dysfunction appears to be a common denominator for the development of the psychotic phenomenon in AD.