Associations of conservatism and jumping to conclusions biases with aberrant salience and default mode network.

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.

Neuronal Loss in the Bilateral Medial Frontal Lobe Revealed by 123I-iomazenil Single-photon Emission Computed Tomography in Patients with Moyamoya Disease: The First Report from Cognitive Dysfunction Survey of Japanese Patients with Moyamoya Disease (COSMO-Japan Study).

Cognitive impairment in adult patients with moyamoya disease (MMD) is sometimes overlooked and can occur in patients with no ischemic or hemorrhagic lesions. Better profiling and reliable diagnostic methods that characterize the group and associate the impairments and pathology of MMD are required in order to deliver appropriate treatments and support. The potential of 123I-iomazenil single-photon emission computed tomography (SPECT) for this issue has been reported in some studies, but the universality of this method remains unclear. A multicenter study of adult patients (aged 18-60 years) with MMD who experienced difficulties in social lives despite normal activities of daily living was implemented to delineate the common characteristics of this group of patients. In this study, iomazenil SPECT, besides patient characteristics, cognitive functions, and conventional imaging, was acquired to examine whether this method is suitable as a universal diagnostic tool. A total of 36 patients from 12 institutes in Japan were included in this study. Domain scores of world health organization quality of life 26 indicated low self-rating in physical health and psychological domains. The percentages of patients who had <85 in each index were 27.8%-33.3% in the WAIS-III and 16.7%-47.2% in the Wechsler Memory Scale-Revised. The group analysis of iomazenil SPECT demonstrated a decreased accumulation in the bilateral medial frontal areas in comparison with the normal control, whereas there were no specific characteristics on conventional imaging in the cohort. Iomazenil SPECT is a possible universal diagnostic method for the extraction of patients with cognitive impairment in MMD.

Voice Patterns as Markers of Schizophrenia: Building a Cumulative Generalizable Approach Via a Cross-Linguistic and Meta-analysis Based Investigation.

BACKGROUND AND HYPOTHESIS: Voice atypicalities are potential markers of clinical features of schizophrenia (eg, negative symptoms). A recent meta-analysis identified an acoustic profile associated with schizophrenia (reduced pitch variability and increased pauses), but also highlighted shortcomings in the field: small sample sizes, little attention to the heterogeneity of the disorder, and to generalizing findings to diverse samples and languages. STUDY DESIGN: We provide a critical cumulative approach to vocal atypicalities in schizophrenia, where we conceptually and statistically build on previous studies. We aim at identifying a cross-linguistically reliable acoustic profile of schizophrenia and assessing sources of heterogeneity (symptomatology, pharmacotherapy, clinical and social characteristics). We relied on previous meta-analysis to build and analyze a large cross-linguistic dataset of audio recordings of 231 patients with schizophrenia and 238 matched controls (>4000 recordings in Danish, German, Mandarin and Japanese). We used multilevel Bayesian modeling, contrasting meta-analytically informed and skeptical inferences. STUDY RESULTS: We found only a minimal generalizable acoustic profile of schizophrenia (reduced pitch variability), while duration atypicalities replicated only in some languages. We identified reliable associations between acoustic profile and individual differences in clinical ratings of negative symptoms, medication, age and gender. However, these associations vary across languages. CONCLUSIONS: The findings indicate that a strong cross-linguistically reliable acoustic profile of schizophrenia is unlikely. Rather, if we are to devise effective clinical applications able to target different ranges of patients, we need first to establish larger and more diverse cross-linguistic datasets, focus on individual differences, and build self-critical cumulative approaches.

A model for estimating the brainstem volume in normal healthy individuals and its application to diffuse axonal injury patients.

Diffuse axonal injury (DAI) is a subtype of traumatic brain injury that causes acute-phase consciousness disorders and widespread chronic-phase brain atrophy. Considering the importance of brainstem damage in DAI, a valid method for evaluating brainstem volume is required. We obtained volume measurements from 182 healthy adults by analyzing T1-weighted magnetic resonance images, and created an age-/sex-/intracranial volume-based quantitative model to estimate the normal healthy volume of the brainstem and cerebrum. We then applied this model to the volume measurements of 22 DAI patients, most of whom were in the long-term chronic phase and had no gross focal injury, to estimate the percentage difference in volume from the expected normal healthy volume in different brain regions, and investigated its association with the duration of posttraumatic amnesia (which is an early marker of injury severity). The average loss of the whole brainstem was 13.9%. Moreover, the percentage loss of the whole brainstem, and particularly of the pons and midbrain, was significantly negatively correlated with the duration of posttraumatic amnesia. Our findings suggest that injury severity, as denoted by the duration of posttraumatic amnesia, is among the factors affecting the chronic-phase brainstem volume in patients with DAI.

Combining Multiple Indices of Diffusion Tensor Imaging Can Better Differentiate Patients with Traumatic Brain Injury from Healthy Subjects.

Aim: Diffuse axonal injury (DAI) is one of the most common pathological features of traumatic brain injury (TBI). Diffusion tensor imaging (DTI) indices can be used to identify and quantify white matter microstructural changes following DAI. Recently, many studies have used DTI with various machine learning approaches to predict white matter microstructural changes following TBI. The current study sought to examine whether our classification approach using multiple DTI indices in conjunction with machine learning is a useful tool for diagnosing/classifying TBI patients and healthy controls. Methods: Participants were adult patients with chronic TBI (n = 26) with DAI pathology, and age- and sex-matched healthy controls (n = 26). DTI images were obtained from all participants. Tract-based spatial statistics analyses were applied to DTI images. Classification models were built using principal component analysis and support vector machines. Receiver operator characteristic curve analysis and area under the curve were used to assess the classification performance of the different classifiers. Results: Tract-based spatial statistics revealed significantly decreased fractional anisotropy, as well as increased mean diffusivity, axial diffusivity, and radial diffusivity in patients with TBI compared with healthy controls (all p-values < 0.01). The principal component analysis and support vector machine-based machine learning classification using combined DTI indices classified patients with TBI and healthy controls with an accuracy of 90.5% with an area under the curve of 93 ± 0.09. Conclusion: These results highlight the potential of our approach combining multiple DTI measures to identify patients with TBI.

Extracting Apathy From Depression Syndrome in Traumatic Brain Injury by Using a Clustering Method.

OBJECTIVE: Depression and apathy are common after traumatic brain injury (TBI), and different intervention strategies are recommended for each. However, a differential diagnosis can be difficult in clinical settings, especially given that apathy is considered to be a symptom of depression. In this study, the investigators aimed to isolate apathy from depression among patients with TBI and to examine whether apathy is exclusively associated with the amount of daily activity, as previously reported in the literature. METHODS: Eighty-eight patients with chronic TBI completed the Japanese versions of the 21-item Beck Depression Inventory-II (BDI-II) and the Starkstein Apathy Scale (AS). Daily activity was measured with a 24-hour life log. A hierarchical cluster analysis was applied to divide the BDI-II data into separable components, and components' correlations with results of the AS and 24-hour life log scale were evaluated. RESULTS: The BDI-II and AS revealed that 37 patients (42.0%) had both depression and apathy. BDI-II data were classified into four separate clusters (somatic symptoms, loss of self-worth, affective symptoms, and apathy symptoms). Loss of self-worth and apathy symptoms subscores were significantly positively correlated with total AS score (r=0.32, p=0.002, and r=0.52, p<0.001, respectively). The apathy symptoms subscore was significantly correlated with the amount of daily activity (r=-0.29, p=0.009). CONCLUSIONS: The findings suggest that the BDI-II can differentiate between apathy and depression among patients with TBI, which is essential when selecting intervention options. Moreover, apathy symptoms predicted patients' real-life daily activity.

Spatial Patterns of Amyloid Deposition in Patients with Chronic Focal or Diffuse Traumatic Brain Injury Using 18F-FPYBF-2 PET.

AIM: Amyloid-ß (Aß) accumulation, accelerated by traumatic brain injury (TBI), may play a crucial role in neurodegeneration in chronic-stage TBI. The injury type could influence Aß dynamics because of TBI's complex, heterogeneous nature. We, therefore, investigated spatial patterns of amyloid deposition according to injury type after TBI using 5-(5-(2-(2-(2-[F]-fluoroethoxy)ethoxy)ethoxy)benzofuran-2-yl)-N-methylpyridin-2-amine (18F-FPYBF-2) positron emission tomography (PET). METHODS: Altogether, 20 patients with chronic TBI [12 with focal injury, 8 with diffuse axonal injury (DAI)] underwent 18F-FPYBF-2 PET, structural magnetic resonance imaging (MRI), and neuropsychological examination. Additionally, 50 healthy controls underwent either 18F-FPYBF-2 PET (n=30) or structural MRI (n=20). RESULTS: Standardized uptake value ratio (SUVR) on PET images and regional brain volumes were measured in four cortical (frontal, parietal, occipital, temporal) and subcortical (combined caudate, putamen, pallidum, thalamus) regions. Patients with DAI showed significantly increased (compared with controls) SUVR in occipital and temporal cortices and decreased brain volume in occipital cortex (corrected p < 0.05). Although patients with focal injury showed decreased SUVR in all regions except occipital cortex, there were no significant differences (compared with controls) in the SUVR in any regions. There were no significant correlations between increased SUVR and neuropsychological impairments in patients with DAI. CONCLUSION: Varying spatial patterns of amyloid deposition suggest amyloid pathology diversity depending on the injury type in chronic-TBI patients.

A venous mechanism of ventriculomegaly shared between traumatic brain injury and normal ageing.

Recently, age-related timing dissociation between the superficial and deep venous systems has been observed; this was particularly pronounced in patients with normal pressure hydrocephalus, suggesting a common mechanism of ventriculomegaly. Establishing the relationship between venous drainage and ventricular enlargement would be clinically relevant and could provide insight into the mechanisms underlying brain ageing. To investigate a possible link between venous drainage and ventriculomegaly in both normal ageing and pathological conditions, we compared 225 healthy subjects (137 males and 88 females) and 71 traumatic brain injury patients of varying ages (53 males and 18 females) using MRI-based volumetry and a novel perfusion-timing analysis. Volumetry, focusing on the CSF space, revealed that the sulcal space and ventricular size presented different lifespan profiles with age; the latter presented a quadratic, rather than linear, pattern of increase. The venous timing shift slightly preceded this change, supporting a role for venous drainage in ventriculomegaly. In traumatic brain injury, a small but significant disease effect, similar to idiopathic normal pressure hydrocephalus, was found in venous timing, but it tended to decrease with age at injury, suggesting an overlapping mechanism with normal ageing. Structural bias due to, or a direct causative role of ventriculomegaly was unlikely to play a dominant role, because of the low correlation between venous timing and ventricular size after adjustment for age in both patients and controls. Since post-traumatic hydrocephalus can be asymptomatic and occasionally overlooked, the observation suggested a link between venous drainage and CSF accumulation. Thus, hydrocephalus, involving venous insufficiency, may be a part of normal ageing, can be detected non-invasively, and is potentially treatable. Further investigation into the clinical application of this new marker of venous function is therefore warranted.

Reduced Enhancement of Memory for Faces Encoded by Semantic and Socioemotional Processes in Patients with Parkinson's Disease.

OBJECTIVES: Patients with Parkinson's disease (PD) exhibit impaired semantic and socioemotional processes, which are thought to be related to dysfunctions in the fronto-striatal circuit. However, little is known about how the memory enhancement by these processes was reduced in PD. The present study investigated this issue. METHODS: The retrieval performance of face memories encoded by semantic and socioemotional processes was compared between 24 PD patients and 24 age-matched healthy controls (HC). During encoding, participants were presented with unfamiliar faces and made judgment about them in three encoding conditions of semantic judgment (Semantics), attractiveness judgment (Attractiveness), and form judgment (Form). In Semantics, participants rated to what degree each face looked like an office worker, whereas in Attractiveness, participants rated how attractive each face was. The Form condition as a control required participants to judge the shape of each face. During retrieval after encoding, participants made old or new judgment for target and distracter faces. RESULTS: In HC, the retrieval of faces encoded by Semantics and Attractiveness was significantly more accurate than that encoded by Form, whereas this memory enhancement was not identified in PD. In addition, individual scores in frontal lobe function and long-term memory correlated with the retrieval performance of memories encoded in Semantics and Attractiveness but not Form. CONCLUSIONS: These findings suggest that the processing of semantic and socioemotional signals conveyed from faces could be impaired in PD and that the impairment of these processes could decrease the enhancement of face memories by semantic and socioemotional elaborations.

[Social Behavioral Problems after Brain Injury].

Various types of aberrant social behaviors may occur after brain injury. Some of these behaviors might be understood as direct consequences of brain injury; apathy, disinhibition, and executive dysfunction are the three major domains of aberrant social behaviors after injury of the prefrontal cortex. In addition, psychosis, pseudobulbar affect, depression, and fatigue are common symptoms that affect social behavior after brain injury. To evaluate behavioral symptoms, it is important to obtain information based on the context of patient's daily life. Individualized interventions such as pharmacotherapy, disease education and environmental control would improve the patient's social function.

Transcallosal Fiber Disruption and its Relationship with Corresponding Gray Matter Alteration in Patients with Diffuse Axonal Injury.

Diffuse axonal injury (DAI) is characterized by diffuse white matter (WM) disruption caused by shearing forces acting on the brain. Cortical atrophy can be accompanied by WM disruption, which is assumed to reflect the loss of neuron cell bodies in gray matter (GM) regions adjacent to disrupted WM. It remains unclear whether WM disruption leads to regional GM alteration in DAI. The aim of the present study was to assess WM disruption and corresponding GM alterations in patients with DAI using a connectome-based approach. Twenty-four patients and 24 healthy controls underwent magnetic resonance imaging with diffusion tensor imaging (DTI). Deterministic fiber tracking was conducted to investigate structural connectivity between the corpus callosum (CC) and each pre-defined regional cortical area. We calculated 85 × 85 connectivity matrices for fractional anisotropy (FA). Group comparisons were conducted to identify abnormal connectivity in patients. Further, the regional cortical volume of each connectivity matrix was compared between patients and controls. Finally, correlation analyses between the matrices and regional cortical volumes were performed within the patient group. Connectome analyses revealed that, compared with controls, patients exhibited a FA reduction in connectivity via CC to 32 cortical regions including the frontal, parietal, and occipital cortices. Among these regions, GM volume was reduced in 19 of 32 regions. There were no significant correlations between WM disruption in which abnormal connectivity was identified and the corresponding GM alterations. These results suggest that GM pathology is, at least in part, independent of the corresponding WM damage in DAI.

[Brodmann Areas 11, 46, and 47: Emotion, Memory, and Empathy].

Brodmann area 11 is one of the main constituent of the orbitofrontal cortex, and area 46 is that of the dorsolateral prefrontal cortex. The main function of Brodmann area 11 is the processing of emotion and value, whereas the main function of Brodmann area 46 is the processing of cognitive information, including working memory. In comparison, the function of area 47 is more complex. This area is related to the feeling of empathy towards the story contents of others, which is thought to be the emotional aspect of this area, while this area is also activated during automated action. This is in contrast with the function of area 46, which is involved in willed action. In addition, area 47 in the left hemisphere plays an important role in syntax processing.

Facial emotion recognition in patients with focal and diffuse axonal injury.

OBJECTIVE: Facial emotion recognition impairment has been well documented in patients with traumatic brain injury. Studies exploring the neural substrates involved in such deficits have implicated specific grey matter structures (e.g. orbitofrontal regions), as well as diffuse white matter damage. Our study aims to clarify whether different types of injuries (i.e. focal vs. diffuse) will lead to different types of impairments on facial emotion recognition tasks, as no study has directly compared these patients. METHODS: The present study examined performance and response patterns on a facial emotion recognition task in 14 participants with diffuse axonal injury (DAI), 14 with focal injury (FI) and 22 healthy controls. RESULTS: We found that, overall, participants with FI and DAI performed more poorly than controls on the facial emotion recognition task. Further, we observed comparable emotion recognition performance in participants with FI and DAI, despite differences in the nature and distribution of their lesions. However, the rating response pattern between the patient groups was different. CONCLUSION: This is the first study to show that pure DAI, without gross focal lesions, can independently lead to facial emotion recognition deficits and that rating patterns differ depending on the type and location of trauma.

Discriminating autism spectrum disorders from schizophrenia by investigation of mental state attribution on an on-line mentalizing task: A review and meta-analysis.

In recent years, theories of how humans form a "theory of mind" of others ("mentalizing") have increasingly been called upon to explain impairments in social interaction in mental disorders, such as autism spectrum disorders (ASD) and schizophrenia. However, it remains unclear whether tasks that assess impairments in mentalizing can also contribute to determining differential deficits across disorders, which may be important for early identification and treatment. Paradigms that challenge mentalizing abilities in an on-line, real-life fashion have been considered helpful in detecting disease-specific deficits. In this review, we are therefore summarizing results of studies that assess the attribution of mental states using an animated triangles task. Behavioral as well as brain imaging studies in ASD and schizophrenia have been taken into account. While for neuroimaging methods, data are sparse and investigation methods inconsistent, we performed a meta-analysis of behavioral data to directly investigate performance deficits across disorders. Here, more impaired abilities in the appropriate description of interactions were found in ASD patients than in patients with schizophrenia. Moreover, an analysis of first-episode (FES) versus longer lasting (LLS) schizophrenia showed that usage of mental state terms was reduced in the LLS group. In our review and meta-analysis, we identified performance differences between ASD and schizophrenia that seem helpful in targeting differential deficits, taking into account different stages of schizophrenia. However, to tackle the deficits in more detail, studies are needed that directly compare patients with ASD and schizophrenia using behavioral or neuroimaging methods with more standardized task versions.

Corpus Callosum Pathology as a Potential Surrogate Marker of Cognitive Impairment in Diffuse Axonal Injury.

Diffuse axonal injury is a major form of traumatic brain injury. Neuropsychological assessments and high-resolution structural MRI were conducted using T1-weighted and diffusion tensor imaging. This study included 10 patients with diffuse axonal injury (all men, mean age 30.8±10.5 years) and 12 age- and sex-matched normal control participants. Patients with diffuse axonal injury had widespread volume reductions and lower fractional anisotropy in the corpus callosum (CC) compared with controls. Furthermore, cognitive processing speed was associated with reductions in white matter volume and fractional anisotropy in the CC. These findings suggest that CC pathology may be a potential surrogate marker of the cognitive deficits in these patients.

Insular Gray Matter Volume and Objective Quality of Life in Schizophrenia.

Improving quality of life has been recognized as an important outcome for schizophrenia treatment, although the fundamental determinants are not well understood. In this study, we investigated the association between brain structural abnormalities and objective quality of life in schizophrenia patients. Thirty-three schizophrenia patients and 42 age-, sex-, and education-matched healthy participants underwent magnetic resonance imaging. The Quality of Life Scale was used to measure objective quality of life in schizophrenia patients. Voxel-based morphometry was performed to identify regional brain alterations that correlate with Quality of Life Scale score in the patient group. Schizophrenia patients showed gray matter reductions in the frontal, temporal, limbic, and subcortical regions. We then performed voxel-based multiple regression analysis in these regions to identify any correlations between regional gray matter volume and Quality of Life Scale scores. We found that among four subcategories of the scale, the Instrumental Role category score correlated with gray matter volume in the right anterior insula in schizophrenia patients. In addition, this correlation was shown to be mediated by negative symptoms. Our findings suggest that the neural basis of objective quality of life might differ topographically from that of subjective QOL in schizophrenia.

Hypothalamic-amygdalar-brainstem volume reduction in a patient with narcolepsy secondary to diffuse axonal injury.

A 17-year-old male with diffuse axonal injury (DAI) was referred to our psychiatric clinic with a diagnosis of depression. However, further investigation indicated that he had narcolepsy without cataplexy secondary to DAI. We assessed regional volume alterations in the patient; MRI analysis showed a significant decrease in the volume of the hypothalamus, left amygdala, and brainstem. Our findings add to further understanding of the structural basis of secondary narcolepsy, and may provide basis for future neuroimaging studies on sleep disturbances in traumatic brain injury (TBI).

Social cognition and its relationship to functional outcomes in patients with sustained acquired brain injury.

Deficits in social cognition are common after traumatic brain injury (TBI). However, little is known about how such deficits affect functional outcomes. The purpose of this study was to investigate the relationship between social cognition and functional outcomes in patients with TBI. We studied this relationship in 20 patients with TBI over the course of 1 year post-injury. Patients completed neurocognitive assessments and social cognition tasks. The social cognition tasks included an emotion-perception task and three theory of mind tasks: the Faux Pas test, Reading the Mind in the Eyes (Eyes) test, and the Moving-Shapes paradigm. The Craig Handicap Assessment and Reporting Technique was used to assess functional outcomes. Compared with our database of normal subjects, patients showed impairments in all social cognition tasks. Multiple regression analysis revealed that theory of mind ability as measured by the Eyes test was the best predictor of the cognitive aspects of functional outcomes. The findings of this pilot study suggest that the degree to which a patient can predict what others are thinking is an important measure that can estimate functional outcomes over 1 year following TBI.

Cognitive function of patients with adult moyamoya disease.

BACKGROUND: Neurocognitive impairment is one of several unsolved social issues faced by patients with moyamoya disease. Although efforts have been made to investigate cognitive function using neuropsychologic tasks, generalizability has been limited. Here, in a preliminary study, we used structured neuropsychologic tasks to establish a standardized neuropsychologic assessment for adult moyamoya patients with and without difficulty in social independence. METHODS: Ten patients with neuroradiologically confirmed adult moyamoya disease (3 male, 7 female) participated. Half of all subjects did not have difficulty with social independence (group 1) and the others had (group 2). Group differences were evaluated after basic cognitive abilities and frontal lobe function were tested. RESULTS: Although the mean age of group 1 was substantially higher than that of group 2, disease duration did not differ significantly between groups. Means scores for intelligence functions including all subtests for basic cognitive abilities were higher in group 1 compared with group 2. Scores from only 2 frontal lobe evaluation tasks (Trail Making Test B and Theory of Mind) were significantly different between groups. CONCLUSIONS: This preliminary study provides a profile of neurocognitive dysfunction in adult patients with moyamoya disease using structured neuropsychologic tasks. A broad range of cognitive functions was disrupted particularly in the patients who had difficulty with social independence. To obtain stronger evidence regarding neurocognitive dysfunction in patients with moyamoya disease, a multicenter prospective study is essential.