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This study aimed to investigate alterations in white matter (WM) microstructure in patients with psychotic and non-psychotic bipolar disorder (PBD and NPBD, respectively). We used 3T-magnetic resonance imaging to examine 29 PBD, 23 NPBD, and 65 healthy control (HC) subjects. Using tract-based spatial statistics for diffusion tensor imaging data, we compared fractional anisotropy (FA) and mean diffusion (MD) pairwise among the PBD, NPBD, and HC groups. We found several WM areas of decreased FA or increased MD in the PBD and NPBD groups compared to HC. PBD showed widespread FA decreases in the corpus callosum as well as the bilateral internal capsule and fornix. However, NPBD showed local FA decreases in a part of the corpus callosum body as well as in limited regions within the left cerebral hemisphere, including the anterior and posterior corona radiata and the cingulum. In addition, both PBD and NPBD shared widespread MD increases across the posterior corona radiata, cingulum, and sagittal stratum. These findings suggest that widespread WM microstructural alterations might be a common neuroanatomical characteristic of bipolar disorder, regardless of being psychotic or non-psychotic. Particularly, PBD might involve extensive inter-and intra-hemispheric WM connectivity disruptions. [ABSTRACT FROM AUTHOR]

Cognitive complaints after chemotherapy are common in breast cancer patients, but the neural bases for these complaints remain unclear. This pilot study explored resting-state functional connectivity (FC) as a marker of subtle cognitive changes in breast cancer patients who experience cognitive complaints. Chemotherapy-treated (n = 20, at least 6 months off therapy) and untreated (n = 17, disease-control) female breast cancer patients with cognitive complaints and healthy controls (n = 20) were recruited. The FC of the right dorsolateral prefrontal cortex was calculated, and any correlations between this FC and neuropsychological assessments were determined. Chemotherapy-treated patients with cognitive complaints displayed increased FC between the right dorsolateral prefrontal cortex and both the contralateral cerebellar lobule VII and the cerebellar vermis XI, compared to the disease-control and healthy-control groups, despite unimpaired neuropsychological performance. The increased FC was negatively correlated with executive function and attention in breast cancer survivors with cognitive complaints. Our pilot study findings provide evidence that cerebellar-cortical FC changes may be a pathophysiological basis for chemotherapy-related cognitive complaints. In addition, the FC changes have the potential to reflect minor or compensated cognitive function impairment in breast cancer patients. [ABSTRACT FROM AUTHOR]

Insomnia is prevalent among dialysis patients and affects their mortality. Although cognitive behavioral therapy for insomnia (CBTi) is recommended, attending regular face-to-face CBTi sessions is a major challenge for patients. We evaluated the effectiveness of a self-directed computerized CBTi (cCBTi) in dialysis patients, and investigated changes in resting-state brain connectivity and inflammatory cytokines following cCBTi. Thirty-five patients undergoing maintenance hemodialysis or peritoneal dialysis who had insomnia were screened for participation in the study, with 17 participants included in the final analyses. A self-directed cCBTi protocol accessed via tablet computer during dialysis or at home was developed and applied. Information about sleep, anxiety, depression, laboratory data, and resting-state functional magnetic resonance imaging data was obtained 3–5 days before and after cCBTi. cCBTi improved sleep quality, and this was correlated with increased resting-state brain connectivity between the default-mode network and the premotor/dorsolateral prefrontal cortex. The decrement of interleukin-1β levels were correlated with improved sleep quality and increased brain connectivity after cCBTi. Our pilot study findings suggest that cCBTi is effective for dialysis patients with insomnia, and the therapeutic effects of cCBTi are related to changes in brain functional connectivity and inflammatory cytokines. • Computerized CBT for insomnia (cCBTi) improved sleep quality in dialysis patients. • Changes in brain connectivity after cCBTi correlated with improved sleep. • Decrease in IL-1β correlated with improved sleep and increased brain connectivity. [ABSTRACT FROM AUTHOR]

This study aimed to investigate abnormalities in the gray matter and white matter (GM and WM, respectively) that are shared between schizophrenia (SZ) and bipolar disorder (BD). We used 3T-magnetic resonance imaging to examine patients with SZ, BD, or healthy control (HC) subjects (aged 20–50 years, N = 65 in each group). We generated modulated GM maps through voxel-based morphometry (VBM) for T1-weighted images and skeletonized fractional anisotropy, mean diffusion, and radial diffusivity maps through tract-based special statistics (TBSS) methods for diffusion tensor imaging (DTI) data. These data were analyzed using a generalized linear model with pairwise comparisons between groups with a family-wise error corrected P < 0.017. The VBM analysis revealed widespread decreases in GM volume in SZ compared to HC, but patients with BD showed GM volume deficits limited to the right thalamus and left insular lobe. The TBSS analysis showed alterations of DTI parameters in widespread WM tracts both in SZ and BD patients compared to HC. The two disorders had WM alterations in the corpus callosum, superior longitudinal fasciculus, internal capsule, external capsule, posterior thalamic radiation, and fornix. However, we observed no differences in GM volume or WM integrity between SZ and BD. The study results suggest that GM volume deficits in the thalamus and insular lobe along with widespread disruptions of WM integrity might be the common neural mechanisms underlying the pathologies of SZ and BD. [ABSTRACT FROM AUTHOR]

How the brain supports normal episodic memory function without medial temporal lobe (MTL) structures has not been well characterized, which could provide clues for new therapeutic targets for people with MTL dysfunction‐related memory impairment. To characterize brain network supporting effective episodic memory function in the absence of unilateral MTL, we investigated the whole‐brain cortical interactions during functional magnetic resonance imaging memory encoding paradigms of words and figures in patients who showed a normal range of memory capacity following unilateral MTL resection and healthy controls (HC). Compared to the HC, the patients showed less activation in the left inferior frontal areas and right thalamus together with greater activation in the many cortical areas including the medial prefrontal cortex (mPFC). Task‐based functional connectivity (FC) analysis revealed that the mPFC showed stronger interactions with widespread brain areas in both patient groups, including the hippocampus contralateral to the resection. Moreover, the strength of the mPFC FC predicts the individual memory capacity of the patients. Our data suggest that hyperconnectivity of distributed brain areas, especially the mPFC, is a neural mechanism for memory function in the absence of one MTL. [ABSTRACT FROM AUTHOR]

Objectives. Anhedonia in schizophrenia results from a deficit in anticipatory pleasure rather than consummatory pleasure. This study aimed to determine the neural basis of the predictive and experiential components of anticipatory pleasure in schizophrenia. Methods. A hedonic rating task was performed by 15 patients with schizophrenia and 17 controls while undergoing functional magnetic resonance imaging. Participants evaluated the level of pleasantness for the preview/predictive phase, comprising a narration and adjunctive audiovisual stimuli for pleasurable experience, and the subsequent viewing/experiential phase, comprising a video clip for a pleasant event. Results. A significant group-by-phase interaction was seen in the rostral anterior cingulate cortex (ACC) and caudate, resulting from reduced activations in patients during the preview phase. Patients showed significantly reduced activation in the frontopolar cortex and rostral ACC during the preview phase. The signal changes in the caudate and frontopolar cortex were associated with increase in hedonic response during the sequential pleasure experiences. Conclusions. Augmentation of hedonic enjoyment between the predictive and experiential stages of anticipatory pleasure is reduced in schizophrenia because of diminished activity in the reward-related regions during the prediction of pleasure. During cued-emotional experiences of anticipatory pleasure, patients seem to have difficulties in the integration of emotional information. [ABSTRACT FROM AUTHOR]

Patients with schizophrenia often show abnormal social interactions, which may explain their social exclusion behaviors. This study aimed to elucidate patients’ brain responses to social rejection in an interactive situation. Fifteen patients with schizophrenia and 16 healthy controls participated in the functional magnetic resonance imaging experiment with the virtual handshake task, in which socially interacting contents such as acceptance and refusal of handshaking were implemented. Responses to the refusal versus acceptance conditions were evaluated and compared between the two groups. Controls revealed higher activity in the refusal condition compared to the acceptance condition in the right superior temporal sulcus, whereas patients showed higher activity in the prefrontal regions, including the frontopolar cortex. In patients, contrast activities of the right superior temporal sulcus were inversely correlated with the severity of schizophrenic symptoms, whereas contrast activities of the left frontopolar cortex were positively correlated with the current anxiety scores. The superior temporal sulcus hypoactivity and frontopolar hyperactivity of patients with schizophrenia in social rejection situations may suggest the presence of mentalizing deficits in negative social situations and inefficient processes of socially aberrant stimuli, respectively. These abnormalities may be one of the neural bases of distorted or paranoid beliefs in schizophrenia. [ABSTRACT FROM AUTHOR]

Background Schizophrenia is a mental disorder characterized by impairments in diverse thinking and emotional responses, which are related to social perception dysfunction. This fMRI study was designed to investigate a neurobiological basis of social perception deficits of patients with schizophrenia in various social situations of daily life and their relationship with clinical symptoms and social dysfunction. Methods Seventeen patients and 19 controls underwent functional magnetic resonance imaging, during which participants performed a virtual social perception task, containing an avatar's speech with positive, negative or neutral emotion in a virtual reality space. Participants were asked to determine whether or not the avatar's speech was appropriate to each situation. Results The significant group × appropriateness interaction was seen in the left dorsolateral prefrontal cortex (DLPFC), resulting from lower activity in patients in the inappropriate condition, and left DLPFC activity was negatively correlated with the severity of negative symptoms and positively correlated with the level of social functioning. The significant appropriateness × emotion interaction observed in the left superior temporal sulcus (STS) was present in controls, but absent in patients, resulting from the existence and absence of a difference between the inappropriate positive and negative conditions, respectively. Conclusions These findings indicate that dysfunction of the DLPFC-STS network may underlie patients' abnormal social perception in various social situations of daily life. Abnormal functioning of this network may contribute to increases of negative symptoms and decreases of social functioning. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Most patients with schizophrenia suffer from various types of hallucinations, which commonly produce distress, functional disability or behavioral dyscontrol. The neural process of adapting to hallucinations in patients with schizophrenia remains unknown. Methods: Functional magnetic resonance imaging (MRI) responses to an unusual threatening visual stimulus designed to simulate a hallucinatory experience were compared between 16 patients with schizophrenia and 17 healthy controls. Linear and quadratic repetition-variant as well as repetition-invariant responses to the stimulus were compared between the two groups. Results: Repetition-invariant responses were similar between patients with schizophrenia and healthy controls. Patients with schizophrenia exhibited a linear activation pattern in the anterior cingulate, whereas healthy controls exhibited a parabolic activation pattern in the anterior prefrontal cortex, occipito-temporal junction and amygdala. Conclusions: These results provide us with a better understanding of the neural processes involved in gaining insight into unreality. Patients with schizophrenia may use a salience-related region instead of reality monitoring-related regions to react to the unusual stimuli, and this peculiarity of the neural processes may be related to vulnerability to psychosis. [Copyright &y& Elsevier]

• Studies on social functioning in obsessive-compulsive disorder (OCD) are lacking. • This study examined neural responses of OCD during handshake with a virtual avatar. • We found hypoactivation of left anterior cingulate cortex in OCD patients. • The deactivation was correlated with OCD severity as well was social anxiety trait. • Interaction of OCD symptoms and social cognition impairment may affect the results. Studies about social functioning in obsessive-compulsive disorder (OCD) are lacking, even though neuroimaging studies and metacognition evaluation results suggest abnormal neural responses during social interactions. This study examined neural responses of OCD patients during handshakes with a virtual avatar. Because of the nature of the handshaking task, we expected that OCD patients with predominantly contamination/washing symptoms (CON) would show different neural responses compared to healthy controls (HCs) and to disease-controlled (NCON) patients. Thirteen CON, 13 NCON, and 18 HC participants performed handshake tasks with clean or dirty virtual avatars while undergoing functional magnetic resonance imaging. During handshakes with a clean avatar, deactivation in the left anterior cingulate cortex was found in CON patients compared to NCON and HC subjects. This cortical deactivation also occurred with dirty-avatar handshakes, but the difference was significant only between the two OCD groups and HC patients. Deactivation in the left anterior cingulate cortex was correlated with both OCD symptom severity and social anxiety traits. This cortical deactivation in OCD, especially in CON patients, suggests that social dysfunction in OCD may be due to interactions between OCD symptoms and impairment in social cognition, including emotional processing. [ABSTRACT FROM AUTHOR]

Abstract: Neurobiological models of obsessive–compulsive disorder (OCD) emphasize disturbances of the corticostriatal circuit, but it remains unclear as to how these complex network dysfunctions correspond to heterogeneous OCD phenotypes. We aimed to investigate corticostriatal functional connectivity alterations distinct to OCD characterized predominantly by contamination/washing symptoms. Functional connectivity strengths of the striatal seed regions with remaining brain regions during the resting condition and the contamination symptom provocation condition were compared among 13 OCD patients with predominant contamination/washing symptoms (CON), 13 OCD patients without these symptoms (NCON), and 18 healthy controls. The CON group showed distinctively altered functional connectivity between the ventral striatum and the insula during both the resting and symptom-provoking conditions. Also, the connectivity strength between the ventral striatum and the insula significantly correlated with contamination/washing symptom severity. As common connectivity alterations of the whole OCD subjects, corticostriatal circuits involving the orbitofrontal and temporal cortices were again confirmed. To our knowledge, this is the first study that examined specific abnormalities in functional connectivity of contamination/washing symptom dimension OCD. The findings suggest limbic network dysfunctions to play a pivotal role in contamination/washing symptoms, possibly associated with emotionally salient error awareness. Our study sample allowed us to evaluate the corticostriatal network dysfunction underlying the contamination/washing symptom dimension, which leaves other major symptom dimensions to be explored in the future. [Copyright &y& Elsevier]

Aim Attention deficit has been reported in both schizophrenia patients and patients with major depressive disorder (MDD). The aim of this study was to elucidate the deficits in sustained attention and associated neural network dysfunctions in schizophrenia patients and MDD patients, and to investigate the difference between the two patient groups. Methods Twelve schizophrenia patients, 12 patients with non-psychotic MDD, and 12 healthy control subjects participated in this study. A sustained attention to response task ( SART) was used to measure attention capacity. Cerebral blood flow ( CBF) during attention tasks was measured using H215O positron emission tomography. Statistical parametric mapping and analysis of covariance were performed to compare the behavioral performance and CBF changes during SART among three groups. Results Behavioral performances were not significantly different among the three groups except for an increased commission error rate in the schizophrenia group. Regional CBF during SART was significantly reduced in the left inferior frontal gyrus, the left cuneus, and the right superior parietal lobule and increased in the right superior frontal gyrus and the right cuneus in the schizophrenia group compared to the healthy control group. In the MDD group, neither significant regional CBF difference nor behavioral deficit was found compared to the healthy control group. Conclusion Behavioral performance deficit and perfusion changes in the prefrontal and parietal cortices during SART were observed only in the schizophrenia group. Prefrontal and parietal network dysfunction for sustained attention may be involved in the pathophysiology of schizophrenia. [ABSTRACT FROM AUTHOR]

Abstract: The anterior insula has been proposed to play a crucial role in eating disorders. However, it is still poorly understood how the anterior insula is involved in anorexia nervosa (AN) and bulimia nervosa (BN), which are characterized by opposite motivational responses to food. We applied a cue-reactivity paradigm using blood oxygen level-dependent functional magnetic resonance imaging in women with AN (N =18) and BN (N =20) and age-matched healthy controls (N =20). We defined the left anterior insula as a region-of-interest and performed seed-based functional connectivity and effective connectivity MRI analysis. In response to food images compared to non-food images, both the AN group and BN group demonstrated increased activity in the left anterior insula. In the AN group, the left anterior insula demonstrated significant interactions with the right insula and right inferior frontal gyrus. In the BN group, the left anterior insula demonstrated significant interactions with the medial orbitofrontal cortex. The distinct patterns of functional and effective connectivity of the anterior insula may contribute to the different clinical features of AN and BN. [Copyright &y& Elsevier]

Abstract: Resting-state functional MRI (fMRI) is now providing further understanding of neuropsychiatric illnesses. However, its practical applicability in the clinical realms is still questionable. Here we report three consecutive followed-up resting-state fMRI data in a single case with Wernicke encephalopathy before and after high-dose thiamine replacement therapy ranging over 20 months. We measured the mammillothalamic functional connectivity strength between the first ROI (mammillary body) and a voxel which showed the highest co-activation among voxels within the anterior thalamus (the second ROI) to enhance the specificity of the functional connectivity data. We found that the time-series changes in the mammillothalamic functional connectivity generally paralleled to the changes in delayed verbal and nonverbal recall memory scores in the left and right hemisphere, respectively. Among these, the left-side connectivity and delayed verbal recall score seemed to be related to the overall clinical status change. Modified directed transfer function (dDTF) analysis also identified significant information flows with mammillary-to-thalamic direction except at the acute illness state. Our findings, though preliminary in nature, suggest the practical applicability of resting-state fMRI to trace an effect of thiamine replacement therapy on the memory tract function in Wernicke encephalopathy at single-patient level. [Copyright &y& Elsevier]

Abstract: Social cognition entails both cognitive and affective processing, and impairments in both have accounted for residual symptoms of bipolar disorder (BD). However, there has been a lack of studies identifying neural substrates responsible for social cognitive difficulties in BD patients. Fourteen euthymic BD patients and 14 healthy normal controls underwent functional MRI while performing a virtual reality social cognition task, which incorporated both cognitive and emotional dimensions, simulating real-world social situations. During the scanning, subjects tried to guess (attribute) possible reasons for expressed emotion of virtual humans (avatars) while viewing their facial expressions, just after observing their verbal and nonverbal (facial) expressions which were emotionally valenced (happy, angry and neutral). BD patients compared to normal controls showed delayed reaction times in emotional conditions, with comparable response accuracy. Healthy normal controls activated the right anterior cingulate cortex, inferior frontal, and insular cortex in emotional conditions contrasted with neutral control conditions, that is, the regions that have been related to empathic processes during viewing others'' emotional expression. Relative to normal controls, BD patients showed reduced activations in the ‘mirror neuron system’, including the right inferior frontal cortex, premotor cortex, and insula, mainly in angry or happy condition. These results may suggest that, even during euthymic state, BD patients have difficulties in recruiting brain regions for the utilization of emotional cues as a means for understanding others. Clinical attention should be paid to emotion-related residual symptoms to help improve social outcomes in these patients. [Copyright &y& Elsevier]

Abstract: Virtual reality may be a good alternative method for measuring personal space and overcoming some limitations in previous studies on the social aspects of schizophrenia. Using this technology, we aimed to investigate the characteristics of personal space in patients with schizophrenia and evaluate the relationship between their social behaviors and schizophrenic symptoms. The distance from a virtual person and the angle of head orientation while talking to a virtual person in a virtual environment were measured in 30 patients with schizophrenia and 30 normal controls. It was found that patients with schizophrenia had longer distances and larger angles than did normal controls. The severity of the negative syndrome had significant inverse correlations with the distance from the angry and neutral virtual persons and with the angle of head orientation toward the happy and angry virtual persons, suggesting that negative symptoms may have a close relationship with personal space, including distancing and eye gaze. The larger personal space of patients may reflect their discomfort in close situations or cognitive deficits. Showing these profiles to patients could help them realize the amount of personal space they need. [Copyright &y& Elsevier]

Abstract: Individuals sometimes experience an illusory or hallucinatory perception. This unreal perception is usually resolved after the individual recognizes that the perception was not real. In this study, we investigated the brain mechanisms involved in the process to an illusory or hallucinatory perception through ‘obtaining insight into unreality’. We used a novel and intuitive paradigm designed by combining functional magnetic resonance imaging and augmented reality technology to simulate visual illusory stimuli that mimic hallucinations during brain scanning. The results showed various brain activations, predominantly in the amygdala in the early phase, the medial frontal cortex and the occipitotemporal junction in the middle phase, and the thalamus in the late phase, which correlated with a subject''s proneness to hallucinating. These activations may correspond to a ‘responding stage’ for a perception-based immediate emotional reaction, a ‘monitoring stage’ for integration and recalibration to ascertain that the perception was not real, and a ‘resolving stage’ for controlling the information and finally settling it, respectively. Our paradigm and findings may be useful in understanding the mechanisms for discriminating and coping with hallucinatory perceptions. [Copyright &y& Elsevier]