Subcortical volumetric alterations in four major psychiatric disorders: a mega-analysis study of 5604 subjects and a volumetric data-driven approach for classification.

Differential diagnosis is sometimes difficult in practical psychiatric settings, in terms of using the current diagnostic system based on presenting symptoms and signs. The creation of a novel diagnostic system using objective biomarkers is expected to take place. Neuroimaging studies and others reported that subcortical brain structures are the hubs for various psycho-behavioral functions, while there are so far no neuroimaging data-driven clinical criteria overcoming limitations of the current diagnostic system, which would reflect cognitive/social functioning. Prior to the main analysis, we conducted a large-scale multisite study of subcortical volumetric and lateralization alterations in schizophrenia, bipolar disorder, major depressive disorder, and autism spectrum disorder using T1-weighted images of 5604 subjects (3078 controls and 2526 patients). We demonstrated larger lateral ventricles volume in schizophrenia, bipolar disorder, and major depressive disorder, smaller hippocampus volume in schizophrenia and bipolar disorder, and schizophrenia-specific smaller amygdala, thalamus, and accumbens volumes and larger caudate, putamen, and pallidum volumes. In addition, we observed a leftward alteration of lateralization for pallidum volume specifically in schizophrenia. Moreover, as our main objective, we clustered the 5,604 subjects based on subcortical volumes, and explored whether data-driven clustering results can explain cognitive/social functioning in the subcohorts. We showed a four-biotype classification, namely extremely (Brain Biotype [BB] 1) and moderately smaller limbic regions (BB2), larger basal ganglia (BB3), and normal volumes (BB4), being associated with cognitive/social functioning. Specifically, BB1 and BB2-3 were associated with severe and mild cognitive/social impairment, respectively, while BB4 was characterized by normal cognitive/social functioning. Our results may lead to the future creation of novel biological data-driven psychiatric diagnostic criteria, which may be expected to be useful for prediction or therapeutic selection.

Cerebral cortical structural alteration patterns across four major psychiatric disorders in 5549 individuals.

According to the operational diagnostic criteria, psychiatric disorders such as schizophrenia (SZ), bipolar disorder (BD), major depressive disorder (MDD), and autism spectrum disorder (ASD) are classified based on symptoms. While its cluster of symptoms defines each of these psychiatric disorders, there is also an overlap in symptoms between the disorders. We hypothesized that there are also similarities and differences in cortical structural neuroimaging features among these psychiatric disorders. T1-weighted magnetic resonance imaging scans were performed for 5,549 subjects recruited from 14 sites. Effect sizes were determined using a linear regression model within each protocol, and these effect sizes were meta-analyzed. The similarity of the differences in cortical thickness and surface area of each disorder group was calculated using cosine similarity, which was calculated from the effect sizes of each cortical regions. The thinnest cortex was found in SZ, followed by BD and MDD. The cosine similarity values between disorders were 0.943 for SZ and BD, 0.959 for SZ and MDD, and 0.943 for BD and MDD, which indicated that a common pattern of cortical thickness alterations was found among SZ, BD, and MDD. Additionally, a generally smaller cortical surface area was found in SZ and MDD than in BD, and the effect was larger in SZ. The cosine similarity values between disorders were 0.945 for SZ and MDD, 0.867 for SZ and ASD, and 0.811 for MDD and ASD, which indicated a common pattern of cortical surface area alterations among SZ, MDD, and ASD. Patterns of alterations in cortical thickness and surface area were revealed in the four major psychiatric disorders. To our knowledge, this is the first report of a cross-disorder analysis conducted on four major psychiatric disorders. Cross-disorder brain imaging research can help to advance our understanding of the pathogenesis of psychiatric disorders and common symptoms.

Cerebral activation caused by dental sounds: a functional magnetic resonance imaging study.

Dental drilling sounds can induce anxiety in some patients. This study aimed to use functional magnetic resonance imaging (fMRI) to assess the relationship between dental fear and auditory stimuli. Thirty-four right-handed individuals (21 women and 13 men; average age, 31.2 years) were selected. The level of dental fear was assessed using the dental fear survey (DFS). Based on a threshold DFS score > 52, participants were categorized into two groups: dental fear (DF) group (n = 12) and control group (n = 22). Two types of stimuli were presented in a single session: dental and neutral sounds. Cerebral activation during the presentation of these sounds was evaluated using contrast-enhanced blood oxygenation level-dependent fMRI. In the DF group, dental sounds induced significantly stronger activation in the left inferior frontal gyrus and left caudate nucleus (one-sample t test, P < 0.001). In contrast, in the control group, significantly stronger activation was observed in the bilateral Heschl's gyri and left middle frontal gyrus (one-sample t test, P < 0.001). Additionally, a two-sample t test revealed that dental sounds induced a significantly stronger activation in the left caudate nucleus in the DF group than in the control group (P < 0.005). These findings suggest that the cerebral activation pattern in individuals with DF differs from that in controls. Increased activation of subcortical regions may be associated with sound memory during dental treatment.

Trends in big data analyses by multicenter collaborative translational research in psychiatry.

The underlying pathologies of psychiatric disorders, which cause substantial personal and social losses, remain unknown, and their elucidation is an urgent issue. To clarify the core pathological mechanisms underlying psychiatric disorders, in addition to laboratory-based research that incorporates the latest findings, it is necessary to conduct large-sample-size research and verify reproducibility. For this purpose, it is critical to conduct multicenter collaborative research across various fields, such as psychiatry, neuroscience, molecular biology, genomics, neuroimaging, cognitive science, neurophysiology, psychology, and pharmacology. Moreover, collaborative research plays an important role in the development of young researchers. In this respect, the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium and Cognitive Genetics Collaborative Research Organization (COCORO) have played important roles. In this review, we first overview the importance of multicenter collaborative research and our target psychiatric disorders. Then, we introduce research findings on the pathophysiology of psychiatric disorders from neurocognitive, neurophysiological, neuroimaging, genetic, and basic neuroscience perspectives, focusing mainly on the findings obtained by COCORO. It is our hope that multicenter collaborative research will contribute to the elucidation of the pathological basis of psychiatric disorders.

Effects of anodal transcranial direct current stimulation on implicit motor learning and language-related brain function: An fMRI study.

AIM: Anodal transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (DLPFC) is known as a useful application for improving depressive symptoms or cognitive performance. Antidepressive effects by anodal tDCS over the left DLPFC are expected, but the neural mechanisms of these effects are still unclear. Further, in depression, reduced performance and left prefrontal hypofunction during the verbal fluency task (VFT) are generally known. However, few studies have examined the effect of tDCS on the language-related cerebral network. We aimed to investigate whether anodal tDCS at the left DLPFC affects cognitive performance and the neural basis of verbal fluency. METHODS: Nineteen healthy volunteers participated in this study. The effects of tDCS on cognitive behavior and cerebral function were evaluated by (i) performance and accuracy of implicit/explicit motor learning task (serial reaction time task/sequential finger-tapping task), and (ii) cerebral activation while the subjects were performing the VFT by using a functional MRI protocol of a randomized sham-controlled, within-subjects crossover design. RESULTS: Reaction times of the implicit motor learning task were significantly faster with tDCS in comparison with the sham. Further, language-related left prefrontal-parahippocampal-parietal activation was significantly less with tDCS compared with the sham. Significant correlation was observed between shortened response time in serial reaction time task and decreased cerebral activation during VFT with tDCS. CONCLUSION: Anodal tDCS over the left DLPFC could improve cognitive behavior of implicit motor learning by improving brain function of the frontoparietal-parahippocampal region related to motor learning, as well as language-related regions.

Comparison of Aversion to Visual Dental Stimuli Between Patients and Dentists: A Preliminary Study.

Purpose: Fearful dental patients often cite various dental instruments or procedures as triggers for their dental fear. Thus, visual dental stimuli provoke anxiety. This preliminary study aimed to assess the level of aversion to visual stimuli in dental patients and compare it with that in dentists. Patients and Methods: A total of 43 dental patients (25 women, 18 men; average age, 29.9 ± 13.3 years; patient group) and 13 dentists (4 women, 9 men; average age, 28.2 ± 2.0 years; dentist group) were included. All participants had previously undergone dental treatment. The dental fear level was assessed using the self-reported Dental Fear Survey (DFS). Thirty-two images associated with dental treatment were prepared and classified into three categories: dental instruments, dental procedures, and the dental environment. All participants rated their level of disgust toward each image on a visual analog scale with scores ranging from 0 to 100. Results: In the patient group, the disgust ratings for tooth extraction, dental drilling, and local anesthesia were >60, which were significantly different from those in the dentist group (Mann-Whitney U-test, p<0.001, p=0.001, and p=0.001, respectively). The ranking order of the disgust ratings for the 32 images showed significant correlation between the patient and dentist groups (Spearman correlation coefficient, r=0.80, p<0.001). In the patient group, the disgust ratings for dental impressions and the interdental brush, dental light, and dental chair were significantly correlated with DFS scores (r=0.61, p<0.001; r=0.47, p=0.001; r=0.41, p=0.006; and r=0.40, p=0.008, respectively). Conclusion: This study revealed that patients have more negative feelings toward invasive procedures than dentists. However, a significant correlation was identified between the ranking of aversion-provoking dental stimuli by patients and dentists. Furthermore, the level of aversion to several dental-related items that do not cause pain was correlated with the dental fear level.

Characteristics of healthy Japanese young adults with respect to recognition of facial expressions: a preliminary study.

BACKGROUND: Emotional cognitive impairment is a core phenotype of the clinical symptoms of psychiatric disorders. The ability to measure emotional cognition is useful for assessing neurodegenerative conditions and treatment responses. However, certain factors such as culture, gender, and generation influence emotional recognition, and these differences require examination. We investigated the characteristics of healthy young Japanese adults with respect to facial expression recognition. METHODS: We generated 17 models of facial expressions for each of the six basic emotions (happiness, sadness, anger, fear, disgust, and surprise) at three levels of emotional intensity using the Facial Acting Coding System (FACS). Thirty healthy Japanese young adults evaluated the type of emotion and emotional intensity the models represented to them. RESULTS: Assessment accuracy for all emotions, except fear, exceeded 60% in approximately half of the videos. Most facial expressions of fear were rarely accurately recognized. Gender differences were observed with respect to both faces and participants, indicating that expressions on female faces were more recognizable than those on male faces, and female participants had more accurate perceptions of facial emotions than males. CONCLUSION: The videos used may constitute a dataset, with the possible exception of those that represent fear. The subject's ability to recognize the type and intensity of emotions was affected by the gender of the portrayed face and the evaluator's gender. These gender differences must be considered when developing a scale of facial expression recognition.

Cerebral response to emotional working memory based on vocal cues: an fNIRS study.

Introduction: Humans mainly utilize visual and auditory information as a cue to infer others' emotions. Previous neuroimaging studies have shown the neural basis of memory processing based on facial expression, but few studies have examined it based on vocal cues. Thus, we aimed to investigate brain regions associated with emotional judgment based on vocal cues using an N-back task paradigm. Methods: Thirty participants performed N-back tasks requiring them to judge emotion or gender from voices that contained both emotion and gender information. During these tasks, cerebral hemodynamic response was measured using functional near-infrared spectroscopy (fNIRS). Results: The results revealed that during the Emotion 2-back task there was significant activation in the frontal area, including the right precentral and inferior frontal gyri, possibly reflecting the function of an attentional network with auditory top-down processing. In addition, there was significant activation in the ventrolateral prefrontal cortex, which is known to be a major part of the working memory center. Discussion: These results suggest that, compared to judging the gender of voice stimuli, when judging emotional information, attention is directed more deeply and demands for higher-order cognition, including working memory, are greater. We have revealed for the first time the specific neural basis for emotional judgments based on vocal cues compared to that for gender judgments based on vocal cues.

Transdiagnostic comparisons of intellectual abilities and work outcome in patients with mental disorders: multicentre study.

BACKGROUND: Cognitive impairment is common in people with mental disorders, leading to transdiagnostic classification based on cognitive characteristics. However, few studies have used this approach for intellectual abilities and functional outcomes. AIMS: The present study aimed to classify people with mental disorders based on intellectual abilities and functional outcomes in a data-driven manner. METHOD: Seven hundred and forty-nine patients diagnosed with schizophrenia, bipolar disorder, major depression disorder or autism spectrum disorder and 1030 healthy control subjects were recruited from facilities in various regions of Japan. Two independent k-means cluster analyses were performed. First, intelligence variables (current estimated IQ, premorbid IQ, and IQ discrepancy) were included. Second, number of work hours per week was included instead of premorbid IQ. RESULTS: Four clusters were identified in the two analyses. These clusters were specifically characterised in terms of IQ discrepancy in the first cluster analysis, whereas the work variable was the most salient feature in the second cluster analysis. Distributions of clinical diagnoses in the two cluster analyses showed that all diagnoses were unevenly represented across the clusters. CONCLUSIONS: Intellectual abilities and work outcomes are effective classifiers in transdiagnostic approaches. The results of our study also suggest the importance of diagnosis-specific strategies to support functional recovery in people with mental disorders.

Bupropion increases cerebral activation in auditory affective processing: A randomized controlled fMRI study.

INTRODUCTION: Bupropion is an antidepressant with less possibility to give rise to emotional blunting as side effect, and it also acts on improving negative self-recognition in a depressive state. Previous neuroimaging studies indicated a change in brain function by facial expression as an effect of antidepressants. As well as facial expression, vocal affective processing is essential for accurately recognizing another's feelings, but to our knowledge, no study has investigated whether bupropion affects the cerebral function of recognition of auditory affective processing. In this study, we aimed to investigate the acute effect of bupropion on cerebral response to vocal affective processing. METHODS: Sixteen healthy volunteers (male = 8) participated in this study. With a randomized placebo-controlled within-subject trial, two series of fMRI scans, using either placebo or bupropion (150 mg), were examined. An auditory emotional valence judgement task was performed during fMRI scanning. The acute effects of bupropion on cerebral activation in the emotional circuit and behavioral performance during emotional processing were analyzed. RESULTS: Compared with placebo, bupropion caused a significantly greater activation of emotional voices in the left insula and right superior temporal gyrus, whereas the amygdala was not activated. By bupropion, a significantly greater activation of the positive emotional circuit was observed at the superior temporal gyrus and middle frontal gyrus. As for behavioral performance, no significant difference was observed between placebo and bupropion. CONCLUSIONS: Our findings suggest that bupropion enhances the cerebral response to affective processing, especially positive emotional vocalizations, indicating a possible mechanism underlying the therapeutic effects for patients with depression.

Modafinil Decreased Thalamic Activation in Auditory Emotional Processing: A Randomized Controlled Functional Magnetic Resonance Imaging Study.

BACKGROUND: Modafinil improves wakefulness and attention, is approved in Japan for treatment of narcolepsy, and was reported to be effective for attention-deficit/hyperactivity disorder. However, it was reported to induce emotional instability, including mania, depression, and suicidal ideation. Such side effects may be related to changes in cognitive behavior caused by the effects of modafinil on emotional recognition. However, the effects of modafinil on the neural basis of emotional processing have not been fully verified. We used functional magnetic resonance imaging to investigate the effects of modafinil on the neural basis of auditory emotional processing. METHODS: This study adopted a placebo-controlled within-subject crossover design. Data from 14 participants were analyzed. The effects of modafinil on cerebral activation and task performance during an emotional judgement task were analyzed. RESULTS: Task accuracy decreased significantly and response time of emotional judgement was significantly delayed by modafinil, as compared with placebo. Right thalamic activation in auditory emotional processing was significantly less in the modafinil condition than in the placebo condition. In addition, reduction of right thalamic activation by modafinil was positively correlated with accuracy of emotional judgement. CONCLUSIONS: Our findings suggest that modafinil acts on the right thalamus and changes behavior and brain function associated with auditory emotional processing. These results indicate that modafinil might change emotional recognition by reducing emotional activation related to social communication.

Relationship of psychological characteristics and self-efficacy in gastrointestinal cancer survivors.

To characterize gastrointestinal cancer survivors' ability to psychologically adjust, we examined the relationship between psychological characteristics (quality of life (QOL), anxiety, depression, and post-traumatic stress symptoms) and self-efficacy (perceived ability to initiate coping strategies). Forty-seven subjects (32 males and 15 females) were recruited from outpatient clinics or general surgical wards after readmission for therapy unrelated to cancer. All had undergone treatment for gastrointestinal cancer. Japanese version of the Functional Assessment of Cancer Therapy--General (FACT-G), Japanese version of Hospital Anxiety and Depression Scale (HADS), Japanese version of Impact of Event Scale--Revised (IES-R), and The Self-Efficacy Scale for Advanced Cancer (SEAC) were administered. Correlation analyses revealed a statistically significant positive correlation between three subscales of SEAC and QOL (total of FACT-G value) and a significant negative correlation between anxiety, depression (the total of HADS value), post-traumatic stress symptoms (the total of IES-R value), and SEAC. In multiple regression analysis, the influence from Affect Regulation Efficacy (subscale of SEAC) was the largest in anxiety and post-traumatic stress symptoms while the influence from Activities of Daily Living Efficacy (subscale of SEAC) was the largest in QOL and depression. Our findings revealed that a strong relationship between self-efficacy and psychological adjustment, and that there should be several psychological intervention forms performed at various treatment stages to enhance self-efficacy in this population of gastrointestinal cancer survivors. These results also imply the effectiveness of interventions on self-efficacy for gastrointestinal cancer survivors and the influence of psychological factors such as QOL, anxiety, depression, and post-traumatic stress symptoms.

Neural correlates of human virtue judgment.

Neuroimaging studies have demonstrated that the brain regions implicated in moral cognition. However, those studies have focused exclusively on violation of social norms and negative moral emotions, and very little effort has been expended on the investigation of positive reactions to moral excellence. It remains unclear whether the brain regions implicated in moral cognition have specific roles in processing moral violation or, more generally, process human morality per se. Using functional magnetic resonance imaging, brain activations during evaluation of moral beauty and depravity were investigated. Praiseworthiness for moral beauty was associated with activation in the orbitofrontal cortex, whereas blameworthiness for moral depravity was related to the posterior superior temporal sulcus. Humans might have developed different neurocognitive systems for evaluating blameworthiness and praiseworthiness. The central process of moral beauty evaluation might be related to that of aesthetic evaluation. Our finding might contribute to a better understanding of human morality.

Brain activations during judgments of positive self-conscious emotion and positive basic emotion: pride and joy.

We aimed to investigate the neural correlates associated with judgments of a positive self-conscious emotion, pride, and elucidate the difference between pride and a basic positive emotion, joy, at the neural basis level using functional magnetic resonance imaging. Study of the neural basis associated with pride might contribute to a better understanding of the pride-related behaviors observed in neuropsychiatric disorders. Sixteen healthy volunteers were studied. The participants read sentences expressing joy or pride contents during the scans. Pride conditions activated the right posterior superior temporal sulcus and left temporal pole, the regions implicated in the neural substrate of social cognition or theory of mind. However, against our prediction, we did not find brain activation in the medial prefrontal cortex, a region responsible for inferring others' intention or self-reflection. Joy condition produced activations in the ventral striatum and insula/operculum, the key nodes of processing of hedonic or appetitive stimuli. Our results support the idea that pride is a self-conscious emotion, requiring the ability to detect the intention of others. At the same time, judgment of pride might require less self-reflection compared with those of negative self-conscious emotions such as guilt or embarrassment.

Development of clinical ontology for mood disorder with combination of psychomedical information.

We have developed a new educational/clinical ontology named the "Haghighi-Koeda Mood Disorder Ontology", which involves both medical and psychological approaches for mood disorders in order to promote the exchange of information between psychiatrists and psychologists. Data was gathered from more than 5000 articles published in journals and websites specialized in life science. We evaluated and selected articles which were related to 4 main categories of mood disorders. Using Protege 3.4 beta, information related to mood disorders was classified by class/subclass tree in an ontological structure. Then we developed a web-based interface system on the internet enabling the implementation of the ontology. In addition, we have designed an online scale for automated diagnosis of mood disorder. For evaluating experiments, we compare this ontology with "Decisionbase" of which content deals with mood disorders. Evaluation was in accordance with our selected criteria via the AHP (Analysis of Hierarchical Processing) method. The results demonstrated the noteworthy superiority of our ontology. We believe that combining knowledge of medical science with that in psychological fields is a key to improving the quality of diagnosis and promoting appropriate treaTMent in all psychiatric disorders.

Differences in the perception of dental sounds: a preliminary study.

PURPOSE: The sound of dental treatments can evoke anxiety in some dental patients. While women have shown greater dental anxiety than men, little is known about the gender differences in the perception of dental sounds. The purpose of this preliminary study was to evaluate differences in the perception of dental sounds according to the level of dental fear and gender. PATIENTS AND METHODS: Based on the level of dental fear, 69 adults (39 women, 30 men; average age, 28.1±8.1 years) were categorized into four groups. Three types of sounds were presented to participants: two sounds associated with dental treatment and a neutral sound. All participants rated their emotional reaction to each sound on a visual analog scale. RESULTS: Significant differences were observed for ratings of valence and disgust for a dental drilling sound among the four groups (p=0.007 and 0.004, respectively). Female participants in the dental fear group rated the dental drilling sound as more negative and disgusting than did female participants in the control group (p=0.002 for both ratings). However, no significant differences were found in ratings between males in the dental fear and control groups. CONCLUSION: Perception of dental sounds appears to differ by level of dental fear and by gender. Considering these differences may contribute to reducing fear in dental patients.

Enhanced activation in the extrastriate body area by goal-directed actions.

AIM: Neuroimaging studies on biological motion have established the view that the posterior superior temporal sulcus (pSTS) is involved in detecting intention of others. Those studies have consistently reported other regions such as body-selective extrastriate body area (EBA) and motion-sensitive middle temporal, in close proximity to pSTS. Whether EBA responds only to static body parts or has a more extended role as part of a system for inferring intention of others has remained an elusive issue. The aim of the present study was to investigate the role of EBA in processing goal-directed actions. METHODS: Twelve healthy volunteers participated in the present study. Using sports-related motions as visual stimuli, brain activations were examined during observation of goal-directed actions and non-goal-directed actions on functional magnetic resonance imaging. RESULTS: Compared to non-goal-directed actions, goal-directed actions produced greater activations in EBA along with the mirror neuron system. CONCLUSIONS: EBA might contribute to understanding others' actions by representing the dynamic aspects of human motions.

Hypofunction of left dorsolateral prefrontal cortex in depression during verbal fluency task: A multi-channel near-infrared spectroscopy study.

BACKGROUND: Previous functional neuroimaging studies of depression have demonstrated frontotemporal dysfunction, including the dorsolateral prefrontal cortex, while patients perform working memory and language comprehension tasks. Recent near-infrared spectroscopy (NIRS) studies have shown frontotemporal hypofunction in depression by verbal fluency task, but the regions of impairment affecting respective depressive symptoms still remain unclear. We investigated frontotemporal function during word production task in depression with multi-channel NIRS. Further, we aimed to clarify whether any depressive symptoms affect frontotemporal dysfunction. METHODS: One hundred seventy-seven major depressive patients and 50 healthy control volunteers participated in this study. Their cerebral activations were compared during verbal fluency task. RESULTS: Although performance was not significantly different, hypoactivation in the bilateral frontotemporal regions was significantly observed in depressed patients, compared with controls. Left lateral frontotemporal activation was significantly reduced in the group with mandatory symptom, which is depressed mood, or loss of interest or pleasure, compared with the group that still has residual depressive symptoms in spite MDD having been remitted. LIMITATION: the MDD group had significantly higher age and education level than the controls. Conclusions Our findings indicate hypofunction of the bilateral frontotemporal regions in depression during verbal fluency task. Further, hypofunction of these regions in the left hemisphere by this task could reflect whether the subjects recovered from depressed mood, or loss of interest or pleasure.

Effect of apolipoprotein E phenotype on the association of plasma amyloid ß and amyloid positron emission tomography imaging in Japan.

INTRODUCTION: The plasma concentration of beta-amyloid (Aß) has been considered another biomarker of Alzheimer's disease and was reportedly associated with cortical Aß accumulation. METHODS: We analyzed 28 subjects with apolipoprotein E4 (ApoE4; E4 group) and 89 subjects without ApoE4 (non-E4 group) to determine the association between cortical Aß accumulation by standard uptake value ratio with [18F]florbetapir positron emission tomography and plasma Aß1-40 and Aß1-42. RESULTS: Aß1-42/Aß1-40 correlated significantly with mean regional [18F]florbetapir standard uptake value ratio in the non-E4 group (R2 = 0.06, P = .02) but not in the E4 group, and receiver operating characteristic curve analysis for Aß1-42/Aß1-40 in the non-E4 group showed sensitivity (92.9%) and specificity (45.9%) with a cutoff value of 0.150 for Aß positivity. DISCUSSION: We verified that the correlation between Aß1-42/Aß1-40 and Aß accumulation differed according to ApoE phenotype. The high sensitivity of plasma Aß1-42/Aß1-40 for Aß positivity in non-E4 subjects indicated a possible role of plasma Aß1-42/Aß1-40 as a screening biomarker before amyloid positron emission tomography in clinical settings.

Language processing and human voice perception in schizophrenia: a functional magnetic resonance imaging study.

BACKGROUND: Neuroimaging studies have demonstrated either reduced left-lateralized activation or reversed language dominance in schizophrenia. These findings of left hemispheric dysfunction could be attributed to language processing tasks, which activate mainly left hemispheric function. Recent functional magnetic resonance imaging studies reported right-lateralized temporal activation by human voice perception, but few studies have investigated activation by human voice in schizophrenia. We aimed to clarify the cerebral function of language processing in schizophrenia patients by considering cerebral activation of human voice perception. METHODS: Fourteen right-handed schizophrenia patients and 14 right-handed controls with matched handedness, sex, and education level were scanned by functional magnetic resonance imaging while listening to sentences (SEN), reverse sentences (rSEN), and identifiable non-vocal sounds (SND). RESULTS: Under the SEN-SND and SEN-rSEN contrasts including language processing, patients showed less activation of the left hemisphere than controls in the language-related fronto-tempo-parietal region, hippocampus, thalamus and cingulate gyrus. Under the rSEN-SND contrast including human voice perception, patients showed less activation than controls in the right-lateralized temporal cortices and bilateral posterior cingulate. CONCLUSIONS: Our results indicate that schizophrenia patients have impairment of broader bilateral cortical-subcortical regions related to both the semantic network in the left hemisphere and the voice-specific network in the right hemisphere.