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Autism spectrum disorder (ASD) is related to impairment in various white matter (WM) pathways. Utility of the recently developed two-compartment model of diffusion kurtosis imaging (DKI) to analyse axial diffusivity of WM is restricted by several limitations. The present study aims to validate the utility of model-free DKI in the evaluation of WM alterations in ASD and analyse the potential relationship between DKI-evident WM alterations and personality scales. Overall, 15 participants with ASD and 15 neurotypical (NT) controls were scanned on a 3 T magnetic resonance (MR) scanner, and scores for autism quotient (AQ), systemising quotient (SQ) and empathising quotient (EQ) were obtained for both groups. Multishell diffusion-weighted MR data were acquired using two b-values (1000 and 2000 s/mm2). Differences in mean kurtosis (MK), radial kurtosis (RK) and axial kurtosis (AK) between the groups were evaluated using tract-based spatial statistics (TBSS). Finally, the relationships between the kurtosis indices and personality quotients were examined. The ASD group demonstrated significantly lower AK in the body and splenium of corpus callosum than the NT group; however, no other significant differences were identified. Negative correlations were found between AK and AQ or SQ, predominantly in WM areas related to social–emotional processing such as uncinate fasciculus, inferior fronto-occipital fasciculus, and inferior and superior longitudinal fasciculi. Model-free DKI and its indices may represent a novel, objective method for detecting the disease severity and WM alterations in patients with ASD.

Differentiating posterior cortical atrophy (PCA) from other diseases can be difficult and time‐consuming, and there is a particularly high possibility of misdiagnosis when psychiatrists diagnose complaints related to visual perception. Here, a case of PCA involving prominent visual perceptual disorders is reported; PCA was difficult to distinguish from psychogenic disturbance of vision in this case. For a year, a 59‐year‐old woman had had visual perceptual disorders, including a distorted view and prosopagnosia. She underwent examinations at multiple clinical departments at several medical institutions before receiving a definitive diagnosis of PCA. This PCA diagnosis was based on clinical symptoms, including Gerstmann syndrome, Bálint's syndrome, and transcortical sensory aphasia, and hypoperfusion in the occipital lobe observed on single‐photon emission computed tomography. This case was initially misdiagnosed as a psychogenic disease partly because characteristic clinical manifestations of PCA include visual agnosia with a disjunctive component. This patient displayed a disordered perception of stationary objects but an intact perception of moving objects. For example, she had to grope her way through a room at home, but she could visit a familiar hair salon on foot without hindrance. Behaviours like claiming to be blind while inexplicably moving without colliding with surrounding objects may lead to the misdiagnosis of PCA as a psychogenic or dissociative disorder involving histrionic or neurologically irrational symptoms with an expectation of sympathy or personal gain. It is critical to make every effort to exclude organic diseases, even in cases provisionally diagnosed as psychogenic disease. Despite its low prevalence, PCA should be considered a syndrome caused by Alzheimer's disease, dementia with Lewy bodies, or other dementias.

ObjectiveThe aims of the present study were to examine the effects of short-term music interventions among patients with fibromyalgia (FM) and to clarify the alterations in functional connectivity and persistent pain.DesignPilot study.SettingAll participants were evaluated at Juntendo University from November 2017 to January 2019.SubjectsWe enrolled female patients who had been clinically diagnosed with FM (N = 23).MethodsAll participants listened to Mozart’s Duo for Violin and Viola No. 1, K. 423, in a quiet room for 17 minutes. We compared the degree of pain using resting-state functional magnetic resonance imaging and the numeric rating scale before and after listening to music.ResultsPain scores were significantly reduced after listening to music. Further, we observed there was a significant difference in connectivity between the right insular cortex (IC) and posterior cingulate cortex (PCC)/precuneus (PCu) before and after listening to music. We also found that the difference between the right IC-PCu connectivity and the difference in pain scores were significantly correlated.ConclusionsWe found that a short period of music intervention reduced chronic pain and altered functional IC–default mode network connectivity. Furthermore, music potentially normalized the neural network via IC–default mode network connectivity, yielding temporary pain relief in patients with FM. Further longitudinal studies with larger sample sizes are required to confirm these results.

Background: Aberrant functional connectivity (FC) is increasingly implicated in the clinical phenomenology of schizophrenia. This study focused on the FC of the cortico-striatal network, which is thought to be disrupted in schizophrenia and to contribute to its clinical manifestations. Methods: We used simultaneous resting-state functional magnetic resonance imaging (rsfMRI) and electroencephalography (EEG) recordings to investigate FC in patients with schizophrenia. The study included 20 patients with schizophrenia and 20 healthy controls (HCs). Simultaneously recorded rsfMRI and EEG data were collected with an MR-compatible amplifier, and rsfMRI data were analyzed with the CONN toolbox to calculate FC. The study focused on the caudate, which was defined as the seed. We also performed between-group comparisons of standardized low-resolution electromagnetic tomography intracortical lagged coherence for each EEG frequency band. Results: Compared to HCs, patients with schizophrenia showed enhanced FC between the caudate nucleus and the posterior cingulate cortex, temporal, and occipital regions on rsfMRI. It is thus possible that HCs have negative FC between these regions, whereas patients with schizophrenia have non-negative FC. The EEG results showed no significant differences in oscillations or in FC between the groups in any frequency band in any region. Conclusions: Increased FC in the caudate may represent aberrant between-network FC resulting from the disruption of segregation between networks.

AIM To evaluate usefulness of single photon emission computed tomography (SPECT) with three-dimensional stereotactic surface projection (3D-SSP) in distinguishing between Alzheimer’s disease (AD) and depression. METHODS We studied 43 patients who presented with both depressive symptoms and memory disturbance. Each subject was evaluated using the following: (1) the Minimal Mental State Examination; (2) the Hamilton Rating Scale for Depression; (3) Clinical Global Impression-Severity scale (CGI-S); and (4) SPECT imaging with 3D-SSP. RESULTS The MMSE scores correlated significantly with the maximum Z-scores of AD-associated regions. CGI-S scores correlated significantly with the maximum Z-scores of depression-associated regions. Factor analysis identified three significant factors. Of these, Factor 1 could be interpreted as favouring a tendency for AD, Factor 2 as favouring a tendency for pseudo-dementia, and Factor 3 as favouring a depressive tendency. CONCLUSION We investigated whether these patients could be categorized as types: Type A (true AD), Type B (pseudo-dementia), Type C (occult AD), and Type D (true depression). The factor scores in factor analysis supported the validity of this classification. Our results suggest that SPECT with 3D-SSP is highly useful for distinguishing between depression and depressed mood in the early stage of AD.

The cortico-thalamocortical network is relevant to music performance in that the network can regulate sensitivity to afferent input or sound, mediate the integration of multimodal information required for the performance, and play a role in skilled performance control. We, therefore, predicted that this network would be reorganized via musical training-induced neuroplasticity. To test this hypothesis, we analyzed resting-state functional connectivity of the thalamocortical network in musicians (n=35) and nonmusicians (n=35). The seed-to-voxel functional connectivity analysis of the left thalamus seed showed enhanced connectivity voxels in the precuneus/posterior cingulate cortex (PCC) in musicians compared with nonmusicians. Region of interest (ROI)-to-ROI functional connectivity analysis showed that the auditory areas were also more strongly connected with the left thalamus in musicians. Discriminant analysis using the ROI-to-ROI functional connectivity data of the precuneus/PCC and auditory areas as predictors yielded an 87% correct discrimination of musicians from nonmusicians. Therefore, we can conclude that, as a consequence of long-term musical training, musicians have a characteristically organized thalamocortical network. The precuneus and PCC are principal nodes of the default mode network and play a pivotal role in the manipulation of mental imagery. We propose that the reorganized thalamocortical network in musicians contributes not only to higher sensitivity to sound but also to the integration of mental imagery with sound, which are both presumed to be important for better music performance.

Aim It remains unclear how functional connectivity (FC) may be related to specific cognitive domains in neuropsychiatric disorders. Here we used simultaneous resting-state functional magnetic resonance imaging (rsfMRI) and electroencephalography (EEG) recording in patients with schizophrenia, to evaluate FC within and outside the default mode network (DMN). Methods Our study population included 14 patients with schizophrenia and 15 healthy control participants. From all participants, we acquired rsfMRI data, and simultaneously recorded EEG data using an MR-compatible amplifier. We analyzed the rsfMRI-EEG data, and used the CONN toolbox to calculate the FC between regions of interest. We also performed between-group comparisons of standardized low-resolution electromagnetic tomography-based intracortical lagged coherence for each EEG frequency band. Results FC within the DMN, as measured by rsfMRI and EEG, did not significantly differ between groups. Analysis of rsfMRI data showed that FC between the right posterior inferior temporal gyrus and medial prefrontal cortex was stronger among patients with schizophrenia compared to control participants. Conclusion Analysis of FC within the DMN using rsfMRI and EEG data revealed no significant differences between patients with schizophrenia and control participants. However, rsfMRI data revealed over-modulated FC between the medial prefrontal cortex and right posterior inferior temporal gyrus in patients with schizophrenia compared to control participants, suggesting that the patients had altered FC, with higher correlations across nodes within and outside of the DMN. Further studies using simultaneous rsfMRI and EEG are required to determine whether altered FC within the DMN is associated with schizophrenia.

Aim To evaluate the safety, tolerability and pharmacokinetic profile of bapineuzumab after a single intravenous injection in Japanese patients with mild to moderate Alzheimer's disease. Methods Participants received either a placebo (n = 8), or bapineuzumab 0.15 (n = 6), 0.5 (n = 6), 1.0 (n = 6) or 2.0 (n = 6) mg/kg. Serum concentrations of bapineuzumab, antibapineuzumab antibody and total plasma β-amyloidx-40 were assayed. Results Adverse events for bapineuzumab and placebo groups were 71% and 88%, respectively. Treatment-emergent adverse events (cataract, injection site hemorrhage, nasopharyngitis, pneumonia and muscle twitching) reported for ≥2 participants were mild or moderate in severity and unrelated to bapineuzumab dose. No deaths, serious adverse events or withdrawals were reported. Mean peak concentration for bapineuzumab increased with dose, from 3.3 ± 0.9 μg/mL with the 0.15 mg/kg dose to 61.0 ± 32.8 μg/mL with 2.0 mg/kg. Mean bapineuzumab exposure (area under the curve from time 0 to last measurable concentration; μg·h/mL) increased in a linear manner with increasing dose (mean 1260 for 0.15 mg/kg, 4264 for 0.5 mg/kg, 7818 for 1.0 mg/kg, 15 313 for 2.0 mg/kg). Mean half-life ranged from 15 to 28 days, and clearance was similar across dose groups (range 0.12–0.17 mL/h/kg). Conclusions Plasma β-amyloidx-40 levels increased with increasing doses of bapineuzumab. Bapineuzumab was safe and well tolerated at all doses in Japanese patients with mild to moderate Alzheimer's disease. Geriatr Gerontol Int 2016; 16: 644–650.

Purpose: We administered olanzapine to 24 outpatients with bipolar disorder who had experienced a depressive or mixed episode as their most recent episode to evaluate the efficacy and safety of olanzapine in clinical practice. Methods: The duration of study treatment was 8 weeks. Symptoms in each subject were assessed using the Montgomery Asberg Depression Rating Scale (MADRS) and the Clinical Global Impressions-Severity of Illness, Bipolar Version (CGI-BP) at the start of treatment with olanzapine and at Week 4 and Week 8 of treatment. Results: A total of 17 subjects underwent the assessments at Week 4, and 13 subjects completed the 8-week treatment regimen and the assessments at Week 8. The mean total score and each individual item score of the MADRS were significantly improved at Week 4 and Week 8 compared to those at the start of treatment. The mean CGI-BP Depression and CGI-BP Overall scores were significantly improved at Week 4 and Week 8, while the mean CGI-BP Mania score was not significantly different at Week 4 or Week 8 compared to that at the start of treatment. Adverse drug reactions were reported in 3 subjects during the study: hyperphagia in 2 subjects and light-headed feeling in 1 subject. No manic switches were observed. Discussion: The results of this study confirmed the efficacy and safety of olanzapine in outpatients with bipolar depression in clinical practice.

Objective:“Mind reading”is the ability to understand another individualʼs mental states. In particular, individuals with developmental disorders, such as autism spectrum disorders, have a deficit in mind reading abilities. Similarly, individual differences in mind reading also exist among the healthy population and are often the cause of misunderstandings. Although the Empathizing and Systemizing Theory (E-S theory) has been used to explain individual developmental differences, its applicability to mind reading among Japanese adolescents has not been investigated. Therefore, the purpose of this study was to examine whether the E-S theory explains individual differences in mind reading among Japanese adolescents. Participants: Participants were 240 Japanese university students (M = 20.58,SD = 0.51). Methods: We administered questionnaires based on Japanese versions of the Empathy and Systemizing Quotients, and the Reading the Mind in the Eyes Test. Results: Empathizing, but not systemizing, was found to be related to mind reading. Additionally, relative differences in empathizing and systemizing, rather than its combination, were associated with mind reading. Conclusion: Since relative differences in empathizing and systemizing affect mind reading, we concluded that the E-S theory explains individual differences in mind reading among Japanese adolescents.

The study of event-related potentials (ERPs) is capable of elucidating the abnormalities in brain network dynamics relevant to the information-processing deficits in schizophrenia patients. In contrast to P50 and P300 ERPs, however, the results of P100 ERP studies in schizophrenia patients are less consistent. We have previously reported that P100 amplitudes did not differ significantly between patients with schizophrenia and healthy subjects. This result raised a question as to whether P100 ERPs carry information on brain network dynamics in schizophrenia patients that is distinct from normal controls. To answer this question, in this study we performed discrimination analysis on the P100 data. The rate of correct classification of patients and controls was high (80-90% depending on stimulus categories), indicating that patients have spatial patterns of P100 amplitudes that are distinguishable from those in healthy subjects. To further explore this possibility, we performed principal component analysis on the P100 data. For the patients, the first principal component represented global activity, the second component represented the reciprocal anterior-posterior activation, and the third component represented the hemispheric reciprocity in activity. The first and second components were similar to those of the control group; however, the third component in control subjects showed activation of the center versus anterior and posterior regions. This result is consistent with the notion of abnormalities in hemispheric asymmetries during the processing of sensory information in schizophrenia. In conclusion, this ERP study demonstrated that P100 amplitudes have information that can successfully classify patients and controls.

Auditory-sensorimotor coupling is critical for musical performance, during which auditory and somatosensory feedback signals are used to ensure desired outputs. Previous studies reported opercular activation in subjects performing or listening to music. A functional connectivity analysis suggested the parietal operculum (PO) as a connector hub that links auditory, somatosensory, and motor cortical areas. We therefore examined whether this PO network differs between musicians and non-musicians. We analyzed resting-state PO functional connectivity with Heschl's gyrus (HG), the planum temporale (PT), the precentral gyrus (preCG), and the postcentral gyrus (postCG) in 35 musicians and 35 non-musicians. In musicians, the left PO exhibited increased functional connectivity with the ipsilateral HG, PT, preCG, and postCG, whereas the right PO exhibited enhanced functional connectivity with the contralateral HG, preCG, and postCG and the ipsilateral postCG. Direct functional connectivity between an auditory area (the HG or PT) and a sensorimotor area (the preCG or postCG) did not significantly differ between the groups. The PO's functional connectivity with auditory and sensorimotor areas is enhanced in musicians relative to non-musicians. We propose that the PO network facilitates musical performance by mediating multimodal integration for modulating auditory-sensorimotor control.

Conceiving concrete mental imagery is critical for skillful musical expression and performance. The precuneus, a core component of the default mode network (DMN), is a hub of mental image processing that participates in functions such as episodic memory retrieval and imagining future events. The precuneus connects with many brain regions in the frontal, parietal, temporal, and occipital cortices. The aim of this study was to examine the effects of long-term musical training on the resting-state functional connectivity of the precuneus. Our hypothesis was that the functional connectivity of the precuneus is altered in musicians. We analyzed the functional connectivity of the precuneus using resting-state functional magnetic resonance imaging (fMRI) data recorded in female university students majoring in music and nonmusic disciplines. The results show that the music students had higher functional connectivity of the precuneus with opercular/insular regions, which are associated with interoceptive and emotional processing; Heschl’s gyrus (HG) and the planum temporale (PT), which process complex tonal information; and the lateral occipital cortex (LOC), which processes visual information. Connectivity of the precuneus within the DMN did not differ between the two groups. Our finding suggests that functional connections between the precuneus and the regions outside of the DMN play an important role in musical performance. We propose that a neural network linking the precuneus with these regions contributes to translate mental imagery into information relevant to musical performance.

Aripiprazole (APZ) has a unique pharmacological profile, as a partial agonist at the dopamine D2 and serotonin 5HT1A receptors and an antagonist at the serotonin 5HT2A receptor; this drug has few side effects (such as extrapyramidal syndrome, hyperprolactinemia, weight gain, metabolic disorders, and sedation) which are typical problems with other antipsychotic drugs. Due to its high tolerability, it is possible to safely administer it to children and adolescents. Efficacy and tolerability of APZ in children and adolescents have been well demonstrated in many clinical studies, which supported approvals granted by the US Food and Drug Administration (FDA) for schizophrenia, bipolar diseases, and irritability associated with autistic disorder in children and adolescents. APZ is expected to exert sedative, anti-depressive, and anti-anxiety effects, and stabilize emotion. APZ is an antipsychotic drug which could be useful for a wider spectrum of psychiatric disorders in children and adolescents. There is little risk of deterioration (such as disinhibition and acting out) and rapid stabilization is easy to achieve in children and adolescents without definitive diagnoses or with a combination of more than one spectrum of disorders. The effectiveness of APZ in children and adolescents is reviewed and discussed, given its pharmacological profile and the outcomes of various clinical studies. However, randomized or blind studies are still limited, and the majority of reports referenced here are open-label studies and case reports. Conclusions drawn from such studies must be evaluated with caution, and a further accumulation of controlled studies is thus needed.

Schizophrenic patients and healthy controls participated in event-related potential experiments, in which illusory contour (IC) and control objects [no contour (NC), real contour (RC)] were passively presented. As a result, P100 latency for IC in schizophrenic patients was significantly prolonged (+10.6 ms) compared to those for RC. The present findings indicate that an abnormality of IC processing, including ‘bottom-up’ as well as ‘top-down’ processing, may reflect basal pathogenesis of various clinical representations of schizophrenia. However, the P100 latency difference between IC and RC was very small in the patient group. Rather, ‘cognitive’ in the Positive and Negative Syndrome Scale (PANSS) model of Bell et al. significantly correlated with P100 latencies for NC. Such an association between PANSS and NC processing, where the shape must be inferred with increased attentional demands and ‘top-down’ processing, indicates that the abnormality of schizophrenic patients’ preattentive process might be a problem of ‘top-down’ processing rather than ‘bottom-up’ processing.

Herein, we report on a patient with spinocerebellar degeneration who exhibited subclinical rhythmic electrographic discharge of adults (SREDA). Thyrotropin-releasing hormone (TRH) improved the clinical symptoms and SREDA was observed only when administration of thyrotropin-releasing hormone was discontinued and the symptoms worsened. Furthermore, after resuming administration of taltirelin hydrate, a TRH analog, the improvement in motor function was accompanied by a decrease in delirium. It is plausible that taltirelin hydrate improved the distorted cerebral blood flow, which has been reported previously as the mechanism underlying SREDA, as a consequence of the functional improvement in neurotransmitter systems.

The purpose of this study was to examine the effects of coordination exercises on brain activation as measured by functional MRI. In this study, we defined coordination exercises as exercises with a greater degree of complexity and quality, as compared to the control exercises. We hypothesized that coordination tasks evoke more brain activation than control tasks, based on the attributes of coordination exercises requiring adjustment and judgment. Two experiments were designed to study the differences in the effects of brain activation between the coordination exercises and the simpler movements of the control exercises. The first experiment compared brain activation when subjects viewed video images of the coordination exercises with that when they viewed video images of the control exercises. The second experiment compared brain activation when subjects actually performed the coordination exercises with that when they performed the control exercises. These experiments demonstrated that performing and viewing coordination exercises activated the brain activities related to motor control to a much greater degree than those of the control exercises. The results of this study indicate that coordination exercises contribute to the improvement of motor activities and also cognitive control, lending support to claims for the effectiveness of coordination training in medicine as well as in sports.

It remains unclear how functional connectivity (FC) may be related to specific cognitive domains in neuropsychiatric disorders. Here we used simultaneous resting-state functional magnetic resonance imaging (rsfMRI) and electroencephalography (EEG) recording in patients with schizophrenia, to evaluate FC within and outside the default mode network (DMN).Our study population included 14 patients with schizophrenia and 15 healthy control participants. From all participants, we acquired rsfMRI data, and simultaneously recorded EEG data using an MR-compatible amplifier. We analyzed the rsfMRI-EEG data, and used the CONN toolbox to calculate the FC between regions of interest. We also performed between-group comparisons of standardized low-resolution electromagnetic tomography-based intracortical lagged coherence for each EEG frequency band.FC within the DMN, as measured by rsfMRI and EEG, did not significantly differ between groups. Analysis of rsfMRI data showed that FC between the right posterior inferior temporal gyrus and medial prefrontal cortex was stronger among patients with schizophrenia compared to control participants.Analysis of FC within the DMN using rsfMRI and EEG data revealed no significant differences between patients with schizophrenia and control participants. However, rsfMRI data revealed over-modulated FC between the medial prefrontal cortex and right posterior inferior temporal gyrus in patients with schizophrenia compared to control participants, suggesting that the patients had altered FC, with higher correlations across nodes within and outside of the DMN. Further studies using simultaneous rsfMRI and EEG are required to determine whether altered FC within the DMN is associated with schizophrenia.

Escitalopram (escitalopram oxalate; Cipralex®, Lexapro®) is a selective serotonin reuptake inhibitor (SSRI) used for the treatment of major depressive disorder (MDD) and anxiety disorder. This drug exerts a highly selective, potent, and dose-dependent inhibitory effect on the human serotonin transport. By inhibiting the reuptake of serotonin into presynaptic nerve endings, this drug enhances the activity of serotonin in the central nervous system. Escitalopram also has allosteric activity. Moreover, the possibility of interacting with other drugs is considered low.

Background: The goal of the present study is to identify the effect of nicotine on auditory automatic processing, as reflected by mismatch negativity (MMN), in nonsmoking schizophrenic patients. Methods: Ten nonsmoking schizophrenic patients and 10 healthy volunteers underwent a reference session and 2 test sessions. The test sessions involved administration of a placebo patch and a nicotine skin patch, which were counterbalanced. Nicotine was administered transdermally under controlled dosage. Results: Nicotine administration shortened the MMN latencies (at Fz on nicotine/placebo: 134.8 ± 5.7/157.6 ± 6.4 ms) in healthy volunteers. In contrast, there were no significant differences in MMN latencies in schizophrenic patients (169.6 ± 5.7/165.0 ± 6.4 ms). Conclusion: Nicotine activates and accelerates preattentive and automatic processing in healthy controls, whereas there were no such effects observed in nonsmoking patients. The impaired MMN response to nicotine administration in nonsmoking schizophrenic patients may be attributed to low nicotinic receptor function, implicated in dysregulation of the glutamatergic system.

The present study examined the pathophysiology of dissociative phenomena using the P300 component of event-related potentials, quantitative electroencephalography (QEEG), and morphology measures of computed tomography scan. Event-related potentials during an auditory oddball paradigm and QEEG in resting state were recorded. Patients exhibited attenuation of P300 amplitudes compared with controls during dissociative episodes, but exhibited recovery to control levels in remission. Patients had a larger Sylvian fissure-brain ratio than did controls. QEEG findings revealed no significant differences between the patients and controls or between episodes and remission in the patient group. Attenuation of the P300 can be interpreted as the result of a negative feedback loop from the medial temporal lobe to the cortex, which decreases the amount of information flow, allocation of attentional resources, and updating of working memory to avoid both excessive long-term memory system activity in medial temporal lobe and resurgence of affect-laden memories.

Schizophrenic patients and healthy controls participated in functional MRI (fMRI) experiments with blocked design using Echo Planner Imaging, in which illusory contour (IC) (Kanizsa's square) and control objects (no contour: NC; real contour: RC) were passively presented. Subjects underwent ERP (event-related potentials) sessions using identical stimuli with fMRI studies, and then LORETA (low resolution brain electromagnetic tomography) was reconstructed using ERPs. Controls exhibited more eminent activations for IC in the extrastriate cortex encompassing the V2 area than did schizophrenics. In contrast, schizophrenics demonstrated more prominent activations for IC in the right anterior cingulate gyrus (ACC) and bilateral middle frontal gyrus than those of controls. Comparing LORETA values of ERPs for IC at each time frame between patients and controls, patients showed greater current density in the left insula than that of controls. Schizophrenics might be deficient in perceptual integration during processing in the extrastriate cortex, which might consequently increase the loads needed for higher processing in the prefrontal cortex reflected by the enhanced fMRI activation in ACC. Otherwise, an ambiguous object like IC, unless processed optimally at the pre-attentive level, might be perceived as disgusting stimuli and evoke activation in the insula of schizophrenic patients.

Schizophrenics and controls participated in functional MRI (fMRI) and event-related potential (ERP) experiments, in which they viewed a face, eyes and moving eyes. Low-resolution brain electromagnetic tomography (LORETA) was reconstructed using ERPs. In fRMI, controls exhibited more eminent activations for the face in the fusiform gyrus and superior temporal gyrus bilaterally than did schizophrenics. For eyes, controls exhibited more prominent activations in the left inferior temporal gyrus and fusiform gyrus than did schizophrenics. In controls, moving eyes activated the posterior portion of the superior temporal region and transverse temporal gyrus right-dominantly or the middle and inferior occipital gyrus bilaterally. In contrast, schizophrenics tended to have greater activation in the left amygdala than controls. In LORETA, controls exhibited greater current density for the static face in the right middle temporal gyrus than did patients. In contrast, patients showed greater current density for the static eyes in the left insula. Furthermore, patients showed greater current density for moving eyes to the left in the left insula. Overactivation for eyes or moving eyes in the amygdala, insula, or extrastriate cortex observed in patients might indicate their hypersensitivity in the processing of feature details before processing the gestalt of the face or facial expression as a whole, which might be implicated in their deficits in interpersonal skills or in the formation of a variety of their clinical manifestations.

Carter et al. [Science 280 (1998) 747] demonstrated that anterior cingulate cortex (ACC) detects conditions in which errors are likely to occur. Kirino and Belger [E. Kirino, A. Belger, fMRI and ERP evidence of prefrontal cortex mediation of novelty bias and distractibility in Schizophrenia, in: K. Hirata, Y. Koga, K. Nagata, K. Yamazaki, (Eds.), Recent Advances in Human Brain Mapping, Elsevier, Amsterdam, 2002, pp. 691–696.] further observed aberrant prefrontal cortex (PFC) activation during a visual oddball paradigm containing task-irrelevant distracters in schizophrenia. We hypothesized that schizophrenics show distorted PFC and ACC activation during response competition. We imaged patients and controls performing variants of Continuous Performance Test (CPT) that were designed to increase error rates and manipulate response competition. Subjects made a response whenever the probe was an X proceeded by a cue A, and to make a nontarget response to all other stimuli (AY, BX and BY). When targets (AX) occurred with 70% frequency, AY and BX were previously reported to elicit higher levels of response competition than BY (1998). Event-related design for the functional MRI (fMRI) experiment was employed with AX (p=86%) as baseline response and AY, BX, and BY (p=4.7% for each) as event stimuli. Echo Planner images were acquired on a 1.5-T MR system. Schizophrenics showed attenuated activation in PFC and ACC under condition that elicits response competition. These findings might indicate that they are less sensitive to override prepotent responses. Schizophrenics' deficits in working memory might be attributed to the deteriorated central executive system, which involved response competition, rather than slave systems in the working memory model of Baddeley [Science 255 (1992) 556].

The goal of the present study is to explore schizophrenic patients' deteriorations of global–local (hierarchical stimulus) processing. Schizophrenics and healthy controls participated in functional MRI (fMRI) and event-related potentials (ERP) experiments. Low-resolution brain electromagnetic tomography (LORETA) was reconstructed using ERPs. In fMRI, global attention in controls exhibited more prominent activations for incongruent stimuli in the posterior portion of the superior temporal region and bilaterally transverse temporal gyrus than did schizophrenics. In global/local attention, controls exhibited more prominent activations for incongruent stimuli in the middle and inferior occipital gyrus right-dominantly than did schizophrenics. In local attention, schizophrenics showed greater activation in the left precuneus than did controls. Further, even in global attention, schizophrenics showed greater activation in the left middle occipital gyrus than did controls. In LORETA, global attention in controls showed greater current density in the posterior portion of the superior/middle temporal region and transverse temporal gyrus right-dominantly than did patients. In contrast, patients exhibited greater current density in the middle frontal gyrus and inferior frontal gyrus left-dominantly than did controls. The present results support the concept of left hemisphere overactive-right hemisphere underactive in schizophrenic patients. Schizophrenics' processing of hierarchical visual stimuli might be deficient in perceptual integration during processing in the occipitemporal cortex or be interfered with by the to-be-ignored local level, which might consequently increase the loads needed in higher processing in the prefrontal cortex reflected by enhanced activation in the left inferior frontal gyrus.

Mind reading is the ability to understand another person's thoughts, intentions, and feelings (Whiten, 1991). The purpose of this study was to clarify which part of the brain is evoked while mind reading in functional Magnetic Resonance Imaging (fMRI) experiments, using a mind reading task, the Reading Mind in the Eyes Test (RME: Baron-Cohen et al., 2001) with four choices (mental state words). The participants were right-handed and sex-matched healthy Japanese university stu- dents (10 males and 10 females, age range 19-25). We used periodic ABA…block design in the fMRI sessions. Task A (an experimental task) was the mind reading task and Task B (a control task) was the age-gender task. In order to clarify the acti- vated region of the brain while mind reading, we calculated the difference between the degrees of BOLD (Blood-oxygen-level dependent) activation during the Task A and Task B. The results showed that there was a significant difference in activation of the right superior occipital gyrus, and the left parietal lobe. These findings indicated that these regions were used while mind reading. The role of these regions was discussed in terms of the findings from previous studies.

To evaluate the safety, tolerability and pharmacokinetic profile of bapineuzumab after a single intravenous injection in Japanese patients with mild to moderate Alzheimer's disease.Participants received either a placebo (n = 8), or bapineuzumab 0.15 (n = 6), 0.5 (n = 6), 1.0 (n = 6) or 2.0 (n = 6) mg/kg. Serum concentrations of bapineuzumab, antibapineuzumab antibody and total plasma β-amyloidx-40 were assayed.Adverse events for bapineuzumab and placebo groups were 71% and 88%, respectively. Treatment-emergent adverse events (cataract, injection site hemorrhage, nasopharyngitis, pneumonia and muscle twitching) reported for ≥2 participants were mild or moderate in severity and unrelated to bapineuzumab dose. No deaths, serious adverse events or withdrawals were reported. Mean peak concentration for bapineuzumab increased with dose, from 3.3 ± 0.9 μg/mL with the 0.15 mg/kg dose to 61.0 ± 32.8 μg/mL with 2.0 mg/kg. Mean bapineuzumab exposure (area under the curve from time 0 to last measurable concentration; μg·h/mL) increased in a linear manner with increasing dose (mean 1260 for 0.15 mg/kg, 4264 for 0.5 mg/kg, 7818 for 1.0 mg/kg, 15 313 for 2.0 mg/kg). Mean half-life ranged from 15 to 28 days, and clearance was similar across dose groups (range 0.12-0.17 mL/h/kg).Plasma β-amyloidx-40 levels increased with increasing doses of bapineuzumab. Bapineuzumab was safe and well tolerated at all doses in Japanese patients with mild to moderate Alzheimer's disease. Geriatr Gerontol Int 2016; 16: 644-650.

Using a combination of functional MRI (fMRI) and electroencephalogram (EEG), the present study explored the differences between cognitive response to an oddball paradigm task by schizophrenic patients and healthy subjects. In event-related potential (ERP) findings, schizophrenics showed reduced P300 amplitude for both targets and novels in comparison with controls, consistently with previous reports. In fMRI findings, schizophrenics demonstrated attenuated activation for targets in the dorsolateral prefrontal cortex (DLPFC), particularly in the right middle frontal gyrus (MFG), in comparison with controls. Nonetheless, they demonstrated stronger activation than controls, which is associated with delayed peak for novels than for targets in the right inferior frontal gyrus (IFG). The different profiles of MFG and IFG activation in schizophrenia, than in controls, might be implicated to the patients' impairment in reciprocal relationship between the dorsal and ventral system of the prefrontal cortex (PFC), which is manifested by their distorted stimulus–response mapping during goal-directed response for targets and distractibility to task irrelevant novel stimuli.

Bipolar disorder is a pernicious illness. Compared with the later-onset form, early onset bipolar disorder is associated with worse psychosocial outcomes, and is characterized by rapid cycling and increased risks of substance abuse and suicide attempts. Controlling mood episodes and preventing relapse in this group of pediatric patients requires careful treatment. Here, we review the effectiveness of aripiprazole for bipolar disorder in children and adolescents, with discussion of this drug’s unique pharmacological profile and various clinical study outcomes. Aripiprazole acts as a serotonin 5-HT2A receptor antagonist, as well as a partial agonist of the serotonin 5-HT1A and dopamine D2 receptors. It can be safely used in children and adolescents, as it is highly tolerated and shows lower rates of the side effects typically observed with other antipsychotic drugs, including sedation, weight gain, hyperprolactinemia, and extrapyramidal syndrome. The presently reviewed randomized controlled trials (RCTs) and non-RCTs generally reported aripiprazole to be effective and well-tolerated in children and adolescents with bipolar disorder. However, due to the limited number of RCTs, the present conclusions must be evaluated cautiously. Furthermore, aripiprazole cannot yet be considered a preferred treatment for children and adolescents with bipolar disorder, as there is not yet evidence that aripiprazole shows greater efficacy compared to other second-generation antipsychotics. Additional data are needed from future head-to-head comparison studies.

Objectives This study compared the sociodemographic characteristics, comorbidities, healthcare resource utilization, and work productivity among Japanese adults who reported being diagnosed with attention-deficit/hyperactivity disorder (ADHD) to those of a non-ADHD control population. Methods Data for this study were captured from an online survey of adults in Japan conducted by Kantar Health using consumer panels. A total of 84 survey participants reported they had received a diagnosis of ADHD from a physician. Survey responses pertaining to functional status and resource utilization from this ADHD group were compared to those from a non-ADHD control group of 100 participants. Comparisons between the ADHD and non-ADHD groups were made using chi-square tests for categorical variables and t-tests for continuous variables. Results Participants in the ADHD group were on average slightly younger with a higher proportion of males. ADHD respondents reported significantly more comorbid depression, sleep difficulties, headaches, and anxiety than non-ADHD controls. Over the previous 6 months, the ADHD group made more visits to healthcare providers and the emergency room, and had more hospitalizations than non-ADHD controls. The ADHD group also rated their overall health status lower than the non-ADHD control group. Respondents with ADHD reported a significantly higher degree of health-related work impairment compared to non-ADHD, with greater absenteeism and decreased work productivity. The ADHD group indicated their symptoms negatively impacted relationships, self-esteem, and regular daily activities. Conclusions Japanese adults with ADHD face a substantial burden of illness, including lower overall health status, increased number of comorbidities, greater healthcare utilization, and significant health-related occupational impairment compared to those without ADHD. Additional research is needed to develop a better understanding of both the consequences and treatment approaches for Japanese adults with ADHD.

The temporal and spatial processing of face perception in normal subjects was traced by magnetoencephalography (MEG) and electroencephalography (EEG). We used 5 different visual stimuli: (1) face with opened eyes, (2) face with closed eyes, (3) eyes, (4) scrambled face, and (5) hand, and they were shown in random order. Subjects were asked to count the number of hand stimuli. To analyze the complicated brain responses to visual stimuli, we used brain electric source analysis (BESA) as the spatio-temporal multiple source model. In MEG recording, the 1M and 2M components were identified in all subjects. The 1M component was recorded to all kinds of stimuli. The 2M component was clearly identified only to face stimulation in all subjects, but to eyes stimulation in only 3 subjects with a small amplitude. The 2M component was not identified to scrambled face nor hand stimulation. The 2M component was recorded from the right hemisphere in all subjects, but in only 5 of 10 subjects from the left hemisphere. The mean peak latencies of the 1M and 2M components were approximately 132 and 179 ms, respectively. The interpeak latency between 1M and 2M was approximately 47 ms on average but the interindividual difference was large. There was no significant difference of the 2M latency between face with opened eyes and face with closed eyes. The 1M component was generated in the primary visual cortex in the bilateral hemispheres, and the 2M component was generated in the inferior temporal cortex, around the fusiform gyrus. In the EEG recording, face-specific components, positive at the vertex, P200 (Cz), and the negative at the temporal areas, N190 (T5') and N190 (T6'), were clearly recorded. The EEG results were fundamentally compatible with the MEG results. The amplitude of the component recorded from the right hemisphere was significantly larger than that from the left hemisphere. These findings suggest that the fusiform gyrus is considered to play an important role in face perception in humans, and that the right hemisphere is more dominant. Face perception takes place approximately 47 ms after the primary response to visual stimulation in the primary visual cortex, but the period of information transfer to the fusiform gyrus is variable among subjects. Detailed temporal and spatial analyses of the processing of face perception can be achieved with MEG.