Search

Background and Purpose: An early and accurate diagnosis of Dementia with Lewy bodies (DLB) is critical because treatments and prognosis of DLB are different from Alzheimer's disease (AD). This study was carried out in Japan to validate an Electroencephalography (EEG)-derived machine learning algorithm for discriminating DLB from AD which developed based on a database of EEG records from two different European countries., Methods: In a prospective multicenter study, patients with probable DLB or with probable AD were enrolled in a 1:1 ratio. A continuous EEG segment of 150 seconds was recorded, and the EEG data was processed using MC-004, the EEG-based machine learning algorithm, with all clinical information blinded except for age and gender., Results: Eighteen patients with probable DLB and 21 patients with probable AD were the included for the analysis. The performance of MC-004 differentiating probable DLB from probable AD was 72.2% (95% CI 46.5-90.3%) for sensitivity, 85.7% (63.7-97.0%) for specificity, and 79.5% (63.5-90.7%) for accuracy. When limiting to subjects taking ≤5 mg donepezil, the sensitivity was 83.3% (95% CI 51.6-97.9), the specificity 89.5% (66.9-98.7), and the accuracy 87.1% (70.2-96.4)., Conclusions: MC-004, the EEG-based machine learning algorithm, was able to discriminate between DLB and AD with fairly high accuracy. MC-004 is a promising biomarker for DLB, and has the potential to improve the detection of DLB in a diagnostic process., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: YS, MS,TA and EM report grants and personal fees from Mentis Cura (https://www.mentiscura.com) during the conduct of the study. KShig, KShin, YA, HK, TB and MH report grants from Mentis Cura, during the conduct of the study. KJ is an employee of Mentis Cura. All the authors have sufficiently participated in the work and take responsibility for the content and agree to transfer copyright to PLOS. We disclose potential conflicts of interest and describe their financial support. This does not alter our adherence to PLOS ONE policies on sharing data and materials. Our manuscript contains no extractions from other copyrighted works. We confirm that this manuscript has not been accepted for publication elsewhere, is not being considered for publication elsewhere, and does not duplicate previously published material. I confirm that all the authors consent to publication of this manuscript.

Introduction: The corpus callosum serves the essential role of relaying cognitive information between the homologous regions in the left and the right hemispheres of the brain. Cognitive impairment is a core dysfunction of schizophrenia, but much of its pathophysiology is unknown. The aim of this study was to elucidate the association between microstructural abnormalities of the corpus callosum and cognitive dysfunction in schizophrenia., Methods: We examined stepwise multiple regression analysis to investigate the relationship of the fractional anisotropy (FA) of callosal fibers in each segment with z-scores of each brief assessment of cognition in schizophrenia subtest and cognitive composite score in all subjects (19 patients with schizophrenia [SZ group] and 19 healthy controls [HC group]). Callosal fibers were separated into seven segments based on their cortical projection using tract-specific analysis of diffusion tensor imaging., Results: The FA of callosal fibers in the temporal segment was significantly associated with z-scores of token motor test, Tower of London test, and the composite score. In the SZ group, the FA of callosal fibers in the temporal segment was significantly associated with the z-score of the Tower of London test. In addition, the FA of callosal fibers in temporal segment showed significant negative association with the positive and negative syndrome scale negative score in the SZ group. Compared to the HC group, the FA in temporal segment was significantly decreased in the SZ group., Conclusion: Our results suggest that microstructural abnormalities in the callosal white matter fibers connecting bilateral temporal lobe cortices contribute to poor executive function and severe negative symptom in patients with schizophrenia., (© 2019 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.)

Objective: Elucidation of abnormal connections throughout the whole brain is necessary to understand temporal lobe epilepsy (TLE). We examined abnormalities in whole-brain white matter integrity and their relationship with duration of illness in patients with TLE., Methods: The subjects were 15 patients with TLE and 17 healthy controls. Mean duration of illness in the TLE group was 21.6 years. Tract-based spatial statistics (TBSS) were used for diffusion tensor imaging (DTI) analysis. Four diffusion tensor metrics, that is, fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were calculated and then examined for differences between the TLE and healthy control groups. We also examined for correlations between DTI parameters and duration of illness in the TLE group., Results: In the TLE group, compared with the healthy control group, FA was reduced, and MD and RD were increased, not only in the limbic and temporal lobe regions and their directly connecting regions in both hemispheres, but also in remote white matter regions. Duration of illness showed a significant negative correlation with mean whole-brain FA and a significant positive correlation with both mean whole-brain MD and RD. Brain regions showing correlation between disease duration and DTI metrics also extended to the limbic area and its connecting regions, and to remote white matter regions., Significance: The results of this study suggest that widespread abnormalities in white matter integrity in patients with TLE are associated with long-term disease.

Background: Little is known regarding interhemispheric functional connectivity (FC) abnormalities via the corpus callosum in subjects with bipolar disorder (BD), which might be a key pathophysiological basis of emotional processing alterations in BD., Methods: We performed tract-based spatial statistics (TBSS) using diffusion tensor imaging (DTI) in 24 healthy control (HC) and 22 BD subjects. Next, we analyzed the neural networks with independent component analysis (ICA) in 32HC and 25 BD subjects using resting-state functional magnetic resonance imaging., Results: In TBSS analysis, we found reduced fractional anisotropy (FA) in the corpus callosum of BD subjects. In ICA, functional within-connectivity was reduced in two clusters in the sensorimotor network (SMN) (right and left primary somatosensory areas) of BD subjects compared with HCs. FC between the two clusters and FA values in the corpus callosum of BD subjects was significantly correlated. Further, the functional within-connectivity was related to Young Mania Rating Scale (YMRS) total scores in the right premotor area in the SMN of BD subjects., Limitations: Almost all of our BD subjects were taking several medications which could be a confounding factor., Conclusions: Our findings suggest that interhemispheric FC dysfunction in the SMN is associated with the impaired nerve fibers in the corpus callosum, which could be one of pathophysiological bases of emotion processing dysregulation in BD patients.

Cognitive impairment is strongly associated with functional outcome in patients with schizophrenia but its pathophysiology remains largely unclear. Involvement of omega-3 fatty acids in the cognitive function of healthy individuals and patients with neuropsychiatric disease has received increasing attention. The aim of this study was to examine the relationship between omega-3 fatty acids with cognitive function, social function, and psychiatric symptoms in patients with schizophrenia. The subjects included 30 patients with schizophrenia or schizoaffective disorder. Psychiatric symptoms, cognitive function, and social function were assessed using the Positive and Negative Syndrome Scale, the Brief Assessment of Cognition in Schizophrenia (BACS), and the Social Functioning Scale (SFS), respectively. Blood serum omega-3 fatty acids were assessed using gas chromatography. The BACS composite score was significantly correlated with blood eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) levels. In addition, a daily dose of antipsychotic medication was negatively and significantly correlated with the blood DHA level and with the BACS composite score. Step-wise multiple regression analyses demonstrated that the SFS score was significantly associated with the BACS composite score. Our results indicate that reduced blood omega-3 fatty acids are associated with cognitive impairment, which then impacts social functioning outcomes in schizophrenia.

Introduction: One leading hypothesis suggests that schizophrenia (SZ) is a neurodevelopmental disorder caused by genetic defects in association with environmental risk factors that affect synapse and myelin formation. Recent magnetic resonance imaging (MRI) studies of SZ brain showed both gray matter (GM) reduction and white matter (WM) fractional anisotropy reduction. In this study, we used T1-weighted (T1w)/T2-weighted (T2w) MRI ratio images, which increase myelin-related signal contrast and reduce receiver-coil bias., Methods: We measured T1w/T2w ratio image signal intensity in 29 patients with SZ and 33 healthy controls (HCs), and then compared them against bias-corrected T1w images., Results: Mean T1w/T2w ratio signal intensity values across all SZ GM and WM voxels were significantly lower than those for the HC values (analysis of covariance with age, gender, handedness, and premorbid intelligence quotient as nuisance covariates). SZ mean WM T1w/T2w ratio values were related to Global Assessment of Functioning (GAF) scores and were inversely related to the positive psychotic symptoms of the Positive and Negative Syndrome Scale. Voxel-based analysis revealed significantly lower T1w/T2w ratio image signal intensity values in the right ventral putamen in SZ GM. T1w image intensities did not differ between the SZ and HC groups., Conclusions: T1-weighted/T2-weighted ratio imaging increased the detectability of SZ pathological changes. Reduced SZ brain signal intensity is likely due to diminished myelin content; therefore, mapping myelin-related SZ brain changes using T1w/T2w ratio images may be useful for studies of SZ brain abnormalities.

Tinnitus is the perception of phantom sound without an external auditory stimulus. Using neuroimaging techniques, such as positron emission tomography, electroencephalography, magnetoencephalography, and functional magnetic resonance imaging (fMRI), many studies have demonstrated that abnormal functions of the central nervous system are closely associated with tinnitus. In our previous research, we reported using resting-state fMRI that several brain regions, including the rectus gyrus, cingulate gyrus, thalamus, hippocampus, caudate, inferior temporal gyrus, cerebellar hemisphere, and medial superior frontal gyrus, were associated with tinnitus distress and loudness. To reconfirm these results and probe target regions for repetitive transcranial magnetic stimulation (rTMS), we investigated the regional cerebral blood flow (rCBF) between younger tinnitus patients (<60 years old) and the age-matched controls using single-photon emission computed tomography and easy Z-score imaging system. Compared with that of controls, the rCBF of tinnitus patients was significantly lower in the bilateral medial superior frontal gyri, left middle occipital gyrus and significantly higher in the bilateral cerebellar hemispheres and vermis, bilateral middle temporal gyri, right fusiform gyrus. No clear differences were observed between tinnitus patients with normal and impaired hearing. Regardless of the assessment modality, similar brain regions were identified as characteristic in tinnitus patients. These regions are potentially involved in the pathophysiology of chronic subjective tinnitus.

Subjective tinnitus is characterized by the perception of phantom sound without an external auditory stimulus. We hypothesized that abnormal functionally connected regions in the central nervous system might underlie the pathophysiology of chronic subjective tinnitus. Statistical significance of functional connectivity (FC) strength is affected by the regional autocorrelation coefficient (AC). In this study, we used resting-state functional MRI (fMRI) and measured regional mean FC strength (mean cross-correlation coefficient between a region and all other regions without taking into account the effect of AC (rGC) and with taking into account the effect of AC (rGCa) to elucidate brain regions related to tinnitus symptoms such as distress, depression and loudness. Consistent with previous studies, tinnitus loudness was not related to tinnitus-related distress and depressive state. Although both rGC and rGCa revealed similar brain regions where the values showed a statistically significant relationship with tinnitus-related symptoms, the regions for rGCa were more localized and more clearly delineated the regions related specifically to each symptom. The rGCa values in the bilateral rectus gyri were positively correlated and those in the bilateral anterior and middle cingulate gyri were negatively correlated with distress and depressive state. The rGCa values in the bilateral thalamus, the bilateral hippocampus, and the left caudate were positively correlated and those in the left medial superior frontal gyrus and the left posterior cingulate gyrus were negatively correlated with tinnitus loudness. These results suggest that distinct brain regions are responsible for tinnitus symptoms. The regions for distress and depressive state are known to be related to depression, while the regions for tinnitus loudness are known to be related to the default mode network and integration of multi-sensory information.

Slow (<0.1 Hz) oscillatory activity in the human brain, as measured by functional magnetic imaging, has been used to identify neural networks and their dysfunction in specific brain diseases. Its intrinsic properties may also be useful to investigate brain functions. We investigated the two functional maps: variance and first order autocorrelation coefficient (r(1)). These two maps had distinct spatial distributions and the values were significantly different among the subdivisions of the precuneus and posterior cingulate cortex that were identified in functional connectivity (FC) studies. The results reinforce the functional segregation of these subdivisions and indicate that the intrinsic properties of the slow brain activity have physiological relevance. Further, we propose a sample size (degree of freedom) correction when assessing the statistical significance of FC strength with r(1) values, which enables a better understanding of the network changes related to various brain diseases.

Aim: While the underlying therapeutic mechanisms of repetitive transcranial magnetic stimulation (rTMS) treatment for depression remain unclear, recent animal studies have suggested that hippocampal neurogenesis might be required for the effects of antidepressant treatments including antidepressant drugs and electroconvulsive therapy. The aim of this study was to examine chronic rTMS effects on hippocampal neurogenesis in rats., Methods: Using a 70-mm figure-of-eight coil, the stimulating parameters were set to 25 Hz and 70% of the rTMS device's maximum power. For 14 consecutive days, bromodeoxyuridine (BrdU) and 1000 pulses of rTMS were administered daily. Cell proliferation in the dentate gyrus was examined with immunohistochemistry., Results: In the rTMS-treated group, BrdU-positive cells were significantly increased in the dentate gyrus., Conclusion: Our results suggest that hippocampal neurogenesis might be involved in the antidepressant effects of chronic rTMS., (© 2011 The Authors. Psychiatry and Clinical Neurosciences © 2011 Japanese Society of Psychiatry and Neurology.)

We investigated the possible association between genetic polymorphisms in the dopamine receptor and serotonin transporter genes and the responses of schizophrenic patients treated with either risperidone or perospirone. The subjects comprised 27 patients with schizophrenia who were clinically evaluated both before and after treatment. The genotyping of the polymorphisms of the dopamine D2 receptor gene (DRD2) (rs1801028 and rs6277), the dopamine D4 receptor gene (DRD4) (120-bp tandem repeats and rs1800955), and serotonin transporter gene (5HTT)(variable number of tandem repeats; VNTR) were performed using the real-time polymerase chain reaction and sequencing. In DRD2 and 5HTT-VNTR, there were no significant correlations between clinical response and polymorphism in the case of risperidone, and for perospirone treatment it was impossible to analyze the clinical evaluation due to the absence of genotype information. On the other hand, in DRD4 there were significant correlations in the two-factor interaction effect on the Positive and Negative Syndrome Scale (PANSS) between the two drugs [120-bp tandem repeat, p=0.003; rs1800955, p=0.043]. Although the small sample represents a serious limitation, these results suggest that variants in DRD4 are a predictor of whether treatment will be more effective with risperidone or with perospirone in individual patients.

Aim: Perospirone is classified as a second-generation antipsychotic agent for the treatment of schizophrenia. Perospirone binds with high affinity to serotonin 5-HT2A receptors and dopamine D2 receptors. There are no reports of clinical comparisons of perospirone and risperidone in multicenter studies. To clarify the clinical traits of perospirone in the treatment of schizophrenia, the clinical efficacies and side-effects of perospirone and risperidone were compared in a randomized clinical multicenter trial., Methods: Sixty-six schizophrenia patients were enrolled in the trial. The Positive and Negative Syndrome Scale (PANSS) total, positive, negative and general symptoms scores and Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS) scores were investigated at 0, 4, 8 and 12 weeks., Results: Significant reductions in the PANSS total and subscale scores were observed in both the perospirone and risperidone groups, with no significant between-group differences at 4 and 12 weeks. Risperidone improved the total scores and overall psychopathologic symptom total scores more effectively than perospirone at week 8. There were no significant differences in the DIEPSS scores at 0, 4, 8 and 12 weeks between the perospirone and risperidone groups. The numbers of patients who dropped out did not differ between the perospirone and risperidone groups., Conclusions: Perospirone was as effective as risperidone against positive and negative symptoms in patients with schizophrenia. Both antipsychotic agents were equally well-tolerated.

Musical hallucinations (MH) typically occur among elderly individuals and are associated with hearing impairment. The authors describe a patient with features of typical MH who was successfully treated with donepezil, a cholinesterase inhibitor, as a combination therapy and who has not shown any subsequent cognitive decline for approximately 5 years. The efficacy of donepezil in this patient indicates that age-dependent dysfunction of cholinergic neurons might be related to the development of MH.

We report the case of a patient with Fahr disease presenting with schizophrenia-like psychosis for whom a technetium Tc99 methyl cysteinate dimmer brain study was used to evaluate regional blood flow. A brain single photon-emission CT study showed increased cerebral blood flow to the bilateral temporal lobes. Such perfusion abnormalities may reflect psychotic symptoms, including auditory hallucinations and delusions, which suggests a disruption of the cortico-subcortical neural circuits in psychosis.

Recent dementia studies indicate that behavioral and psychological symptoms of dementia (BPSD) are not merely an epiphenomenon of cognitive impairment, but could be attributed to specific biological brain dysfunction. We describe findings from different research modalities related with BPSD (psychopathological, neuropsychological, neurochemical, and psychophysiological strategies), and attempt to reconcile them into the more integrated form. Characteristics of delusions in dementia patients should be studied in more detail from a psychopathological aspect, aiming for the integration of psychopathology and neurobiology. Imperfect integration of memory function and cognitive function, assigned to the limbic systems and association areas, respectively, may result in BPSD. More intimate collaboration of psychopathological and neurobiological study would be fruitful to promote the research in psychological basis of BPSD. Neurochemical studies indicated that density of extracellular tangles and/or PHF-tau protein have relationships with delusion or misidentification. These changes in neurochemical parameters should be the key to understanding the pathogenesis of BPSD. More importantly, neurochemical and psychological study could be linked by the research in psychophysiology. Computer-assisted electroencephalogram analysis suggests that the right posterior hemisphere shows significant age-associated change earlier than the left in the elderly. Cerebral metabolic rate by positron emission tomography study indicates that paralimbic, left medial temporal, and left medial occipital area are involved in pathogenesis of BPSD in some dementia patients.

The authors applied cluster analysis and multidimensional scaling to the analyses of 59 patients with personality pathology. Cluster analysis yielded eight typologies of patients: detached, anankastic, phobic, dramatic, erratic, emotional, milder emotional, and masochistic negativistic. Multidimensional scaling identified the dimensions of classifying patients: anxious rumination versus behavioural acting out, overall severity of personality pathology, and assertiveness versus withdrawal. Considering the distinction between personality disorder (dysfunctional personality) and abnormal personality (extreme personality), the following changes in current classification system are proposed: use of a hierarchy and exclusion criteria in a categorical-type model or use of a personality profile in a dimensional-trait model, in either case, with a dimensional rating for severity of psychopathology to define personality 'disorder'.