Reduction of cortical excitability and increase of thalamic activity in a low-frequency rTMS treatment for chronic tinnitus.

Low-frequency repetitive transcranial magnetic stimulation (rTMS) has received increasing attention for the treatment of tinnitus, but its therapeutic mechanisms are unclear. We performed low-frequency rTMS treatment for a patient with chronic tinnitus and examined changes of cortical excitability and cerebral blood flow using paired-pulse TMS and single-photon emission computed tomography. After the rTMS treatment, tinnitus loudness was decreased, cortical excitability was reduced, and blood flow in the thalamus was increased. Our results suggest that low-frequency rTMS treatment reduces tinnitus loudness by an inhibitory effect on the cortical excitability and a remote activation effect on the thalamus through the corticothalamic networks.

Evaluation of regional cerebral blood flow in patient with atypical senile dementia with asymmetrical calcification.

We report an 83-year-old woman with atypical senile dementia with Fahr-type calcification. Brain computed tomography demonstrated asymmetrical calcification predominant in the basal ganglia on the right side and pronounced diffuse cortical atrophy in the frontotemporal areas. The patient was clinically diagnosed with diffuse neurofibrillary tangles with calcification. Brain single photon emission computed tomography findings revealed that cerebral blood flow was reduced on the right side, as compared with the left side, in widespread areas. Hemispheric asymmetry in both calcification and cerebral blood flow suggests a relationship between calcification and vascular changes.

[The Problems with Domestic Introduction of rTMS from the Three Viewpoints of Scientific Evidence, Specialty and Social Responsibility].

The domestic introduction of rTMS is expected as a new treatment option for treatment-resistant depression. I discussed some problems with the introduction from three viewpoints : scientific evidence, specialty, and social responsibility. I surveyed scientific evidence for rTMS regarding the action mechanism, effectiveness, side effects, and its positioning in the treatment guidelines. To secure the quality of rTMS treatment, I proposed rTMS guidelines, nurturing of the specialists, and a center hospital plan, and pointed out some medium-term problems after its introduction and the consistency of rTMS treatment and standard depression treatment. From the viewpoint of social responsibility, rTMS treatment should be a medical service covered by health insurance to avoid its misuse. We should prepare to overcome the public suspicion of brain stimulation treatment for mental disease.

Real-world outcome of rTMS treatment for depression within the Japanese public health insurance system: Registry data from Kansai TMS network.

This study registered consecutive cases to elucidate the efficacy of rTMS treatment for depression within the Japanese public health insurance system. Of the 102 patients with depression who received rTMS over the left dorsolateral prefrontal cortex, 44 (43.1 %) patients reached remission and 14 (13.7 %) patients did not reach remission but responded to treatment. No serious adverse events occurred. Low baseline HAMD-17 score was associated with remission after rTMS treatment. Favorable outcomes of rTMS treatment were shown in this cohort within the Japanese public insurance system. Our results provide insights into rTMS treatment for depression in real-world clinical setting.

Cerebral blood flow in the subgenual anterior cingulate cortex and modulation of the mood-regulatory networks in a successful rTMS treatment for major depressive disorder.

The subgenual anterior cingulate cortex (Cg25) has been reported to be a node of mood-regulatory networks. Using a responder and a non-responder of repetitive transcranial magnetic stimulation (rTMS) for depression, we examined pre/post-treatment cerebral blood flow (CBF) in the Cg25 and treatment-related CBF changes in cortical/subcortical regions. In the responder, pre-treatment Cg25 perfusion was higher and was decreased after treatment, in addition, CBF was increased in the frontal and parietal regions and decreased in the hippocampus and basal ganglia. Our results suggest that rTMS treatment response may be related to pre-treatment Cg25 activity and modulation of the Cg25 and mood-regulatory networks.

A prospective multicenter validation study of a machine learning algorithm classifier on quantitative electroencephalogram for differentiating between dementia with Lewy bodies and Alzheimer's dementia.

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.

Brain activity during the Clock-Drawing Test: multichannel near-infrared spectroscopy study.

The Clock-Drawing Test (CDT) is widely used in clinical practice for the screening of dementia. However, neural activity during real clock drawing has not been investigated due to motion artifacts. In the present study, we examined brain activity during real clock drawing using multichannel near-infrared spectroscopy (NIRS). We measured hemoglobin concentration changes in the prefrontal and temporal surface areas during clock drawing using 52-channel NIRS. Data obtained from 37 right-handed healthy volunteers were analyzed. We found significant increases in oxy-Hb in more than 96.2% of the channels (false-discovery rate corrected, p < .025). The time required for CDT performance showed a negative correlation with changes in oxy-Hb in the prefrontal region (r = -.529, p = .002). The mean value for oxy-Hb changes was higher in the left hemisphere in 20 subjects (54%) and in the right hemisphere in 17 subjects (46%). The NIRS/CDT combination is acceptable as a clinical tool, as the method has the advantages of direct measurement of cortical activation with high temporal resolution. Our results confirm the aspects of the CDT involving the frontal-lobe battery.

Chronic repetitive transcranial magnetic stimulation increases hippocampal neurogenesis in rats.

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.

Evaluation of regional cerebral blood flow in a patient with musical hallucinations.

A 52-year-old woman with musical hallucinations was examined using brain single photon emission computed tomography (SPECT) with 99mTc-ECD. Changes in regional cerebral blood flow (rCBF) after carbamazepine treatment were assessed using a three-dimensional stereotaxic ROI template. Following treatment, rCBF was decreased in the subcortical structures and increased in the global cortical regions. From our findings, we propose that rCBF values in subcortical structures represent abnormalities similar to those reported in previous reports or other psychiatric disorders, while those in cortical regions suggest background brain dysfunctions that result in generation of musical hallucinations.

Randomized clinical comparison of perospirone and risperidone in patients with schizophrenia: Kansai Psychiatric Multicenter Study.

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.

Microstructural abnormalities in callosal fibers and their relationship with cognitive function in schizophrenia: A tract-specific analysis study.

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.

Widespread abnormalities in white matter integrity and their relationship with duration of illness in temporal lobe epilepsy.

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.

Schizophrenia-like symptoms in a patient with Leigh syndrome.

Leigh syndrome is a mitochondrial disease characterized by subacute necrotizing encephalomyelopathy. Almost all cases of Leigh syndrome develop at infancy or early childhood and die within several years due to rapidly progressive muscle weakness and respiratory failure. Here, we present a rare case of a patient who developed Leigh syndrome associated with thiamine-responsive pyruvate dehydrogenase-complex deficiency at 2 years of age and has survived to adolescence through effective high dose thiamin therapy. At 15 years of age, the patient presented persecutory delusions and auditory hallucinations, suggesting an association between mitochondrial dysfunction and schizophrenia-like psychotic symptoms.

Omega-3 fatty acids related to cognitive impairment in patients with schizophrenia.

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.

Interhemispheric disconnectivity in the sensorimotor network in bipolar disorder revealed by functional connectivity and diffusion tensor imaging analysis.

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.

Elucidating the aberrant brain regions in bipolar disorder using T1-weighted/T2-weighted magnetic resonance ratio images.

Although diffusion tensor imaging (DTI) have revealed brain abnormalities in bipolar disorder (BD) subjects, DTI methods might not detect disease-related abnormalities in the white matter (WM) where nerve fibers are crossing. We investigated BD myelin-related abnormal brain regions in both gray matter and WM for 29 BD and 33 healthy control (HC) participants using T1-weighted (T1w)/T2-weighted (T2w) ratio images that increase myelin-related contrast irrespective of nerve fiber orientation. To check effect of the brain volume, the results were compared with those of voxel-based morphometry (VBM). We found significantly lower T1w/T2w signal intensity in broad WM regions in BD subjects, including the corpus callosum, corona radiata, internal capsule, middle cerebellar peduncle and cerebellum. Regional volume reduction was found in the WM bilateral posterior thalami and retrolenticular part of the internal capsules of BD subjects. We also performed tract-based spatial statistics (TBSS) in 25 BD and 24 HC participants and compared those for the T1w/T2w ratio images. Both methods detected the BD corpus callosum abnormality. Further, the ratio images detected the corona radiata and the cerebellar abnormality in BD. These results suggest that T1w/T2w ratio image analysis could take a complementary role with the DTI method in elucidating myelin-related abnormalities in BD.

Evaluation of regional cerebral blood flow in fahr disease with schizophrenia-like psychosis: a case report.

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.

Use of T1-weighted/T2-weighted magnetic resonance ratio images to elucidate changes in the schizophrenic brain.

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.