Keiichiro Nishida

EEG microstates associated with salience and frontoparietal networks in frontotemporal dementia, schizophrenia and Alzheimer’s disease

OBJECTIVE There are relevant links between resting-state fMRI networks, EEG microstate classes and psychopathological alterations in mental disorders associated with frontal lobe dysfunction. We hypothesized that a certain microstate class, labeled C and correlated with the salience network, was impaired early in frontotemporal dementia (FTD), and that microstate class D, correlated with the frontoparietal network, was impaired in schizophrenia. METHODS We measured resting EEG microstate parameters in patients with mild FTD (n = 18), schizophrenia (n = 20), mild Alzheimers disease (AD; n = 19) and age-matched controls (old n = 19, young n = 18) to investigate neuronal dynamics at the whole-brain level. RESULTS The duration of class C was significantly shorter in FTD than in controls and AD, and the duration of class D was significantly shorter in schizophrenia than in controls, FTD and AD. Transition analysis showed a reversed sequence of activation of classes C and D in FTD and schizophrenia patients compared with that in controls, with controls preferring transitions from C to D, and patients preferring D to C. CONCLUSION The duration and sequence of EEG microstates reflect specific aberrations of frontal lobe functions in FTD and schizophrenia. SIGNIFICANCE This study highlights the importance of subsecond brain dynamics for understanding of psychiatric disorders.

Differences in quantitative EEG between frontotemporal dementia and Alzheimer’s disease as revealed by LORETA

OBJECTIVE To determine the electrophysiological characteristics of frontotemporal dementia (FTD) and the distinction with Alzheimers disease (AD). METHODS We performed analyses of global field power (GFP) which is a measure of whole brain electric field strength, and EEG neuroimaging analyses with sLORETA (standardized low resolution electromagnetic tomography), in the mild stages of FTD (n = 19; mean age = 68.11 ± 7.77) and AD (n = 19; mean age = 69.42 ± 9.57) patients, and normal control (NC) subjects (n = 22; mean age = 66.13 ± 6.02). RESULTS In the GFP analysis, significant group effects were observed in the delta (1.5-6.0 Hz), alpha1 (8.5-10.0 Hz), and beta1 (12.5-18.0 Hz) bands. In sLORETA analysis, differences in activity were observed in the alpha1 band (NC > FTD) in the orbital frontal and temporal lobe, in the delta band (AD>NC) in widespread areas including the frontal lobe, and in the beta1 band (FTD > AD) in the parietal lobe and sensorimotor area. CONCLUSIONS Differential patterns of brain regions and EEG frequency bands were observed between the FTD and AD groups in terms of pathological activity. SIGNIFICANCE FTD and AD patients in the early stages displayed different patterns in the cortical localization of oscillatory activity across different frequency bands.

Increased Omega Complexity and Decreased Microstate Duration in Nonmedicated Schizophrenic Patients

To explore brain functions in schizophrenic patients, the global analytic strategy of multichannel EEG was performed that combines measures of global complexity (Ω), total power (Σ) and generalized frequency (Φ), and EEG microstate analysis was applied to multichannel EEG data for 24 nonmedicated patients and 24 healthy subjects. The patients had higher Ω and Σ values, and lower Φ values compared with healthy subjects. Three topographical classes were obtained from all EEG data by EEG microstate analysis. The mean duration of one topographical class in the patients was shortened compared to healthy subjects. These results indicated looser cooperativity, or decreased connectivity of the active brain process and deviant brain information processing in schizophrenic patients.

Effect of basic fibroblast growth factor (FGF2) gene polymorphisms on SSRIs treatment response and side effects

Antidepressant response usually appears in 2 to 4 weeks and 30-40% of patients do not show a significant response although biochemical changes of monoaminergic system occur within hours after administration. Genetic factors could play a role in this process and genes involved in synaptic plasticity and neurogenesis are possible candidates. In fact, antidepressants and electroconvulsive therapy increase basic fibroblast growth factor (FGF2) and the rs1449683C/T polymorphism within this gene has been found to be a predictor for both an elevated mRNA and protein level of FGF2. Therefore we examined the possible association of rs1449683C/T and a panel of tagging SNPs in SSRI efficacy and side effects in 144 Japanese major depressive subjects followed for 6 weeks. We observed a significant association of rs1449683T (p=0.010) and rs308393C (p=0.029) variant carriers toward a better response to SSRI and of rs1048201 with higher frequency of drop out due to side effects (p=0.010), independently from clinical variables. Furthermore the rs308447T-rs308393C-rs1449683T haplotype was associated with higher response rate (p=0.012) while the rs1048201T-rs3747676T haplotype was significantly associated with higher dropped out rate (p=0.015). In conclusion, this is the first study investigating the association of antidepressant response and intolerance with FGF2 variants. This finding adds an important piece of information for the pathway of detecting the genetics of antidepressant response.

A 12-week randomized, open-label study of perospirone versus aripiprazole in the treatment of Japanese schizophrenia patients

OBJECT To evaluate the efficacy and safety of aripiprazole and perospirone in Japanese patients with schizophrenia. METHODS In this 12-week, randomized, flexible-dose, open-label study, patients diagnosed with schizophrenia were randomized to receive aripiprazole (3-30 mg/day, n=49) or perospirone (8-48 mg/day, n=51). Efficacy and safety were evaluated using the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression-Severity Scale (CGI-S), the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) and the Barnes Akathisia Rating Scale (BAS) before treatment and every 4 weeks after the initiation of treatment. RESULTS Fifty-eight patients completed this study (aripiprazole, n=31; perospirone, n=27). No significant differences in gender, episode, age, schizophrenia type, weight, previous treatment and PANSS score were observed between the two groups at baseline. Both groups showed significant improvements during the study, with reductions in the total PANSS scores (Repeated measure analysis of variance, both p<0.0001). There were no significant differences in the PANSS change scores, CGI-S change scores, DIEPSS total score, BAS total score or over time between groups. The most common adverse event was insomnia in both groups. CONCLUSIONS In Japanese schizophrenia patients, aripiprazole and perospirone showed equal efficacy, tolerability and patient compliance. Both drugs showed good efficacy for treating schizophrenia. This paper is the first randomized study to evaluate the comparative efficacy and safety of aripiprazole and perospirone in the treatment of patients with schizophrenia.

Integrating Different Aspects of Resting Brain Activity: A Review of Electroencephalographic Signatures in Resting State Networks Derived from Functional Magnetic Resonance Imaging

Electroencephalography (EEG) is an established measure in the field of brain resting state with a range of quantitative methods (qEEG) that yield unique information about neuronal activation and synchronization. Meanwhile, in the last decade, functional magnetic resonance imaging (fMRI) studies have revealed the existence of more than a dozen resting state networks (RSNs), and combined qEEG and fMRI have allowed us to gain understanding about the relationship of qEEG and fMRI-RSNs. However, the overall picture is less clear because there is no a priori hypothesis about which EEG features correspond well to fMRI-RSNs. We reviewed the associations of several types of qEEG features to four RSNs considered as neurocognitive systems central for higher brain processes: the default mode network, dorsal and ventral frontoparietal networks, and the salience network. We could identify 12 papers correlating qEEG and RSNs in adult human subjects and employing a simultaneous design under a no-task resting state condition. A systematic overview investigates which qEEG features replicably relate to the chosen RSNs. This review article leads to the conclusion that spatially delimited θ and whole/local α may be the most promising measures, but the time domain methods add important additional information.

Cognitive insight and functional outcome in schizophrenia; a multi-center collaborative study with the specific level of functioning scale–Japanese version

The Specific Levels of Functioning Scale (SLOF) has been reported to provide a measure of social function in patients with schizophrenia. The aim of this multi-center study was to determine convergent validity of the Japanese version of SLOF, and if cognitive insight would be associated with social function. Fifty-eight patients with schizophrenia participated in the study. Social function, neurocognition, and daily activity skills were evaluated by the Social Functioning Scale (SFS), Brief Assessment of Cognition in Schizophrenia (BACS) and UCSD Performance-based Skills Assessment-Brief (UPSA-B), respectively. We also assessed cognitive insight with the Beck Cognitive Insight Scale (BCIS). Significant relationships were noted between scores on the SLOF vs. those of the SFS, BACS, UPSA-B, and BCIS. Specifically, the correlation between performance on the UPSA-B and SLOF scores was significantly more robust compared to the correlation between performance on the UPSA-B and scores on the SFS. Similarly, the correlation between scores on the BACS and SLOF tended to be more robust than that between the BACS and SFS. Importantly, while the correlation between scores on the BCIS and SLOF reached significance, it was not so between scores on the BCIS and SFS. The SLOF Japanese version was found to provide a measure of social consequences in patients with schizophrenia. Importantly, this study is the first to indicate the relationship between cognitive insight and social function evaluated by the SLOF. This finding is consistent with the observation that SLOF scores were considerably associated with performances on objective functional measures.

Healthy and Pathological Brain Aging: From the Perspective of Oscillations, Functional Connectivity, and Signal Complexity

Healthy aging is associated with impairment in cognitive information processing. Several neuroimaging methods such as functional magnetic resonance imaging, positron emission tomography and near-infrared spectroscopy have been used to explore healthy and pathological aging by relying on hemodynamic or metabolic changes that occur in response to brain activity. Since electroencephalography (EEG) and magnetoencephalography (MEG) are able to measure neural activity directly with a high temporal resolution of milliseconds, these neurophysiological techniques are particularly important to investigate the dynamics of brain activity underlying neurocognitive aging. It is well known that age is a major risk factor for Alzheimer’s disease (AD), and that synaptic dysfunction represents an early sign of this disease associated with hallmark neuropathological findings. However, the neurophysiological mechanisms underlying AD are not fully elucidated. This review addresses healthy and pathological brain aging from a neurophysiological perspective, focusing on oscillatory activity changes during the resting state, event-related potentials and stimulus-induced oscillatory responses during cognitive or motor tasks, functional connectivity between brain regions, and changes in signal complexity. We also highlight the accumulating evidence on age-related EEG/MEG changes and biological markers of brain neurodegeneration, including genetic factors, structural abnormalities on magnetic resonance images, and the biochemical changes associated with Aβ deposition and tau pathology.

The Comparative Effects of Risperidone Long-Acting Injection and Paliperidone Palmitate on Social Functioning in Schizophrenia: A 6-Month, Open-Label, Randomized Controlled Pilot Trial

Purpose: The aim of this study was to compare the effects of risperidone long-acting injection (RLAI) and paliperidone palmitate (PP) on non-acute-phase social functioning in patients with schizophrenia. Patients and Methods: In this 6-month pilot, open-label, randomized controlled study, 30 patients with schizophrenia who had been treated with RLAI were randomly allocated to the RLAI continuation group or switched to the PP group. Patients were evaluated at baseline and 6 months with the Social Functioning Scale (SFS) as the primary outcome variable and University of California San Diego Performance-Based Skills Assessment Brief (UPSA-B), Social Emotional Cognition Task (SECT), Positive and Negative Syndrome Scale (PANSS), and Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) scores as secondary outcomes. Results: At baseline, the two groups did not significantly differ in demographic or clinical features. The two groups did not differ in total score changes for the UPSA-B, the SECT, the PANSS, and the DIEPSS. However, the total scores and the two subscales of the SFS, i.e. independence-competence and independence-performance, were more improved in the PP group compared to the RLAI group (total scores, p = 0.038; competence, p = 0.001, and performance, p = 0.007, respectively). Conclusion: These results suggest that PP may improve the total social functioning, independent life competence, and performance as compared to the RLAI group. However, these results are preliminary and need independent replication in larger samples before any definitive statement can be made.

Discovering EEG resting state alterations of semantic dementia

OBJECTIVE Diagnosis of semantic dementia relies on cost-intensive MRI or PET, although resting EEG markers of other dementias have been reported. Yet the view still holds that resting EEG in patients with semantic dementia is normal. However, studies using increasingly sophisticated EEG analysis methods have demonstrated that slightest alterations of functional brain states can be detected. METHODS We analyzed the common four resting EEG microstates (A, B, C, and D) of 8 patients with semantic dementia in comparison with 8 healthy controls and 8 patients with Alzheimers disease. RESULTS Topographical differences between the groups were found in microstate classes B and C, while microstate classes A and D were comparable. The data showed that the semantic dementia group had a peculiar microstate E, but the commonly found microstate C was lacking. Furthermore, the presence of microstate E was significantly correlated with lower MMSE and language scores. CONCLUSION Alterations in resting EEG can be found in semantic dementia. Topographical shifts in microstate C might be related to semantic memory deficits. SIGNIFICANCE This is the first study that discovered resting state EEG abnormality in semantic dementia. The notion that resting EEG in this dementia subtype is normal has to be revised.