Hub structure in functional network of EEG signals supporting high cognitive functions in older individuals.

Introduction: Maintaining high cognitive functions is desirable for "wellbeing" in old age and is particularly relevant to a super-aging society. According to their individual cognitive functions, optimal intervention for older individuals facilitates the maintenance of cognitive functions. Cognitive function is a result of whole-brain interactions. These interactions are reflected in several measures in graph theory analysis for the topological characteristics of functional connectivity. Betweenness centrality (BC), which can identify the "hub" node, i.e., the most important node affecting whole-brain network activity, may be appropriate for capturing whole-brain interactions. During the past decade, BC has been applied to capture changes in brain networks related to cognitive deficits arising from pathological conditions. In this study, we hypothesized that the hub structure of functional networks would reflect cognitive function, even in healthy elderly individuals. Method: To test this hypothesis, based on the BC value of the functional connectivity obtained using the phase lag index from the electroencephalogram under the eyes closed resting state, we examined the relationship between the BC value and cognitive function measured using the Five Cognitive Functions test total score. Results: We found a significant positive correlation of BC with cognitive functioning and a significant enhancement in the BC value of individuals with high cognitive functioning, particularly in the frontal theta network. Discussion: The hub structure may reflect the sophisticated integration and transmission of information in whole-brain networks to support high-level cognitive function. Our findings may contribute to the development of biomarkers for assessing cognitive function, enabling optimal interventions for maintaining cognitive function in older individuals.

Enhanced temporal complexity of EEG signals in older individuals with high cognitive functions.

Recent studies suggest that the maintenance of cognitive function in the later life of older people is an essential factor contributing to mental wellbeing and physical health. Particularly, the risk of depression, sleep disorders, and Alzheimer's disease significantly increases in patients with mild cognitive impairment. To develop early treatment and prevention strategies for cognitive decline, it is necessary to individually identify the current state of cognitive function since the progression of cognitive decline varies among individuals. Therefore, the development of biomarkers that allow easier measurement of cognitive function in older individuals is relevant for hyperaged societies. One of the methods used to estimate cognitive function focuses on the temporal complexity of electroencephalography (EEG) signals. The characteristics of temporal complexity depend on the time scale, which reflects the range of neuron functional interactions. To capture the dynamics, composed of multiple time scales, multiscale entropy (MSE) analysis is effective for comprehensively assessing the neural activity underlying cognitive function in the brain. Thus, we hypothesized that EEG complexity analysis could serve to assess a wide range of cognitive functions in older adults. To validate our hypothesis, we divided older participants into two groups based on their cognitive function test scores: a high cognitive function group and a low cognitive function group, and applied MSE analysis to the measured EEG data of all participants. The results of the repeated-measures analysis of covariance using age and sex as a covariate in the MSE profile showed a significant difference between the high and low cognitive function groups (F = 10.18, p = 0.003) and the interaction of the group × electrodes (F = 3.93, p = 0.002). Subsequently, the results of the post-hoc t-test showed high complexity on a slower time scale in the frontal, parietal, and temporal lobes in the high cognitive function group. This high complexity on a slow time scale reflects the activation of long-distance neural interactions among various brain regions to achieve high cognitive functions. This finding could facilitate the development of a tool for diagnosis of cognitive decline in older individuals.

Delayed posthypoxic leukoencephalopathy following alcohol and psychotropic drug overdose: a case report.

Delayed posthypoxic leukoencephalopathy (DPHL), a demyelinating syndrome, can easily be misdiagnosed as a psychiatric condition. Our case study shows that magnetic resonance imaging is highly useful for an early diagnosis of DPHL and that vascular endothelial growth factor might be a supplementary biomarker for the early detection of DPHL.

Abnormal functional connectivity of high-frequency rhythms in drug-naïve schizophrenia.

OBJECTIVE: The "dysconnection hypothesis" has been proposed as a core neural basis for schizophrenia. Although growing neuroimaging-based evidence suggests atypical functional connectivity in patients with schizophrenia, the results are inconsistent and the effects of antipsychotic treatment remain elusive. METHODS: We performed resting-state electroencephalography (EEG) in 21 drug-naïve patients with schizophrenia (14 patients were re-evaluated after administration of antipsychotic treatment) and 31 age-matched healthy control subjects. We estimated functional connectivity, using the phase lag index (PLI), which captures the true synchronization of EEG signals. RESULTS: The patients had reduced functional connectivity of the beta band across frontal regions and of the gamma band throughout the scalp when compared to the control subjects. In the schizophrenia group, symptom severity did not seem associated with functional connectivity. Antipsychotic treatment led to no alterations in functional connectivity. CONCLUSIONS: Synchronous activity within and across brain areas over multiple frequencies reflect the integration of various types of information processing. Our findings of abnormal frequency- and region-specific functional connectivity patterns may provide further insight into the "dysconnection hypothesis" of schizophrenia. SIGNIFICANCE: The PLI may serve as a useful measure for the characterization and understanding of the intrinsic pathophysiological mechanisms of schizophrenia, and as a reliable biomarker for this disease.

Changes in EEG complexity with electroconvulsive therapy in a patient with autism spectrum disorders: a multiscale entropy approach.

Autism spectrum disorders (ASD) are heterogeneous neurodevelopmental disorders that are reportedly characterized by aberrant neural networks. Recently developed multiscale entropy analysis (MSE) can characterize the complexity inherent in electroencephalography (EEG) dynamics over multiple temporal scales in the dynamics of neural networks. We encountered an 18-year-old man with ASD whose refractory catatonic obsessive-compulsive symptoms were improved dramatically after electroconvulsive therapy (ECT). In this clinical case study, we strove to clarify the neurophysiological mechanism of ECT in ASD by assessing EEG complexity using MSE. Along with ECT, the frontocentral region showed decreased EEG complexity at higher temporal scales, whereas the occipital region expressed an increase at lower temporal scales. Furthermore, these changes were associated with clinical improvement associated with the elevation of brain-derived neurotrophic factor, which is a molecular hypothesis of ECT, playing key roles in ASD pathogenesis. Changes in EEG complexity in a region-specific and temporal scale-specific manner that we found might reflect atypical EEG dynamics in ASD. Although MSE is not a direct approach to measuring neural connectivity and the results are from only a single case, they might reflect specific aberrant neural network activity and the therapeutic neurophysiological mechanism of ECT in ASD.

Effects of electroconvulsive therapy on neural complexity in patients with depression: report of three cases.

BACKGROUND: The exact neurophysiological mechanism of electroconvulsive therapy (ECT) for treating patients with depression remains elusive. Results of previous neurophysiological studies support the hypothesis that aberrant functional connectivity underlies the pathophysiology of depression, which engenders abnormal electroencephalogram (EEG) complexity. METHODS: Recently developed multiscale entropy analysis, which has underpinned aberrant functional connectivity in mental disorders, was introduced to explore changes in EEG complexity occurring with ECT in three patients with depression. RESULTS: All patients demonstrated a decrease in EEG complexity, especially at higher frequencies. This decrease was associated with improvement of depressive symptoms. LIMITATIONS: The generalizability of our findings was constrained because of the small sample size and lack of a comparison with healthy controls. CONCLUSIONS: The decrease in EEG complexity with ECT might be a result of amelioration of functional connectivity in the brain of a depressed patient. Multiscale entropy analysis might be a useful analytical method to elucidate neurophysiological mechanisms and evaluate the therapeutic efficacy of ECT in depression.

Native EEG and treatment effects in neuroleptic-naïve schizophrenic patients: time and frequency domain approaches.

Time domain analysis of electroencephalography (EEG) can identify subsecond periods of quasi-stable brain states. These so-called microstates assumingly correspond to basic units of cognition and emotion. On the other hand, Global Field Synchronization (GFS) is a frequency domain measure to estimate functional synchronization of brain processes on a global level for each EEG frequency band [Koenig, T., Lehmann, D., Saito, N., Kuginuki, T., Kinoshita, T., Koukkou, M., 2001. Decreased functional connectivity of EEG theta-frequency activity in first-episode, neuroleptic-naive patients with schizophrenia: preliminary results. Schizophr Res. 50, 55-60.]. Using these time and frequency domain analyzes, several previous studies reported shortened microstate duration in specific microstate classes and decreased GFS in theta band in drug naïve schizophrenia compared to controls. The purpose of this study was to investigate changes of these EEG parameters after drug treatment in drug naïve schizophrenia. EEG analysis was performed in 21 drug-naive patients and 21 healthy controls. 14 patients were reevaluated 2-8 weeks (mean 4.3) after the initiation of drug administration. The results extended findings of treatment effect on brain functions in schizophrenia, and imply that shortened duration of specific microstate classes seems a state marker especially in patients with later neuroleptic responsive, while lower theta GFS seems a state-related phenomenon and that higher gamma GFS is a trait like phenomenon.

Reduction in event-related alpha attenuation during performance of an auditory oddball task in schizophrenia.

EEG frequency-domain analyses have demonstrated that cognitive performance produces a reduction in alpha activity, i.e., alpha attenuation, such as event-related desynchronization (ERD), reflecting brain activation. To examine whether schizophrenic patients have abnormalities in frequency-domain, event-related alpha attenuation, as well as in time-domain EEG phenomena, such as event-related potential, we compared alpha power change and P300 elicited simultaneously in response to the presentation of target tones in an auditory oddball paradigm between patients with schizophrenia and normal control subjects. In both patients and controls, alpha power was smaller during the time window of 512 ms following targets than following non-targets, particularly at the parietal and the posterior temporal locations (Pz, T5, and T6). The size of alpha attenuation measured as percent reduction in alpha power produced by targets relative to non-targets was smaller in patients than in controls at the posterior temporal locations. The size of alpha attenuation showed no correlation with P300 amplitude or latency in either patients or controls. Furthermore, in patients, the size of alpha attenuation showed no correlation with symptom severity, while P300 amplitude was correlated negatively with the positive subscale score of the Positive and Negative Syndrome Scale. These findings suggest that the symptom-independent reduction in event-related alpha attenuation in schizophrenia may be useful as an electrophysiological index of the impairment of neural processes distinct from that indexed by symptom-dependent P300 abnormalities.

State-dependent changes in intrahemispheric EEG coherence for patients with acute exacerbation of schizophrenia.

Abnormalities of electroencephalographic (EEG) coherence in schizophrenia are thought to reflect functional disconnections between different brain regions associated with the onset of this disease. To clarify whether these abnormalities change in a symptom-dependent manner in individual patients, we analyzed the coherence of resting EEGs recorded at two time points with a 36.6-day interval during the course of treatment for 14 patients who had been hospitalized for acute exacerbation of schizophrenia. Symptom severity was quantitatively measured by means of the Brief Psychiatric Rating Scale (BPRS). Beta (13-20 Hz) coherence for the left frontal (F7)-temporal (T5) electrode pair was less than that for the corresponding right pair (F8-T6) at the initial test. At the second test, when symptoms had improved, the left frontal-temporal beta coherence had increased, resulting in disappearance of the laterality. This change in beta coherence for the left frontal-temporal pair correlated negatively with the change in the total BPRS score, particularly the positive symptom score. Similar correlations were found for eight patients who had been drug-free at the first examination. These results suggest that a functional disconnection between the frontal and the temporal lobe in the left hemisphere may be associated with the generation of acute psychotic symptoms in schizophrenia.

Functional connectivity between hemispheres and schizophrenic symptoms: a longitudinal study of interhemispheric EEG coherence in patients with acute exacerbations of schizophrenia.

To clarify whether interhemispheric electroencephalogram (EEG) coherence reflecting functional connectivity between the two cerebral hemispheres can change in a symptom-dependent manner in schizophrenia, we measured resting EEG and symptom severity twice at an average interval of 32.7 days during the course of treatment in 15 patients hospitalized for acute exacerbations of schizophrenia. Symptom severity was estimated quantitatively by means of the Brief Psychiatric Rating Scale (BPRS). Correlation analysis showed that increases in the beta-band coherence for frontal electrode pairs during the treatment were associated with improvement in the total score and the score on the positive subscale of BPRS. This result suggests that functional disconnection between the left and right frontal lobes may be related to the generation of psychotic symptoms and can normalize following antipsychotic treatment.

Neuropsychological correlates of an attention-related negative component elicited in an auditory oddball paradigm in schizophrenia.

An attention-related, negative component can be detected between the N100 peak and 200 ms after stimulus by subtracting event-related potentials (ERPs) elicited to background tones when subjects ignore tones, from ERPs elicited to background tones when subjects attend to tones to detect target tones in an oddball paradigm. To clarify the cognitive significance of this component in schizophrenia, we examined the correlations of 24 patients between the amplitude and latency of the negative component and results obtained using neuropsychological measurement methods, including the Wisconsin Card Sorting Test, the Trail Making Test, the Verbal Fluency Test and some subtests from the Wechsler Memory Scale. The latency prolongation of the negative component correlated positively with the difference in performance time between parts A and B of the Trail Making Test, which estimates set shift, a frontal-lobe executive function, but not with any other neuropsychological measurements, while the amplitude showed no such correlation. These results suggest that the latency prolongation of the attention-related, negative component induced in an auditory oddball paradigm may serve as an index for frontal dysfunction in schizophrenia.

Individual analysis of EEG band power and clinical drug response in schizophrenia.

The main purpose of this study was to investigate the relationship between short-term clinical outcome and changes in electroencephalogram (EEG) power after drug treatment in patients with schizophrenia, and also to compare two different methods for quantitative EEG analysis. EEG power analysis was performed by both conventional fixed frequency band and adjusted frequency band based on individual alpha frequency (IAF) in 16 drug-naive patients before and after drug administration. In the theta bands determined by both conventional fixed band and IAF methods, the EEG power after treatment was larger than that before treatment. In addition, there was a correlation between EEG power and clinical drug response evaluated by changes in BPRS score. With regard to this correlation, IAF methods showed no apparent advantage over methods using conventional fixed frequency bands. Conventional quantitative EEG analysis can still serve as a useful tool for the assessment of short-term outcome of drug treatment.

Severe delirium due to basal forebrain vascular lesion and efficacy of donepezil.

A severe intractable delirium caused by the basal forebrain vascular lesion and its dramatic recovery after donepezil administration were reported. A 68-year-old man had suffered for a month from delirium of mixed type caused by the right basal forebrain vascular lesion after surgery for craniopharyngioma. Magnetic resonance imaging (MRI) showed hemorrhagic infarcts in the head of the right caudate nucleus and the right basal forebrain of the medial septal nucleus, diagonal band of Broca and nucleus basalis of Meynert. He had been treated with anti-psychotics, anti-depressants and hypnotics, which resulted in little improvement. Donepezil administration dramatically improved his intractable delirium at the 19th post-donepezil administration day, but this was followed by amnestic symptoms. Clinical correlates of delirium with the basal forebrain lesion and efficacy of donepezil support the hypocholinergic theory of delirium.

Event-related potentials elicited by non-target tones in an auditory oddball paradigm in schizophrenia.

It has been reported that in event-related potentials (ERPs) elicited by non-target tones in oddball paradigms, the superimposition of a negative component on the descending slope of N100 depends on subjects' attention to the task. We tested the possibility that this attention-related change is abnormal for patients with schizophrenia. ERPs induced by non-target, frequent tones were measured for 52 patients and 31 healthy controls under two oddball conditions: a passive condition where the subjects were told to disregard the tones, and an active condition where they were instructed to respond to infrequent tones. For both groups, a negative component was superimposed from the descending slope of N100 to the end of P150 (latency, 120-200 ms) for the active condition. The peak latency of this attention-related negative component was longer for the patients than for the controls, while the amplitude showed no group difference. In addition, the active P150 for the patients was more enlarged than that for the controls. Furthermore, the active P150 amplitude for the patients correlated positively with the score for the negative symptom factor of the Positive and Negative Syndrome Scale. These findings suggest that the enlargement of non-target P150 observed in conjunction with the latency prolongation of the attention-related negative component may be a biological marker for the severity of the negative symptoms in schizophrenia.

Auditory P300 amplitude as a state marker for positive symptoms in schizophrenia: cross-sectional and retrospective longitudinal studies.

The amplitude of the P300 component of the auditory event-related brain potential (ERP) is consistently reduced in schizophrenia. To determine whether this P300 abnormality can be used as a state marker to reflect the severity of symptoms, we examined both cross-sectionally and longitudinally the relationship between auditory P300 amplitude and symptom severity in patients with schizophrenia. For the cross-sectional study, ERP was elicited by an auditory oddball paradigm, and symptom severity was quantitatively measured by means of the Positive and Negative Syndrome Scale in 93 patients with schizophrenia or schizophreniform disorder (DSM-III-R). For the longitudinal study, ERP and psychopathology measured twice at an average interval of 238 days for 20 patients were retrospectively analyzed. The cross-sectional data showed that P300 amplitude correlated negatively with the positive but not with the negative syndrome scale score. The longitudinal data also showed a significant negative correlation between changes in P300 amplitude and in the positive syndrome scores of the first and second tests. In particular, P300 amplitude recorded at the left, but not right, posterior temporal region significantly correlated with the positive syndrome in both the cross-sectional and longitudinal studies. These findings support the hypotheses that auditory P300 amplitude recorded in the left hemisphere can be used as a state marker to reflect the severity of the positive symptoms and that the positive symptoms may be caused by a possible left-hemisphere deficit in schizophrenia.

Cyclic AMP-mediated modulation of epileptiform afterdischarge generation in rat hippocampal slices.

This study assessed the effects of drugs which manipulate the cAMP system on afterdischarges (ADs) induced in the CA1 region of rat hippocampal slices. The adenylate cyclase activator forskolin (50 microM) and the phosphodiesterase inhibitor rolipram (0.1 and 1 microM) enhanced AD generation. These effects were reversed by the cAMP-dependent protein kinase inhibitors H-89 (5 microM) and Rp-cAMPS (100 microM). These findings suggest that AD generation can be modulated through cAMP generation and the subsequent activation of the cAMP-dependent protein kinase.