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Power spectral analysis of electrocardiogram (ECG) R-R intervals is useful for the detection of autonomic dysfunction in various clinical disorders. Although both panic disorder (PD) and major depressive disorder (MDD) are known to have effects on the cardiac autonomic nervous system, no previous study has tested this among drug-naïve (i.e. no history of treatment) patients with MDD and PD in the same study. The purpose of this study was to compare cardiac autonomic functions among drug-naïve patients with MDD and PD and those of healthy controls. Subjects were 17 drug-naïve PD patients, 15 drug-naïve MDD patients and 15 normal controls. ECGs were recorded under both supine resting and supine deep-breathing conditions (10-12 breaths/min; 0.17-0.20 Hz). We measured the low-frequency power (LF; 0.05-0.15 Hz), which may reflect baroreflex function, the high-frequency power (HF; 0.15-0.40 Hz), which reflects cardiac parasympathetic activity, as well as the LF/HF ratio. As expected, deep breathing induced an increase in HF power and a decrease in the LF/HF ratio in healthy controls. Compared to these controls, however, the MDD group had a lower response to regular deep breathing in LF power and in LF/HF ratio. PD patients showed intermediate results between normal controls and MDD patients. The results indicate that the reactivity to deep breathing revealed diminished cardiac autonomic reactivity in drug-naïve MDD patients.

A case of familial frontotemporal dementia with parkinsonism (FTDP) similar to progressive supranuclear palsy (PSP) was reported. A 58-year-old man developed personality change followed by parkinsonism and dementia. Three family members showed similar symptoms. Cerebral atrophy was marked on the anterior frontotemporal lobes. The substantia nigra, hippocampus, peri-aqueductal gray matter and pontine nucleus were affected with globose neurofibrillary tangles (NFT) and glial tangles. Argyrophilic grains were distributed in the CA1-CA2. NFT, glial tangles and argyrophilic grains expressed four-repeat microtubule-associated protein tau (MAPT). MAPT gene had no mutation. Familial occurrence of FTDP with PSP-like tauopathy is rare.

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.

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.

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.

We report a 57-year-old patient with Creutzfeldt-Jakob disease that initially presented with right parietal lobe syndrome. He featured early dystonic and hemiparetic posture of the left upper limb, finger agnosia, geographic disorientation and acalculia and developed myoclonus from the left upper extremity and right-sided periodic synchronized discharges. He died 2 years and 3 months later. Brain autopsy revealed a marked reduction in brain weight, extensive cortical spongiform changes and white matter degeneration. Immunolabeled prion proteins were deposited diffusely in the neuropil. Accentuation of the cortical change was unclear but white matter degeneration was more severe in the right parietal lobe than in the left parietal lobe. Right parietal lobe syndrome is rarely reported as an initial symptom of Creutzfeldt-Jakob disease and can be a clinical variant of the disease.

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.

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.

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.

The aim of this study was to investigate correlations between thyroid function and severity of anxiety or panic attacks in patients with panic disorder. The authors examined 66 out-patients with panic disorder (medicated, n=41; non-medicated, n=25), and measured their free thriiodothyronine (T3), free thyroxine (T4) and thyroid-stimulating hormone (TSH) levels. Significant correlations between the thyroid hormone levels and clinical features were observed in the non-medicated patients. The more severe current panic attacks were, the higher the TSH levels were. In addition, severity of anxiety correlated negatively with free T4 levels. In this study, we discuss relationship between thyroid function and the clinical severity or features of panic disorder.

We report the second phenotype of frontotemporal dementia and parkinsonism linked to chromosome 17 with S305N similar to Pick’s disease pathology in two brothers. The brain of the older brother showed macroscopic atrophy compatible with Pick’s disease, and subsequent tau gene analysis revealed heterozygous S305N mutation in exon 10 of the tau gene. Round-shaped neuronal inclusions similar to Pick’s bodies were positive for phosphorylated serine 262 as well as other anti-tau antisera, which is different from immunoexpression of Pick’s bodies. Ultrastructurally, these neuronal inclusions consisted of straight, randomly orientated fibrils measuring approximately 10–20 nm in width and 60–600 nm in length. This ultrastructural profile is similar to that of the first case of S305N. S305N reported here can cause another phenotype closely resembling Pick’s disease.

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.

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.

In order to investigate whether Alzheimer's disease (AD) is the end result of aging of the brain or the result of some other mechanism, we analyzed EEGs showing the absolute power of harmonic responses to photic stimulation (PS) in younger subjects, non-demented elderly subjects and AD patients. At rest, the AD patients generally showed less absolute power than the younger and elderly subjects, with significant differences found at 10Hz and 20Hz. Analysis of EEGs recorded during PS indicated that the elderly subjects generally demonstrated more absolute power than the younger subjects and AD patients. These findings suggest a failure of stimulation-related brain activation in AD patients, and provide further evidence that normal aging and AD employ different mechanisms for functional organization during PS.

The present study of coherence analysis, in 16 healthy male volunteers, aged 24-31 years, showed that the administration of 0.25 mg of scopolamine significantly reduced interhemispheric coherence in the delta and beta-1 bands in the resting state. Scopolamine also caused a significant increase both in EEG coherence during PS and in PS-related coherence reactivity in the beta band. In addition, this compound significantly reduced total WMS scores. These findings suggest that, in addition to causing cognitive impairments, central cholinergic dysfunction can alter interhemispheric functional connectivity under both nonstimulus and stimulus conditions.

金沢大学附属病院, To clarify the cognitive significance of event-related potential (ERP) abnormalities in schizophrenia, we examined the relationships of amplitudes and latencies of ERP components with performance on neuropsychological tests in schizophrenic patients. Twenty patients underwent the Trail Making B Test (TM-B), which is sensitive to frontal lobe dysfunction, and the logical memory, verbal paired-association, and visual reproduction subtests of the Wechsler Memory Scale (WMS), which are sensitive to temporal lobe dysfunctions, and ERP recordings during performance of an oddball auditory discrimination task. Pearson product–moment correlations indicated that an increased P200 amplitude was correlated with poor performance on the TM-B, whereas a decreased P300 amplitude was correlated with poor performance on the verbal paired-association subtest of the WMS. These findings suggest that a P200 abnormality represents the frontal lobe dysfunction, and a P300 abnormality represents the left temporal lobe dysfunction in schizophrenia.

A single dose of allylnitrile in mice might induce persistent behavioral abnormalities, of which the mechanism is not yet known. The present study was undertaken to explore the relationship between behavioral abnormalities and pathological changes in the brain of mice following exposure to allylnitrile. Exposure to allylnitrile (63, 84, and 112 mg/kg, p.o.) resulted in dose-dependent changes in behavioral abnormalities, including increased locomotor activity, circling, retropulsion, head twitching, and alteration in reflexive behavior, which appeared at day 2 postdosing and were persistent throughout the experimental period (60 days) at the higher dose levels. Allylnitrile produced neuronal retraction including hyperchromasia of the nuclei in the raphe nuclei, cerebral cortex, hypothalamus, hippocampal CA1 and dentate gyrus later than 30 days. No gliosis was observed in these regions. Not all but a significant number of neurons in the hippocampal CA1, medial habenula and raphe nuclei were immuno-reactive to CPP32 (Caspase-3) even at day 2. These neurons were also positive to Hoechst 33258 staining, indicating allylnitrile caused apoptotic changes in specific neurons when neuronal behaviors became apparent. These apoptotic changes were persistent even in the area without neuronal contraction such as medial habenula. However, almost all neurons in these areas were also positive to terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling (TUNEL). It is conceivable that allylnitrile caused apoptotic changes in neurons but did not always lead them to cell death immediately. Moreover, even when neuronal contraction resulted in retention of behavioral abnormalities, onset of these abnormalities seems to be associated with the impairment in the habenulo-raphe relay due to activation of apoptotic cascade in neurons.

Electroencephalography (EEG) coherence provides a measure of functional correlations between two EEG signals. The present study was conducted to examine intrahemispheric EEG coherence at rest and during photic stimulation (PS; 5, 10 and 15 Hz) in ten unmedicated patients with presenile dementia of the Alzheimer type (AD; mean age at onset 56 years). In the resting EEG, the AD patients had significantly lower coherence than gender- and age-matched control subjects in the alpha-1, alpha-2 and beta-1 frequency bands. The EEG analysis during PS also showed that the patients had significantly lower coherence in the frequency corresponding to PS at 10 and 15 Hz. In this study, the changes in coherence from the resting state to the stimulus condition (i.e. PS-related coherence reactivity) were examined. The patients were found to show significantly smaller coherence reactivity to PS at 5 and 15 Hz. These findings suggest that, in addition to the resting state, AD patients have an impairment of intrahemispheric functional connectivity during PS. They also suggest that AD shows a failure of PS-related functional reorganization.

The present study was conducted to examine interhemispheric electroencephalogram (EEG) coherence at rest and during photic stimulation (5, 10, and 15 Hz) in 10 patients with presenile dementia of the Alzheimer type (AD; mean age at onset, 56 years) and 10 sex- and age-matched control subjects. Compared with the control subjects, the AD patients had significantly lower interhemispheric coherence in the resting EEG for the delta, theta-2, alpha, and beta-1 frequency bands. EEG analysis during photic stimulation also showed that the patients had significantly lower coherence, irrespective of the stimulus frequency. In addition, when we examined the changes in coherence from the resting state to the stimulus condition (i.e., coherence reactivity), significant group differences were found at the brain region primarily involved in visual functioning; the patients had significantly smaller coherence reactivity to photic stimulation at 5 and 15 Hz over the posterior regions. These findings suggest that AD patients have an impairment of interhemispheric functional connectivity in both nonstimulus and stimulus conditions. The findings also suggest a failure of normal stimulation-related brain activation in AD.

The dipole tracing method is a technique whereby an electric source generator is estimated as an equivalent current dipole (ECD) based on potential distribution on the scalp. To estimate the electric source generator of low amplitude spikes, a manual zero potential shifting (MZPS) method was introduced in which a zero potential is set manually in dipole analysis. The subjects were three patients with localization-related epilepsy with temporal spikes. When low-amplitude spikes (

We used the CA1 region of rat hippocampal slices to compare the effects of non-benzodiazepine zolpidem, which binds preferentially to the omega1 sites of gamma-aminobutyric acid A (GABA(A)) receptors, and of benzodiazepine diazepam, which binds equipotently to the omega1 and omega2 sites, on the hippocampal inhibitory mechanism and on long-term potentiation (LTP), a possible cellular mechanism for memory. First, 1 microM diazepam had an enhancing effect on recurrent inhibition by alveus stimulation of orthodromically-induced population spikes, but 1 microM zolpidem had no significant effect. Second, 1 microM diazepam blocked LTP induction of the population spikes, whereas 1 microM zolpidem had no such effect. Only at a higher concentration of 10 microM, zolpidem had a significant effect on recurrent inhibition and LTP. These findings suggest that only the omega2 sites are mainly involved in modulation of the hippocampal inhibitory mechanism and LTP, and that the low affinity of zolpidem for the omega2 sites may account for less memory impairment caused by zolpidem than by benzodiazepines.

We investigated the significance of mitral valve prolapse (MVP) and autonomic function in 121 patients diagnosed with panic disorder (PD). The incidence of MVP was higher in these patients (32.2%) than in the healthy controls (16.7%), but the difference was not significant. In the group with PD accompanied by depression, the MVP rate was 58.1%, significantly higher than the value of 25.7% observed in the PD patients without depression. The severity of MVP was mild; nearly all of the cases were silent, without cardiac murmur, and there was no problem with the left ventricular function. The coefficient of variation for R-R intervals on electrocardiograms (CV R-R) was smaller in patients with PD than in healthy controls. The CV R-R of PD patients was significantly lower in the group with MVP than in the group without MVP, suggesting a strong association with the parasympathetic nervous system. Since the CV R-R tended to decrease in the presence of depression, involvement of the parasympathetic nervous system was inferred.

EEG coherence provides a measure of functional correlations between two EEG signals. The present study was conducted to examine intrahemispheric EEG coherence at rest and during photic stimulation (PS) in 18 drug-naive patients with paranoid schizophrenia and 30 control subjects. Compared with the controls, the schizophrenic patients had significantly higher intrahemispheric coherence of the resting EEG for the delta band, although no significant group differences were found for other frequency bands. EEG analysis during PS showed that the patients also had significantly higher EEG coherence over the left posterior regions. In this study, we also examined the changes in intrahemispheric coherence from rest to the stimulus condition (i.e., PS-related coherence reactivity); the patients were found to show significantly smaller changes, with significant group differences being also confined to the posterior regions in the left hemisphere. These findings provide evidence that schizophrenic patients have abnormal EEG coherence in both resting and stimulus conditions and suggest more diffuse, undifferentiated functional organization within hemispheres. In addition, diminished coherence reactivity suggests a failure of PS-related functional reorganization in schizophrenia.

It is well known that congenital heart abnormalities are common in children with Down's syndrome. However there are few studies on cardiac abnormalities in adults with Down's syndrome. Therefore, we estimated cardiac abnormalities by means of echocardiography in 30 institutionalized Japanese adults with Down's syndrome, but without cardiac symptoms. Two-dimensional echocardiography showed an incidence of 26.7% in mitral valve prolapse and 20% increase of echo brightness in the mitral valve. Doppler echocardiography revealed an incidence of 16.7% in mitral valve regurgitation, and 13.3% in aortic valve regurgitation. Thus, even adults with Down's syndrome who are apparently free of cardiac symptoms may be at risk for valvular disease.

To clarify the possible involvement of Ca2+ channel subtypes in epileptogenesis, the CA1 region of rat hippocampal slices was examined for the pharmacological effects of Ca2+ channel blockers on ictal-like afterdischarges (ADs) observed following the repetition of high-frequency electrical stimulation, as well as on interictal-like bursts of population spikes following single stimuli in the presence of bicuculline. Ni2+ and amiloride, which predominantly block T-type Ca2+ channels, suppressed the number of spikes in ADs at concentrations of these two channel blockers sufficient to eliminate this type of Ca2+ channel in acutely dissociated and cultured hippocampal neurons. On the other hand, neither the L-type Ca2+ channel blocker nifedipine nor the N-type Ca2+ channel blocker, ω-conotoxin GVIA had any effect on the generation of ADs. In addition, none of these T-, L- and N-type channel blockers had any effect on the bicuculline-induced, interictal-like epileptiform discharges. We therefore conclude that the activation of T-type Ca2+ channels, which is distinct from the mechanisms involved in interictal activity, may play a causative role in the generation of ictal-like ADs.

Twenty-five schizophrenic patients diagnosed by DSM-III-R underwent event-related potentials and magnetic resonance imaging scans. Latency and amplitude of P300 waveform were measured using an auditory odd-ball paradigm. Anterior and posterior volumes of the superior temporal gyrus and medial temporal structure were measured from contiguous coronal images using the level of the mammillary body as an anatomical landmark. Principal component analysis of P300 latency and amplitude disclosed two orthogonal independent factors each: overall latency and residual, and amplitudes from posterior and anterior recordings, respectively. Structural volumes consisted of four orthogonally independent factors: left superior temporal volume, anterior medial temporal volume, right superior temporal volume, and posterior medial temporal volume. The factor score of the P300 amplitude from posterior recordings correlated with the factor score of volumetric changes in the anterior medial temporal structures. The present study failed to replicate a previously reported association between auditory P300 amplitude and superior temporal volume. Furthermore, the factor score of the P300 amplitude was correlated with the severity of clinical ratings of attentional impairments and positive thought disorder. These findings demonstrate that the information processing dysfunction of schizophrenia indicated by reduced P300 amplitude is associated with structural abnormality in the medial temporal lobe.

It has been reported that the clinical and electroencephalographic profiles of zolpidem, a non-benzodiazepine drug which binds preferentially to the omega 1 benzodiazepine recognition sites located within the GABAA receptor complex, are different from those of benzodiazepine drugs, which bind non-selectively to the omega 1 and omega 2 sites. In order to clarify the electrophysiological mechanism underlying the unique profile of zolpidem, the present study compared the enhancing effects of zolpidem and two benzodiazepine drugs, triazolam and diazepam, on recurrent inhibition. This inhibition was expressed as suppression of the orthodromically induced population spikes by the preceding antidromic stimulation of the alveus in the CA1 region of rat hippocampal slices. The rank order of potency for enhancing recurrent inhibition was triazolamdiazepamzolpidem. From the present results and previously reported findings that zolpidem has a lower affinity for the omega 2 sites than diazepam while both have the same affinity for the omega 1 sites, we concluded that the hippocampal recurrent inhibition appears to be enhanced mainly by activation of the omega 2 sites, but not by that of the omega 1 sites. Furthermore, the lower potency of zolpidem for enhancing recurrent inhibition may underlie its unique profile in terms of its clinical and electroencephalographic effects.

This study assessed the action of the serotonin3 (5-HT3) receptor agonist, 1-(m-chlorophenyl)-biguanide (m-CPBG), against both kindled seizures and kindling development from the rat amygdala (AM). The intracerebroventricular (i.c.v.) administration of 40 microg m-CPBG significantly increased the duration of afterdischarge and bilateral forelimb clonus of generalized kindled seizures. In addition, daily i.c.v. treatment with m-CPBG at the same dose prior to each electrical stimulation to the AM significantly facilitated behavioral and electrographic seizure development and reduced the number of stimulations needed to elicit generalized seizures. The present results indicate that m-CPBG increases the duration of fully kindled seizures and facilitates the developmental seizure process, suggesting an excitatory role of 5-HT3 receptors in the kindling model of epilepsy.

In the present study, quantitative electroencephalographic (EEG) analysis was performed at rest and during photic stimulation (5, 10, and 15 Hz) in nine patients with presenile dementia of the Alzheimer type (AD; mean age at onset, 55 years) and nine sex- and age-matched control subjects. Compared with the normal controls, the AD patients had a significantly lower alpha-2 and beta band power in the resting EEG as well as a significant increase in delta and theta band power. EEG analysis during the photic stimulation demonstrated that the AD patients had a significantly lower EEG power during photic stimulation for the alpha (9.8-10.2 Hz) and beta bands (14.8-15.2 Hz) corresponding to photic stimulation at 10 Hz and 15 Hz, respectively. In addition, when we examined EEG changes from rest to the stimulus condition, the AD patients were found to show significantly smaller changes in EEG power mainly over the posterior regions, irrespective of the stimulus frequency. These findings provide evidence that AD patients have EEG abnormalities in both non-stimulus and stimulus conditions, and suggest diminished EEG reactivity to photic stimulation.

A 36-year-old Japanese woman presented with progressive cerebellar signs and mental deterioration of subacute course after her return from the USA. Her serum antibody to spirochete Borrelia burgdorferi was significantly elevated. A necropsy 4 years after her initial neurological signs revealed multifocal inflammatory change in the cerebral cortex, thalamus, superior colliculus, dentate nucleus, inferior olivary nucleus and spinal cord. The lesions showed spongiform change, neuronal cell loss, astrocytosis and proliferation of activated microglial cells. The internal capsule was partially vacuolated and the spinal cord, notably at the thoracic level, was demyelinated and cavitated in the lateral funiculus. Microglial cells aggregated within and around the spongiform lesions and microglial nodules were present in the medulla oblongata. Use of Warthin-Starry stain demonstrated silver-impregnated organisms strongly suggesting B. burgdorferi in the central nervous tissues. The dentate nucleus and inferior olivary nucleus showed the most advanced lesions with profound fibrillary gliosis. Occlusive vascular change was relatively mild, and fibrous thickening of the leptomeninges with lymphocyte infiltrates was localized in the basal midbrain. The ataxic symptoms were due to the dentate and olivary nucleus lesions and mental deterioration was attributable to the cortical and thalamic lesions. Spongiform change, neuronal cell loss, and microglial activation are characteristic pathological features in the present case. The cerebellar ataxia and subsequent mental deterioration are unusual clinical features of Lyme neuroborreliosis. Spirochete B. burgdorferi can cause focal inflammatory parenchymal change in the central nervous tissues and the present case may be an encephalitic form of Lyme neuroborreliosis.

Yoshifumi Koshino,1 Won-Myong Bahk,2 Hideaki Sakai,3 Takayuki Kobayashi4 1Iris Medical Clinic, Kanazawa University, Ishikawa, Japan; 2Yeouido St Mary’s Hospital, The Catholic University of Korea, Seoul, South Korea; 3Meguro Station East Mental Clinic, Shinagawa, Tokyo, Japan; 4Medicines Development (Neurosciences), Development and Medical Affairs, GlaxoSmithKline, Shibuya, Tokyo, Japan Abstract: This study was conducted to compare the efficacy and safety of bupropion sustained-release (SR) formulation orally administered at daily doses of 150 mg/day (once daily) and 300 mg/day (150 mg twice daily) for 8 weeks versus placebo in Asian patients with major depressive disorder. The mean change from baseline in Montgomery–Åsberg Depression Rating Scale (MADRS) total score at week 8 was compared between each of the bupropion SR dose groups and the placebo group using an analysis of covariance with the multiplicity adjustment by Dunnett’s step-down procedure. A total of 569 subjects met all of the inclusion criteria and proceeded to the treatment phase. The subjects proceeding to the treatment phase included 454 Japanese patients and 115 Korean patients. There was no statistically significant difference between each of the bupropion SR dose groups and the placebo group in the primary efficacy endpoint of change from baseline in MADRS total score at week 8. Similar results were generally obtained for all of the secondary efficacy endpoints. The secondary analysis and the other subgroup analysis did not show a statistically significant difference in efficacy. There was no substantial difference in the type, severity, and incidence of adverse events (AEs) between the bupropion SR dose groups and the placebo group, which indicates a favorable safety profile for bupropion SR. There were no significant findings in subjects treated with bupropion SR in regard to sexual dysfunction, weight change, and withdrawal syndrome, which are frequently recognized as clinical concerns associated with selective serotonin reuptake inhibitors, widely used for the treatment of depression. Keywords: bupropion SR, placebo, major depressive disorder, Japan, Korea

The subject presented with intellectual decline followed by progressive muscle weakness of the bilateral upper limbs when he was 60 years old. He had a point mutation (methionin-valine) at 129 prion protein codon. He died at the age of 63 and necropsy revealed bilateral frontal lobe atrophy. The frontal cortex showed neuronal cell loss in layers II and III with spongiform change. Reusche silver impregnation technique for beta-peptide combined with ubiquitin immunostaining revealed perineuronal structures encircling degenerated neurons and ubiquitin-immunoreactive (IR) dot-like deposits. They were distributed particularly in the temporal neocortex and entorhinal cortex. They differed from either classic senile or diffuse plaque by the absence of amyloid core in the center and of amyloid fibrils. Ubiquitin-IR materials were also found as neuronal inclusions in the hippocampal granular cells. Nigral degeneration and neuronal loss in the hypoglossal nerve nucleus and in the anterior horn of the spinal cord were also found and spinal cord motoneurons had Bunina body inclusions. The clinical features and pathological findings were consistent with non-Alzheimer dementia with status spongiosus and neuronal cell loss. The unusual perineuronal structures found in our case might be a specific cellular pathology of dementia of the frontal lobe type.

Reduced amplitude of the P300 component has been reported consistently in patients with neurological and psychiatric disorders. It is unclear, however, how such patients' cognitive dysfunction is related to their P300 abnormality. Further basic knowledge regarding neural substrates for P300 generation is required for gaining an understanding of the pathological significance of the P300 amplitude reduction. To determine the brain structures involved in P300 generation, we observed the event-related potential and the regional cerebral blood flow (rCBF) in 10 normal subjects performing an oddball discrimination of pure tones. The rCBF value was assessed quantitatively with the aid of single photon emission computed tomography using technetium-99m hexamethylpropylene amine oxime. During the task performance, significant activation was observed in the posterior superior temporal and inferior parietal regions of the right hemisphere. In addition, positive correlation of the task-related increase in rCBF with the simultaneously recorded P300 amplitude was observed in the right but not the left posterior superior temporal region. These findings indicate that activation of the right non-verbal auditory area might modulate P300 generation during pure-tone discrimination.

In a patient with acute carbon monoxide (CO) poisoning in whom no delayed sequelae have been observed, MRI was performed serially from the time of exposure. When few clear findings were noted on conventional T2-weighted spin echo (SE) imaging, distinct hyperintense areas in the deep cerebral white matter were already evident on fluid attenuated inversion recovery (FLAIR) pulse imaging. These abnormal findings appeared to reflect a disease process differing from the acute phase disturbance of consciousness, namely the course of a gradually progressive demyelination. Neither serial intelligence tests nor single photon emission CT (SPECT) studies of regional cerebral blood flow conducted in the same period revealed any abnormalities. These results suggest that, in the subclinical phase in which there are few significant findings on T2-weighted SE imaging or SPECT, insidious demyelinating changes are already apparent on FLAIR imaging and that FLAIR imaging may thus be useful in the early diagnosis of the interval form of CO poisoning.

Patients with panic disorder (PD) have a bias to respond to normal stimuli in a fearful way. This may be due to the preactivation of fear-associated networks prior to stimulus perception. Based on EEG, we investigated the difference between patients with PD and normal controls in resting state activity using features of transiently stable brain states (microstates). EEGs from 18 drug-naive patients and 18 healthy controls were analyzed. Microstate analysis showed that one class of microstates (with a right-anterior to left-posterior orientation of the mapped field) displayed longer durations and covered more of the total time in the patients than controls. Another microstate class (with a symmetric, anterior-posterior orientation) was observed less frequently in the patients compared to controls. The observation that selected microstate classes differ between patients with PD and controls suggests that specific brain functions are altered already during resting condition. The altered resting state may be the starting point of the observed dysfunctional processing of phobic stimuli.

To investigate the brain bction of elderly schizophrenic patients, quantitative EECs of such patients were compared with thoee of healthy elderly controls. In schizophrenics, increases in delta and slow theta (4.0–6.0 Hz) waves were thought to be due to the influence of antlpsychotics. Characteristic EEC featurea of these patients included the following: 1) more fast theta (6.0–8.0 Hz) wave was observed, with less alpha wave faster than 9.0 Hz, 2) the reduction in alpha 3: (10.0–11.0 Hz) wave was limited to the frontal regions. The present EEG Andings are thought to characterize the traits of the subtype of chronic severe schizophrenia. The reduction in alpha 3: wave in the frontal regions may be one expression of the hypofrontality of schizophrenia.

The effectiveness of a once-weekly i.m. injection of ceruletide (0.8 μg/kg) in suppressing the symptoms of neuroleptic-induced tardive dyskinesia (TD) was evaluated in a double-blind, placebo-controlled, matched-pairs study. Global evaluation of the severity of TD symptoms over the 8-week study period revealed a significant improvement with ceruletide as compared with placebo. Analysis of the therapeutic response to ceruletide over the course of treatment revealed a slow, but long-lasting improvement of TD symptoms. Side effects, which were mild and transient, consisted mainly of nausea and epigastric discomfort. The incidence of side effects did not differ between the ceruletide-and placebo-treated groups. Ceruletide appears to be a novel and practical treatment that can substantially alleviate the symptoms of dyskinesia.

To investigate the prevalence of tardive dyskinesia (TD) in a group of psychiatric patients receiving low doses of antipsychotic drugs, we examined 647 Japanese inpatients (361 men and 286 women) with a mean age of 49.8 years, receiving a mean dose of antipsychotic drugs of 276.8 mg of chlorpromazine equivalent. TD was diagnosed according to the criteria of Schooler and Kane with the Abnormal Involuntary Movement Scale. The overall prevalence of TD was 22.3%. Mild TD was found in 67.4% of TD patients, moderate TD in 29.2%, and severe TD in 3.5%. The TD patients were older (59.0 years) than those without this condition (47.2 years). The prevalence of TD increased with advancing age until the 7th decade, when it reached a plateau. The dose of daily antipsychotic drugs was lower in the TD patients (207.6 mg) than in the patients without TD (296.6 mg). The duration of primary illness was longer in the TD patients (28.9 years) than in the patients without TD (20.4 years). Patients receiving antiparkinsonism drugs showed TD less frequently (20.7%) than those not receiving such drugs (31.0%). No significant associations were found between the presence of TD and sex or primary illness.

Purpose Lewy body disease (LBD) is comprised of a spectrum of diseases that includes Parkinson's disease (PD), PD dementia (PDD) and dementia with LBD (DLBD), an array of dementia, and motor symptoms. Low uptake of myocardial meta-iodobenzylguanidine (MIBG) validates diagnosis of LBD. Psychiatric symptoms sometimes precede atypical Parkinsonian syndromes in LBD. Of 34 patients with low MIBG uptake, late-onset depressive, anxiety, or psychotic symptoms were analyzed in term of clinical profiles. Method Thirty-four patients were classed into three groups according to three main symptoms, 11 patients with visual hallucination (VH), 13 with depression-anxiety (DA), and 10 with psychosis with cognitive disturbance (PCD). Cutoff values of heart-to-mediastinum (HM) ratio of MIBG were set at 1.78 in early phase or 1.68 in late phase. Results Group VH patients showed a trend toward higher age at onset and occipital lobe hypoperfusion. Group DA patients lacked central and core features of DLBD and five of them showed frontal lobe hypoperfusion. Group PCD patients had the highest frequencies of suggestive symptoms and UPDRS scores and showed temporal lobe hypoperfusion. HM ratio was not associated with clinical profiles of three groups. Cognitive function was more severely disturbed in atypical Parkinsonian syndrome cases at an initial visit. Conclusion Group VH was considered to DLBD, and Group PCD was regarded as PDD or DLBD with early psychotic presentation. Group DA has a possibility of early depression or anxiety disorder of LBD although it lacked DLBD criteria. Atypical Parkinsonian syndromes are associated with cognitive disturbance irrespective of psychiatric profiles. Copyright © 2009 John Wiley & Sons, Ltd.

A case of CJD with PLD in the first EEG is reported. The PLD became bilateral in the next EEG. The subsequent EEGs showed shifting asymmetries. In this case, PSD reappeared after 5 months' absence. The PLD occasionally appeared over the hemisphere ipsilateral to the side of the myoclonic jerks. The clinical significance of the PLD and reappearance of PD, and the diagnostic importance of PLD are discussed.

14-3-3 proteins play roles in phosphorylation of tau proteins in neurofibrillary tangles (NFT) in Alzheimer's disease (AD). Tau is phosphorylated at serine (pSer) and threonine (pThr) in NFT, and NFT morphology varies according to phosphorylated sites and tau isoform. The roles of 14-3-3 proteins in NFT morphology remain unknown. This study was performed to examine the relationships between 14 and 3-3 proteins and tau phosphorylation of NFT. NFT were labeled with Gallyas impregnation, tau and 14-3-3 immunohistochemistry in paraffin-embedded hippocampal sections from seven AD and three control brains. Anti-tau antisera included monoclonal antisera that recognize pSer262 (pSer262), pSer422 (pSer422), pSer202/pThr205 (AT8), Thr231 (AT180), three-repeat (RD3) and four-repeat (RD4) tau isoform. Anti-14-3-3 protein isoform antisera included polyclonal antisera to beta, gamma, zeta, epsilon, tau, mu and sigma isoforms and monoclonal antiserum to beta antiserum (H8-beta). NFT density was obtained by counting labeled NFT in cornu ammonis (CA) 1-CA4, subiculum and entorhinal cortex. H8-beta and zeta isoforms were strongly expressed in NFT. Regional densities of NFT positive for pSer262, AT8, AT180, and Gallyas impregnation were similar to RD3-positive NFT density with high densities in CA1 and entorhinal cortex. NFT positive for pSer422 showed a similar regional distribution to RD4-positive NFT with high NFT density in CA2-CA4. H8-beta-positive NFT showed a similar regional distribution to RD3-positive NFT. In contrast, zeta isoform-positive NFT showed no specific distribution. In conclusion, H8-beta isoform is associated with development of 3-repeats NFT but a role of 14-3-3 zeta isoform in NFT could not be specified.

In Hegura Island, Japan, we have recently found female divers who suffer from a disorder called 'Chiyamai'. From interviews, questionnaires and temporarily proposed diagnostic criteria for Chiyamai, nine cases from 44 female divers interviewed, were diagnosed as having Chiyamai. Clinically, Chiyamai is characterized by a panic-like attack. Ten symptoms were observed during a panic-like attack, compared with 13 symptoms in a panic attack described in the DSM-IV. The average age at onset was 30 years and the average duration of illness was approximately 26 years. Several cases were so severe that the patients were unable to continue diving. Additionally, we report a typical case of Chiyamai, and discussed the similarities and differences between Chiyamai and anxiety disorders in the DSM-IV. We suggest that Chiyamai is a panic-like disorder specific to female divers from Hegura Island and that it is a result of heavy diving.