Mitsutoshi Okazaki

National Center of Neurology and Psychiatry, Кодаиры, Tōkyō, Japan

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Publications (32)64.54 Total impact

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    ABSTRACT: Classic antidepressants have been known to induce convulsive seizures and nonconvulsive status epilepticus (NCSE). On the other hand, many reports have emphasized the safety of novel antidepressants. However, we encountered three cases of NCSE in the elderly associated with the use of newer antidepressants at therapeutic doses. All three patients were male and were 73 years of age or older. One patient was recently diagnosed with temporal lobe epilepsy and treated with low-dose lamotrigine. In all patients, newer antidepressants were initiated because of depressive symptoms. After titrating to therapeutic doses (paroxetine 20 mg/day, sertraline 50 mg/day, and combination of sertraline 50 mg/day and mirtazapine 30 mg/day in one patient each), impaired consciousness appeared. Electroencephalography (EEG) showed generalized slow waves with intermittent spike–slow-wave complexes. Intravenous injection of antiepileptic drugs improved EEG findings and clinical symptoms. After discontinuance of the abovementioned antidepressants, NCSE did not recur in any of patients. These reports raise the question of whether the newer antidepressants, like classic antidepressants, might also induce NCSE in the elderly, even when used at therapeutic doses. Physicians should consider monitoring for possible NCSE when using newer antidepressants in patients who may have low drug tolerability. Active continuous video-EEG monitoring is essential when behavioral and psychological symptoms or change in consciousness level is suspected.
    12/2015; 3. DOI:10.1016/j.ebcr.2014.10.003
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    ABSTRACT: Although the clinical efficacy of electroconvulsive therapy (ECT) is well established, the underlying mechanisms of action remain elusive. The aim of this study was to elucidate structural changes of the brain following ECT in patients with major depressive disorder (MDD). Fifteen patients with MDD underwent magnetic resonance imaging scanning before and after ECT. Their gray matter volumes were compared between pre- and post-ECT. There were significant volume increases after ECT in the bilateral medial temporal cortices, inferior temporal cortices, and right anterior cingulate. Further, the increase ratio was correlated with the clinical improvement measured by the Hamilton Depression Rating scale. All subjects were treated with antidepressants that could have a neurotoxic or neuroprotective effect on the brain. We found that there were significant increases of gray matter volume in medial temporal lobes following ECT, suggesting that a neurotrophic effect of ECT could play a role in its therapeutic effect. Copyright © 2015 Elsevier B.V. All rights reserved.
    Journal of Affective Disorders 07/2015; 186:186-191. DOI:10.1016/j.jad.2015.06.051 · 3.71 Impact Factor
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    ABSTRACT: The association between amygdala enlargement (AE) and temporal lobe epilepsy (TLE) has increasingly been reported. However, the pathology of AE remains poorly understood. The purpose of this study was to explore AE pathology using (11)C-methionine (Met) positron emission tomography (PET)/computed tomography (CT) in patients who have TLE with AE. Twenty-six TLE patients with AE and 18 TLE patients without AE underwent (11)C-Met PET/CT and magnetic resonance imaging (MRI). (11)C-Met uptake in amygdala was evaluated by both visual inspection and semi-quantitative measurement. MRI was assessed visually and semi-quantitatively for AE. Laterality index (LI) was obtained by comparing the amygdala volumes of ipsilateral and contralateral sides. The clinical course and histopathological findings of all patients were also analyzed. On (11)C-Met PET/CT images, visual examination detected increased uptake in the enlarged amygdala in 7 of 26 (27%) TLE patients with AE, and the results were confirmed by semi-quantitative analysis. Among six TLE patients with AE who underwent surgery, histopathology revealed neoplasms (low grade astrocytoma and gangliocytoma) in two patients and focal cortical dysplasia in one patient with increased (11)C-Met uptake, but non-neoplastic lesions (focal cortical dysplasia, vacuolar degeneration, and hamartoma) in all three patients with no increased (11)C-Met uptake. On MRI, volume of the affected amygdala was significantly larger compared to the contralateral amygdala. LI was significantly higher in the group with AE than in the group without AE. This study revealed that some TLE patients with AE showed increased (11)C-Met uptake in the enlarged amygdala. (11)C-Met PET/CT is potentially useful for the evaluation of AE pathology, and may provide beneficial information for appropriate decision-making. Copyright © 2015 Elsevier B.V. All rights reserved.
    Epilepsy Research 03/2015; 112. DOI:10.1016/j.eplepsyres.2015.02.018 · 2.19 Impact Factor
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    ABSTRACT: Psychogenic nonepileptic seizures (PNESs) in patients with epilepsy can be categorized as dissociative disorders. The prevalence of PNESs in patients with epilepsy appears to be much higher than that of dissociative experiences in nonclinical subjects. In order to clarify as to whether epilepsy-related factors were associated with pathological dissociation, we conducted a controlled study with 225 patients with epilepsy and 334 nonclinically matched individuals. All participants completed the Japanese version of the Dissociative Experiences Scale (DES). There was no significant difference in the DES score (DES-S) between the group with epilepsy and the control group. The group with epilepsy showed a significantly higher DES taxon (DES-T; a subset of DES-S and an index of pathological dissociation) than the control group. Thirty-one out of the 225 patients with epilepsy (13.8%) had PNESs. Because of its strong association with the DES-S and DES-T, PNESs can be regarded as a symptom of dissociation. With multiple regression analysis, the patients with a shorter duration of epilepsy, higher seizure frequency, or shorter period in education tend to suffer from pathological dissociation. These findings demonstrate that patients with epilepsy are more prone to experiencing pathological dissociation when having certain clinical factors. Copyright © 2014 Elsevier Inc. All rights reserved.
    Epilepsy & Behavior 02/2015; 44:185–191. DOI:10.1016/j.yebeh.2014.12.018 · 2.06 Impact Factor
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    ABSTRACT: To investigate whether addition of antipsychotic drugs (APD) would increase seizure frequency in epilepsy patients who were already treated with anti-epileptic drugs (AED), we compared a one-year seizure control outcome in 150 epilepsy patients with APD treatment for psychiatric conditions and 309 epilepsy patients without APD treatment matched for ages at epilepsy onset and the baseline evaluation and types of epilepsy. The seizure frequency was recorded at the baseline (immediately before the start of APD) and after the 1st, 3rd, 6th and 12th month. The seizure outcome at each of the four follow-up points was compared with the baseline. The seizure outcome was compared between the two groups as a whole and according to the types of epilepsy (idiopathic generalised and partial epilepsies). In the APD group, the seizure outcome was also analysed according to the types of APD (first and second generation APD and combination of first and second generation APD) and the types of psychiatric conditions (psychosis and non-psychosis). The seizure outcome was significantly better in the APD group than control group at all the four follow-up points. According to the epilepsy types, the improvement in the seizure outcome was only observed in the patients with partial epilepsy. Of the APD group, there was no significant difference in the seizure outcome according to the types of APD or the psychiatric conditions. In epilepsy patients who are already treated with AED, APD treatment seems safe in seizure control outcome for treatment of psychiatric conditions. (245 words)
    European Neuropsychopharmacology 11/2014; 24(11). DOI:10.1016/j.euroneuro.2014.09.012 · 5.40 Impact Factor
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    ABSTRACT: Previous studies have suggested that schizophrenia patients have dysfunctional thermoregulation. The aim of this study was to examine whether brain temperature (BT) in schizophrenia patients differs from that in patients with bipolar disorder and healthy subjects by using magnetic resonance imaging. We also evaluated the possible relationship between BT and cerebral blood flow (CBF). We analyzed the temperature of lateral ventricles as the mean BT using diffusion-weighted imaging (DWI) thermometry, and evaluated the relationships between the BT and the CBF using pseudo-continuous arterial spin labeling (pCASL) among 3 diagnostic groups, 22 male patients with schizophrenia, 19 male patients with bipolar disorder, and 23 healthy male subjects. There were significant positive correlations between BT in the lateral ventricles and CBF in both the patients with bipolar disorder and healthy subjects. By contrast, there were significant negative correlations in patients with schizophrenia. We could not detect the significant difference in the surrogates of BT among three diagnostic groups. We showed that patients with schizophrenia, but not those with bipolar disorder, have dysfunctional thermoregulation in the brain. Brain temperature is highly dependent on cerebral metabolism and CBF, and thus uncoupling of cerebral metabolism and CBF may occur in schizophrenics.Journal of Cerebral Blood Flow & Metabolism advance online publication, 3 September 2014; doi:10.1038/jcbfm.2014.151.
    Journal of Cerebral Blood Flow & Metabolism 09/2014; 34(12). DOI:10.1038/jcbfm.2014.151 · 5.34 Impact Factor
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    ABSTRACT: While research on remission in schizophrenia has gained attention, personality characteristics associated with remission in schizophrenia have been under-studied. A functional valine-to-methionine (Val158Met) polymorphism in the catechol-O-methyltransferase (COMT) gene is shown to modify clinical presentation of schizophrenia despite weak or no association with the disorder itself. Studies also report that this polymorphism can affect personality traits. We aimed to examine personality traits of remitted patients with schizophrenia as compared to symptomatic patients and healthy controls and to investigate whether the COMT Val158Met polymorphism influences their personality. Scores on the Temperament and Character Inventory were compared between 34 remitted outpatients with schizophrenia, age- and sex-matched 72 symptomatic outpatients with schizophrenia, and matched 247 healthy individuals. The effect of COMT Val158Met polymorphism on personality was examined in each group. The analysis of covariance, controlling for confounding variables, revealed that compared to healthy controls, symptomatic patients exhibited a pervasively altered personality profile whereas remitted patients showed alterations in more limited personality dimensions and demonstrated normal levels of novelty-seeking, reward dependence and cooperativeness. The two-way analysis of covariance, with genotype and sex as between-subject factors and confounders as covariates, revealed that Met carriers demonstrated significantly lower reward dependence and cooperativeness than Val homozygotes in symptomatic patients; while no significant genotype effect was found in remitted patients or in healthy individuals. These findings indicate that remitted patients with schizophrenia have a relatively adaptive personality profile compared to symptomatic patients. The COMT Val158Met polymorphism might have a modulating effect on the relationship between personality and remission.
    Journal of Psychiatric Research 05/2014; 56(1). DOI:10.1016/j.jpsychires.2014.05.006 · 4.09 Impact Factor
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    ABSTRACT: Arterial spin labeling (ASL) magnetic resonance imaging (MRI) is a novel noninvasive technique that can measure regional cerebral blood flow (rCBF). To our knowledge, few studies have examined rCBF in patients with schizophrenia by ASL-MRI. Here we used pseudo-continuous ASL (pCASL) to examine the structural and functional imaging data in schizophrenic patients, taking the regional cerebral gray matter volume into account. The subjects were 36 patients with schizophrenia and 42 healthy volunteers who underwent 3-tesla MRI, diffusion tensor imaging (DTI), and pCASL. We evaluated the gray matter volume imaging, DTI, and pCASL imaging data in a voxel-by-voxel statistical analysis. The schizophrenia patients showed reduced rCBF in the left prefrontal and bilateral occipital cortices compared to the healthy volunteers. There was a significant reduction of gray matter volume in the left inferior frontal cortex in the schizophrenia patients. With respect to the fractional anisotropy (FA) values in the DTI, there were significant FA reductions in the left superior temporal, left external capsule, and left inferior prefrontal regions in the patients compared to the controls. Conclusion Our pCASL study with partial volume effect correction together with volumetry and DTI data demonstrated hypoactivity in the left prefrontal area beyond structural abnormalities in schizophrenia patients. There were also hypofunction areas in bilateral occipital cortices, although structural abnormalities were not apparent.
    Schizophrenia Research 04/2014; 154(1-3). DOI:10.1016/j.schres.2014.01.035 · 4.43 Impact Factor
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    ABSTRACT: Impaired dexterity is a major psychomotor deficit reported in patients with schizophrenia. In the present study, the Purdue pegboard test was used to compare the manual dexterity in patients with schizophrenia and healthy controls. We also examined the influence of antipsychotics, benzodiazepines, and benzodiazepine-like drugs on manual dexterity. Subjects were 93 patients with schizophrenia and 93 healthy controls, matched for sex and age distributions. Control subjects scored significantly higher on all scores of Purdue pegboard than patients with schizophrenia. Age, PANSS negative symptom scale, typical antipsychotic dose, and use of benzodiazepines and/or benzodiazepine-like drugs were negatively correlated with the pegboard scores in patients with schizophrenia. The present results indicate that patients with schizophrenia have impaired gross and fine fingertip dexterity compared to healthy controls. The use of typical antipsychotics and benzodiazepines and/or benzodiazepine-like drugs, but not atypical antipsychotics, had significant negative impact on dexterity in patients with schizophrenia. Psychiatrists should be aware that some psychotropic medications may enhance the disability caused by the impairment of dexterity in patients with schizophrenia.
    Journal of Psychiatric Research 11/2013; 49. DOI:10.1016/j.jpsychires.2013.10.019 · 4.09 Impact Factor
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    ABSTRACT: Objective: The purpose of this retrospective study was to clarify the cellular activities of ectopic neurons in subcortical bands and to evaluate the imaging features of (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and (99m)Tc ethyl cysteinate dimer (ECD) single-photon emission computed tomography (SPECT) in a series of patients with subcortical band heterotopia (SBH). Materials and methods: The cases of 12 patients with SBH (3 men and 9 women; age range, 2-51years) were evaluated on the basis of their MRI findings. Eight (18)F-FDG PET and 12 (99m)Tc-ECD SPECT images were obtained. The uptakes of these images were compared with electroencephalography (EEG) or MRI findings such as band thickness. In all patients, easy Z-score Imaging System (eZIS) software was used to statistically analyze the SPECT images. Results: Of the eight (18)F-FDG PET images, five showed higher uptake in the thick subcortical bands than in the overlying cortex. Of the 12 (99m)Tc-ECD SPECT examinations with eZIS images, nine indicated increased regional cerebral blood flow (rCBF) areas corresponding to the band locations. Of the eight (18)F-FDG PET examination findings, six were congruent with the rCBF distributions on the eZIS images. Eight of the 12 patients showed correspondence to the increased rCBF on the eZIS images, the band locations on MRI, and abnormal discharge sites on EEG. Conclusions: Ectopic neurons in subcortical bands may have higher glucose metabolism and/or increased rCBF compared to the overlying cortex. (18)F-FDG PET and (99m)Tc-ECD SPECT using eZIS can be helpful to clearly detect the cellular activities of ectopic neurons in patients with SBH.
    Brain & development 08/2013; 36(7). DOI:10.1016/j.braindev.2013.07.017 · 1.54 Impact Factor
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    ABSTRACT: Treatment protocols for interictal psychosis (IIP) of patients with epilepsy have not yet been established. We aimed to clarify the effects of antipsychotic drugs (APDs) on duration of IIP episodes. We studied 393 IIP episodes in 200 patients with epilepsy in accordance with our empirical treatment protocol. The duration of all the episodes and APD treatments were reviewed. Antipsychotic drugs were used in 338 episodes and not used in 55 episodes (non-APD group). The APDs used in the treatment of IIP episodes were divided into the following three groups: first-generation APDs (FAPD, n=252), second-generation APDs (SAPD, n=44), and the combination of first- and second-generation APDs (CAPD, n=42). The non-APD group showed a significantly shorter episode duration than did the APD group (F=6.05, p=0.014). Among the 3 APD groups (FAPD, SAPD, and CAPD), there was a significant difference in duration of IIP episode (F=8.65, p=0.000). Whereas the duration of episodes was significantly longer in the CAPD group than in the other two groups, it was not significantly different between the FAPD and SAPD groups. Our findings further to clarify the nature of IIP and add further perspectives on treatment protocols for IIP.
    Epilepsy & Behavior 03/2013; 27(2):342-345. DOI:10.1016/j.yebeh.2013.02.025 · 2.06 Impact Factor
  • Journal of the Japan Epilepsy Society 01/2013; 31(1):30-39. DOI:10.3805/jjes.31.30
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    ABSTRACT: We conducted a questionnaire survey to investigate the situation of transitional medicine for epilepsy. Among the epilepsy patients cared by pediatric neurologists, 27% were adult patients including some elderly epilepsy patients. Seventy-six percent of the pediatric neurologists felt some difficulties in providing care for adult epilepsy. The main issues were psychiatric/psychological co-morbidity, medical co-morbidity, and a lack of in-patient facilities in the vicinity. This survey demonstrated that the lack of the transitional medicine for epilepsy in Japan is a profound problem, and the factors that hamper transfer of epilepsy patients to adult specialties should be resolved. To solve this problem, it is imperative that the Japanese Society of Child Neurology and Japan Epilepsy Society conduct collaborative activities with three relevant societies; Societas Neurologica Japonica, the Japanese Society of Psychiatry and Neurology, and the Japan Neurosurgical Society.
    No to hattatsu. Brain and development 07/2012; 44(4):311-4.
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    ABSTRACT: There have been few reports showing the distribution of the duration of interictal psychosis (IIP) episodes and their association with clinical characteristics. To clarify the nature of IIP, we studied the duration of IIP episodes and their related factors. One hundred fifty-five patients with epilepsy exhibited 320 IIP episodes during our follow-up period (mean 16.9 years). The duration of all the episodes and the longest episode in each patient during the follow-up periods were studied. Characteristics of the patients (e.g., epilepsy type, age of onset, and family history of psychosis) and episode-specific factors (e.g., age of the episode, seizure frequency, administrations of antiepileptic drugs [AEDs] and antipsychotic drugs [APDs]) were analyzed in association with the duration of the episodes. Mean duration of the 320 IIP episodes was 82.7 weeks and that of the longest IIP episodes was 150.1 weeks. During the follow-up period, 17 patients (11.0%) showed all episodes remitting within a month and 54 (34.8%) showed all episodes lasting for 6 months or longer. The IIP episodes that occurred at a younger age were often prolonged. Patients with a family history of psychosis or with early onset of psychosis tended to have more prolonged IIP episodes. Among the episodes treated with APDs, early administration of APDs was significantly associated with shorter IIP duration. The distribution of the duration of IIP episodes indicated the broad spectrum and heterogeneity of the IIP phenomena. The individual vulnerability to psychosis may be associated with prolonged episodes. Administration of APDs soon after onset of the episodes appeared to be effective in controlling them. These findings support empirical treatment principles for IIP to administer APDs at an early stage of its development.
    Epilepsia 03/2012; 53(6):1088-94. DOI:10.1111/j.1528-1167.2012.03438.x · 4.58 Impact Factor
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    ABSTRACT: We conducted a questionnaire survey on 7,500 members of the Societas Neurologica Japonica regarding the carry-over from pediatric to adult epilepsy care. The response rate was 16.9%. Analysis of the responses showed that 46% of the neurologists were aware of the term "carry-over" in epilepsy care, and 78% felt difficulties with epilepsy care in general. The most common reasons included "not familiar with interpreting EEG" and "not familiar with the laws, regulations and medical and welfare systems specific to epilepsy". Among the neurologists who felt difficulties when accepting epilepsy patients aged 20 years or older referred from the pediatric department, 68% had experienced accepting these patients. The two major reasons for feeling difficulties when accepting these patients were "difficult to have good understanding of the disease course from infancy" and "not familiar with the epilepsy syndrome specific to infancy". The above findings highlight the importance of recognizing the existence of the issue of carry-over in adult epilepsy care and its significance, and to resolve the factors that hinder the transition of care. To achieve this goal, joint activities of the Japanese Society of Child Neurology and the Japan Epilepsy Society in collaboration with the Societas Neurologica Japonica, the Japanese Society of Psychiatry and Neurology, and the Japan Neurosurgical Society are critical.
    01/2012; 52(10):730-8. DOI:10.5692/clinicalneurol.52.730
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    ABSTRACT: To investigate the clinical effects of antidepressants on seizure frequency of patients with epilepsy treated with antiepileptic drugs, we retrospectively evaluated the 1-year course of seizure frequency. One hundred twenty-one patients with epilepsy treated with antidepressants and 300 patients with epilepsy not treated with antidepressants (controls) were the subjects of this study. Seizure frequency over the 1-year period of administration of antidepressants was retrospectively evaluated and compared with that for controls. In the patients with epilepsy taking antidepressants, seizure frequencies at four observation points (1, 3, 6, and 12 months after starting antidepressants) were equivalent to those of the control group. There was no significant difference in seizure frequency between first- and second-generation antidepressants. Patients with epilepsy treated with antiepileptic drugs can take antidepressants without a significant risk of exacerbation of seizures. Most antidepressants can be used for psychiatric treatment of patients with epilepsy.
    Epilepsy & Behavior 08/2011; 22(2):331-5. DOI:10.1016/j.yebeh.2011.07.016 · 2.06 Impact Factor
  • Masumi Ito · Naoto Adachi · Mitsutoshi Okazaki · Masaaki Kato · Teiichi Onuma
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    ABSTRACT: We investigated the relationship between dissociation and psychogenic nonepileptic seizures (PNES) and evaluated the clinical utility of the Dissociative Experience Scale (DES) in patients with epilepsy. The DES was administered to 30 patients with epilepsy and PNES, 50 patients with epilepsy and no PNES, and 85 nonclinical individuals. Patients with epilepsy and PNES scored significantly higher on the DES (29.3) than patients with epilepsy without PNES (13.5) and nonclinical individuals (11.1). High DES scores (>30) were more frequently observed in patients with epilepsy and PNES (53%) than in patients with epilepsy without PNES (12%) and nonclinical individuals (6%). DES score did not differ significantly with respect to epilepsy-related variables. Neither the frequency nor severity of PNES was significantly associated with the DES score. Our findings confirm some associations between PNES and dissociation in patients with coexisting epilepsy and PNES. The DES could be helpful in determining the tendency to have PNES in patients with epilepsy.
    Epilepsy & Behavior 09/2009; 16(3):491-4. DOI:10.1016/j.yebeh.2009.08.017 · 2.06 Impact Factor
  • Yuu Kaneko · Tawasuke Otsuki · Mitsutoshi Okazaki
    Clinical Neurophysiology 05/2009; 120(5). DOI:10.1016/j.clinph.2009.02.097 · 2.98 Impact Factor
  • Mitsutoshi Okazaki · Yuu Kaneko · Masato Yumoto · Kunimasa Arima
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    ABSTRACT: The purpose of the present study was to examine by whole-head magnetoencephalography (MEG) brain oscillatory responses related to visual perceptual change of short-term duration in the absence of morphologic change. Twenty healthy volunteers participated in this study. We used three pictures: a bistable picture with ambiguous contours that could represent two different objects ('target') and two preceding pictures that were clear representations of either object ('face' or 'saxophone'). Two types of stimulus conditions were created, the 'face-target' (F-T) condition and the 'saxophone-target' (S-T) condition, and data acquisition was performed mainly during presentation of the 'target' picture. Time-frequency analysis was performed by means of fast Fourier transform. All subjects reported that they perceived the 'target' picture predominantly as a 'face' regardless of the preceding picture. We suspect that perceptual change occurred more frequently in the S-T condition than in the F-T condition. We found significantly greater synchronization in the beta (14-30-Hz) frequency band, ranging from 250 to 450ms predominantly over the occipital and parietal regions, after stimulus alternation for the S-T condition than for the F-T condition. Results of the present study show that the change in beta-band activity reflects a change in visual perception.
    Neuroscience Research 08/2008; 61(3):319-28. DOI:10.1016/j.neures.2008.03.010 · 2.15 Impact Factor
  • Chihiro Nakata · Masumi Ito · Mitsutoshi Okazaki
    Journal of the Japan Epilepsy Society 01/2008; 26(1):26-32. DOI:10.3805/jjes.26.26

Publication Stats

73 Citations
64.54 Total Impact Points

Institutions

  • 2007–2015
    • National Center of Neurology and Psychiatry
      • • Department of Mental Disorder Research
      • • Department of Neurosurgery
      Кодаиры, Tōkyō, Japan
  • 2008
    • Tokyo Medical and Dental University
      • Department of Psychiatry and Behavioral Science
      Edo, Tōkyō, Japan