Eisuke Matsushima

Functional MRI mapping of brain activation during visually guided saccades and antisaccades: cortical and subcortical networks.

Antisaccade tasks require a subject to inhibit a saccade toward a briefly appearing peripheral target and instead to immediately generate a saccade to an equivalent point in the opposite hemifield. Using functional magnetic resonance imaging (fMRI), we investigated the neural networks required to inhibit reflexive saccades and to voluntarily generate saccades. The results demonstrated that saccade and antisaccade tasks often bilaterally activate frontal, parietal and supplementary eye fields, lenticular nuclei and occipital cortex. Additional activation of bilateral dorsolateral prefrontal cortices, supramarginal gyri, anterior cingulate cortices and thalamus was observed during antisaccade tasks. These results indicate that fronto-parietal and fronto-striato-thalamo-cortical circuits are involved in antisaccade tasks. The fronto-parietal circuit is thought to be related to the planning of saccadic eye movements that involve attentional control, while the fronto-striato-thalamo-cortical circuits connect to cortical region as a feedback network. We speculate that the abnormalities in spatial attention and eye movement control observed in schizophrenia stem from dysfunctions in the fronto-parietal and fronto-striato-thalamo-cortical circuits.

Serotonin 5-HT2 receptors in schizophrenic patients studied by positron emission tomography.

Using positron emission tomography (PET) and [11C]N-methylspiperone (NMSP), we examined 5-HT2 receptors in the cortex of schizophrenic patients in whom we previously observed decreased prefrontal D1 receptor binding. The subjects were 10 neuroleptic-naive schizophrenic patients, 7 schizophrenic patients who were drug-free but had previously been treated with neuroleptics, and 12 normal controls. A non-significant trend towards decreased prefrontal [11C]NMSP binding was observed in the neuroleptic-treated patients, suggesting a possible effect of previous neuroleptic treatment on the alteration in cortical 5-HT2 function. However, the neuroleptic-naive patients showed no noticeable difference in cortical [11C]NMSP binding compared to controls. Our results do not rule out the role of 5-HT2 function as a crucial site of therapeutic activity of schizophrenia, but they do suggest that cortical 5-HT2 receptors might not be primarily involved in the pathophysiology of schizophrenia.

Stability of exploratory eye movements as a marker of schizophrenia-A WHO multi-center study

The exploratory eye movements of patients with schizophrenia reportedly differ from those of patients without schizophrenia and healthy controls. In an attempt to determine whether exploratory eye movements provide valid markers for schizophrenia, the present collaborative study was conducted in six countries to analyze the stability of and variation in the following parameters of exploratory eye movements: the number of eye fixations (NEFs) and mean eye scanning length (MESL) in a retention task; the cognitive search score (CSS) that indicates how frequently the eye focused on each important area of a figure in order to recognize it in a comparison task; and the responsive search score (RSS), which reflects the frequency of eye fixations on each section of a figure in response to questioning in a comparison task. In addition, we investigated the validity of the currently employed discriminant function to extract a common feature of schizophrenia by applying it to the findings of the present study. The exploratory eye movements of 145 patients with schizophrenia, 116 depressed patients and 124 healthy controls at seven WHO collaborative centers in six countries were measured using eye mark recorders during viewing of stationary S-shaped figures in two sequential tasks. The RSSs of patients with schizophrenia were found to be significantly lower than those of depressed patients or healthy controls irrespective of geographical location, with no significant difference existing between the RSSs for depressed patients and those for healthy controls. By inserting the RSS and NEF data for each subject into the formula used to calculate discriminant function, patients with schizophrenia could be discriminated from depressed patients and healthy controls with a sensitivity of 89.0% and a specificity of 86.7%. The RSS is an exploratory eye movement parameter that detected schizophrenia irrespective of culture, race and various other subject variables. Furthermore, it is indicative of the stable, significant difference that exists between subjects with and without schizophrenia. The results of discriminant analysis confirm the previously reported validity of discriminant function.

Cognitive dysfunction in systemic lupus erythematosus

Abstract  Systemic lupus erythematosus (SLE) is an autoimmune‐mediated collagen disease that results in multiorgan failure. It is the collagen disease most frequently associated with neuropsychiatric symptoms, which have been hypothesized to stem from certain types of cognitive dysfunction. Subjects were 21 patients with SLE (one man, 20 women; aged 16–55 years; mean age, 35.1 ± 10.7 years) who were undergoing treatment in the rheumatology unit of a general hospital, and 17 healthy control subjects matched to the patient group with respect to age and gender (two men, 15 women; mean age, 35.9 ± 6.3 years). They were administered various tests of cognitive function including verbal reasoning, non‐verbal reasoning, verbal memory, non‐verbal memory, attention and mental flexibility, psychomotor speed and frontal lobe function. In addition, the SLE patients were tested for antiphospholipid antibodies. The SLE patients performed worse than the control group on immediate, delayed and interference of the Rey verbal test and paired associate tests of Wechsler Memory Scale, and their reaction time was slower in Trail A and Trail B tests. Moreover, these findings were more pronounced in the group with major neuropsychiatric symptoms. However, no relationship was apparent between these deficits in cognitive function and the presence or absence of antiphospholipid antibodies. The results suggest that verbal memory and psychomotor speed underlie the neuropsychiatric symptoms seen in SLE patients.

Regional cerebral blood flow in depressed patients with white matter magnetic resonance hyperintensity

BACKGROUND Functional neuroimaging studies have consistently demonstrated decreased regional cerebral blood flow (rCBF) or metabolism in the frontal lobe, temporal lobe, or anterior cingulate gyrus of depressed patients. On the other hand, white matter hyperintensity as defined by magnetic resonance imaging (MRI) has been the most consistently replicated finding in structural neuroimaging studies on depression; however, these functional and structural neuroimaging findings of depression have not been well integrated. We aimed to clarify the possible associations of MRI-defined subcortical hyperintensities with rCBF changes in depressed patients. METHODS Twelve depressed patients with subcortical hyperintensities defined by MRI, 11 depressed patients without MRI hyperintensities, and 25 healthy volunteers underwent 99mTc ECD SPECT. Group comparisons of their rCBF and correlation analysis between MRI hyperintensity and rCBF in patients were performed with a voxel-based analysis using statistical parametric mapping (SPM) software. RESULTS Depressed patients showed decreased rCBF compared with control subjects in the frontal lobe, temporal lobe, and anterior cingulate gyrus whether subcortical hyperintensity existed or not; however, the patients with MRI hyperintensity showed decreased rCBF in the thalamus, basal ganglia, and brainstem in addition to cortical areas. Further, the score for white matter hyperintensity correlated negatively with rCBF in subcortical brain structures, including the thalamus and right basal ganglia. CONCLUSION Our study indicates that depressed patients with MRI hyperintensities may have dysfunction in subcortical brain structures in addition to dysfunction in the fronto-temporal cortical structures.

An event-related potential study in schizophrenia using Japanese sentences

To examine the neurophysiological and cognitive characteristics of language disorder in schizophrenia, the N400 component and late positive component (LPC) of event-related potentials (ERPs) were investigated in medicated schizophrenic patients and health comparison subjects. The subjects were required to indicate whether Japanese sentence completions were semantically congruous or incongruous. The ERPs for the range of 300-500 ms to the incongruous completions contained a more negative component (N400), followed by LPC, which was inversely more positive for the incongruous than congruous condition. The N400 effect and the mean amplitude of the LPC were reduced in the patients. The attenuated N400 effect in schizophrenics mainly originated from an enhanced negativity for the congruous completions, suggesting that the use of context is poor in schizophrenia.

Insomnia in Japanese peri- and postmenopausal women

Objective To determine the prevalence and to identify the correlates of insomnia in Japanese peri- and postmenopausal women. Method We retrospectively analyzed the records of 1451 peri- and postmenopausal women enrolled in the Systematic Health and Nutrition Education Program, conducted at the Menopause Clinic of the Tokyo Medical and Dental University Hospital, between 1995 and 2009. Results The prevalence of insomnia was 50.8%. The severity of insomnia correlated negatively with health-related quality of life (HR-QOL) scores on all the four domains assessed: physical health, mental health, life satisfaction and social involvement. With regard to other menopausal symptoms, insomnia correlated more strongly with depressed mood than with vasomotor symptoms, and one-third of insomniac women were seriously depressed. On categorizing the participants into four groups – not insomniac or depressed, N; insomniac but not depressed, I; not insomniac but depressed, D; insomniac and depressed, ID – the HR-QOL scores were observed to worsen in order N > I > D > ID. No significant difference was detected between groups I and ID with regard to their sleep quality measures. The number of heavy smokers was high in groups I and ID. With regard to the effect of the combination of medication and health/nutrition education, hormone therapy and nightly hypnotics significantly improved the insomnia symptoms, but hypnotics administered ‘as needed’ did not. Conclusions Insomnia in Japanese peri- and postmenopausal women correlates more strongly with depressed mood than with vasomotor symptoms. Cessation of smoking may improve the womens sleep quality, and hormone therapy and nightly hypnotics are both effective treatments.

Significant linkage to chromosome 22q for exploratory eye movement dysfunction in schizophrenia

A genome‐wide scan for a locus responsible for exploratory eye movement (EEM), which is quantitative and can be disturbed in association with schizophrenia, was performed. A 10‐cM resolution genome‐wide linkage analysis of the EEM disturbance with 358 highly polymorphic microsatellite markers in 38 nuclear families with 122 members (38 probands, 47 sibs, and 37 parents) including 58 sib‐pairs yielded the suggestive linkage to the GCT10C10 marker on chromosome 22q11.2 (LOD = 2.48). Dense mapping with additional markers around the GCT10C10 marker yielded evidence for significant linkage between EEM disturbance and markers D22S429 and D22S310 on chromosome 22q12.1 (LOD score of 4.63) with suggestive evidence for the chromosome region 22q11.2–q12.1. Our findings suggest that a relatively small number of loci may control the schizophrenia‐related quantitative EEM trait. We believe that identifying gene(s) on chromosome 22q associated with the EEM phenotype may forward our understanding of the etiology of schizophrenia.

Exploratory eye movement dysfunctions in patients with schizophrenia: possibility as a discriminator for schizophrenia

In our previous studies patients with schizophrenia and their parents had less frequent eye fixations and a more limited area of inspection than normal controls while freely viewing stationary S-shaped figures. The present study attempted to discriminate schizophrenics from non-schizophrenics using exploratory eye movements. Two groups (A and B) were formed, each comprising 30 schizophrenic and 70 non-schizophrenic subjects (10 each of patients with depression, methamphetamine psychosis, alcohol psychosis, anxiety disorder, temporal lobe epilepsy, frontal lobe lesions and healthy normal controls). Discriminant analysis was performed on group A to obtain a discriminant. The validity of applying this discriminant to group B was investigated. By focussing on exploratory eye movements, schizophrenics could be discriminated from non-schizophrenics with a sensitivity of 76.7% and a specificity of 81.4%. These results show that exploratory eye movements are a useful discriminator for schizophrenia.

Associations between anxiety, depression and insomnia in peri- and post-menopausal women

OBJECTIVES To determine the correlation between somatic and psychological symptoms and insomnia and the contribution of depression and anxiety to insomnia in a sample of peri- and post-menopausal women in a clinical setting. STUDY DESIGN The responses of 237 peri- and post-menopausal women enrolled in the Systematic Health and Nutrition Education Program (SHNEP) at the Menopause Clinic of the Tokyo Medical and Dental University Hospital between November 2007 and December 2010 to the Menopausal Health-Related Quality of Life (MHR-QOL) and Hospital Anxiety and Depression Scale (HADS) questionnaires were subjected to Spearmans rank correlation and logistic regression analyses. RESULTS The analysis revealed that (1) insomnia is highly prevalent, (2) the symptoms of difficulty in initiating sleep (DIS) and experiencing non-restorative sleep (NRS) are more strongly correlated with psychological than somatic symptoms, and (3) DIS is strongly associated with anxiety while NRS is strongly associated with depression in the population studied. CONCLUSIONS Insomnia is highly prevalent among peri- and post-menopausal female patients in a clinical setting and more closely associated with psychological than somatic symptoms. DIS is strongly correlated with anxiety while NRS is strongly correlated with depression.