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Biomedical subjects

Akira Iwanami

Publications and source records attributed to Akira Iwanami.

At least 19 recordsLinked to original sources

Human brain structural change related to acute single exposure to sarin.

OBJECTIVE: This study aimed to identify persistent morphological changes subsequent to an acute single-time exposure to sarin, a highly poisonous organophosphate, and the neurobiological basis of long-lasting somatic and cognitive symptoms in victims exposed to sarin. METHODS: Thirty-eight victims of the 1995 Tokyo subway sarin attack, all of whom had been treated in an emergency department for sarin intoxication, and 76 matched healthy control subjects underwent T1-weighted and diffusion tensor magnetic resonance imaging (DTI) in 2000 to 2001. Serum cholinesterase (ChE) levels measured immediately and longitudinally after the exposure and the current severity of chronic reports in the victims were also evaluated. RESULTS: The voxel-based morphometry exhibited smaller than normal regional brain volumes in the insular cortex and neighboring white matter, as well as in the hippocampus in the victims. The reduced regional white matter volume correlated with decreased serum cholinesterase levels and with the severity of chronic somatic complaints related to interoceptive awareness. Voxel-based analysis of diffusion tensor magnetic resonance imaging further demonstrated an extensively lower than normal fractional anisotropy in the victims. All these findings were statistically significant (corrected p < 0.05). INTERPRETATION: Sarin intoxication might be associated with structural changes in specific regions of the human brain, including those surrounding the insular cortex, which might be related to elevated subjective awareness of internal bodily status in exposed individuals.

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Auditory P300 latency prolongation with age in schizophrenia: gender and subcomponent effects.

Previous studies showing prolongation of auditory P300b latency with increasing age provided support for post-onset progressive change in schizophrenia. We sought to extend the findings by evaluating the effects of gender and the subcomponents (P3b versus P3a) in schizophrenia (N=108) and controls (N=70). P3b latency significantly correlated with age in schizophrenia (Spearman's rho=0.214, P=0.026) and in male patients with schizophrenia (rho=0.260, P=0.049) whereas, it did not reach significance in female patients with schizophrenia (rho=0.174, P=0.23). P3a latency showed no correlation. Our findings may provide evidence for progressive change in the brain function in schizophrenia, and this change may be slower in female than male patients. P3b may serve as a more sensitive index for cognitive decline than P3a.

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The effect of perospirone on auditory P300 in schizophrenia: a preliminary study.

The present study was performed to determine the effect of perospirone, a novel antipsychotic drug with D(2)/5-HT(2A) antagonist and partial 5-HT(1A) agonist properties, on auditory P300 in eight patients with chronic schizophrenia. Switching to an equivalent dose of perospirone from prior antipsychotic medication was associated with a significant improvement in the negative symptoms of the positive and negative syndrome scale (PANSS). The change in P300 amplitude following a switch to perospirone correlated significantly with the improvement of general psychopathology symptoms, as well as with the change in scores on items of delusions, hallucinatory behavior, emotional withdrawal, depression, poor attention, and disturbance of volition. These results suggest that clinical improvement in response to perospirone in some patients may, at least in part, be mediated through cognitive change indexed by P300 in chronic schizophrenia.

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Voxel-based diffusion tensor analysis reveals aberrant anterior cingulum integrity in posttraumatic stress disorder due to terrorism.

Recent functional neuroimaging work has suggested that interregional functional connectivity between the anterior cingulate cortex (ACC), other limbic, and prefrontal regions may be involved in the pathophysiology of posttraumatic stress disorder (PTSD). However, less attention has been paid to the white matter network. Voxel-based analysis enables an exploration of morphological or functional changes throughout the entire brain. Here we undertook the first application of this technology to diffusion tensor data in patients with PTSD. Participants were 9 victims of the Tokyo subway sarin attack with PTSD and 16 matched victims of the same traumatic event without PTSD. The voxel-based analysis showed a significant fractional anisotropy increase in the left anterior cingulum, subjacent to the left ACC gray matter where we previously found a volume decrement, in PTSD subjects. Moreover, the severity was positively, but not significantly associated with the fractional anisotropy of the left anterior cingulum in the victims with PTSD, using the region of interest defined in the native space with the inverse normalization technique. The present study demonstrated further evidence of abnormalities of both the ACC, a structure that is pivotally involved in attention, emotional regulation, and fear conditioning, and of subjacent white matter in the pathology of PTSD.

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Comparison between mismatch negativity amplitude and magnetic mismatch field strength in normal adults.

The auditory mismatch negativity (MMN) or its magnetic counterpart (magnetic mismatch field, MMF) has been widely used to assess the ability of stimulus-driven change detection process in humans. The authors evaluated the similarity of inter-individual variation of the response strength between MMN and MMF recordings. Three types of MMN or MMF were recorded in ten healthy subjects: change in duration of pure-tone stimuli, change in duration of the Japanese vowel /a/, and difference between the Japanese vowels /a/ and /o/. There was no significant correlation between MMN amplitude and MMF strength under any condition and in either hemisphere. These results suggest that widely used indices of MMN in the two technologies, i.e., EEG-amplitude and MEG-ECD may not be proportional in an individual. To further clarify the differential significance of recording MMN/MMF may be important to establish MMN/MMF as clinical indices of individual ability of preattentive stage of auditory processing.

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Perospirone in the treatment of schizophrenia: effect on verbal memory organization.

The present study was performed to determine if perospirone, a novel antipsychotic drug with D2/5-HT2A antagonist and partial 5-HT1A agonist properties, would improve memory organization in twelve patients with chronic schizophrenia. Switching to equivalent dose of perospirone from prior antipsychotic medication was associated with a significant improvement in indices of verbal memory organization of the Auditory Verbal Learning Test. Negative symptoms and extrapyramidal side effects were also ameliorated after switching to perospirone. The distinct cognitive enhancement profile of perospirone may be attributable to its partial 5-HT1A agonist action.

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Confirmation of a relationship between reduced auditory P300 amplitude and thought disorder in schizophrenia.

We have previously reported an association between reduced amplitude of auditory P300 event-related potential and severity of positive thought disorder as assessed by the Comprehensive Index of Positive Thought Disorder in a sample of patients with chronic schizophrenia. Here we replicate those findings using a different measure, Thought Disorder Index (TDI), in a new larger sample of 55 patients. The auditory P300 amplitude showed a significant negative correlation with scores on TDI. This correlation was relatively more pronounced in the left temporal region than in the right temporal region. These results further suggest that electrophysiological abnormalities of information processing may underlie positive thought disorder in schizophrenia.

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Delayed automatic detection of change in speech sounds in adults with autism: a magnetoencephalographic study.

OBJECTIVE: Autism is a form of pervasive developmental disorder in which dysfunction in interpersonal relationships and communication is fundamental. This study evaluated neurophysiological abnormalities at the basic level of language processing, i.e. automatic change detection of speech and non-speech sounds, using magnetoencephalographic recording of mismatch response elicited by change in vowels and tones. METHODS: The auditory magnetic mismatch field (MMF) was evaluated in 9 adults with autism and 19 control subjects using whole-head magnetoencephalography. The MMF in response to the duration change of a pure tone or vowel /a/ and that in response to across-phoneme change between vowels /a/ and /o/, were recorded. RESULTS: The groups were not significantly different in MMF power under any conditions. However, the autism group showed a left-biased latency prolongation of the MMF particularly under the across-phoneme change condition, and this latency delay was significantly associated with greater symptom severity. CONCLUSIONS: These results suggest that adults with autism are associated with delayed processing for automatic change detection of speech sounds. These electrophysiological abnormalities at the earliest level of information processing may contribute to the basis for language deficits observed in autism. SIGNIFICANCE: These results provide the first evidence for delayed latency of phonetic MMF in adults with autism.

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Electrophysiological indices associated with social functioning outcome in schizophrenia: a 5-year follow-up study.

We previously demonstrated that event-related potentials (ERPs), such as N1/N2b amplitudes in an auditory selective attention task, were significantly associated with communication skills of schizophrenia. The present study investigated the relationship between N1/N2b amplitudes and the quality of life (QOL) 5 years after ERP measurement. QOL of 15 patients with schizophrenia was assessed using the quality of life scale (QLS). Correlational analyses revealed a significant relationship between N2b, but not N1, amplitude and specific domains of QOL. N2b amplitude, an electrophysiological index of orienting response, may be associated with longitudinal social functioning outcome in schizophrenia.

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Association between lower P300 amplitude and smaller anterior cingulate cortex volume in patients with posttraumatic stress disorder: a study of victims of Tokyo subway sarin attack.

Previous investigations of auditory P300 event-related potentials have provided electrophysiological evidence for attentional problems in patients with posttraumatic stress disorder (PTSD). The present study sought to evaluate the relationship between P300 deficits and underlying brain morphological abnormalities in never-treated, comorbidity-free patients with PTSD following the Tokyo subway sarin attack. Out of 47 victims recruited, 8 victims with PTSD and 13 victims without PTSD were identified. Correlational analyses were performed between auditory P300 amplitude at Pz electrode site elicited in an oddball task and anterior cingulate gray matter volume that was shown to be reduced in our previous study using voxel-based morphometry on magnetic resonance imaging. Victims with PTSD showed significantly lower amplitudes of P300 compared with victims without PTSD, and the lower P300 amplitudes at Pz were significantly associated with higher avoidance/numbing scores in the PTSD group. Furthermore, in the PTSD group only, the P300 amplitudes showed a trend toward significant positive correlation with voxel densities of the anterior cingulate cortex gray matter. These results provide the first evidence that electrophysiological deficits of controlled attention observed in patients with PTSD may be linked to underlying brain morphological abnormalities.

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Brain electric activity for active inhibition of auditory irrelevant information.

We applied high resolution event-related potentials (ERPs) to assess brain activities associated with inhibition of irrelevant information processing during auditory selective attention. Ten healthy subjects performed an auditory selective attention task. ERPs in response to standard stimuli delivered to the unattended ear (irrelevant stimuli) and those delivered to the attended ear (relevant stimuli) were evaluated using temporally sequential scalp current density (SCD) mappings. For the irrelevant stimuli, current sources were located in the mid-frontal regions at 140-220 ms post-stimuli, and these SCD values were significantly larger than those for the relevant stimuli. These results suggest that auditory selective attention process involves not only focusing attention on relevant information, but also inhibitory processing of irrelevant information mediated by the frontal cortex.

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Localized volume reduction in prefrontal, temporolimbic, and paralimbic regions in schizophrenia: an MRI parcellation study.

Functional and structural abnormalities of the anterior cingulate gyrus (ACG) in patients with schizophrenia have been repeatedly reported. However, one remaining issue is whether gray matter volume reduction in ACG exists to an extent comparable with, or even in excess of, that in other prefrontal and temporolimbic regions. High-spatial-resolution magnetic resonance imaging was performed on patients with schizophrenia (n=27) and on age-, gender-, and parental socioeconomic-status-matched healthy control subjects (n=27). After the gray and white matter were semiautomatically segmented, whole prefrontal and temporal lobes were manually parceled into 15 subregions-by-two hemispheres (30 regions of interest) constituting seven prefrontal gray matter regions, six temporal gray matter regions, the prefrontal white matter, and the temporal white matter. Compared with healthy subjects, schizophrenic patients showed significant gray matter volume reduction in the bilateral ACG, this being the largest effect size (left, 0.84; right, 0.56) among all the regions examined. There were also significant gray matter volume reductions in the bilateral posterior STG, bilateral inferior frontal gyrus, left posterior amygdala-hippocampal complex (mostly hippocampus), and the left insula. These results suggest that gray matter volume reductions in the ACG are prominent among prefrontal and temporolimbic regions in patients with schizophrenia. These findings indicate the importance of ACG abnormalities in the pathophysiology of schizophrenia.

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Spatial attention in individuals with pervasive developmental disorders using the gap overlap task.

The present study examined spatial attention in individuals with pervasive developmental disorders (PDD) using the gap overlap task and analyzed the express saccade, which is defined by its extremely short reaction time, as a measure of the state of attention. Participants were required to move their eyes to the target stimulus appearing on the left or right side of a fixation point. In this task, participants had to disengage their attention from the central fixation point and shift it to the peripheral target stimulus. In the gap condition, the fixation point disappeared 200 ms before the target stimulus was presented, and in the overlap condition, the fixation point remained while the target stimulus was presented. Saccade latencies were not different between the groups. However, the express saccade was more frequent in the PDD group than in the normal group in the overlap condition. We conclude that individuals with PDD have deficiencies in attentional engagement. Moreover, our study suggests that analysis of the express saccade will be useful in further examinations of attentional processes in PDD.

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Effects of corollary discharge on event-related potentials during selective attention task in healthy men and women.

Corollary discharge is a brain electrical activity associated with self-monitoring, which distinguishes self from others in thoughts or behaviors. Corollary discharge can be non-invasively assessed using event-related potential (ERP) recordings in humans. Previous studies have revealed that the amplitude of the N100 component elicited during an "odd-ball" task is reduced while a healthy subject is vocalizing, which may index the effect of corollary discharge on auditory ERPs. In this study, we attempted to assess the effect of vocalization on ERP components including N100, mismatch negativity (MMN), negative difference wave (Nd), and P300 during a selective attention task in 22 healthy adults. We also evaluated the possible contribution of gender to these effects. N100 amplitudes elicited by unattended standard stimuli were reduced under the vocalization condition compared with those under the baseline condition. However, there were no significant effects of vocalization on MMN, Nd or P300. Moreover, there was no significant effect of gender to the corollary discharge. These results suggest that the effect of corollary discharge on auditory ERPs is limited to the perceptual stage of information processing in healthy men and women.

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Executive and prefrontal dysfunction in unipolar depression: a review of neuropsychological and imaging evidence.

This paper reviews recent empirical findings related to prefrontal and executive function in unipolar depression. While a number of reviews have dealt with either the neuropsychological literature or findings from imaging studies, the present review addresses both, as well as findings from studies that have combined brain-imaging techniques with neuropsychological measures. This combined approach is of great interest as the performance of a structured task may act to load the areas of interest and reduce variance, thus making the imaging evidence more valuable; while the use of imaging provides a check that the neuropsychological tasks are indeed engaging the structures whose performance they are intended to assess. Prominent models of the neurobiology of depression implicate involvement of the anterior cingulate cortex (ACC) and the dorsolateral prefrontal cortex (DLPFC). The evidence from combined imaging and neuropsychological studies supports the involvement of the ACC, but is less clear in the case of the DLPFC. However, the limited number of such studies conducted to date means that conclusions must be tentative and further studies employing this combined approach may be of great value.

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Abnormal association between reduced magnetic mismatch field to speech sounds and smaller left planum temporale volume in schizophrenia.

Schizophrenia is associated with language-related dysfunction. A previous study [Schizophr. Res. 59 (2003c) 159] has shown that this abnormality is present at the level of automatic discrimination of change in speech sounds, as revealed by magnetoencephalographic recording of auditory mismatch field in response to across-category change in vowels. Here, we investigated the neuroanatomical substrate for this physiological abnormality. Thirteen patients with schizophrenia and 19 matched control subjects were examined using magnetoencephalography (MEG) and high-resolution magnetic resonance imaging (MRI) to evaluate both mismatch field strengths in response to change between vowel /a/ and /o/, and gray matter volumes of Heschl's gyrus (HG) and planum temporale (PT). The magnetic global field power of mismatch response to change in phonemes showed a bilateral reduction in patients with schizophrenia. The gray matter volume of left planum temporale, but not right planum temporale or bilateral Heschl's gyrus, was significantly smaller in patients with schizophrenia compared with that in control subjects. Furthermore, the phonetic mismatch strength in the left hemisphere was significantly correlated with left planum temporale gray matter volume in patients with schizophrenia only. These results suggest that structural abnormalities of the planum temporale may underlie the functional abnormalities of fundamental language-related processing in schizophrenia.

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Post-traumatic stress disorder symptoms in victims of Tokyo subway attack: a 5-year follow-up study.

Sarin gas was dispersed in a Tokyo subway in 1995. This study investigates the mental and somatic symptoms of the 34 victims 5 years after the attack. Structured interviews (Clinician-Administered Post-Traumatic Stress Disorder [CAPS] and Mini International Neuropsychiatric Interview) and self-rating questionnaires were used to assess the symptoms. Not only post-traumatic stress disorder (PTSD) but also non-specific mental symptoms persisted in the victims at a high rate. A total of 11 victims were diagnosed with current or lifetime PTSD according to CAPS. Victims with PTSD showed higher anxiety levels and more visual memory impairment. A significant correlation between the total score of Impact of Event Scale-Revised (IES-R) and CAPS was found, indicating that IES-R is a useful tool for evaluating PTSD.

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