Kuniaki Kiuchi

Demyelination in the juvenile period, but not in adulthood, leads to long-lasting cognitive impairment and deficient social interaction in mice.

BACKGROUND Dysmyelination is hypothesized to be one of the causes of schizophrenic symptoms. Supporting this hypothesis, demyelination induced by cuprizone was recently shown to cause schizophrenia-like symptoms in adult rodents [Xiao L, Xu H, Zhang Y, Wei Z, He J, Jiang W, et al. Quetiapine facilitates oligodendrocyte development and prevents mice from myelin breakdown and behavioral changes. Mol Psychiatry 2008;13:697-708]. The present study asked if the timing of demyelination (i.e., juvenile period or adulthood) influenced abnormal behavior. METHODS B57BL/6 mice were fed with 0.2% cuprizone either from postnatal day 29 (P29) to P56 (early demyelination group) or from P57 to P84 (late demyelination group), and then returned to normal mouse chow until P126, when the behavioral analysis was initiated. RESULTS In both groups, the intake of cuprizone for 28 days produced massive demyelination in the corpus callosum by the end of the treatment period, and subsequent normal feeding restored myelination by P126. In a Y-maze test, the spatial working memory was impaired in both groups right after the cuprizone feeding ceased, consistent with previous studies, whereas only the early demyelination group exhibited impaired working memory after remyelination took place. In an open field test, social interactions were decreased in the early demyelination group, but not in the late group. Novel cognition and anxiety-related behaviors were comparable between the two groups. CONCLUSIONS Our findings suggest that the timing of demyelination has substantial impacts on behaviors of adult mice.

Fractional anisotropy--threshold dependence in tract-based diffusion tensor analysis: evaluation of the uncinate fasciculus in Alzheimer disease.

BACKGROUND AND PURPOSE: Tract-based analysis can be used to investigate required tracts extracted from other fiber tracts. However, the fractional anisotropy (FA) threshold influences tractography analysis. The current study evaluated the influence of the FA threshold in measuring diffusion tensor parameters for tract-based analysis of the uncinate fasciculus in subjects with Alzheimer disease (AD). MATERIALS AND METHODS: Subjects included 30 patients with AD and 10 healthy controls. We acquired tractographies of the uncinate fasciculus by using different FA thresholds. We measured mean FA and the apparent diffusion coefficient (ADC) along the uncinate fasciculus for different FA thresholds and evaluated the correlation between diffusion tensor parameters (FA, ADC) and the Mini-Mental State Examination (MMSE) scores. RESULTS: The uncinate fasciculus showed lower mean FA and higher mean ADC values in cases with more severe AD. A higher FA threshold led to a lower mean ADC value and a higher mean FA value along the uncinate fasciculus, whereas the relative order of measured values according to the severity of AD was not influenced by the FA threshold. An FA threshold of 0.2 showed higher correlation between mean ADC values and MMSE scores. FA thresholds of 0.15 and 0.20 showed higher correlation between mean FA values and MMSE scores. CONCLUSIONS: Appropriate selection of the FA threshold leads to higher correlation between diffusion tensor parameters and the severity of AD. For tract-based analysis of degenerative diseases such as AD, appropriate selection of the FA threshold for tractography is important.

Association between depressive symptoms and metabolic syndrome in Japanese community‐dwelling older people: a cross‐sectional analysis from the baseline results of the Fujiwara‐kyo prospective cohort study

Metabolic syndrome contains many risks for medical diseases such as cardiovascular disease and diabetes, which might precipitate depressive symptoms in the older people. However, the association between depressive symptoms and metabolic syndrome in Japanese community‐dwelling older people is unclear. This study was performed to answer this important question.

Uncinate fasciculus‐correlated cognition in Alzheimer's disease: a diffusion tensor imaging study by tractography

Background:  Neuroimaging studies show increased diffusivity and decreased anisotropy in Alzheimers disease (AD) patients by diffusion tensor imaging (DTI). Previous reports have analyzed a correlation with cognitive function and DTI parameters, but their results are inconsistent. A reason for this might be a region of interest (ROI) method, used to calculate parameters for DTI, because this method has various usages of how to place a ROI and includes summations of values for various neuronal fiber tracts, resulting in contamination of unintended fibers. To improve the instability with ROI placement, a tractography‐based method might be useful. Our coworker reported decreased fractional anisotropy (FA) and increased apparent diffusion coefficient (ADC) of uncinate fasciculus (UF) in patients with AD by tractography. To confirm whether DTI parameter values are related to severity of cognitive function in patients with AD, we measured mean diffusion anisotropy and diffusivity of coregistered voxels along the tracking lines (i.e. tract of interest) of UF.

Longitudinal white matter changes in Alzheimer's disease: a tractography-based analysis study.

Alzheimers disease (AD) classically presents with gray matter atrophy, as well as feature significant white matter abnormalities. Previous evidence indicates the overall burden of these pathological changes continues to advance as the disease progresses. The aim of this study was to investigate whether pathological alterations of white matter tracts correlate with the course of AD disease progression. 35 AD patients and 29 normal controls were recruited to the study and administered baseline magnetic resonance diffusion tensor imaging (DTI) acquisition and a cognitive function assessment at the time of initial evaluation. Subjects were re-evaluated with secondary DTI scan and cognitive function assessment at intervals of about 1.5 years on average. For the DTI acquired scans, we calculated diffusion tensor parameters, fractional anisotropy (FA), apparent diffusion coefficient (ADC), radial diffusivity (DR), and axial diffusivity (DA) along with the uncinate fasciculus (UNC), the inferior longitudinal fasciculus (ILF), and the inferior occipitofrontal fasciculus (IOFF). Compared to baseline, a significant mean FA reduction of the bilateral UNC, as well as a significant mean DR increase of the left UNC, was evident in AD patients at follow-up. Compared with normal controls, AD patients exhibited significant diffusion parameter abnormalities in their UNC, ILF, and IOFF. Taken together, these results indicate that progressive pathological white matter alterations can be quantified using the DTI parameters utilized here and may prove to be a useful biological marker for monitoring the pathophysiological course of AD.

Delayed atrophy in posterior cingulate cortex and apathy after stroke

A few studies have been performed on chronic structural changes after stroke. The primary purpose of the present study was to investigate regional cortical volume changes after the onset of stroke and to examine how the cortical volume changes affected neuropsychiatric symptoms.

Decision-making deficit of a patient with axonal damage after traumatic brain injury

Patients with traumatic brain injury (TBI) were reported to have difficulty making advantageous decisions, but the underlying deficits of the network of brain areas involved in this process were not directly examined. We report a patient with TBI who demonstrated problematic behavior in situations of risk and complexity after cerebral injury from a traffic accident. The Iowa gambling task (IGT) was used to reveal his deficits in the decision-making process. To examine underlying deficits of the network of brain areas, we examined T1-weighted structural MRI, diffusion tensor imaging (DTI) and Tc-ECD SPECT in this patient. The patient showed abnormality in IGT. DTI-MRI results showed a significant decrease in fractional anisotropy (FA) in the fasciculus between the brain stem and cortical regions via the thalamus. He showed significant decrease in gray matter volumes in the bilateral insular cortex, hypothalamus, and posterior cingulate cortex, possibly reflecting Wallerian degeneration secondary to the fasciculus abnormalities. SPECT showed significant blood flow decrease in the broad cortical areas including the ventromedial prefrontal cortex (VM). Our study showed that the patient had dysfunctional decision-making process. Microstructural abnormality in the fasciculus, likely from the traffic accident, caused reduced afferent feedback to the brain, resulting in less efficient decision-making. Our findings support the somatic-marker hypothesis (SMH), where somatic feedback to the brain influences the decision-making process.

Gray and White Matter Changes in Subjective Cognitive Impairment, Amnestic Mild Cognitive Impairment and Alzheimer's Disease: A Voxel-Based Analysis Study

Subjective cognitive impairment may be a very early at-risk period of the continuum of dementia. However, it is difficult to discriminate at-risk states from normal aging. Thus, detection of the early pathological changes in the subjective cognitive impairment period is needed. To elucidate these changes, we employed diffusion tensor imaging and volumetry analysis, and compared subjective cognitive impairment with normal, mild cognitive impairment and Alzheimers disease. The subjects in this study were 39 Alzheimers disease, 43 mild cognitive impairment, 28 subjective cognitive impairment and 41 normal controls. There were no statistically significant differences between the normal control and subjective cognitive impairment groups in all measures. Alzheimers disease and mild cognitive impairment had the same extent of brain atrophy and diffusion changes. These results are consistent with the hypothetical model of the dynamic biomarkers of Alzheimers disease.

Asymmetry, sex differences and age-related changes in the white matter in the healthy elderly: a tract-based study

BackgroundHemispherical asymmetry, sex differences and age-related changes have been reported for the human brain. Meanwhile it was still unclear the presence of the asymmetry or sex differences in the human brain occurred whether as a normal development or as consequences of any pathological changes. The aim of this study was to investigate hemispherical asymmetry, sex differences and age-related changes by using a tract-based analysis in the nerve bundles.Methods40 healthy elderly subjects underwent magnetic resonance diffusion tensor imaging, and we calculated fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values along the major white matter bundles.ResultsWe identified hemispherical asymmetry in the ADC values for the cingulate fasciculus in the total subject set and in males, and a sex difference in the FA values for the right uncinate fasciculus. For age-related changes, we demonstrated a significant increase in ADC values with advancing age in the right cingulum, left temporal white matter, and a significant decrease in FA values in the right superior longitudinal fasciculus.ConclusionIn this study, we found hemispherical asymmetry, sex differences and age-related changes in particular regions of the white matter in the healthy elderly. Our results suggest considering these differences can be important in imaging studies.

Brain structural changes and neuropsychological impairments in male polydipsic schizophrenia

BackgroundPolydipsia frequently occurs in schizophrenia patients. The excessive water loading in polydipsia occasionally induces a hyponatremic state and leads to water intoxication. Whether polydipsia in schizophrenic patients correlates with neuropsychological impairments or structural brain changes is not clear and remains controversial.MethodsEight polydipsic schizophrenia patients, eight nonpolydipsic schizophrenia patients, and eight healthy controls were recruited. All subjects underwent magnetic resonance imaging (MRI) and neuropsychological testing. Structural abnormalities were analyzed using a voxel-based morphometry (VBM) approach, and patients’ neuropsychological function was assessed using the Brief Assessment of Cognition in Schizophrenia, Japanese version (BACS-J).ResultsNo significant differences were found between the two patient groups with respect to the clinical characteristics. Compared with healthy controls, polydipsic patients showed widespread brain volume reduction and neuropsychological impairment. Furthermore, the left insula was significantly reduced in polydipsic patients compared with nonpolydipsic patients. These nonpolydipsic patients performed intermediate to the other two groups in the neuropsychological function test.ConclusionsIt is possible that polydipsia or the secondary hyponatremia might induce left insula volume reduction. Furthermore, this structural brain change may indirectly induce more severe neuropsychological impairments in polydipsic patients. Thus, we suggest that insula abnormalities might contribute to the pathophysiology of polydipsic patients.