Regional gray matter density associated with emotional intelligence: Evidence from voxel‐based morphometry

Emotional Intelligence (EI) is the ability to monitor one's own and others' emotions and the ability to use the gathered information to guide one's thinking and action. EI is thought to be important for social life making it a popular subject of research. However, despite the existence of previous functional imaging studies on EI, the relationship between regional gray matter morphology and EI has never been investigated. We used voxel‐based morphometry (VBM) and a questionnaire (Emotional Intelligence Scale) to measure EI to identify the gray matter correlates of each factor of individual EI (Intrapersonal factor, Interpersonal factor, Situation Management factor). We found significant negative relationships between the Intrapersonal factor and regional gray matter density (rGMD) (1‐a) in an anatomical cluster that included the right anterior insula, (1‐b) in the right cerebellum, (1‐c) in an anatomical cluster that extends from the cuneus to the precuneus, (1‐d) and in an anatomical cluster that extends from the medial prefrontal cortex to the left lateral fronto‐polar cortex. We also found significant positive correlations between the Interpersonal factor and rGMD in the right superior temporal sulcus, and significant negative correlations between the Situation Management factor and rGMD in the ventromedial prefrontal cortex. These findings suggest that each factor of EI in healthy young people is related to the specific brain regions known to be involved in the networks of social cognition and self‐related recognition, and in the somatic marker circuitry. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.     

Coexistence of TDP‐43 and tau pathology in neurodegeneration with brain iron accumulation type 1 (NBIA‐1, formerly Hallervorden‐Spatz syndrome)

We report here an autopsy case of sporadic adult‐onset Hallervorden‐Spatz syndrome, also known as neurodegeneration with brain iron accumulation type 1 (NBIA1), without hereditary burden. A 49‐year‐old woman died after a 27‐year disease course. At the age of 22, she suffered from akinesia, resting tremor, and rigidity. At the age of 28, she was admitted to our hospital because of worsening parkinsonism and dementia. Within several years, she developed akinetic mutism. At the age of 49, she died of bleeding from a tracheostomy. Autopsy revealed a severely atrophic brain weighing 460 g. Histologically, there were iron deposits in the globus pallidus and substantia nigra pars reticulata, and numerous axonal spheroids in the subthalamic nuclei. Neurofibrillary tangles were abundant in the hippocampus, cerebral neocortex, basal ganglia, and brain stem. Neuritic plaques and amyloid deposits were absent. Lewy bodies and Lewy neurites, which are immunolabeled by anti‐α‐synuclein, were absent. We also observed the presence of TDP‐43‐positive neuronal perinuclear cytoplasmic inclusions, with variable frequency in the dentate gyrus granular cells, frontal and temporal cortices, and basal ganglia. TDP‐43‐positive glial cytoplasmic inclusions were also found with variable frequency in the frontal and temporal lobes and basal ganglia. The present case was diagnosed with adult‐onset NBIA‐1 with typical histological findings in the basal ganglia and brainstem. However, in this case, tau and TDP‐43 pathology was exceedingly more abundant than α‐synuclein pathology. This case contributes to the increasing evidence for the heterogeneity of NBIA‐1.     

Nicotinic receptor stimulation protects nigral dopaminergic neurons in rotenone-induced Parkinson's disease models

Parkinson's disease (PD) is the second most common neurodegenerative disease and is characterized by dopaminergic (DA) neuronal cell loss in the substantia nigra. Although the entire pathogenesis of PD is still unclear, both environmental and genetic factors contribute to neurodegeneration. Epidemiologic studies show that prevalence of PD is lower in smokers than in nonsmokers. Nicotine, a releaser of dopamine from DA neurons, is one of the candidates of antiparkinson agents in tobacco. To assess the protective effect of nicotine against rotenone-induced DA neuronal cell toxicity, we examined the neuroprotective effects of nicotine in rotenone-induced PD models in vivo and in vitro. We observed that simultaneous subcutaneous administration of nicotine inhibited both motor deficits and DA neuronal cell loss in the substantia nigra of rotenone-treated mice. Next, we analyzed the molecular mechanisms of DA neuroprotective effect of nicotine against rotenone-induced toxicity with primary DA neuronal culture. We found that DA neuroprotective effects of nicotine were inhibited by dihydro-beta-erythroidine (DHbetaE), alpha-bungarotoxin (alphaBuTx), and/or PI3K-Akt/PKB (protein serine/threonine kinase B) inhibitors, demonstrating that rotenone-toxicity on DA neurons are inhibited via activation of alpha4beta2 or alpha7 nAChRs-PI3K-Akt/PKB pathway or pathways. These results suggest that the rotenone mouse model may be useful for assessing candidate antiparkinson agents, and that nAChR (nicotinic acetylcholine receptor) stimulation can protect DA neurons against degeneration.     

Effect of yokukansan on the behavioral and psychological symptoms of dementia in elderly patients with Alzheimer's disease

Objective

The aim of this study was to investigate the effects of yokukansan (YKS) on the behavioral and psychological symptoms of dementia (BPSD) in elderly patients with Alzheimer's disease (AD).

Methods

Fifteen patients with AD (mean age: 80.2 ± 4.0 years) participated in the study. The Mini-Mental State Examination (MMSE) was used for the assessment of cognitive function. BPSD were evaluated using the Neuropsychiatric Inventory (NPI). The Barthel Index was used for the assessment for the activities of daily living (ADL). The treatment with YKS along with sulpiride, a dopamine D₂ selective antipsychotic, was performed for 12 weeks.

Results

Fourteen patients completed the trial. After the 12 weeks of treatment with YKS, significant improvement of the mean NPI score was observed while no significant improvement was observed in the control group. The average dose of sulpiride at the end of the present study was less in the YKS group than in the control group. The MMSE results did not change either in the YKS group or in the control group. The Barthel Index did not significantly change either in the YKS group or in the control group. No serious adverse effects were noted.

Conclusions

Twelve weeks of the YKS treatment significantly improved BPSD with less antipsychotics in elderly patients with AD. The YKS treatment did not cause any cognitive decline or ADL decline and no serious adverse effects were noted. The present study suggests that YKS is beneficial for the treatment of BPSD and that it can possibly reduce the doses of antipsychotics required for the treatment of BPSD. Further studies with larger patient populations using a double-blind placebo-controlled design should be performed.     

Histological changes in monoaminergic neurons of Long–Evans Cinnamon rats

The Long–Evans Cinnamon rat, an animal model of Wilson’s disease, is an inbred mutant strain with spontaneous hepatitis isolated from Long–Evans rats. The copper concentration in the brains of Long–Evans Cinnamon rats at 4 weeks of age was lower than that of controls, but higher than that of controls at 20 weeks of age. We investigated the tyrosine hydroxylase and 5-hydroxytryptamine immunoreactive fiber densities in the brains of Long–Evans Cinnamon rats aged 4, 10, and 20 weeks by immunohistochemistry, comparing them with Long–Evans Agouti rats used as controls. Tyrosine hydroxylase immunoreactive fiber densities in the cingulate cortex, hippocampus and cerebellum in Long–Evans Cinnamon rats were significantly lower than those of Long–Evans Agouti rats at 4 and 10 weeks of age. On the other hand, 5-hydroxytryptamine immunoreactive fiber densities in the cingulate cortex, caudate-putamen, hypothalamus, and hippocampus in Long–Evans Cinnamon rats were significantly higher than those of controls at 4, 10 and 20 weeks of age. In the cingulate cortex and caudate-putamen, 5-hydroxytryptamine immunoreactive fiber densities became gradually higher with age. The number of aberrant 5-hydroxytryptamine immunoreactive fibers in the cingulate cortex, caudate-putamen, hypothalamus and hippocampus in LEC rats was significantly higher than that of controls. The number of another type of aberrant 5-hydroxytryptamine immunoreactive fibers, which were detected only at 20 weeks of age in the caudate-putamen in LEC rats was significantly higher than that of controls. These results suggest that age-dependent changes in copper concentrations of Long–Evans Cinnamon rats were related to changes in monoaminergic neuron systems.     

Creative females have larger white matter structures: Evidence from a large sample study

The importance of brain connectivity for creativity has been theoretically suggested and empirically demonstrated. Studies have shown sex differences in creativity measured by divergent thinking (CMDT) as well as sex differences in the structural correlates of CMDT. However, the relationships between regional white matter volume (rWMV) and CMDT and associated sex differences have never been directly investigated. In addition, structural studies have shown poor replicability and inaccuracy of multiple comparisons over the whole brain. To address these issues, we used the data from a large sample of healthy young adults (776 males and 560 females; mean age: 20.8 years, SD = 0.8). We investigated the relationship between CMDT and WMV using the newest version of voxel‐based morphometry (VBM). We corrected for multiple comparisons over whole brain using the permutation‐based method, which is known to be quite accurate and robust. Significant positive correlations between rWMV and CMDT scores were observed in widespread areas below the neocortex specifically in females. These associations with CMDT were not observed in analyses of fractional anisotropy using diffusion tensor imaging. Using rigorous methods, our findings further supported the importance of brain connectivity for creativity as well as its female‐specific association. Hum Brain Mapp 38:414–430, 2017. © 2016 Wiley Periodicals, Inc.     

Insular primary glioblastomas with IDH mutations: Clinical and biological specificities

Isocitrate dehydrogenase (IDH) mutation is a good prognostic marker for glioblastoma (GBM). Although it is infrequent in primary tumors, it is found in most lower‐grade gliomas. Thus, it is unclear whether IDH mutation is a marker for a specific phenotype of apparently primary de novo GBMs (pGBMs), or a marker for secondary tumors (sGBMs). We addressed this issue by analyzing clinical, radiographic and molecular findings in our institutional case series. Our cases included 92 pGBMs, with five cases of IDH1 mutations at R132 and no IDH2 mutations. The median overall survival of these five patients was 29 months (range: 4 to >40 months), which is considered good prognoses. Clinical and radiographic characteristics were distinct from IDH‐wildtype (IDH‐wt) pGBMs. IDH‐mutant (IDH‐mut) tumors consistently involved insular lesions and were subdivided into: (i) the two cases of elderly patients with long clinical histories and features implying multistep tumor development; and (ii) the three cases of younger patients with diffusely swelling insular tumors, slight contrast enhancement and no necrosis. Genetic and expression analyses of IDH‐mut pGBMs were similar to those of sGBMs, suggesting that they are indeed distinct from their IDH‐wt counterparts. TERT promoter mutation, a genetic marker of oligodendroglial derivation, was detected in one long‐surviving case, but genetic alterations in the astrocyte‐sGBM pathway were generally prevalent in IDH‐mut pGBMs. Our results present a unique phenotype of IDH‐mut pGBMs arising from insular cortex region, the molecular backgrounds of which are similar to sGBMs.     

Abnormalities in perineuronal nets and behavior in mice lacking CSGalNAcT1, a key enzyme in chondroitin sulfate synthesis

Chondroitin sulfate (CS) is an important glycosaminoglycan and is mainly found in the extracellular matrix as CS proteoglycans. In the brain, CS proteoglycans are highly concentrated in perineuronal nets (PNNs), which surround synapses and modulate their functions. To investigate the importance of CS, we produced and precisely examined mice that were deficient in the CS synthesizing enzyme, CSGalNAcT1 (T1KO). Biochemical analysis of T1KO revealed that loss of this enzyme reduced the amount of CS by approximately 50% in various brain regions. The amount of CS in PNNs was also diminished in T1KO compared to wild-type mice, although the amount of a major CS proteoglycan core protein, aggrecan, was not changed. In T1KO, we observed abnormalities in several behavioral tests, including the open-field test, acoustic startle response, and social preference. These results suggest that T1 is important for plasticity, probably due to regulation of CS-dependent PNNs, and that T1KO is a good model for investigation of PNNs.     

p38 mitogen-activated protein kinase inhibitor reduces neurocan production in cultured spinal cord astrocytes

Chondroitin sulfate proteoglycans are formed in scar tissue after a spinal cord injury and inhibit axon regrowth. The production of neurocan, one of these chondroitin sulfate proteoglycans, in cultured spinal cord astrocytes increased after the addition of epidermal growth factor (EGF) in a dose-dependent manner (2-200 ng/ml). In astrocytes stimulated by 20 ng/ml of EGF, neurocan production was inhibited after the addition of the p38 mitogen-activated protein kinase (MAPK) inhibitor (SB203580: 3-10 μM) in a dose-dependent manner. These results suggest that the activation of p38 MAPK is one of the mechanisms of neurocan production in EGF-stimulated astrocytes. The p38 MAPK inhibitor may reduce neurocan production and accelerate axonal regrowth after a spinal cord injury.