Cognitive impairments associated with morphological changes in cortical and subcortical structures in multiple system atrophy of the cerebellar type.

BACKGROUND AND PURPOSE: Patients with the cerebellar variant of multiple system atrophy (MSA-C) often show cognitive deficits in various cognitive domains. The association between morphometric changes in cortical and subcortical structures and cognitive impairments in MSA-C were investigated to explore the neural correlates responsible for cognitive deficits in MSA-C patients. METHODS: Using surface-based morphometry, region-of-interest cortical thickness and the volumes and shapes of subcortical structures were examined in 18 patients who fulfilled the criteria of probable MSA-C and were compared to 50 healthy controls. The association between regional changes and cognitive functions in MSA-C were investigated by applying linear regression analyses after controlling for confounding factors. RESULTS: Compared with controls, the patients with MSA-C showed significant cortical thinning in the fronto-temporo-parietal regions and volume reduction in subcortical structures with shape changes. Cerebellar volume had no significant effect on cortical and subcortical volumes. The severity of atrophic changes in the bilateral thalamus, the left cerebellum and the left pericalcarine gyrus were significantly correlated with attentional, executive and visuospatial dysfunctions. CONCLUSION: Cognitive impairment in MSA-C might result from functional disruption of the corticostriatal and pontocerebellar circuit mediated by primary cortical, cerebellar or thalamic pathology.

Williams syndrome: a relationship between genetics, brain morphology and behaviour.

BACKGROUND: Genetically Williams syndrome (WS) promises to provide essential insight into the pathophysiology of cortical development because its ∼28 deleted genes are crucial for cortical neuronal migration and maturation. Phenotypically, WS is one of the most puzzling childhood neurodevelopmental disorders affecting most intellectual deficiencies (i.e. low-moderate intelligence quotient, visuospatial deficits) yet relatively preserving what is uniquely human (i.e. language and social-emotional cognition). Therefore, WS provides a privileged setting for investigating the relationship between genes, brain and the consequent complex human behaviour. METHODS: We used in vivo anatomical magnetic resonance imaging analysing cortical surface-based morphometry, (i.e. surface area, cortical volume, cortical thickness, gyrification index) and cortical complexity, which is of particular relevance to the WS genotype-phenotype relationship in 22 children (2.27-14.6 years) to compare whole hemisphere and lobar surface-based morphometry between WS (n = 10) and gender/age matched normal controls healthy controls (n = 12). RESULTS: Compared to healthy controls, WS children had a (1) relatively preserved Cth; (2) significantly reduced SA and CV; (3) significantly increased GI mostly in the parietal lobe; and (4) decreased CC specifically in the frontal and parietal lobes. CONCLUSION: Our findings are then discussed with reference to the Rakic radial-unit hypothesis of cortical development, arguing that WS gene deletions may spare Cth yet affecting the number of founder cells/columns/radial units, hence decreasing the SA and CV. In essence, cortical brain structure in WS may be shaped by gene-dosage abnormalities.

[200 - 400 m breaststroke event dominate among knee overuse injuries in elite swimming athletes]. / Die 200- bis 400 m-Brustlage dominiert bei Knieüberlastungsschäden im Schwimmsport.

HYPOTHESIS: We hypothesized that pool swimming has a low risk for acute injuries; however overuse injuries are predominant, depending on exposure time and swimming discipline. METHODS: 341 elite swimmers (19 +/- 11 years, BMI 20.3 +/- 3) were enrolled. Swimming was performed at mean since 10.1 +/- 8 years with 3.8 units every week during 43 weeks every year. RESULTS: The overall pool swimming injury rate was 0.39 / 1000 h. Overuse injuries (0.22 / 1000 h) were more frequent than acute injuries (0.17 / 1000 h). The upper extremity was involved more frequently (0.11 / 1000 h) than the trunk (0.067 / 1000 h) or the lower extremity (0.085 / 1000 h). Knee pain was predominant (0.17 / 1000 h) followed by shoulder overuse injuries (0.11 / 1000 h). Especially the 200 - 400 m breaststroke event had a fivefold higher risk for knee pain (relative risk, RR 5.1, p = 0.001). Freestyle had a reduced relative risk for knee pain (RR 0.5, p = 0.03), where shoulder overuse syndromes were predominant. Butterfly increased acute shoulder injury with RR 4.4 (p = 0.004), cervical spine injuries (RR 4.0, p = 0.03) and lower back pain (RR 2.5, p = 0.011). Swimming for more than four times a week had a higher risk for knee injuries (RR 2.1) and shoulder injuries (RR 4.0). We found that stretching was associated with a fivefold reduced risk for overuse knee injuries. CONCLUSION: Competitive swimming is a reasonable safe sport, where overuse injuries are predominant. 200 - 400 m breaststroke events increase the risk for knee overuse injuries more than other disciplines. Training for more than four times a week increases the risk twofold for knee and fourfold for shoulder overuse injuries.

Different Functional and Microstructural Changes Depending on Duration of Mild Cognitive Impairment in Parkinson Disease.

BACKGROUND AND PURPOSE: The higher cortical burden of Lewy body and Alzheimer disease-type pathology has been reported to be associated with a faster onset of cognitive impairment of Parkinson disease. So far, there has been a few studies only about the changes of gray matter volume depending on duration of cognitive impairment in Parkinson disease. Therefore, our aim was to evaluate the different patterns of structural and functional changes in Parkinson disease with mild cognitive impairment according to the duration of parkinsonism before mild cognitive impairment. MATERIALS AND METHODS: Fifty-nine patients with Parkinson disease with mild cognitive impairment were classified into 2 groups on the basis of shorter (<1 year, n = 16) and longer (≥1 year, n = 43) durations of parkinsonism before mild cognitive impairment. Fifteen drug-naïve patients with de novo Parkinson disease with intact cognition were included for comparison. Cortical thickness, Tract-Based Spatial Statistics, and seed-based resting-state functional connectivity analyses were performed. Age, sex, years of education, age at onset of parkinsonism, and levodopa-equivalent dose were included as covariates. RESULTS: The group with shorter duration of parkinsonism before mild cognitive impairment showed decreased fractional anisotropy and increased mean and radial diffusivity values in the frontal areas compared with the group with longer duration of parkinsonism before mild cognitive impairment (corrected P < .05). The group with shorter duration of parkinsonism before mild cognitive impairment showed decreased resting-state functional connectivity in the default mode network area when the left or right posterior cingulate was used as a seed, and in the dorsolateral prefrontal areas when the left or right caudate was used as a seed (corrected P < .05). The group with longer duration of parkinsonism before mild cognitive impairment showed decreased resting-state functional connectivity mainly in the medial prefrontal cortex when the left or right posterior cingulate was used as a seed, and in the parieto-occipital areas when the left or right caudate was used as a seed (corrected P < .05). No differences in cortical thickness were found in all group contrasts. CONCLUSIONS: Resting-state functional connectivity and WM alterations might be useful imaging biomarkers for identifying changes in patients with Parkinson disease with mild cognitive impairment according to the duration of parkinsonism before mild cognitive impairment. The functional and microstructural substrates may topographically differ depending on the rate of cognitive decline in these patients.

Prediction for human intelligence using morphometric characteristics of cortical surface: partial least square analysis.

A number of imaging studies have reported neuroanatomical correlates of human intelligence with various morphological characteristics of the cerebral cortex. However, it is not yet clear whether these morphological properties of the cerebral cortex account for human intelligence. We assumed that the complex structure of the cerebral cortex could be explained effectively considering cortical thickness, surface area, sulcal depth and absolute mean curvature together. In 78 young healthy adults (age range: 17-27, male/female: 39/39), we used the full-scale intelligence quotient (FSIQ) and the cortical measurements calculated in native space from each subject to determine how much combining various cortical measures explained human intelligence. Since each cortical measure is thought to be not independent but highly inter-related, we applied partial least square (PLS) regression, which is one of the most promising multivariate analysis approaches, to overcome multicollinearity among cortical measures. Our results showed that 30% of FSIQ was explained by the first latent variable extracted from PLS regression analysis. Although it is difficult to relate the first derived latent variable with specific anatomy, we found that cortical thickness measures had a substantial impact on the PLS model supporting the most significant factor accounting for FSIQ. Our results presented here strongly suggest that the new predictor combining different morphometric properties of complex cortical structure is well suited for predicting human intelligence.

Mapping genetic and environmental influences on cortical surface area of pediatric twins.

Cortical surface area has been largely overlooked in genetic studies of human brain morphometry, even though phylogenetic differences in cortical surface area between individuals are known to be influenced by differences in genetic endowment. In this study, we examined the relative contribution of genetic and environmental influences on cortical surface areas in both the native and stereotaxic spaces for a cohort of homogeneously-aged healthy pediatric twins. Bilateral hemispheric surface and all lobar surface areas except the occipital lobes in native space showed high heritable estimates, while the common environmental effect on bilateral occipital lobes reached statistical significance. The proportion of genetic variance for cortical surface areas measured in stereotaxic space was lower than that measured in native space, whereas the unique environmental influences increased. This is reasonable since whole brain volume is also known to be heritable itself and so removing that component of areal variance due to overall brain size via stereotaxic transformation will reduce the genetic proportion. These findings further suggest that cortical surface areas involved in cognitive, attention and emotional processing, as well as in creating and retaining of long-term memories are likely to be more useful for examining the relationship between genotype and behavioral phenotypes.

Increased temporolimbic cortical folding complexity in temporal lobe epilepsy.

OBJECTIVE: Converging evidence suggests that abnormalities of brain development may play a role in the pathogenesis of temporal lobe epilepsy (TLE). As sulco-gyral patterns are thought to be a footprint of cortical development, we set out to quantitatively map folding complexity across the neocortex in TLE. Additionally, we tested whether there was a relationship between cortical complexity and features of hippocampal maldevelopment, commonly referred to as malrotation. METHODS: To quantify folding complexity, we obtained whole-brain surface-based measures of absolute mean cortical curvature from MRI scans acquired in 43 drug-resistant patients with TLE with unilateral hippocampal atrophy, and 40 age- and sex-matched healthy controls. In patients, we correlated changes in cortical curvature with 3-dimensional measures of hippocampal positioning. RESULTS: We found increased folding complexity in the temporolimbic cortices encompassing parahippocampal, temporopolar, insular, and fronto-opercular regions. Increased complexity was observed ipsilateral to the seizure focus in patients with left TLE (LTLE), whereas these changes were bilateral in patients with right TLE (RTLE). In both TLE groups, increased temporolimbic complexity was associated with increased hippocampal malrotation. We found tendencies for increased complexity in bilateral posterior temporal cortices in LTLE and contralateral parahippocampal cortices in RTLE to be predictive of unfavorable seizure outcome after surgery. CONCLUSION: The anatomic distribution of increased cortical complexity overlapping with limbic seizure networks in TLE and its association with hippocampal maldevelopment further imply that neurodevelopmental factors may play a role in the epileptogenic process of TLE.

The synthetic potential of phthalimide SET photochemistry.

The authors' studies in the area of phthalimide photochemistry are discussed in the context of the development of new methods for N-heterocycle synthesis. Emphasis is given to reactions which are initiated by both intermolecular and intramolecular SET from silicon-containing electron donors to excited states of phthalimides and related maleimides and conjugated imides. The photoaddition and photocyclization processes which ensue follow mechanistic pathways, in which efficient desilylation of initially formed radical cation occurs to generate radical pair and biradical intermediates that serve as precursors of the products. Several examples that demonstrate the preparative potential of these reactions are presented. These are taken from the authors' investigations of (1) phthalimido-alkylsilane photocyclization reactions, (2) azomethine ylide-forming excited-state processes of N-(trimethylsilylmethyl)phthalimide, and (3) photoaddition and photocyclization reactions of phthalimide alpha-silyl ether, thioether, amine, and amide systems.

Coexpression of the myc gene family members in human neuroblastoma cell lines.

Members of the myc oncogene family such as c, N-, and L-myc are expressed in many malignant tumors. Expression of c-, N-, and L-myc oncogenes in 7 human neuroblastoma cell lines (GOTO, IMR-32, TGW, SCCH-26, TNB 9, NBL-S, and SK-N-SH), a human small cell lung carcinoma SBC-5 cell line, and a human monocytic leukemia THP-1-S cell line at mRNA and protein levels was studied to know the specificity of a newly developed antibody against homologous region at C-terminus of N-Myc, designated as anti pan-Myc antibody. By RT-PCR and immunoblot analysis, coexpression of three myc genes was detected in all neuroblastoma cell lines tested. c-and L-myc expression were observed that anti pan-Myc antibody recognizes c-Myc and N-Myc proteins but not L-Myc. These results indicate that neuroblastoma cells may acquire an aberrant transcriptional control system in myc family gene expression.

Adaptable fuzzy C-Means for improved classification as a preprocessing procedure of brain parcellation.

Parcellation, one of several brain analysis methods, is a procedure popular for subdividing the regions identified by segmentation into smaller topographically defined units. The fuzzy clustering algorithm is mainly used to preprocess parcellation into several segmentation methods, because it is very appropriate for the characteristics of magnetic resonance imaging (MRI), such as partial volume effect and intensity inhomogeneity. However, some gray matter, such as basal ganglia and thalamus, may be misclassified into the white matter class using the conventional fuzzy C-Means (FCM) algorithm. Parcellation has been nearly achieved through manual drawing, but it is a tedious and time-consuming process. We propose improved classification using successive fuzzy clustering and implementing the parcellation module with the modified graphic user interface (GUI) for the convenience of users.

Applications of phthalimide photochemistry to macrocyclic polyether, polythioether, and polyamide synthesis.

Irradiation of phthalimides which contain N-linked omega-trimethylsilylmethyl-substituted polyether, polythioether, and polysulfonamide chains results in efficient production of the corresponding macrocyclic polyether, polythioether, and polysulfonamide products. These photocyclization reactions follow sequential single electron transfer (SET)-desilylation pathways. Only in the cases of phthalimides, bearing mixed ether-thioether N-substituents, do these excited-state cyclization reactions proceed with lower degrees of regioselectivity. This is a result of competitive desilylation and alpha-to-sulfur deprotonation reactions of the zwitterionic diradical intermediates formed by initial SET.