The organization of frontostriatal brain wiring in non-affective early psychosis compared with healthy subjects using a novel diffusion imaging fiber cluster analysis.

BACKGROUND: Alterations in brain connectivity may underlie neuropsychiatric conditions such as schizophrenia. We here assessed the degree of convergence of frontostriatal fiber projections in 56 young adult healthy controls (HCs) and 108 matched Early Psychosis-Non-Affective patients (EP-NAs) using our novel fiber cluster analysis of whole brain diffusion magnetic resonance imaging tractography. METHODS: Using whole brain tractography and our fiber clustering methodology on harmonized diffusion magnetic resonance imaging data from the Human Connectome Project for Early Psychosis we identified 17 white matter fiber clusters that connect frontal cortex (FCtx) and caudate (Cd) per hemisphere in each group. To quantify the degree of convergence and, hence, topographical relationship of these fiber clusters, we measured the inter-cluster mean distances between the endpoints of the fiber clusters at the level of the FCtx and of the Cd, respectively. RESULTS: We found (1) in both groups, bilaterally, a non-linear relationship, yielding convex curves, between FCtx and Cd distances for FCtx-Cd connecting fiber clusters, driven by a cluster projecting from inferior frontal gyrus; however, in the right hemisphere, the convex curve was more flattened in EP-NAs; (2) that cluster pairs in the right (p = 0.03), but not left (p = 0.13), hemisphere were significantly more convergent in HCs vs EP-NAs; (3) in both groups, bilaterally, similar clusters projected significantly convergently to the Cd; and, (4) a significant group by fiber cluster pair interaction for 2 right hemisphere fiber clusters (numbers 5, 11; p = .00023; p = .00023) originating in selective PFC subregions. CONCLUSIONS: In both groups, we found the FCtx-Cd wiring pattern deviated from a strictly topographic relationship and that similar clusters projected significantly more convergently to the Cd. Interestingly, we also found a significantly more convergent pattern of connectivity in HCs in the right hemisphere and that 2 clusters from PFC subregions in the right hemisphere significantly differed in their pattern of connectivity between groups.

The Organization of Frontostriatal Brain Wiring in Healthy Subjects Using a Novel Diffusion Imaging Fiber Cluster Analysis.

To assess normal organization of frontostriatal brain wiring, we analyzed diffusion magnetic resonance imaging (dMRI) scans in 100 young adult healthy subjects (HSs). We identified fiber clusters intersecting the frontal cortex and caudate, a core component of associative striatum, and quantified their degree of deviation from a strictly topographic pattern. Using whole brain dMRI tractography and an automated tract parcellation clustering method, we extracted 17 white matter fiber clusters per hemisphere connecting the frontal cortex and caudate. In a novel approach to quantify the geometric relationship among clusters, we measured intercluster endpoint distances between corresponding cluster pairs in the frontal cortex and caudate. We show first, the overall frontal cortex wiring pattern of the caudate deviates from a strictly topographic organization due to significantly greater convergence in regionally specific clusters; second, these significantly convergent clusters originate in subregions of ventrolateral, dorsolateral, and orbitofrontal prefrontal cortex (PFC); and, third, a similar organization in both hemispheres. Using a novel tractography method, we find PFC-caudate brain wiring in HSs deviates from a strictly topographic organization due to a regionally specific pattern of cluster convergence. We conjecture cortical subregions projecting to the caudate with greater convergence subserve functions that benefit from greater circuit integration.

Lifespan Trajectories of White Matter Changes in Rhesus Monkeys.

Progress in neurodevelopmental brain research has been achieved through the use of animal models. Such models not only help understanding biological changes that govern brain development, maturation and aging, but are also essential for identifying possible mechanisms of neurodevelopmental and age-related chronic disorders, and to evaluate possible interventions with potential relevance to human disease. Genetic relationship of rhesus monkeys to humans makes those animals a great candidate for such models. With the typical lifespan of 25 years, they undergo cognitive maturation and aging that is similar to this observed in humans. Quantitative structural neuroimaging has been proposed as one of the candidate in vivo biomarkers for tracking white matter brain maturation and aging. While lifespan trajectories of white matter changes have been mapped in humans, such knowledge is not available for nonhuman primates. Here, we analyze and model lifespan trajectories of white matter microstructure using in vivo diffusion imaging in a sample of 44 rhesus monkeys. We report quantitative parameters (including slopes and peaks) of lifespan trajectories for 8 individual white matter tracts. We show different trajectories for cellular and extracellular microstructural imaging components that are associated with white matter maturation and aging, and discuss similarities and differences between those in humans and rhesus monkeys, the importance of our findings, and future directions for the field. Significance Statement: Quantitative structural neuroimaging has been proposed as one of the candidate in vivo biomarkers for tracking brain maturation and aging. While lifespan trajectories of structural white matter changes have been mapped in humans, such knowledge is not available for rhesus monkeys. We present here results of the analysis and modeling of the lifespan trajectories of white matter microstructure using in vivo diffusion imaging in a sample of 44 rhesus monkeys (age 4-27). We report and anatomically map lifespan changes related to cellular and extracellular microstructural components that are associated with white matter maturation and aging.

Greater extracellular free-water in first-episode psychosis predicts better neurocognitive functioning.

Free Water Imaging is a novel diffusion magnetic resonance (MR) imaging method that is able to separate changes affecting the extracellular space from those that reflect changes in neuronal cells and processes. A previous Free Water Imaging study in schizophrenia identified significantly greater extracellular water volume in the early stages of the disorder; however, its clinical and functional sequelae have not yet been investigated. Here, we applied Free Water Imaging to a larger cohort of 63 first-episode patients with psychosis and 70 healthy matched controls to better understand the functional significance of greater extracellular water. We used diffusion MR imaging data and the Tract-Based Spatial Statistics analytic pipeline to first analyze fractional anisotropy (FA), the most commonly employed metric for assessing white matter. This comparison was then followed by Free Water Imaging analysis, where two parameters, the fractional volume of extracellular free-water (FW) and cellular tissue FA (FA-t), were estimated and compared across the entire white matter skeleton between groups, and correlated with cognitive measures at baseline and following 12 weeks of antipsychotic treatment. Our results indicated lower FA across the whole brain in patients compared with healthy controls that overlap with significant increases in FW, with only limited decreases in FA-t. In addition, higher FW correlated with better neurocognitive functioning following 12 weeks of antipsychotic treatment. We believe this is the first study to suggest that an extracellular water increase during the first-episode of psychosis, which may be indicative of an acute neuroinflammatory process, and/or cerebral edema may predict better functional outcome.

Inter-site and inter-scanner diffusion MRI data harmonization.

We propose a novel method to harmonize diffusion MRI data acquired from multiple sites and scanners, which is imperative for joint analysis of the data to significantly increase sample size and statistical power of neuroimaging studies. Our method incorporates the following main novelties: i) we take into account the scanner-dependent spatial variability of the diffusion signal in different parts of the brain; ii) our method is independent of compartmental modeling of diffusion (e.g., tensor, and intra/extra cellular compartments) and the acquired signal itself is corrected for scanner related differences; and iii) inter-subject variability as measured by the coefficient of variation is maintained at each site. We represent the signal in a basis of spherical harmonics and compute several rotation invariant spherical harmonic features to estimate a region and tissue specific linear mapping between the signal from different sites (and scanners). We validate our method on diffusion data acquired from seven different sites (including two GE, three Philips, and two Siemens scanners) on a group of age-matched healthy subjects. Since the extracted rotation invariant spherical harmonic features depend on the accuracy of the brain parcellation provided by Freesurfer, we propose a feature based refinement of the original parcellation such that it better characterizes the anatomy and provides robust linear mappings to harmonize the dMRI data. We demonstrate the efficacy of our method by statistically comparing diffusion measures such as fractional anisotropy, mean diffusivity and generalized fractional anisotropy across multiple sites before and after data harmonization. We also show results using tract-based spatial statistics before and after harmonization for independent validation of the proposed methodology. Our experimental results demonstrate that, for nearly identical acquisition protocol across sites, scanner-specific differences can be accurately removed using the proposed method.

Synthesis of trifluoromethyl γ-aminophosphonates by nucleophilic aziridine ring opening.

Phosphonated derivatives of trifluoromethyl aziridine were obtained with good yield from aziridine-2-carbaldehyde by two distinct methods, which resulted in different diastereoselectivities. Using thiols as nucleophiles ring opening reactions of trifluoromethylated derivatives of aziridine-2-phosphonates proceeded regio- and diastereoselectively, giving rise to γ-amino-γ-trifluoromethyl phosphonates.

Sexually dimorphic white matter geometry abnormalities in adolescent onset schizophrenia.

The normal human brain is characterized by a pattern of gross anatomical asymmetry. This pattern, known as the "torque", is associated with a sexual dimorphism: The male brain tends to be more asymmetric than that of the female. This fact, along with well-known sex differences in brain development (faster in females) and onset of psychosis (earlier with worse outcome in males), has led to the theory that schizophrenia is a disorder in which sex-dependent abnormalities in the development of brain torque, the correlate of the capacity for language, cause alterations in interhemispheric connectivity, which are causally related to psychosis (Crow TJ, Paez P, Chance SE. 2007. Callosal misconnectivity and the sex difference in psychosis. Int Rev Psychiatry. 19(4):449-457.). To provide evidence toward this theory, we analyze the geometry of interhemispheric white matter connections in adolescent-onset schizophrenia, with a particular focus on sex, using a recently introduced framework for white matter geometry computation in diffusion tensor imaging data (Savadjiev P, Kindlmann GL, Bouix S, Shenton ME, Westin CF. 2010. Local white geometry from diffusion tensor gradients. Neuroimage. 49(4):3175-3186.). Our results reveal a pattern of sex-dependent white matter geometry abnormalities that conform to the predictions of Crow's torque theory and correlate with the severity of patients' symptoms. To the best of our knowledge, this is the first study to associate geometrical differences in white matter connectivity with torque in schizophrenia.

Gray matter alterations in early aging: a diffusion magnetic resonance imaging study.

Many studies have observed altered neurofunctional and structural organization in the aging brain. These observations from functional neuroimaging studies show a shift in brain activity from the posterior to the anterior regions with aging (PASA model), as well as a decrease in cortical thickness, which is more pronounced in the frontal lobe followed by the parietal, occipital, and temporal lobes (retrogenesis model). However, very little work has been done using diffusion MRI (dMRI) with respect to examining the structural tissue alterations underlying these neurofunctional changes in the gray matter. Thus, for the first time, we propose to examine gray matter changes using diffusion MRI in the context of aging. In this work, we propose a novel dMRI based measure of gray matter "heterogeneity" that elucidates these functional and structural models (PASA and retrogenesis) of aging from the viewpoint of diffusion MRI. In a cohort of 85 subjects (all males, ages 15-55 years), we show very high correlation between age and "heterogeneity" (a measure of structural layout of tissue in a region-of-interest) in specific brain regions. We examine gray matter alterations by grouping brain regions into anatomical lobes as well as functional zones. Our findings from dMRI data connects the functional and structural domains and confirms the "retrogenesis" hypothesis of gray matter alterations while lending support to the neurofunctional PASA model of aging in addition to showing the preservation of paralimbic areas during healthy aging.

Synthesis, characterization, and binding properties towards CT-DNA and lipoxygenase of mixed-ligand silver(I) complexes with 2-mercaptothiazole and its derivatives and triphenylphosphine.

Mixed-ligand silver(I) complexes of formulae [AgCl(TPP)2(MTZD)] (1), {[AgCl(TPP)2(MBZT)]·(MBZT)·2(toluene)} (2), and [AgCl(TPP)2(CMBZT)] (3) were obtained by refluxing toluene solutions of silver(I) chloride with triphenylphosphine (TPP) and the appropriate heterocyclic thioamides 2-mercaptothiazolidine (MTZD), 2-mercaptobenzothiazole (MBZT), and 5-chloro-2-mercaptobenzothiazole (CMBZT). The complexes were characterized by the melting point, vibrational spectroscopy (Fourier transform mid-IR), (1)H-NMR spectroscopy, UV-vis spectroscopy, and X-ray crystallography. DNA binding tests indicate the ability of complexes 1-3 to modify the activity of cells. The binding constants of 1-3 towards calf-thymus DNA (CT-DNA) [(3.5 ± 8.5) × 10(4) M(-1) for 1, (10.0 ± 0.0) × 10(4) M(-1) for 2, and (46.4 ± 7.0) × 10(4) M(-1) for 3] indicate strong interaction of 3. Changes in the fluorescence of ethidium bromide in the presence of DNA suggest intercalation into or electrostatic interactions with DNA. The corresponding apparent binding constants (K app) towards CT-DNA calculated through fluorescence spectra are (3.5 ± 0.7) × 10(4) M(-1) for 1, (10.0 ± 0.0) × 10(4) M(-1) for 2, and (46.4 ± 7.0) × 10(4) M(-1) for 3. Docking studies on DNA complexes confirm the binding of 1 and 2 in the major groove of CT-DNA and of 3 in the minor groove. Moreover, the influence of 1-3 on the catalytic peroxidation of linoleic acid to hydroperoxylinoleic acid by the enzyme lipoxygenase was studied kinetically and theoretically. The antibacterial effect of 1-3 against the bacterial species Pseudomonas aeruginosa and Escherichia coli was evaluated. Complex 1 exhibits the strongest activity.

Mono- and binuclear copper(I) complexes of thionucleotide analogues and their catalytic activity on the synthesis of dihydrofurans.

The reaction of copper(I) halides with 2-thiouracil (TUC), 6-methyl-2-thiouacil (MTUC), and 4-methyl-2-mercaptopyrimidine (MPMTH) in the presence of triphenylphosphine (tpp) in a 1:1:2 molar ratio results in a mixed-ligand copper(I) complex with the formulas [Cu2(tpp)4(TUC)Cl] (1), [Cu2(tpp)4(MTUC)Cl] (2), [Cu(tpp)2(MPMTH)Cl]·(1)/2CH3OH (3), [Cu(tpp)2(MTUC)Br] (4), and [Cu(tpp)2(MTUC)I]·(1)/2CH3CN (5). The complexes have been characterized by FT-IR, (1)H NMR, and UV-vis spectroscopic techniques and single-crystal X-ray crystallography. Complexes 1 and 2 are binuclear copper(I) complexes. Two phosphorus atoms from tpp ligands are coordinated to the copper(I) ions, forming two units that are linked to each other by a deprotonated TUC or MTUC chelating ligand through a sulfur bridge. A linear Cu-S-Cu moiety is formed. The tetrahedral geometry around the metal centers is completed by the nitrogen-donor atom from the TUC or MTUC ligand for the one unit, while for the other one, it is completed by the chloride anion. Two phosphorus atoms from two tpp ligands, one sulfur atom from MPMTH or MTUC ligand, and one halide anion (Cl, Br, and I) form a tetrahedron around the copper ion in 3-5 and two polymorphic forms of 4 (4a and 4b). In all of the complexes, either mono- or binuclear intramolecular O-H···X hydrogen bonds enhance the stability of the structures. On the other hand, in almost all cases of mononuclear complexes (with the exception of a symmetry-independent molecule in 4a), intermolecular NH···O hydrogen-bonding interactions lead to dimerization. Complexes 1-5 were studied for their catalytic activity for the intermolecular cycloaddition of iodonium ylides toward dihydrofuran formation by HPLC, (1)H NMR, and LC-HRMS spectroscopic techniques. The results show that the geometry and halogen and ligand types have a strong effect on the catalytic properties of the complexes. The highest yield of dihydrofurans was obtained when "linear" complexes 1 and 2 were used as the catalysts. The activity of the metal complexes on the copper(I)-catalyzed and uncatalyzed intramolecular cycloaddition of iodonium ylide is rationalized through electronic structure calculation methods, and the results are compared with the experimental ones.

Synthesis and structural characterization of new Cu(I) complexes with the antithyroid drug 6-n-propyl-thiouracil. study of the Cu(I)-catalyzed intermolecular cycloaddition of iodonium ylides toward benzo[b]furans with pharmaceutical implementations.

The reaction of copper(I) iodide with 6-n-propylthiouracil (ptu) in the presence or absence of the triphenylphosphine (tpp) or tri(p-tolyl)phosphine (tptp) in a 1:1:2 molar ratio forms the mixed ligand Cu(I) complex with formula [CuI(ptu)2](toluene) (1), [CuI(tpp)2(ptu)] (2), and [CuI(tptp)2(ptu)] (3). The complexes have been characterized by FT-IR, (1)H NMR, UV-vis, spectroscopic techniques, and single crystal X-ray crystallography. Two sulfur atoms from two ptu ligands and one iodide form a trigonal geometry around the metal center in 1. Intramolecular interactions through hydrogen bonds lead to a bend ribbon polymeric supramolecular architecture with zigzag conformation. Two phosphorus atoms from two arylphosphines, one sulfur atom, and one iodide anion form a tetrahedron around the copper ion in case of 2 and 3. Intramolecular hydrogen bonding interactions lead to dimerization. Complexes 1-3 and the already known ones with formulas, [(tpSb)2Cu(µ2-I)2Cu(tpSb)2] (4) (tbSb = triphenylstibine), [(tpp)Cu(µ2-I)2Cu(tpp)2] (5), [(tpp)Cu(µ2-Cl)2Cu(tpp)2] (6), [CuCl(tpp)3·(CH3CN)] (7), and [AuCl(tpp)] (8), were used to study their catalytic activity on the intermolecular cycloaddition of iodonium ylides toward benzo[b]furans formation. The results show that both the metal and the ligand type affect the catalytic affinity of the complexes. The highest yield of benzo[b]furan was derived when complexes 2, 3, and 4 were used as catalysts. The mechanism of the Cu(I)-catalyzed and uncatalyzed intramolecular cycloaddition of iodonium ylide has been also thoroughly explored by means of ab initio electronic structure calculation methods, and the results are compared with the experimental ones.

Electrophysiological and diffusion tensor imaging evidence of delayed corollary discharges in patients with schizophrenia.

BACKGROUND: Patients with schizophrenia (SZ) characteristically exhibit supranormal levels of cortical activity to self-induced sensory stimuli, ostensibly because of abnormalities in the neural signals (corollary discharges, CDs) normatively involved in suppressing the sensory consequences of self-generated actions. The nature of these abnormalities is unknown. This study investigated whether SZ patients experience CDs that are abnormally delayed in their arrival at the sensory cortex. METHOD: Twenty-one patients with SZ and 25 matched control participants underwent electroencephalography (EEG). Participants' level of cortical suppression was calculated as the amplitude of the N1 component evoked by a button press-elicited auditory stimulus, subtracted from the N1 amplitude evoked by the same stimulus presented passively. In the three experimental conditions, the auditory stimulus was delivered 0, 50 or 100 ms subsequent to the button-press. Fifteen SZ patients and 17 healthy controls (HCs) also underwent diffusion tensor imaging (DTI), and the fractional anisotropy (FA) of participants' arcuate fasciculus was used to predict their level of cortical suppression in the three conditions. RESULTS: While the SZ patients exhibited subnormal N1 suppression to undelayed, self-generated auditory stimuli, these deficits were eliminated by imposing a 50-ms, but not a 100-ms, delay between the button-press and the evoked stimulus. Furthermore, the extent to which the 50-ms delay normalized a patient's level of N1 suppression was linearly related to the FA of their arcuate fasciculus. CONCLUSIONS: These data suggest that SZ patients experience temporally delayed CDs to self-generated auditory stimuli, putatively because of structural damage to the white-matter (WM) fasciculus connecting the sites of discharge initiation and destination.

Structural properties, cytotoxicity, and anti-inflammatory activity of silver(I) complexes with tris(p-tolyl)phosphine and 5-chloro-2-mercaptobenzothiazole.

The synthesis and characterization of the silver(I) chloride complex of formula {[AgCI(CMBZT)(TPTP)(2)] . (MeOH)} (1) (CMBZT = 5-chloro-2-mercaptobenzothiazole, TPTP = tris(p-tolyl)phosphine) is described. Also the structure of the hydrate derivative {[AgCI(TPTP)(3)] . (0.5 . H(2)O)} (2) of the corresponding known anhydrous silver complex (Zartilas et al., 2009), and the polymorph 3 of the known [AgI(TPTP)(3)] complex (Zartilas et al., 2009) were determined and compared with the known ones. In addition, the structure of the known one silver(I) cluster {[AgI(TPTP)](4)} (4) (Meijboom et al., 2009) was re-determined at 120(2) K and possible Ag-Ag interactions were analyzed. The compounds 1-4 were characterized by X-ray crystallography at r.t (1) and 120 K (2-4). All these complexes and {[(Et(3)NH)(+)](2) . [Ag(6)(mu(3)-Hmna)(4)(mu(3)-mna)(2)](2-) . (DMSO)(2) . (H(2)O)} (5) (Hmna = 2-mercaptonicotinic acid) were evaluated for cytotoxic and anti-inflammatory activity. The in vitro testing of cytotoxic activity of 1-5 against leiomyosarcoma cancer cells (LMS), were evaluated with Trypan Blue and Thiazolyl Blue Tetrazolium Bromide or 3-(4.5-dimethylthiazol-2-yl)-2.5-diphenyltetrazolium bromide (MTT) assays. The flow cytometry assay for complex 1 and showed that at 15 muM of 1, 62.38% of LMS cells undergo apoptosis, while 7% of LMS cells undergo cell necrosis. The antitumor activity of 3 is comparable with that of its reported polymorph (Zartilas et al., 2009). The anti-inflammatory, activity of complexes 1-3 and 5 was also studied. The activity towards cell viability was 2 > 3 > 5 > 1 > 4, while the order of the inhibitory activity in cell growth proliferation follows the order, 2 > 3 > 1 > 4 > 5. The anti-inflammatory activity on the other hand is 1 > 2 > 5 > cdots, three dots, centered >3.

Diffusion tractography of the fornix in schizophrenia.

BACKGROUND: White matter fiber tracts, especially those interconnecting the frontal and temporal lobes, are likely implicated in pathophysiology of schizophrenia. Very few studies, however, have focused on the fornix, a compact bundle of white matter fibers, projecting from the hippocampus to the septum, anterior nucleus of the thalamus and the mamillary bodies. Diffusion Tensor Imaging (DTI), and a new post-processing method, fiber tractography, provides a unique opportunity to visualize and to quantify entire trajectories of fiber bundles, such as the fornix, in vivo. We applied these techniques to quantify fornix diffusion anisotropy in schizophrenia. METHODS: DTI images were used to evaluate the left and the right fornix in 36 male patients diagnosed with chronic schizophrenia and 35 male healthy individuals, group matched on age, parental socioeconomic status, and handedness. Regions of interest were drawn manually, blind to group membership, to guide tractography, and fractional anisotropy (FA), a measure of fiber integrity, was calculated and averaged over the entire tract for each subject. The Doors and People test (DPT) was used to evaluate visual and verbal memory, combined recall and combined recognition. RESULTS: Analysis of variance was performed and findings demonstrated a difference between patients with schizophrenia and controls for fornix FA (p=0.006). Protected post-hoc independent sample t-tests demonstrated a bilateral FA decrease in schizophrenia, compared with control subjects (left side: p=0.048; right side p=0.006). Higher fornix FA was statistically significantly correlated with DPT and measures of combined visual memory (r=0.554, p=0.026), combined verbal memory (r=0.647, p=0.007), combined recall (r=0.516, p=0.041), and combined recognition (r=0.710, p=0.002) for the control group. No such statistically significant correlations were found in the patient group. CONCLUSIONS: Our findings show the utility of applying DTI and tractography to study white matter fiber tracts in vivo in schizophrenia. Specifically, we observed a bilateral disruption in fornix integrity in schizophrenia, thus broadening our understanding of the pathophysiology of this disease.

Abnormalities in thalamo-cortical connections in patients with first-episode schizophrenia: a two-tensor tractography study.

The "cognitive dysmetria" hypothesis suggests that impairments in cognition and behavior in patients with schizophrenia can be explained by disruptions in the cortico-cerebellar-thalamic-cortical circuit. In this study we examine thalamo-cortical connections in patients with first-episode schizophrenia (FESZ). White matter pathways are investigated that connect the thalamus with three frontal cortex regions including the anterior cingulate cortex (ACC), ventrolateral prefrontal cortex (VLPFC), and lateral oribitofrontal cortex (LOFC). We use a novel method of two-tensor tractography in 26 patients with FESZ compared to 31 healthy controls (HC), who did not differ on age, sex, or education. Dependent measures were fractional anisotropy (FA), Axial Diffusivity (AD), and Radial Diffusivity (RD). Subjects were also assessed using clinical functioning measures including the Global Assessment of Functioning (GAF) Scale, the Global Social Functioning Scale (GF: Social), and the Global Role Functioning Scale (GF: Role). FESZ patients showed decreased FA in the right thalamus-right ACC and right-thalamus-right LOFC pathways compared to healthy controls (HCs). In the right thalamus-right VLPFC tract, we found decreased FA and increased RD in the FESZ group compared to HCs. After correcting for multiple comparisons, reductions in FA in the right thalamus- right ACC and the right thalamus- right VLPC tracts remained significant. Moreover, reductions in FA were significantly associated with lower global functioning scores as well as lower social and role functioning scores. We report the first diffusion tensor imaging study of white matter pathways connecting the thalamus to three frontal regions. Findings of white matter alterations and clinical associations in the thalamic-cortical component of the cortico-cerebellar-thalamic-cortical circuit in patients with FESZ support the cognitive dysmetria hypothesis and further suggest the possible involvement of myelin sheath pathology and axonal membrane disruption in the pathogenesis of the disorder.

Reduced interhemispheric connectivity in schizophrenia-tractography based segmentation of the corpus callosum.

BACKGROUND: A reduction in interhemispheric connectivity is thought to contribute to the etiology of schizophrenia. Diffusion Tensor Imaging (DTI) measures the diffusion of water and can be used to describe the integrity of the corpus callosum white matter tracts, thereby providing information concerning possible interhemispheric connectivity abnormalities. Previous DTI studies in schizophrenia are inconsistent in reporting decreased Fractional Anisotropy (FA), a measure of anisotropic diffusion, within different portions of the corpus callosum. Moreover, none of these studies has investigated corpus callosum systematically, using anatomical subdivisions. METHODS: DTI and structural MRI scans were obtained from 32 chronic schizophrenic subjects and 42 controls. Corpus callosum cross sectional area and its probabilistic subdivisions were determined automatically from structural MRI scans using a model based deformable contour segmentation. These subdivisions employ a previously generated probabilistic subdivision atlas, based on fiber tractography and anatomical lobe subdivision. The structural scan was then co-registered with the DTI scan and the anatomical corpus callosum subdivisions were propagated to the associated FA map. RESULTS: Results revealed decreased FA within parts of the corpus interconnecting frontal regions in schizophrenia compared with controls, but no significant changes for callosal fibers interconnecting parietal and temporo-occipital brain regions. In addition, integrity of the anterior corpus was statistically significantly correlated with negative as well as positive symptoms, while posterior measures correlated with positive symptoms only. CONCLUSIONS: This study provides quantitative evidence for a reduction of interhemispheric brain connectivity in schizophrenia, involving corpus callosum, and further points to frontal connections as possibly disrupted in schizophrenia.

Highly selective hydrosilylation of olefins and acetylenes by platinum(0) complexes bearing bulky N-heterocyclic carbene ligands.

Platinum complexes bearing bulky N-heterocyclic carbene (NHC) ligands, i.e., [Pt(IPr*)(dvtms)] (where, IPr* = 1,3-bis{2,6-bis(diphenylmethyl)-4-methylphenyl}imidazol-2-ylidene) and [Pt(IPr*OMe)(dvtms)] (where, IPr*OMe = 1,3-bis{2,6-bis(diphenylmethyl)-4-methoxyphenyl}imidazol-2-ylidene, dvtms = divinyltetramethyldisiloxane) catalyse nearly quantitatively and highly or completely the selective hydrosilylation of terminal olefins as well as terminal or internal acetylenes.

Tetra-functional double-decker silsesquioxanes as anchors for reactive functional groups and potential synthons for hybrid materials.

A series of double-decker silsesquioxane derivatives with four reactive functional groups were designed, efficiently synthesized, and characterized. These novel inorganic-organic hybrids show highly attractive features for applications as building blocks with Si-O-Si rigid cores (good thermal properties) with four reactive moieties, which can be functionalized in further processes.

Mapping temporo-parietal and temporo-occipital cortico-cortical connections of the human middle longitudinal fascicle in subject-specific, probabilistic, and stereotaxic Talairach spaces.

Originally, the middle longitudinal fascicle (MdLF) was defined as a long association fiber tract connecting the superior temporal gyrus and temporal pole with the angular gyrus. More recently its description has been expanded to include all long postrolandic cortico-cortical association connections of the superior temporal gyrus and dorsal temporal pole with the parietal and occipital lobes. Despite its location and size, which makes MdLF one of the most prominent cerebral association fiber tracts, its discovery in humans is recent. Given the absence of a gold standard in humans for this fiber tract, its precise and complete connectivity remains to be determined with certainty. In this study using high angular resolution diffusion MRI (HARDI), we delineated for the first time, six major fiber connections of the human MdLF, four of which are temporo-parietal and two temporo-occipital, by examining morphology, topography, cortical connections, biophysical measures, volume and length in seventy brains. Considering the cortical affiliations of the different connections of MdLF we suggested that this fiber tract may be related to language, attention and integrative higher level visual and auditory processing associated functions. Furthermore, given the extensive connectivity provided to superior temporal gyrus and temporal pole with the parietal and occipital lobes, MdLF may be involved in several neurological and psychiatric conditions such as primary progressive aphasia and other aphasic syndromes, some forms of behavioral variant of frontotemporal dementia, atypical forms of Alzheimer's disease, corticobasal degeneration, schizophrenia as well as attention-deficit/hyperactivity Disorder and neglect disorders.

Microwave-assisted one-pot synthesis of new ionic iridium complexes of [Ir(bzq)2(N

Iridium C,N-cyclometalated complexes with an ionic structure are considered to be promising candidates for application in host/guest solid-state phosphorescent single-layer devices because the employment of such dopants offers the possibility of reducing their concentration in organic matrices as well as allows obtaining organic light emitting devices (OLEDs) with interesting emission parameters. We report herein a methodology enabling the synthesis of cyclometalated ionic iridium(iii) complexes of the type [Ir(C^N)2(N^N)]+A- according to a three-component one-pot strategy involving the acceleration of the reaction via microwave irradiation. The developed protocol allowed efficient synthesis of a series of new cationic iridium(iii) coordination derivatives, which were isolated and spectroscopically characterized, while the structures of two of them were determined by the X-ray method. Moreover, the iridium(iii) derivatives were subjected to the cyclic voltammetry studies in order to determine the energies of the HOMO and LUMO levels as well as to estimate their electrochemical properties and to predict some electronic properties. Additionally, the ONIOM calculation scheme that was used to predict HOMO-LUMO gaps for the studied Ir(iii) complexes showed a good correlation between the experimental and calculated values. In order to determine the influence of the structure and nature of the ancillary ligand on the location of the maximum emission band, the photophysical properties of the synthesized iridium complexes were characterized. Finally, the selected compounds were used as emitters for the construction of polymer light emitting diodes (PLEDs) based on a poly(N-vinylcarbazole)/2-(4-tert-butylphenyl)-5-(4-biphenyl)-1,3,4-oxadiazole (PVK/PBD) matrix. The highest luminance, above 10 000 cd m-2, was recorded for the device containing only 1.0 wt% of [Ir(bzq)2(1,10-phenanthroline)]+PF6- in the PVK/PBD. The fabricated PLEDs exhibit current efficiency in the range of 1.0 to 2.2 cd A-1.