Publications by Year: 2008

Recent advances in bioinformatics have opened entire new avenues for organizing, integrating and retrieving neuroscientific data, in a digital, machine-processable format, which can be at the same time understood by humans, using ontological, symbolic data representations. Declarative information stored in ontological format can be perused and maintained by domain experts, interpreted by machines, and serve as basis for a multitude of decision support, computerized simulation, data mining, and teaching applications. We have developed a prototype symbolic model of canonical neuroanatomy of the motor system. Our symbolic model is intended to support symbolic look up, logical inference and mathematical modeling by integrating descriptive, qualitative and quantitative functional neuroanatomical knowledge. Furthermore, we show how our approach can be extended to modeling impaired brain connectivity in disease states, such as common movement disorders. In developing our ontology, we adopted a disciplined modeling approach, relying on a set of declared principles, a high-level schema, Aristotelian definitions, and a frame-based authoring system. These features, along with the use of the Unified Medical Language System (UMLS) vocabulary, enable the alignment of our functional ontology with an existing comprehensive ontology of human anatomy, and thus allow for combining the structural and functional views of neuroanatomy for clinical decision support and neuroanatomy teaching applications. Although the scope of our current prototype ontology is limited to a particular functional system in the brain, it may be possible to adapt this approach for modeling other brain functional systems as well.

The size of the anisotropic domains in a lyotropic liquid crystal is estimated using a new protocol for diffusion NMR. Echo attenuation decays are recorded for different durations of the displacement-encoding gradient pulses, while keeping the effective diffusion time and the range of the wave vectors constant. Deviations between the sets of data appear if there are non-Gaussian diffusion processes occurring on the time-scale defined by the gradient pulse duration and the length-scale defined by the wave vector. The homogeneous length-scale is defined as the minimum length-scale for which the diffusion appears to be Gaussian. Simulations are performed to show that spatial variation of the director orientation in an otherwise homogeneous system is sufficient to induce non-Gaussian diffusion. The method is demonstrated by numerical solutions of the Bloch-Torrey equation and experiments on a range of lamellar liquid crystals with different domain sizes.

The influence of electrostatic interactions on the dynamic properties of complexes containing DNA and mixtures of cationic- (DDA) and zwitterionic (DLPC) lipids are studied by means of NMR. The systems are arranged in lamellar membrane stacks intercalated by DNA molecules. This is confirmed by 31P-NMR, where a superposition of an axially symmetric powder pattern arising from the phospholipid membrane and an asymmetric tensor due to DNA can be fitted to the experimentally observed lineshape. The local mobility and order is assessed using two solid-state NMR techniques applicable to samples with natural isotopic abundance: WIdeline SEparation (WISE) and Separated Local Field (SLF) spectroscopy. Both experiments yield highly resolved 13C spectra in the direct dimension. The indirect dimension contains information about molecular dynamics through the 1H dipolar linewidth (WISE) or the 1H(-13)C dipolar coupling constant (SLF). The experiments suggest that DNA is static while it induces an increased disorder in the hydrocarbon chains as compared to the parent lipid case. DDA chain order is more affected than DLPC due to the attractive electrostatic interaction between DNA and the cationic lipid. Translational dynamics of the lipids and the water was measured with the Pulsed Field Gradient STimulated Echo (PFG STE) technique. The influence of lamellar domain size and the angular dependence of the diffusion coefficients and nuclear relaxation times on the results of the PFG STE experiments are discussed. The local water diffusion coefficient is reduced by a factor four from the value of bulk water, and increases as the DLPC content is increased. We observe two lipid components with an order of magnitude difference in diffusion coefficients in the DNA:DDA:DLPC precipitate and these are assigned to DLPC (fast) and DDA (slow). Cationic lipid (DDA) diffusion is decreasing a factor of 2 when DLPC is added to the pure DNA:DDA system, indicating DNA-induced lipid segregation within the bilayer and the transition from locally 2D to 1D diffusion of the DDA. The results show that DNA-lipid electrostatic interactions reduce the long-range lipid mobility but locally enhance the hydrocarbon chain dynamics by perturbing the preferred lipid packing.

Patients with schizophrenia and healthy control subjects underwent both neuropsychological evaluation and magnetic resonance diffusion tensor imaging, during which the cingulum bundle (CB) and the uncinate fasciculus (UF) were defined with fiber tractography and their integrity was quantified. On the basis of prior findings, it was hypothesized that neuropsychological disturbance in schizophrenia may be characterized, in part, by 2 dissociable functional neuroanatomical relationships: (a) executive functioning-CB integrity and (b) episodic memory-UF integrity. In support of the hypothesis, hierarchical regression results indicated that reduced white matter of the CB and the UF differentially and specifically predicted deficits in executive functioning and memory, respectively. Neuropsychological correlates of the CB also extended to lower generalized intelligence, as well as to reduced visual memory that may be related to failures of contextual monitoring of to-be-remembered scenes. Reduced white matter of the CB and the UF may each make distinct contributions to neuropsychological disturbance in schizophrenia.

BACKGROUND: Controversy exists over the nature and origin of reduced regional brain volumes in posttraumatic stress disorder (PTSD). At issue is whether these reductions represent preexisting vulnerability factors for developing PTSD upon traumatic exposure or acquired PTSD signs due to the traumatic stress that caused the PTSD or the chronic stress of having the disorder (or both). We employed a case-control design in monozygotic twin pairs discordant for combat exposure to address the preexisting versus acquired origin of brain morphometric abnormalities in PTSD.

In the title compound, C(29)H(25)NS(2), both the Cl atoms of the aza-diene precursor 4,4-dichloro-1,1-diphenyl-2-aza-buta-1,3-diene are replaced by two vicinal S-p-tolyl substituents attached to the terminal C atom of a π-conjugated 2-aza-butadiene array. The aza-diene chain is planar to within 0.01 Å. One of the phenyl rings seems to be slightly π-conjugated with the aza-diene core [dihedral angle 5.1 (2)°].

BACKGROUND: Surgical navigation requires registration of the pre-operative image dataset with the patient in the operation theatre. Various marker and marker-free registration techniques are available, each bearing an individual level of precision and clinical practicability. In this study the precision of four different registration methods in a maxillofacial surgical setting is analyzed. MATERIALS AND METHODS: A synthetic full size human skull model was registered with its computer tomography-dataset using (a) a dentally mounted occlusal splint, (b) the laser surface scanning, (c) five facial bone implants and (d) a combination of dental splint and two orbital bone implants. The target registration error was computed for 170 landmarks spread over the entire viscero- and neurocranium in 10 repeats using the VectorVision2 (BrainLAB AG, Heimstetten, Germany) navigation system. Statistical and graphical analyses were performed by anatomical region. RESULTS: An average precision of 1mm was found for the periorbital region irrespective of registration method (range 0.6-1.1mm). Beyond the mid-face, precision linearly decreases with the distance from the reference markers. The combination of splint with two orbital bone markers significantly improved precision from 1.3 to 0.8mm (p

In the present report, estimates of test-retest and between-site reliability of fMRI assessments were produced in the context of a multicenter fMRI reliability study (FBIRN Phase 1, www.nbirn.net). Five subjects were scanned on 10 MRI scanners on two occasions. The fMRI task was a simple block design sensorimotor task. The impulse response functions to the stimulation block were derived using an FIR-deconvolution analysis with FMRISTAT. Six functionally-derived ROIs covering the visual, auditory and motor cortices, created from a prior analysis, were used. Two dependent variables were compared: percent signal change and contrast-to-noise-ratio. Reliability was assessed with intraclass correlation coefficients derived from a variance components analysis. Test-retest reliability was high, but initially, between-site reliability was low, indicating a strong contribution from site and site-by-subject variance. However, a number of factors that can markedly improve between-site reliability were uncovered, including increasing the size of the ROIs, adjusting for smoothness differences, and inclusion of additional runs. By employing multiple steps, between-site reliability for 3T scanners was increased by 123%. Dropping one site at a time and assessing reliability can be a useful method of assessing the sensitivity of the results to particular sites. These findings should provide guidance toothers on the best practices for future multicenter studies.

As cigarette smoking prevalence rates approach 90% in schizophrenia, an important emerging question is the role of nicotine in the disease-related disturbance in cognition. We therefore tested a total of 38 male cigarette smokers (22 schizophrenia, 16 normal control), matched on nicotine dependence, on the Attention Network Test (ANT) at three nicotine conditions (baseline, 8 h overnight withdrawal, 3 h 21 mg nicotine patch). The results indicated that the groups did not differ in performance on either of three ANT measures (alertness, orienting, and executive) across baseline, patch, and withdrawal conditions. However, in comparison to the controls, the participants with schizophrenia showed faster ANT reaction time (RT) for the nicotine patch in relation to the baseline condition. In comparison to controls, the participants with schizophrenia also showed reduced ANT accuracy at withdrawal but not at patch condition. These results suggest that overall processing speed and accuracy are affected differently by nicotine levels in participants with schizophrenia, with evidence supporting greater impairment from withdrawal and greater improvement from nicotine administration.

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.