Publications

2008

BACKGROUND: In cases of slipped capital femoral epiphyses (SCFE) findings on plain radiographs help to determine the further necessary course of action. In severe cases possible surgical procedures are commonly indicated and planned using angular measurements on plain radiographs to describe the extent and direction of the slip. The aim of this study was to quantify the amount of angular errors deriving from this method. METHODS: Data and imaging of 23 consecutive patients with SCFE (31 affected and 15 unaffected femora) were included in this study. We determined shaft-neck/shaft-physis angles on antero-posterior and torsional angles on lateral radiographs in a clinical setting. As a reference we enabled similar angular measurements on CT-based three-dimensional computer models of the same femora bearing no projectional errors and malpositioning problems. RESULTS: In average, shaft-neck- and shaft-physis-angles were overestimated (6.5 degrees and 10.1 degrees ) on plain radiographs and neck torsion underestimated (-15.7 degrees ). In general the variability was high, especially for neck and physeal torsional measurements with standard deviations of +/-11.8 degrees and +/-16.7 degrees . Three out of four torsional measurements on affected femora were outside a +/-10 degrees window of error, about every third outside a +/-20 degrees window. CONCLUSION: Our results suggest to be careful when using plain radiographs as a source to determine the slippage extent in SCFE. Before using a plain radiograph to reject or indicate and plan a correction osteotomy in an individual case of SCFE the surgeon should reassure that radiographic method and patient positioning provide a reproducible and accurate depiction of the femoral geometry. LEVEL OF EVIDENCE: Level II; 23 consecutive patients with SCFE in the senior authors practice; evaluation of the reliability of angular measurements on plain radiographs; CT based 3D computer models of the same femora as a reference.
Spencer KM, Niznikiewicz MA, Shenton ME, McCarley RW. Sensory-evoked gamma oscillations in chronic schizophrenia.. Biol Psychiatry. 2008;63(8):744–7. doi:10.1016/j.biopsych.2007.10.017
BACKGROUND: The early visual-evoked gamma oscillation (VGO) elicited by Gestalt stimuli is reduced in schizophrenia patients compared with healthy individuals, but it is unknown whether this effect is specific to these particular stimuli and task. In contrast, the early auditory-evoked gamma oscillation (AGO) was reported to be unaffected in a sample of unmedicated, mostly first-episode schizophrenics, but it is unknown whether this oscillation is abnormal in chronic, medicated patients. We investigated these issues by examining the VGO and AGO in chronic schizophrenic (SZ) and matched healthy control (HC) subjects. METHODS: Subjects (21 HC, 23 SZ) performed visual and auditory oddball tasks. Visual stimuli were letters, and auditory stimuli were simple tones. Event-related spectral measures (phase locking factor and evoked power) were computed on Morlet wavelet-transformed single epochs from the standard trials. RESULTS: VGO phase locking at occipital electrodes was reduced in SZ compared with HC. In contrast, AGO phase locking and evoked power did not differ between groups. CONCLUSIONS: The VGO deficit may be a general phenomenon in schizophrenia, whereas the AGO evoked by simple tone stimuli does not appear to be abnormal in chronic, medicated schizophrenia patients.
Dickey CC, Mórocz IA, Niznikiewicz MA, Voglmaier M, Toner S, Khan U, Dreusicke M, Yoo S-S, Shenton ME, McCarley RW. Auditory processing abnormalities in schizotypal personality disorder: an fMRI experiment using tones of deviant pitch and duration.. Schizophr Res. 2008;103(1-3):26–39. doi:10.1016/j.schres.2008.04.041
BACKGROUND: One of the cardinal features of schizotypal personality disorder (SPD) is language abnormalities. The focus of this study was to determine whether or not there are also processing abnormalities of pure tones differing in pitch and duration in SPD. METHODS: Thirteen neuroleptic-na ıve male subjects met full criteria for SPD and were group-matched on age and parental socio-economic status to 13 comparison subjects. Verbal learning was measured with the California Verbal Learning Test. Heschl’s gyrus volumes were measured using structural MRI. Whole-brain fMRI activation patterns in an auditory task of listening to tones including pitch and duration deviants were compared between SPD and control subjects. In a second and separate ROI analysis we found that peak activation in superior temporal gyrus (STG), Brodmann Areas 41 and 42, was correlated with verbal learning and clinical measures derived from the SCID-II interview. RESULTS: In the region of the STG, SPD subjects demonstrated more activation to pitch deviants bilaterally (p
Saveyn P, Cocquyt E, Sinnaeve D, Martins J e C, Topgaard D, Van der Meeren P. NMR study of the sorption behavior of benzyl alcohol derivatives into sonicated and extruded dioctadecyldimethylammonium chloride (DODAC) dispersions: the relevance of membrane fluidity.. Langmuir. 2008;24(7):3082–9. doi:10.1021/la703285b
The sorption behavior of three benzyl alcohol derivatives with different hydrophobicities into sonicated and extruded DODAC dispersions has been studied using NMR spectroscopy and NMR diffusometry. We show that there is an increased sorption into a sonicated dispersion below the phase-transition temperature (T(m)) as compared to an extruded dispersion. This may be explained by the incomplete lipid chain freezing of charged lipids as a result of the sonication process. Around T(m), a sorption maximum is found that is attributed to the high bilayer disorder under this condition. In addition, a sorption increase and a fluidizing effect at increasing benzyl alcohol derivative concentrations are observed that provide additional evidence for the relevance of the bilayer fluidity on the sorption of hydrophobic components.
Nakamura M, Nestor PG, Levitt JJ, Cohen AS, Kawashima T, Shenton ME, McCarley RW. Orbitofrontal volume deficit in schizophrenia and thought disorder.. Brain. 2008;131(Pt 1):180–95. doi:10.1093/brain/awm265
Orbitofrontal Cortex (OFC) structural abnormality in schizophrenia has not been well characterized, probably due to marked anatomical variability and lack of consistent definitions. We previously reported OFC sulcogyral pattern alteration and its associations with social disturbance in schizophrenia, but OFC volume associations with psychopathology and cognition have not been investigated. We compared chronically treated schizophrenia patients with healthy control (HC) subjects, using a novel, reliable parcellation of OFC subregions and their association with cognition, especially the Iowa Gambling Task (IGT), and with schizophrenic psychopathology including thought disorder. Twenty-four patients with schizophrenia and 25 age-matched HC subjects underwent MRI. OFC Regions of Interest (ROI) were manually delineated according to anatomical boundaries: Gyrus Rectus (GR); Middle Orbital Gyrus (MiOG); and Lateral Orbital Gyrus (LOG). The OFC sulcogyral pattern was also classified. Additionally, MiOG probability maps were created and compared between groups in a voxel-wise manner. Both groups underwent cognitive evaluations using the IGT, Wisconsin Card Sorting Test, and Trail Making Test (TMT). An 11% bilaterally smaller MiOG volume was observed in schizophrenia, compared with HC (F(1,47) = 17.4, P = 0.0001). GR and LOG did not differ, although GR showed a rightward asymmetry in both groups (F(1,47) = 19.2, P 0.0001). The smaller MiOG volume was independent of the OFC sulcogyral pattern, which differed in schizophrenia and HC (chi2 = 12.49, P = 0.002). A comparison of MiOG probability maps suggested that the anterior heteromodal region was more affected in the schizophrenia group than the posterior paralimbic region. In the schizophrenia group, a smaller left MiOG was strongly associated with worse ’positive formal thought disorder’ (r = -0.638, P = 0.001), and a smaller right MiOG with a longer duration of the illness (r = -0.618, P = 0.002). While schizophrenics showed poorer performance than HC in the IGT, performance was not correlated with OFC volume. However, within the HC group, the larger the right hemisphere MiOG volume, the better the performance in the IGT (r = 0.541, P = 0.005), and the larger the left hemisphere volume, the faster the switching attention performance for the TMT, Trails B (r = -0.608, P = 0.003). The present study, applying a new anatomical parcellation method, demonstrated a subregion-specific OFC grey matter volume deficit in patients with schizophrenia, which was independent of OFC sulcogyral pattern. This volume deficit was associated with a longer duration of illness and greater formal thought disorder. In HC the finding of a quantitative association between OFC volume and IGT performance constitutes, to our knowledge, the first report of this association.
Talos I-F, Rubin DL, Halle M, Musen M, Kikinis R. A prototype symbolic model of canonical functional neuroanatomy of the motor system.. J Biomed Inform. 2008;41(2):251–63. doi:10.1016/j.jbi.2007.11.003
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.
Aslund I, Cabaleiro-Lago C, Söderman O, Topgaard D. Diffusion NMR for determining the homogeneous length-scale in lamellar phases.. J Phys Chem B. 2008;112(10):2782–94. doi:10.1021/jp076174l
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.
Leal C \ilia, Sandström D, Nevsten P, Topgaard D. Local and translational dynamics in DNA-lipid assemblies monitored by solid-state and diffusion NMR.. Biochim Biophys Acta. 2008;1778(1):214–28.
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.
Nestor PG, Kubicki M, Niznikiewicz M, Gurrera RJ, McCarley RW, Shenton ME. Neuropsychological disturbance in schizophrenia: a diffusion tensor imaging study.. Neuropsychology. 2008;22(2):246–54. doi:10.1037/0894-4105.22.2.246
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.
Kasai K, Yamasue H, Gilbertson MW, Shenton ME, Rauch SL, Pitman RK. Evidence for acquired pregenual anterior cingulate gray matter loss from a twin study of combat-related posttraumatic stress disorder.. Biol Psychiatry. 2008;63(6):550–6. doi:10.1016/j.biopsych.2007.06.022
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.