Affine Registration of label maps in Label Space

Two key aspects of coupled multi-object shape\ud analysis and atlas generation are the choice of representation\ud and subsequent registration methods used to align the sample\ud set. For example, a typical brain image can be labeled into\ud three structures: grey matter, white matter and cerebrospinal\ud fluid. Many manipulations such as interpolation, transformation,\ud smoothing, or registration need to be performed on these images\ud before they can be used in further analysis. Current techniques\ud for such analysis tend to trade off performance between the two\ud tasks, performing well for one task but developing problems when\ud used for the other.\ud This article proposes to use a representation that is both\ud flexible and well suited for both tasks. We propose to map object\ud labels to vertices of a regular simplex, e.g. the unit interval for\ud two labels, a triangle for three labels, a tetrahedron for four\ud labels, etc. This representation, which is routinely used in fuzzy\ud classification, is ideally suited for representing and registering\ud multiple shapes. On closer examination, this representation\ud reveals several desirable properties: algebraic operations may\ud be done directly, label uncertainty is expressed as a weighted\ud mixture of labels (probabilistic interpretation), interpolation is\ud unbiased toward any label or the background, and registration\ud may be performed directly.\ud We demonstrate these properties by using label space in a gradient\ud descent based registration scheme to obtain a probabilistic\ud atlas. While straightforward, this iterative method is very slow,\ud could get stuck in local minima, and depends heavily on the initial\ud conditions. To address these issues, two fast methods are proposed\ud which serve as coarse registration schemes following which the\ud iterative descent method can be used to refine the results. Further,\ud we derive an analytical formulation for direct computation of the\ud "group mean" from the parameters of pairwise registration of all\ud the images in the sample set. We show results on richly labeled\ud 2D and 3D data sets

Diffusion Tensor Imaging, Structural Connectivity, and Schizophrenia

A fundamental tenet of the “disconnectivity” theories of schizophrenia is that the disorder is ultimately caused by abnormal communication between spatially disparate brain structures. Given that the white matter fasciculi represent the primary infrastructure for long distance communication in the brain, abnormalities in these fiber bundles have been implicated in the etiology of schizophrenia. Diffusion tensor imaging (DTI) is a magnetic resonance imaging (MRI) technique that enables the visualization of white matter macrostructure in vivo, and which has provided unprecedented insight into the existence and nature of white matter abnormalities in schizophrenia. The paper begins with an overview of DTI and more commonly used diffusion metrics and moves on to a brief review of the schizophrenia literature. The functional implications of white matter abnormalities are considered, particularly with respect to myelin's role in modulating the transmission velocity of neural discharges. The paper concludes with a speculative hypothesis about the relationship between gray and white matter abnormalities associated with schizophrenia

Increased Gray Matter Diffusion Anisotropy in Patients with Persistent Post-Concussive Symptoms following Mild Traumatic Brain Injury

A significant percentage of individuals diagnosed with mild traumatic brain injury (mTBI) experience persistent post-concussive symptoms (PPCS). Little is known about the pathology of these symptoms and there is often no radiological evidence based on conventional clinical imaging. We aimed to utilize methods to evaluate microstructural tissue changes and to determine whether or not a link with PPCS was present. A novel analysis method was developed to identify abnormalities in high-resolution diffusion tensor imaging (DTI) when the location of brain injury is heterogeneous across subjects. A normative atlas with 145 brain regions of interest (ROI) was built from 47 normal controls. Comparing each subject’s diffusion measures to the atlas generated subject-specific profiles of injury. Abnormal ROIs were defined by absolute z-score values above a given threshold. The method was applied to 11 PPCS patients following mTBI and 11 matched controls. Z-score information for each individual was summarized with two location-independent measures: “load” (number of abnormal regions) and “severity” (largest absolute z-score). Group differences were then computed using Wilcoxon rank sum tests. Results showed statistically significantly higher load (p = 0.018) and severity (p = 0.006) for fractional anisotropy (FA) in patients compared with controls. Subject-specific profiles of injury evinced abnormally high FA regions in gray matter (30 occurrences over 11 patients), and abnormally low FA in white matter (3 occurrences over 11 subjects). Subject-specific profiles provide important information regarding the pathology associated with PPCS. Increased gray matter (GM) anisotropy is a novel in-vivo finding, which is consistent with an animal model of brain trauma that associates increased FA in GM with pathologies such as gliosis. In addition, the individualized analysis shows promise for enhancing the clinical care of PPCS patients as it could play a role in the diagnosis of brain injury not revealed using conventional imaging

Magnetic Resonance Imaging Pilot Study of Intravenous Glyburide in Traumatic Brain Injury.

Pre-clinical studies of traumatic brain injury (TBI) show that glyburide reduces edema and hemorrhagic progression of contusions. We conducted a small Phase II, three-institution, randomized placebo-controlled trial of subjects with TBI to assess the safety and efficacy of intravenous (IV) glyburide. Twenty-eight subjects were randomized and underwent a 72-h infusion of IV glyburide or placebo, beginning within 10 h of trauma. Of the 28 subjects, 25 had Glasgow Coma Scale (GCS) scores of 6-10, and 14 had contusions. There were no differences in adverse events (AEs) or severe adverse events (ASEs) between groups. The magnetic resonance imaging (MRI) percent change at 72-168 h from screening/baseline was compared between the glyburide and placebo groups. Analysis of contusions (7 per group) showed that lesion volumes (hemorrhage plus edema) increased 1036% with placebo versus 136% with glyburide (p = 0.15), and that hemorrhage volumes increased 11.6% with placebo but decreased 29.6% with glyburide (p = 0.62). Three diffusion MRI measures of edema were quantified: mean diffusivity (MD), free water (FW), and tissue MD (MDt), corresponding to overall, extracellular, and intracellular water, respectively. The percent change with time for each measure was compared in lesions (n = 14) versus uninjured white matter (n = 24) in subjects receiving placebo (n = 20) or glyburide (n = 18). For placebo, the percent change in lesions for all three measures was significantly different compared with uninjured white matter (analysis of variance [ANOVA], p < 0.02), consistent with worsening of edema in untreated contusions. In contrast, for glyburide, the percent change in lesions for all three measures was not significantly different compared with uninjured white matter. Further study of IV glyburide in contusion TBI is warranted

Button-pressing affects P300 amplitude and scalp topography

Abstract Background: Scant and equivocal research exists examining the effects of button-pressing on P300. Button-pressing may decrease P300 latency and amplitude. The melding of motor potentials and P300 may also confound studies of P300 topography, such as studies of temporal scalp-area asymmetries in schizophrenia. Method: P300 was measured on button-press and silent-count tasks in control subjects. An estimate of motor activity was constructed from a simple reaction time task, with reaction times matched to the button-press task. The motor estimate was subtracted from the buttonpress P300 to assess Results: P300 was smaller and its topography different in the button-pressing task relative to silent-counting. The motor-correction procedure generated a P300 with normal topography. Comparison of the button-press P300 in controls to the silent-count P300 in schizophrenia patients reduced a signi®cant lateral asymmetry to trend level. This asymmetry was signi®cant after the correction procedure. Conclusions: Button-pressing generates smaller P300 than silent-counting. Also, P300 topography in button-pressing tasks is confounded by motor potentials. The distortion can be corrected with a motor potential estimate. Motor potentials can occlude differences in P300 topography between groups.

Left auditory cortex gamma synchronization and auditory hallucination symptoms in schizophrenia

<p>Abstract</p> <p>Background</p> <p>Oscillatory electroencephalogram (EEG) abnormalities may reflect neural circuit dysfunction in neuropsychiatric disorders. Previously we have found positive correlations between the phase synchronization of beta and gamma oscillations and hallucination symptoms in schizophrenia patients. These findings suggest that the propensity for hallucinations is associated with an increased tendency for neural circuits in sensory cortex to enter states of oscillatory synchrony. Here we tested this hypothesis by examining whether the 40 Hz auditory steady-state response (ASSR) generated in the left primary auditory cortex is positively correlated with auditory hallucination symptoms in schizophrenia. We also examined whether the 40 Hz ASSR deficit in schizophrenia was associated with cross-frequency interactions.</p> <p>Sixteen healthy control subjects (HC) and 18 chronic schizophrenia patients (SZ) listened to 40 Hz binaural click trains. The EEG was recorded from 60 electrodes and average-referenced offline. A 5-dipole model was fit from the HC grand average ASSR, with 2 pairs of superior temporal dipoles and a deep midline dipole. Time-frequency decomposition was performed on the scalp EEG and source data.</p> <p>Results</p> <p>Phase locking factor (PLF) and evoked power were reduced in SZ at fronto-central electrodes, replicating prior findings. PLF was reduced in SZ for non-homologous right and left hemisphere sources. Left hemisphere source PLF in SZ was positively correlated with auditory hallucination symptoms, and was modulated by delta phase. Furthermore, the correlations between source evoked power and PLF found in HC was reduced in SZ for the LH sources.</p> <p>Conclusion</p> <p>These findings suggest that differential neural circuit abnormalities may be present in the left and right auditory cortices in schizophrenia. In addition, they provide further support for the hypothesis that hallucinations are related to cortical hyperexcitability, which is manifested by an increased propensity for high-frequency synchronization in modality-specific cortical areas.</p