Browsing by Subject "brain function"

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    Association of structural brain imaging markers with alcoholism incorporating structural connectivity information: a regularized statistical approach
    (Office of the Vice Chancellor for Research, 2016-04-08) Karas, Marta; Dzemidzic, Mario; Goñi, Joaquin; Kareken, David A.; Harezlak, Jaroslaw
    Abstract: Brain imaging studies collect multiple imaging data types, but most analyses are done for each modality separately. Statistical methods that simultaneously utilize and combine multiple data types can instead provide a more holistic view of brain function. Here we model associations between alcohol abuse phenotypes and imaging data while incorporating prior scientific knowledge. Specifically, we utilize cortical thickness and integrated rectified mean curvature measures obtained by FreeSurfer software [1] to predict the alcoholism-related phenotypes while incorporating prior information from the structural connectivity between cortical regions. The sample consisted of 148 young (21-35 years) social-to-heavy drinking male subjects from several alcoholism risk studies [2,3,4]. Structural connectivity model [5] was used to estimate the density of connections between 66 cortical regions based on Desikan-Killiany atlas [6]. We employed a functional linear model with a penalty operator to quantify the relative contributions of imaging markers obtained from high resolution structural MRI (cortical thickness and curvature) as predictors of drinking frequency and risk-relevant personality traits, while co-varying for age. Model parameters were estimated by a unified approach directly incorporating structural connectivity information into the estimation by exploiting the joint eigenproperties of the predictors and the penalty operator [7]. We found that the best predictive imaging markers of the Alcohol Use Disorders Identification Test (AUDIT) score were the average thickness of left frontal pole (-), right transverse temporal gyrus (+), left inferior parietal lobule (+), right supramarginal gyrus (-), right rostral middle frontal gyrus (+), right precentral gyrus (+), left superior parietal lobule (-), left lateral orbitofrontal cortex (+), left rostral middle frontal gyrus (+), left postcentral gyrus (+) and left supramarginal gyrus (-), where (+) denotes positive and (-) negative association. In summary, the use of structural connectivity information allowed the incorporation of different modalities in associating cortical measures and alcoholism risk.
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    Self-Association of CaMKII-Delta in Low ATP/Low pH Conditions
    (Office of the Vice Chancellor for Research, 2015-04-17) Nelson, Ross M.; Hudmon, Andy
    Calcium-Calmodulin Dependent Protein Kinase II (CaMKII), an enzyme critical for brain function and involved in learning and memory, becomes inactive and aggregates following ischemic insult such as seen with stroke or traumatic brain injury. The Hudmon Lab’s working model is that loss of CaMKII signaling exacerbates glutamate excitotoxicity, in turn inducing astrocytes to release neurotoxic levels of ATP, causing secondary cell death. CaMKII can autophosphorylate resulting in autonomous activity, and research by Hudmon Lab reveals that CaMKII will inactivate and self-associate when activating under low pH and low ATP conditions. CaMKII is coded by four genes, and for this study we focus on the alpha and delta isoforms. Alpha is found primarily in neurons and readily aggregates under conditions mimicking ischemic stress. However, delta is primarily expressed in astrocytes and its response to ischemic stress is uncharted territory. We ask how CaMKII delta self-associates under autophosphorylation conditions mimicking ischemic stress (low pH, low ATP) and how it differs from CaMKII alpha self-association. We use real-time light scattering and sedimentation assay to elucidate the time-course of delta aggregation as well as the kinase’s sensitivity to differing pH and ATP concentrations. Light scattering suggests that alpha and delta have a similar aggregation profile, but also that delta has reduced light scattering over time. Sedimentation analysis suggests delta truly does aggregate under these conditions and that it undergoes a molecular weight shift, indicative of autophosphorylation-induced inactivation. In future studies, we plan to investigate delta’s kinase activity under aggregation conditions, perform the same experiments detailed here on the gamma isoform, and investigate delta and gamma aggregation directly in astrocytes. If we can understand how all the isoforms of CaMKII aggregate, it may prove to be a novel research topic for therapies aimed at neuroprotection in victims of ischemic insults.