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Item Altered cerebellar-cortical resting-state functional connectivity in cannabis users(Sage, 2021) Schnakenberg Martin, Ashley M.; Kim, Dae-Jin; Newman, Sharlene D.; Cheng, Hu; Hetrick, William P.; Mackie, Ken; O’Donnell, Brian F.; Psychiatry, School of MedicineBackground: Cannabis use has been associated with abnormalities in cerebellar mediated motor and non-motor (i.e. cognition and personality) phenomena. Since the cerebellum is a region with high cannabinoid type 1 receptor density, these impairments may reflect alterations of signaling between the cerebellum and other brain regions. Aims: We hypothesized that cerebellar-cortical resting-state functional connectivity (rsFC) would be altered in cannabis users, relative to their non-using peers. It was also hypothesized that differences in rsFC would be associated with cannabis use features, such as age of initiation and lifetime use. Methods: Cerebellar-cortical and subcortical rsFCs were computed between 28 cerebellar lobules, defined by a spatially unbiased atlas template of the cerebellum, and individual voxels in the cerebral regions, in 41 regular cannabis users (20 female) and healthy non-using peers (N = 31; 18 female). We also investigated associations between rsFC and cannabis use features (e.g. lifetime cannabis use and age of initiation). Results: Cannabis users demonstrated hyperconnectivity between the anterior cerebellar regions (i.e. lobule I-IV) with the posterior cingulate cortex, and hypoconnectivity between the rest of the cerebellum (i.e. Crus I and II, lobule VIIb, VIIIa, VIIIb, IX, and X) and the cortex. No associations were observed between features of cannabis use and rsFC. Conclusions: Cannabis use was associated with altered patterns of rsFC from the cerebellum to the cerebral cortex which may have a downstream impact on behavior and cognition.Item Cohort study into the neural correlates of postoperative delirium: the role of connectivity and slow-wave activity(Elsevier, 2020-07) Tanabe, Sean; Mohanty, Rosaleena; Lindroth, Heidi; Casey, Cameron; Ballweg, Tyler; Farahbakhsh, Zahra; Krause, Bryan; Prabhakaran, Vivek; Banks, Matthew I.; Sanders, Robert D.; Medicine, School of MedicineBackground: Delirium frequently affects older patients, increasing morbidity and mortality; however, the pathogenesis is poorly understood. Herein, we tested the cognitive disintegration model, which proposes that a breakdown in frontoparietal connectivity, provoked by increased slow-wave activity (SWA), causes delirium. Methods: We recruited 70 surgical patients to have preoperative and postoperative cognitive testing, EEG, blood biomarkers, and preoperative MRI. To provide evidence for causality, any putative mechanism had to differentiate on the diagnosis of delirium; change proportionally to delirium severity; and correlate with a known precipitant for delirium, inflammation. Analyses were adjusted for multiple corrections (MCs) where appropriate. Results: In the preoperative period, subjects who subsequently incurred postoperative delirium had higher alpha power, increased alpha band connectivity (MC P<0.05), but impaired structural connectivity (increased radial diffusivity; MC P<0.05) on diffusion tensor imaging. These connectivity effects were correlated (r2=0.491; P=0.0012). Postoperatively, local SWA over frontal cortex was insufficient to cause delirium. Rather, delirium was associated with increased SWA involving occipitoparietal and frontal cortex, with an accompanying breakdown in functional connectivity. Changes in connectivity correlated with SWA (r2=0.257; P<0.0001), delirium severity rating (r2=0.195; P<0.001), interleukin 10 (r2=0.152; P=0.008), and monocyte chemoattractant protein 1 (r2=0.253; P<0.001). Conclusions: Whilst frontal SWA occurs in all postoperative patients, delirium results when SWA progresses to involve posterior brain regions, with an associated reduction in connectivity in most subjects. Modifying SWA and connectivity may offer a novel therapeutic approach for delirium.Item Connectedness of Existence(2014) Ingram, Margaret Elizabeth; Setser, MeredithI am drawn to the most human of things, the ordinary everyday experiences that connect us. I seek to remember pieces of life that are easily forgotten or left behind. It is within the constructs of interdependence that my work explores the poetic space of a shared human experience. These connections are made evident through the suggestion of memory, identity and the idea of the viewer as collaborator. I seek to create a narrative in which the viewer becomes aware of change and discovery within the behavior of an individual self. In my most recent work, the idea of the viewer has visually and metaphorically manifested into the act of drawing a circle. The shape of the circle is meant to be representative of the nature of experience within the intricacies of both the enlightened mind as well as the confused mind. It is a mutual circle or a circle of togetherness where the connectedness of our existence becomes indisputable. The circle in the beginning and ending, presence and absence. The viewer, then, becomes a silent collaborator who quietly charges my work as I search for social understanding of both the viewer and myself. In this way the viewer becomes a willing participant as well as the subject.Item A Genome Wide Association Study of Interhemispheric Theta EEG Coherence: Implications for Neural Connectivity and Alcohol Use Behavior(Springer Nature, 2021) Meyers, Jacquelyn L.; Zhang, Jian; Chorlian, David B.; Pandey, Ashwini K.; Kamarajan, Chella; Wang, Jen-Chyong; Wetherill, Leah; Lai, Dongbing; Chao, Michael; Chan, Grace; Kinreich, Sivan; Kapoor, Manav; Bertelsen, Sarah; McClintick, Jeanette; Bauer, Lance; Hesselbrock, Victor; Kuperman, Samuel; Kramer, John; Salvatore, Jessica E.; Dick, Danielle M.; Agrawal, Arpana; Foroud, Tatiana; Edenberg, Howard J.; Goate, Alison; Porjesz, Bernice; Medical and Molecular Genetics, School of MedicineAberrant connectivity of large-scale brain networks has been observed among individuals with alcohol use disorders (AUDs) as well as in those at risk, suggesting deficits in neural communication between brain regions in the liability to develop AUD. Electroencephalographical (EEG) coherence, which measures the degree of synchrony between brain regions, may be a useful measure of connectivity patterns in neural networks for studying the genetics of AUD. In 8810 individuals (6644 of European and 2166 of African ancestry) from the Collaborative Study on the Genetics of Alcoholism (COGA), we performed a Multi-Trait Analyses of genome-wide association studies (MTAG) on parietal resting-state theta (3-7 Hz) EEG coherence, which previously have been associated with AUD. We also examined developmental effects of GWAS findings on trajectories of neural connectivity in a longitudinal subsample of 2316 adolescent/young adult offspring from COGA families (ages 12-30) and examined the functional and clinical significance of GWAS variants. Six correlated single nucleotide polymorphisms located in a brain-expressed lincRNA (ENSG00000266213) on chromosome 18q23 were associated with posterior interhemispheric low theta EEG coherence (3-5 Hz). These same variants were also associated with alcohol use behavior and posterior corpus callosum volume, both in a subset of COGA and in the UK Biobank. Analyses in the subsample of COGA offspring indicated that the association of rs12954372 with low theta EEG coherence occurred only in females, most prominently between ages 25 and 30 (p < 2 × 10-9). Converging data provide support for the role of genetic variants on chromosome 18q23 in regulating neural connectivity and alcohol use behavior, potentially via dysregulated myelination. While findings were less robust, genome-wide associations were also observed with rs151174000 and parieto-frontal low theta coherence, rs14429078 and parieto-occipital interhemispheric high theta coherence, and rs116445911 with centro-parietal low theta coherence. These novel genetic findings highlight the utility of the endophenotype approach in enhancing our understanding of mechanisms underlying addiction susceptibility.Item Regression models for partially localized fMRI connectivity analyses(Frontiers Media, 2023-11-13) Smith, Bonnie B.; Zhao, Yi; Lindquist, Martin A.; Caffo, Brian; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public HealthBackground: Brain functional connectivity analysis of resting-state functional magnetic resonance imaging (fMRI) data is typically performed in a standardized template space assuming consistency of connections across subjects. Analysis methods can come in the form of one-edge-at-a-time analyses or dimension reduction/decomposition methods. Common to these approaches is an assumption that brain regions are functionally aligned across subjects; however, it is known that this functional alignment assumption is often violated. Methods: In this paper, we use subject-level regression models to explain intra-subject variability in connectivity. Covariates can include factors such as geographic distance between two pairs of brain regions, whether the two regions are symmetrically opposite (homotopic), and whether the two regions are members of the same functional network. Additionally, a covariate for each brain region can be included, to account for the possibility that some regions have consistently higher or lower connectivity. This style of analysis allows us to characterize the fraction of variation explained by each type of covariate. Additionally, comparisons across subjects can then be made using the fitted connectivity regression models, offering a more parsimonious alternative to edge-at-a-time approaches. Results: We apply our approach to Human Connectome Project data on 268 regions of interest (ROIs), grouped into eight functional networks. We find that a high proportion of variation is explained by region covariates and network membership covariates, while geographic distance and homotopy have high relative importance after adjusting for the number of predictors. We also find that the degree of data repeatability using our connectivity regression model-which uses only partial location information about pairs of ROI's-is comparably as high as the repeatability obtained using full location information. Discussion: While our analysis uses data that have been transformed into a common template-space, we also envision the method being useful in multi-atlas registration settings, where subject data remains in its own geometry and templates are warped instead. These results suggest the tantalizing possibility that fMRI connectivity analysis can be performed in subject-space, using less aggressive registration, such as simple affine transformations, multi-atlas subject-space registration, or perhaps even no registration whatsoever.Item Tractography of Porcine Meniscus Microstructure Using High-Resolution Diffusion Magnetic Resonance Imaging(Frontiers Media, 2022-05-10) Shen, Jikai; Zhao, Qi; Qi, Yi; Cofer, Gary; Johnson, G. Allan; Wang, Nian; Radiology and Imaging Sciences, School of MedicineTo noninvasively evaluate the three-dimensional collagen fiber architecture of porcine meniscus using diffusion MRI, meniscal specimens were scanned using a 3D diffusion-weighted spin-echo pulse sequence at 7.0 T. The collagen fiber alignment was revealed in each voxel and the complex 3D collagen network was visualized for the entire meniscus using tractography. The proposed automatic segmentation methods divided the whole meniscus to different zones (Red-Red, Red-White, and White-White) and different parts (anterior, body, and posterior). The diffusion tensor imaging (DTI) metrics were quantified based on the segmentation results. The heatmap was generated to investigate the connections among different regions of meniscus. Strong zonal-dependent diffusion properties were demonstrated by DTI metrics. The fractional anisotropy (FA) value increased from 0.13 (White-White zone) to 0.26 (Red-Red zone) and the radial diffusivity (RD) value changed from 1.0 × 10-3 mm2/s (White-White zone) to 0.7 × 10-3 mm2/s (Red-Red zone). Coexistence of both radial and circumferential collagen fibers in the meniscus was evident by diffusion tractography. Weak connections were found between White-White zone and Red-Red zone in each part of the meniscus. The anterior part and posterior part were less connected, while the body part showed high connections to both anterior part and posterior part. The tractography based on diffusion MRI may provide a complementary method to study the integrity of meniscus and nondestructively visualize the 3D collagen fiber architecture.