Browsing by Subject "Connectome"
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Item Open Access A Diffusion MRI Tractography Connectome of the Mouse Brain and Comparison with Neuronal Tracer Data.(Cereb Cortex, 2015-11) Calabrese, Evan; Badea, Alexandra; Cofer, Gary; Qi, Yi; Johnson, G AllanInterest in structural brain connectivity has grown with the understanding that abnormal neural connections may play a role in neurologic and psychiatric diseases. Small animal connectivity mapping techniques are particularly important for identifying aberrant connectivity in disease models. Diffusion magnetic resonance imaging tractography can provide nondestructive, 3D, brain-wide connectivity maps, but has historically been limited by low spatial resolution, low signal-to-noise ratio, and the difficulty in estimating multiple fiber orientations within a single image voxel. Small animal diffusion tractography can be substantially improved through the combination of ex vivo MRI with exogenous contrast agents, advanced diffusion acquisition and reconstruction techniques, and probabilistic fiber tracking. Here, we present a comprehensive, probabilistic tractography connectome of the mouse brain at microscopic resolution, and a comparison of these data with a neuronal tracer-based connectivity data from the Allen Brain Atlas. This work serves as a reference database for future tractography studies in the mouse brain, and demonstrates the fundamental differences between tractography and neuronal tracer data.Item Open Access Effect of Autologous Cord Blood Infusion on Motor Function and Brain Connectivity in Young Children with Cerebral Palsy: A Randomized, Placebo-Controlled Trial.(Stem cells translational medicine, 2017-12) Sun, Jessica M; Song, Allen W; Case, Laura E; Mikati, Mohamad A; Gustafson, Kathryn E; Simmons, Ryan; Goldstein, Ricki; Petry, Jodi; McLaughlin, Colleen; Waters-Pick, Barbara; Chen, Lyon W; Wease, Stephen; Blackwell, Beth; Worley, Gordon; Troy, Jesse; Kurtzberg, JoanneCerebral palsy (CP) is a condition affecting young children that causes lifelong disabilities. Umbilical cord blood cells improve motor function in experimental systems via paracrine signaling. After demonstrating safety, we conducted a phase II trial of autologous cord blood (ACB) infusion in children with CP to test whether ACB could improve function (ClinicalTrials.gov, NCT01147653; IND 14360). In this double-blind, placebo-controlled, crossover study of a single intravenous infusion of 1-5 × 107 total nucleated cells per kilogram of ACB, children ages 1 to 6 years with CP were randomly assigned to receive ACB or placebo at baseline, followed by the alternate infusion 1 year later. Motor function and magnetic resonance imaging brain connectivity studies were performed at baseline, 1, and 2 years post-treatment. The primary endpoint was change in motor function 1 year after baseline infusion. Additional analyses were performed at 2 years. Sixty-three children (median age 2.1 years) were randomized to treatment (n = 32) or placebo (n = 31) at baseline. Although there was no difference in mean change in Gross Motor Function Measure-66 (GMFM-66) scores at 1 year between placebo and treated groups, a dosing effect was identified. In an analysis 1 year post-ACB treatment, those who received doses ≥2 × 107 /kg demonstrated significantly greater increases in GMFM-66 scores above those predicted by age and severity, as well as in Peabody Developmental Motor Scales-2 Gross Motor Quotient scores and normalized brain connectivity. Results of this study suggest that appropriately dosed ACB infusion improves brain connectivity and gross motor function in young children with CP. Stem Cells Translational Medicine 2017;6:2071-2078.Item Open Access Effect of Repetitive Transcranial Magnetic Stimulation on the Structural and Functional Connectome in Patients with Major Depressive Disorder(2017-05-08) Asturias, GabrielaThrough this whole-brain exploratory analysis, our aim is to study the effect of repetitive transcranial magnetic stimulation (rTMS) on the structural and functional connectivity of patients with major depressive disorder. Twenty-five currently depressed patients (age 21–68) participated in the study. Patients received daily 10-Hz rTMS over the left dlPFC five days/week for five weeks. Treatment response was assessed using the 24-item Hamilton Rating Scale for Depression (HAMD-24) at baseline and after the course of TMS. MRIs were acquired within seven days prior to starting rTMS and within three days after the end of treatment. Using diffusion tensor images and resting-state fMRI data we computed the whole-brain functional and structural connectomes. We used graph theory techniques to characterize brain architecture to identify potential biomarkers for depression severity and response to treatment. The frontal pole, part of the midline core in the default mode network (DMN) and the exteroception compartment of the depression network (DN), was identified as a potential biomarker for depression severity. The intracalcarine cortex and lateral occipital cortex, neither part of the default mode network and depression network, were defined as potential biomarkers for treatment response. The subcallosal cortex, orbitofrontal cortex, and supramarginal gyrus were identified as potential biomarkers for treatment response and their change across the treatment protocol could explain the simultaneous effect of rTMS on structural and functional connectivity. Ultimately, the goal is to articulate specific hypotheses that will inform treatment strategies for patients with major depressive disorder.Item Open Access Functional modular architecture underlying attentional control in aging.(NeuroImage, 2017-07) Monge, Zachary A; Geib, Benjamin R; Siciliano, Rachel E; Packard, Lauren E; Tallman, Catherine W; Madden, David JPrevious research suggests that age-related differences in attention reflect the interaction of top-down and bottom-up processes, but the cognitive and neural mechanisms underlying this interaction remain an active area of research. Here, within a sample of community-dwelling adults 19-78 years of age, we used diffusion reaction time (RT) modeling and multivariate functional connectivity to investigate the behavioral components and whole-brain functional networks, respectively, underlying bottom-up and top-down attentional processes during conjunction visual search. During functional MRI scanning, participants completed a conjunction visual search task in which each display contained one item that was larger than the other items (i.e., a size singleton) but was not informative regarding target identity. This design allowed us to examine in the RT components and functional network measures the influence of (a) additional bottom-up guidance when the target served as the size singleton, relative to when the distractor served as the size singleton (i.e., size singleton effect) and (b) top-down processes during target detection (i.e., target detection effect; target present vs. absent trials). We found that the size singleton effect (i.e., increased bottom-up guidance) was associated with RT components related to decision and nondecision processes, but these effects did not vary with age. Also, a modularity analysis revealed that frontoparietal module connectivity was important for both the size singleton and target detection effects, but this module became central to the networks through different mechanisms for each effect. Lastly, participants 42 years of age and older, in service of the target detection effect, relied more on between-frontoparietal module connections. Our results further elucidate mechanisms through which frontoparietal regions support attentional control and how these mechanisms vary in relation to adult age.Item Open Access General functional connectivity: Shared features of resting-state and task fMRI drive reliable and heritable individual differences in functional brain networks.(NeuroImage, 2019-04) Elliott, Maxwell L; Knodt, Annchen R; Cooke, Megan; Kim, M Justin; Melzer, Tracy R; Keenan, Ross; Ireland, David; Ramrakha, Sandhya; Poulton, Richie; Caspi, Avshalom; Moffitt, Terrie E; Hariri, Ahmad RIntrinsic connectivity, measured using resting-state fMRI, has emerged as a fundamental tool in the study of the human brain. However, due to practical limitations, many studies do not collect enough resting-state data to generate reliable measures of intrinsic connectivity necessary for studying individual differences. Here we present general functional connectivity (GFC) as a method for leveraging shared features across resting-state and task fMRI and demonstrate in the Human Connectome Project and the Dunedin Study that GFC offers better test-retest reliability than intrinsic connectivity estimated from the same amount of resting-state data alone. Furthermore, at equivalent scan lengths, GFC displayed higher estimates of heritability than resting-state functional connectivity. We also found that predictions of cognitive ability from GFC generalized across datasets, performing as well or better than resting-state or task data alone. Collectively, our work suggests that GFC can improve the reliability of intrinsic connectivity estimates in existing datasets and, subsequently, the opportunity to identify meaningful correlates of individual differences in behavior. Given that task and resting-state data are often collected together, many researchers can immediately derive more reliable measures of intrinsic connectivity through the adoption of GFC rather than solely using resting-state data. Moreover, by better capturing heritable variation in intrinsic connectivity, GFC represents a novel endophenotype with broad applications in clinical neuroscience and biomarker discovery.Item Open Access Human distal lung maps and lineage hierarchies reveal a bipotent progenitor.(Nature, 2022-04) Kadur Lakshminarasimha Murthy, Preetish; Sontake, Vishwaraj; Tata, Aleksandra; Kobayashi, Yoshihiko; Macadlo, Lauren; Okuda, Kenichi; Conchola, Ansley S; Nakano, Satoko; Gregory, Simon; Miller, Lisa A; Spence, Jason R; Engelhardt, John F; Boucher, Richard C; Rock, Jason R; Randell, Scott H; Tata, Purushothama RaoMapping the spatial distribution and molecular identity of constituent cells is essential for understanding tissue dynamics in health and disease. We lack a comprehensive map of human distal airways, including the terminal and respiratory bronchioles (TRBs), which are implicated in respiratory diseases1-4. Here, using spatial transcriptomics and single-cell profiling of microdissected distal airways, we identify molecularly distinct TRB cell types that have not-to our knowledge-been previously characterized. These include airway-associated LGR5+ fibroblasts and TRB-specific alveolar type-0 (AT0) cells and TRB secretory cells (TRB-SCs). Connectome maps and organoid-based co-cultures reveal that LGR5+ fibroblasts form a signalling hub in the airway niche. AT0 cells and TRB-SCs are conserved in primates and emerge dynamically during human lung development. Using a non-human primate model of lung injury, together with human organoids and tissue specimens, we show that alveolar type-2 cells in regenerating lungs transiently acquire an AT0 state from which they can differentiate into either alveolar type-1 cells or TRB-SCs. This differentiation programme is distinct from that identified in the mouse lung5-7. Our study also reveals mechanisms that drive the differentiation of the bipotent AT0 cell state into normal or pathological states. In sum, our findings revise human lung cell maps and lineage trajectories, and implicate an epithelial transitional state in primate lung regeneration and disease.Item Open Access Improved delineation of short cortical association fibers and gray/white matter boundary using whole-brain three-dimensional diffusion tensor imaging at submillimeter spatial resolution.(Brain Connect, 2014-11) Song, Allen W; Chang, Hing-Chiu; Petty, Christopher; Guidon, Arnaud; Chen, Nan-KueiRecent emergence of human connectome imaging has led to a high demand on angular and spatial resolutions for diffusion magnetic resonance imaging (MRI). While there have been significant growths in high angular resolution diffusion imaging, the improvement in spatial resolution is still limited due to a number of technical challenges, such as the low signal-to-noise ratio and high motion artifacts. As a result, the benefit of a high spatial resolution in the whole-brain connectome imaging has not been fully evaluated in vivo. In this brief report, the impact of spatial resolution was assessed in a newly acquired whole-brain three-dimensional diffusion tensor imaging data set with an isotropic spatial resolution of 0.85 mm. It was found that the delineation of short cortical association fibers is drastically improved as well as the definition of fiber pathway endings into the gray/white matter boundary-both of which will help construct a more accurate structural map of the human brain connectome.Item Open Access Low- and High-Frequency Repetitive Transcranial Magnetic Stimulation Effects on Resting-State Functional Connectivity Between the Postcentral Gyrus and the Insula.(Brain connectivity, 2019-05) Addicott, Merideth A; Luber, Bruce; Nguyen, Duy; Palmer, Hannah; Lisanby, Sarah H; Appelbaum, Lawrence GregoryThe insular cortex supports the conscious awareness of physical and emotional sensations, and the ability to modulate the insula could have important clinical applications in psychiatry. Repetitive transcranial magnetic stimulation (rTMS) uses transient magnetic fields to induce electrical currents in the superficial cortex. Given its deep location in the brain, the insula may not be directly stimulated by rTMS; however, rTMS may modulate the insula via its functional connections with superficial cortical regions. Furthermore, low- versus high-frequency rTMS is thought to have opposing effects on cortical excitability, and the present study investigated these effects on brain activity and functional connectivity with the insula. Separate groups of healthy participants (n = 14 per group) received low (1 Hz)- or high (10 Hz)-frequency rTMS in five daily sessions to the right postcentral gyrus, a superficial region known to be functionally connected to the insula. Resting-state functional connectivity (RSFC) was measured pre- and post-rTMS. Both 1 and 10 Hz rTMS increased RSFC between the right postcentral gyrus and the left insula. These results suggest that low- and high-frequency rTMS has similar long-term effects on brain activity and RSFC. However, given the lack of difference, we cannot exclude the possibility that these effects are simply due to a nonspecific effect. Given this limitation, these unexpected results underscore the need for acoustic- and stimulation-matched sham control conditions in rTMS research.Item Open Access Maintenance and Representation of Mind Wandering during Resting-State fMRI.(Scientific reports, 2017-01-12) Chou, Ying-Hui; Sundman, Mark; Whitson, Heather E; Gaur, Pooja; Chu, Mei-Lan; Weingarten, Carol P; Madden, David J; Wang, Lihong; Kirste, Imke; Joliot, Marc; Diaz, Michele T; Li, Yi-Ju; Song, Allen W; Chen, Nan-KueiMajor advances in resting-state functional magnetic resonance imaging (fMRI) techniques in the last two decades have provided a tool to better understand the functional organization of the brain both in health and illness. Despite such developments, characterizing regulation and cerebral representation of mind wandering, which occurs unavoidably during resting-state fMRI scans and may induce variability of the acquired data, remains a work in progress. Here, we demonstrate that a decrease or decoupling in functional connectivity involving the caudate nucleus, insula, medial prefrontal cortex and other domain-specific regions was associated with more sustained mind wandering in particular thought domains during resting-state fMRI. Importantly, our findings suggest that temporal and between-subject variations in functional connectivity of above-mentioned regions might be linked with the continuity of mind wandering. Our study not only provides a preliminary framework for characterizing the maintenance and cerebral representation of different types of mind wandering, but also highlights the importance of taking mind wandering into consideration when studying brain organization with resting-state fMRI in the future.Item Open Access Multi-scale graph principal component analysis for connectomics(2021) Winter, StevenIn brain connectomics, it is common to divide the cortical surface into discrete regions of interest (ROIs), and then to use these regions to induce a graph. Nodes correspond to regions of interest and edges encode summaries of the strength of connections between pairs of regions. These spatial weighted graphs are often reduced to adjacency matrices, which are then used as inputs to downstream statistical analysis. The structure of these adjacency matrices depends critically on the chosen parcellation, with finer resolutions producing unique spare patterns. Consequently, both the available methods of analysis and the conclusions from analysis depend heavily on the chosen parcellation. To solve this problem we develop a multi-scale graph factorization model, which links together scale-specific factorizations through a common set of individual-specific latent factors. These scores combine information across from different parcellations to produce a single interpretable summary of an individuals brain structure. We develop a simple, efficient algorithm, and illustrate substantial advantages over comparable single-scale methods in both simulations and analyses of the Human Connectome Project dataset.
Item Open Access Preschool anxiety disorders predict different patterns of amygdala-prefrontal connectivity at school-age.(PLoS One, 2015) Carpenter, Kimberly LH; Angold, Adrian; Chen, Nan-Kuei; Copeland, William E; Gaur, Pooja; Pelphrey, Kevin; Song, Allen W; Egger, Helen LOBJECTIVE: In this prospective, longitudinal study of young children, we examined whether a history of preschool generalized anxiety, separation anxiety, and/or social phobia is associated with amygdala-prefrontal dysregulation at school-age. As an exploratory analysis, we investigated whether distinct anxiety disorders differ in the patterns of this amygdala-prefrontal dysregulation. METHODS: Participants were children taking part in a 5-year study of early childhood brain development and anxiety disorders. Preschool symptoms of generalized anxiety, separation anxiety, and social phobia were assessed with the Preschool Age Psychiatric Assessment (PAPA) in the first wave of the study when the children were between 2 and 5 years old. The PAPA was repeated at age 6. We conducted functional MRIs when the children were 5.5 to 9.5 year old to assess neural responses to viewing of angry and fearful faces. RESULTS: A history of preschool social phobia predicted less school-age functional connectivity between the amygdala and the ventral prefrontal cortices to angry faces. Preschool generalized anxiety predicted less functional connectivity between the amygdala and dorsal prefrontal cortices in response to fearful faces. Finally, a history of preschool separation anxiety predicted less school-age functional connectivity between the amygdala and the ventral prefrontal cortices to angry faces and greater school-age functional connectivity between the amygdala and dorsal prefrontal cortices to angry faces. CONCLUSIONS: Our results suggest that there are enduring neurobiological effects associated with a history of preschool anxiety, which occur over-and-above the effect of subsequent emotional symptoms. Our results also provide preliminary evidence for the neurobiological differentiation of specific preschool anxiety disorders.Item Open Access The autism brain imaging data exchange: towards a large-scale evaluation of the intrinsic brain architecture in autism.(Molecular psychiatry, 2014-06) Di Martino, A; Yan, C-G; Li, Q; Denio, E; Castellanos, FX; Alaerts, K; Anderson, JS; Assaf, M; Bookheimer, SY; Dapretto, M; Deen, B; Delmonte, S; Dinstein, I; Ertl-Wagner, B; Fair, DA; Gallagher, L; Kennedy, DP; Keown, CL; Keysers, C; Lainhart, JE; Lord, C; Luna, B; Menon, V; Minshew, NJ; Monk, CS; Mueller, S; Müller, R-A; Nebel, MB; Nigg, JT; O'Hearn, K; Pelphrey, KA; Peltier, SJ; Rudie, JD; Sunaert, S; Thioux, M; Tyszka, JM; Uddin, LQ; Verhoeven, JS; Wenderoth, N; Wiggins, JL; Mostofsky, SH; Milham, MPAutism spectrum disorders (ASDs) represent a formidable challenge for psychiatry and neuroscience because of their high prevalence, lifelong nature, complexity and substantial heterogeneity. Facing these obstacles requires large-scale multidisciplinary efforts. Although the field of genetics has pioneered data sharing for these reasons, neuroimaging had not kept pace. In response, we introduce the Autism Brain Imaging Data Exchange (ABIDE)-a grassroots consortium aggregating and openly sharing 1112 existing resting-state functional magnetic resonance imaging (R-fMRI) data sets with corresponding structural MRI and phenotypic information from 539 individuals with ASDs and 573 age-matched typical controls (TCs; 7-64 years) (http://fcon_1000.projects.nitrc.org/indi/abide/). Here, we present this resource and demonstrate its suitability for advancing knowledge of ASD neurobiology based on analyses of 360 male subjects with ASDs and 403 male age-matched TCs. We focused on whole-brain intrinsic functional connectivity and also survey a range of voxel-wise measures of intrinsic functional brain architecture. Whole-brain analyses reconciled seemingly disparate themes of both hypo- and hyperconnectivity in the ASD literature; both were detected, although hypoconnectivity dominated, particularly for corticocortical and interhemispheric functional connectivity. Exploratory analyses using an array of regional metrics of intrinsic brain function converged on common loci of dysfunction in ASDs (mid- and posterior insula and posterior cingulate cortex), and highlighted less commonly explored regions such as the thalamus. The survey of the ABIDE R-fMRI data sets provides unprecedented demonstrations of both replication and novel discovery. By pooling multiple international data sets, ABIDE is expected to accelerate the pace of discovery setting the stage for the next generation of ASD studies.