Workflow and Atlas System for Brain-Wide Mapping of Axonal Connectivity in Rat

Detailed knowledge about the anatomical organization of axonal connections is important for understanding normal functions of brain systems and disease-related dysfunctions. Such connectivity data are typically generated in neuroanatomical tract-tracing experiments in which specific axonal connections are visualized in histological sections. Since journal publications typically only accommodate restricted data descriptions and example images, literature search is a cumbersome way to retrieve overviews of brain connectivity. To explore more efficient ways of mapping, analyzing, and sharing detailed axonal connectivity data from the rodent brain, we have implemented a workflow for data production and developed an atlas system tailored for online presentation of axonal tracing data. The system is available online through the Rodent Brain WorkBench (www.rbwb.org; Whole Brain Connectivity Atlas) and holds experimental metadata and high-resolution images of histological sections from experiments in which axonal tracers were injected in the primary somatosensory cortex. We here present the workflow and the data system, and exemplify how the online image repository can be used to map different aspects of the brain-wide connectivity of the rat primary somatosensory cortex, including not only presence of connections but also morphology, densities, and spatial organization. The accuracy of the approach is validated by comparing results generated with our system with findings reported in previous publications. The present study is a contribution to a systematic mapping of rodent brain connections and represents a starting point for further large-scale mapping efforts

Fine-Granularity Functional Interaction Signatures for Characterization of Brain Conditions

In the human brain, functional activity occurs at multiple spatial scales. Current studies on functional brain networks and their alterations in brain diseases via resting-state functional magnetic resonance imaging (rs-fMRI) are generally either at local scale (regionally confined analysis and inter-regional functional connectivity analysis) or at global scale (graph theoretic analysis). In contrast, inferring functional interaction at fine-granularity sub-network scale has not been adequately explored yet. Here our hypothesis is that functional interaction measured at fine-granularity subnetwork scale can provide new insight into the neural mechanisms of neurological and psychological conditions, thus offering complementary information for healthy and diseased population classification. In this paper, we derived fine-granularity functional interaction (FGFI) signatures in subjects with Mild Cognitive Impairment (MCI) and Schizophrenia by diffusion tensor imaging (DTI) and rsfMRI, and used patient-control classification experiments to evaluate the distinctiveness of the derived FGFI features. Our experimental results have shown that the FGFI features alone can achieve comparable classification performance compared with the commonly used inter-regional connectivity features. However, the classification performance can be substantially improved when FGFI features and inter-regional connectivity features are integrated, suggesting the complementary information achieved from the FGFI signatures

Anatomy-Guided Dense Individualized and Common Connectivity-Based Cortical Landmarks (A-DICCCOL)

Establishment of structural and functional correspondences of human brain that can be quantitatively encoded and reproduced across different subjects and populations is one of the key issues in brain mapping. As an attempt to address this challenge, our recently developed Dense Individualized and Common Connectivity-based Cortical Landmarks (DICCCOL) system reported 358 connectional landmarks, each of which possesses consistent DTI-derived white matter fiber connection pattern that is reproducible in over 240 healthy brains. However, the DICCCOL system can be substantially improved by integrating anatomical and morphological information during landmark initialization and optimization procedures. In this paper, we present a novel anatomy-guided landmark discovery framework that defines and optimizes landmarks via integrating rich anatomical, morphological, and fiber connectional information for landmark initialization, group-wise optimization and prediction, which are formulated and solved as an energy minimization problem. The framework finally determined 555 consistent connectional landmarks. Validation studies demonstrated that the 555 landmarks are reproducible, predictable, and exhibited reasonably accurate anatomical, connectional, and functional correspondences across individuals and populations and thus are named anatomy-guided DICCCOL or A-DICCCOL. This A-DICCCOL system represents common cortical architectures with anatomical, connectional, and functional correspondences across different subjects and would potentially provide opportunities for various applications in brain science