Synergy of image analysis for animal and human neuroimaging supports translational research on drug abuse

pre-printThe use of structural magnetic resonance imaging (sMRI) and diffusion tensor imaging (DTI) in animal models of neurophysiology is of increasing interest to the neuroscience community. In this work, we present our approach to create optimal translational studies that include both animal and human neuroimaging data within the frameworks of a study of post-natal neuro-development in intra-uterine cocaine-exposure. We propose the use of non-invasive neuroimaging to study developmental brain structural and white matter pathway abnormalities via sMRI and DTI, as advanced MR imaging technology is readily available and automated image analysis methodology have recently been transferred from the human to animal imaging setting. For this purpose, we developed a synergistic, parallel approach to imaging and image analysis for the human and the rodent branch of our study. We propose an equivalent design in both the selection of the developmental assessment stage and the neuroimaging setup. This approach brings significant advantages to study neurobiological features of early brain development that are common to animals and humans but also preserve analysis capabilities only possible in animal research. This paper presents the main framework and individual methods for the proposed cross-species study design, as well as preliminary DTI cross-species comparative results in the intra-uterine cocaine-exposure study

Desikan-Killiany-Tourville Atlas Compatible Version of M-CRIB Neonatal Parcellated Whole Brain Atlas: The M-CRIB 2.0

Our recently published M-CRIB atlas comprises 100 neonatal brain regions including 68 compatible with the widely-used Desikan-Killiany adult cortical atlas. A successor to the Desikan-Killiany atlas is the Desikan-Killiany-Tourville atlas, in which some regions with unclear boundaries were removed, and many existing boundaries were revised to conform to clearer landmarks in sulcal fundi. Our first aim here was to modify cortical M-CRIB regions to comply with the Desikan-Killiany-Tourville protocol, in order to offer: (a) compatibility with this adult cortical atlas, (b) greater labeling accuracy due to clearer landmarks, and (c) optimisation of cortical regions for integration with surface-based infant parcellation pipelines. Secondly, we aimed to update subcortical regions in order to offer greater compatibility with subcortical segmentations produced in FreeSurfer. Data utilized were the T2-weighted MRI scans in our M-CRIB atlas, for 10 healthy neonates (post-menstrual age at MRI 40–43 weeks, four female), and corresponding parcellated images. Edits were performed on the parcellated images in volume space using ITK-SNAP. Cortical updates included deletion of frontal and temporal poles and ‘Banks STS,’ and modification of boundaries of many other regions. Changes to subcortical regions included the addition of ‘ventral diencephalon,’ and deletion of ‘subcortical matter’ labels. A detailed updated parcellation protocol was produced. The resulting whole-brain M-CRIB 2.0 atlas comprises 94 regions altogether. This atlas provides comparability with adult Desikan-Killiany-Tourville-labeled cortical data and FreeSurfer-labeed subcortical data, and is more readily adaptable for incorporation into surface-based neonatal parcellation pipelines. As such, it offers the ability to help facilitate a broad range of investigations into brain structure and function both at the neonatal time point and developmentally across the lifespan

Doctor of Philosophy

dissertationMagnetic Resonance (MR) is a relatively risk-free and flexible imaging modality that is widely used for studying the brain. Biophysical and chemical properties of brain tissue are captured by intensity measurements in T1W (T1-Weighted) and T2W (T2-Weighted) MR scans. Rapid maturational processes taking place in the infant brain manifest as changes in co{\tiny }ntrast between white matter and gray matter tissue classes in these scans. However, studies based on MR image appearance face severe limitations due to the uncalibrated nature of MR intensity and its variability with respect to changing conditions of scan. In this work, we develop a method for studying the intensity variations between brain white matter and gray matter that are observed during infant brain development. This method is referred to by the acronym WIVID (White-gray Intensity Variation in Infant Development). WIVID is computed by measuring the Hellinger Distance of separation between intensity distributions of WM (White Matter) and GM (Gray Matter) tissue classes. The WIVID measure is shown to be relatively stable to interscan variations compared with raw signal intensity and does not require intensity normalization. In addition to quantification of tissue appearance changes using the WIVID measure, we test and implement a statistical framework for modeling temporal changes in this measure. WIVID contrast values are extracted from MR scans belonging to large-scale, longitudinal, infant brain imaging studies and modeled using the NLME (Nonlinear Mixed Effects) method. This framework generates a normative model of WIVID contrast changes with time, which captures brain appearance changes during neurodevelopment. Parameters from the estimated trajectories of WIVID contrast change are analyzed across brain lobes and image modalities. Parameters associated with the normative model of WIVID contrast change reflect established patterns of region-specific and modality-specific maturational sequences. We also detect differences in WIVID contrast change trajectories between distinct population groups. These groups are categorized based on sex and risk/diagnosis for ASD (Autism Spectrum Disorder). As a result of this work, the usage of the proposed WIVID contrast measure as a novel neuroimaging biomarker for characterizing tissue appearance is validated, and the clinical potential of the developed framework is demonstrated

Micro-, Meso- and Macro-Connectomics of the Brain

Neurosciences, Neurolog

Early postnatal development of neocortex-wide activity patterns in GABAergic and pyramidal neurons

Before the onset of sensory experience, developing circuits generate synchronised activity that will not only influence its wiring, but ultimately contribute to behaviour. These complex functions rely on widely distributed cortical that simultaneously operate at multiple spatiotemporal scales. The timing of GABAergic maturation appears to align with the developmental trajectories of cortical regions, playing a crucial role in the functional development of individual brain areas. While local connectivity in cortical microcircuits has been extensively studied, the dynamics of brain-wide functional maturation, especially for GABAergic populations, remain underexplored. In this project, a dual-colour widefield calcium imaging approach was developed to examine the neocortex-wide dynamics of cortical GABAergic and excitatory neurons simultaneously across early postnatal development. This study provides the first broad description of neocortex-wide GABAergic developmental trajectories and their cross-talk with excitatory dynamics during the second and third postnatal weeks. The observed spontaneous activity revealed discrete activity domains, reflecting the modular organisation of the cortex. Both excitatory and GABAergic population exhibited an increase in the size and frequency of activity motifs, as well as changes in motif variability. However, as they matured, the distribution of these spatiotemporal properties displayed divergent trajectories across populations and regions. These findings suggest fundamental differences in the spatial organisation of both populations, indicating potential distinct roles in cortical network function development. Moreover, while excitatory and GABAergic dynamics exhibited high correlations, brief deviations from perfect timing were observed. This correlation patterns changed significantly during development and across regions, with the two populations gradually becoming more correlated as they matured. Manipulating inhibition in vivo disrupted these fluctuations, impacting both local activity and the wider functional network.These findings provide valuable insights into the developmental trajectories of spontaneous activity patterns in excitatory and GABAergic cell populations during early postnatal development. The interplay between both neuronal populations plays a critical role in shaping activity patterns, and understanding the underlying mechanisms of their development can provide valuable insights into neurodevelopmental disorders

Bilingualism across the lifespan: Neuroanatomical correlates

187 p.Recently, an increasing number of studies addressing the neuroanatomical bases of bilingualism have appeared (Garcia-Penton et al., 2016). However, the results are variable and in sorne cases conflicting,and consequen y it is still a matter of debate how brain changes due to bilingual experience.The present study will try to shed sorne light on the field by adding fresh new evidence testing children and elderly high proficient early Spanish-Basque bilinguals, two very typologically different languages . The proposed work will use large-scale brain-mapping techniques to explore the relationship between structure and function, as a more holistic and realistic approach to understanding comprehensively the neural bases of bilingualism. This integrational perspectiva will also promote convergent evidence about the specialization and integration of the neural networks in bilingualism. As such, this work will study the organisation of brain networks,either due to slow changes in brain areas and their wiring (namely, the structural plasticity), or due to fast modulation of their interactions (namely, functional plasticity).This thesis will employ Functional Magnetic Resonance lmaging (fMRI) during resting-state in combination with Diffusion-Weighted Magnetic Resonance lmaging (DW-MRI) to determine functional and structural connectivity, respectively. Both techniques will make it possible to model the large-scale structural/functional connectivity maps by means of a high­ dimensional parcellation of the grey matter (GM) in the brain instead of limiting analysis to specific regions of interest, as done in previous studies. A 30 high resolution whole-head anatomical sean (T1-MRI) will be used in order to generate GM parcellations employed in the connectivity analysis, but also to identify regional differential structural patterns associated with bilingualism, using voxel-based and surface-based analyses of the GM. Network­ based statistics (Zalesky et al., 2010) and graph theoretical approaches (Latora & Marchiori, 2001; Rubinov and Spoms, 201O) will be employed to investigate differences between groups in connectiv ity pattems, by isolating sets of regions interconnected differently between groups, and in topological properties of the networks, by measuring global/local efficiency. The main findings of this research on bilingualism across different groups of age (childhood and elderly) suggested that structural brain plasticity related to bilingualism was so small, unstable, subtle and transient that it was very difficult to detect even in lifelong bilinguals. A fact that is consisten! with the curren! ambiguous picture in bilingualism studies (Garcia-Pentón et al.,2016; see also others, Baum & Titone,2014; Costa,& Sebastián-Gallés , 2014; Li, Legault, & Litcofsky, 2014; Paap et al., 2015; de Bruin et al., 2015a). However, this study suggested that even when the brain did not display focal brain differences (i.e. did not show any specialization) it could still show differences at the global level. Specifically,the evidence draws attention that lifelong bilingualism could pinpoint a gain toward a better neural reserve in aging due to the whole-network graph-efficiency observed in elderly lifelono bilinouals