Quantitative MRI of Microstructure and Iron Homeostasis in ADHD Brain

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Attention-Deficit/Hyperactivity Disorder is the most studied condition in child psychiatry, reflecting its high prevalence and significant lifelong impairment. Despite progress in documenting the biological bases for the disorder, we still lack useful models of pathophysiology. Similar to many other psychiatric illnesses, ADHD is believed to result from compromises in the integrity of distributed neural circuits, however, the neural bases of ADHD remain insufficiently specified. Children with ADHD also have globally decreased thickness of the cortical mantle, which is regionally most pronounced in superior and medial prefrontal cortex. Besides this net volumetric deficit, children with ADHD also exhibit profoundly delayed developmental trajectories of the frontal cortical sculpting that normally takes place over late childhood and early adolescence. In general, both the microstructure and the neurophysiology of brain tissues are closely associated with their underlying function and it is well known that iron is important for normal brain development through its essential role in myelination. Although several studies have suggested a link between serum iron abnormalities and ADHD, the involvement of brain iron homeostasis and its effects on ADHD have not been studied directly. All of these findings highlight the importance of addressing the biophysical and neurophysiological foundation of otherwise non-specific morphologic findings. The goal of this proposal is to investigate the relationship between brain iron homeostasis and tissue microstructure in normal and ADHD children with particular focus on the medial frontal-parietal circuits. Specifically, we are interested in whether altered brain iron homeostasis and tissue microstructure are correlated with age, gender and disease severity. To investigate this, we will conduct a cross-sectional study in both typically developing and ADHD children using well established MRI techniques (T2, T2* and diffusion tensor imaging) along with two new quantitative MRI techniques; Magnetic Field Correlation (MFC) imaging and Diffusional Kurtosis Imaging (DKI). This approach will lead to a better understanding of the disease process and, potentially, to a means of monitoring therapy