From toddler to late teenager, the macroscopic pattern of axonal projections in the human brain remains largely unchanged while undergoing dramatic functional modifications that lead to network refinement. These functional modifications are mediated by increasing myelination and changes in axonal diameter and synaptic density, as well as changes in neurochemical mediators. Here we explore the contribution of white matter maturation to the development of connectivity between ages 2 and 18 y using high b-value diffusion MRI tractography and connectivity analysis. We measured changes in connection efficacy as the inverse of the average diffusivity along a fiber tract. We observed significant refinement in specific metrics of network topology, including a significant increase in node strength and efficiency along with a decrease in clustering. Major structural modules and hubs were in place by 2 y of age, and they continued to strengthen their profile during subsequent development. Recording resting-state functional MRI from a subset of subjects, we confirmed a positive correlation between structural and functional connectivity, and in addition observed that this relationship strengthened with age. Continuously increasing integration and decreasing segregation of structural connectivity with age suggests that network refinement mediated by white matter maturation promotes increased global efficiency. In addition, the strengthening of the correlation between structural and functional connectivity with age suggests that white matter connectivity in combination with other factors, such as differential modulation of axonal diameter and myelin thickness, that are partially captured by inverse average diffusivity, play an increasingly important role in creating brain-wide coherence and synchrony.connectome | development | graph | network dynamics | tractography M ost real-world networks do not arise all at once but, guided by rules, develop through a growth process that progressively fine-tunes the configuration of nodes and edges. Thus, an important aspect in the analysis of large-scale networks is the characterization of their dynamic development and evolution. From a theoretical point of view growth rules have been shown to have a significant effect on the emergent behavior of the final large-scale structural topology. For example, the emergence of scale-free networks can be explained by a preferential attachment rule (1, 2), with important functional consequences (3). If we can measure the growth and reshaping of connectivity that occurs with maturation during the developmental process, we can begin to infer growth rules governing this complex process and examine their functional consequences. These growth rules need to be instantiated in a biological system, and therefore the functional consequences would provide hypotheses linking emergent network properties to underlying cellular and molecular mechanisms.Real-world networks rarely grow according to simple statistical models, thus necessitating empirical sampling ov...
Diffusion-weighted magnetic resonance (MR) imaging provides image contrast that is different from that provided by conventional MR techniques. It is particularly sensitive for detection of acute ischemic stroke and differentiation of acute stroke from other processes that manifest with sudden neurologic deficits. Diffusion-weighted MR imaging also provides adjunctive information for other cerebral diseases including neoplasms, intracranial infections, traumatic brain injury, and demyelinating processes. Because stroke is common and in the differential diagnosis of most acute neurologic events, diffusion-weighted MR imaging should be considered an essential sequence, and its use in most brain MR studies is recommended.
Normal development of the cerebral cortex requires long-range migration of cortical neurons from proliferative regions deep in the brain. Lissencephaly ("smooth brain," from "lissos," meaning smooth, and "encephalos," meaning brain) is a severe developmental disorder in which neuronal migration is impaired, leading to a thickened cerebral cortex whose normally folded contour is simplified and smooth. Two identified lissencephaly genes do not account for all known cases, and additional lissencephaly syndromes have been described. An autosomal recessive form of lissencephaly (LCH) associated with severe abnormalities of the cerebellum, hippocampus and brainstem maps to chromosome 7q22, and is associated with two independent mutations in the human gene encoding reelin (RELN). The mutations disrupt splicing of RELN cDNA, resulting in low or undetectable amounts of reelin protein. LCH parallels the reeler mouse mutant (Reln(rl)), in which Reln mutations cause cerebellar hypoplasia, abnormal cerebral cortical neuronal migration and abnormal axonal connectivity. RELN encodes a large (388 kD) secreted protein that acts on migrating cortical neurons by binding to the very low density lipoprotein receptor (VLDLR), the apolipoprotein E receptor 2 (ApoER2; refs 9-11 ), alpha3beta1 integrin and protocadherins. Although reelin was previously thought to function exclusively in brain, some humans with RELN mutations show abnormal neuromuscular connectivity and congenital lymphoedema, suggesting previously unsuspected functions for reelin in and outside of the brain.
These findings support the hypothesis that the limbic system, in particular the hippocampus, may be involved in the pathophysiology of pediatric bipolar disorder. While this report may represent the largest MRI study of pediatric bipolar disorder to date, more work is needed to confirm these findings and to determine if they are unique to pediatric bipolar disorder.
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