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      Maturing Thalamocortical Functional Connectivity Across Development

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          Abstract

          Recent years have witnessed a surge of investigations examining functional brain organization using resting-state functional connectivity MRI (rs-fcMRI). To date, this method has been used to examine systems organization in typical and atypical developing populations. While the majority of these investigations have focused on cortical–cortical interactions, cortical–subcortical interactions also mature into adulthood. Innovative work by Zhang et al. ( 2008) in adults have identified methods that utilize rs-fcMRI and known thalamo-cortical topographic segregation to identify functional boundaries in the thalamus that are remarkably similar to known thalamic nuclear grouping. However, despite thalamic nuclei being well formed early in development, the developmental trajectory of functional thalamo-cortical relations remains unexplored. Thalamic maps generated by rs-fcMRI are based on functional relationships, and should modify with the dynamic thalamo-cortical changes that occur throughout maturation. To examine this possibility, we employed a strategy as previously described by Zhang et al. to a sample of healthy children, adolescents, and adults. We found strengthening functional connectivity of the cortex with dorsal/anterior subdivisions of the thalamus, with greater connectivity observed in adults versus children. Temporal lobe connectivity with ventral/midline/posterior subdivisions of the thalamus weakened with age. Changes in sensory and motor thalamo-cortical interactions were also identified but were limited. These findings are consistent with known anatomical and physiological cortical–subcortical changes over development. The methods and developmental context provided here will be important for understanding how cortical–subcortical interactions relate to models of typically developing behavior and developmental neuropsychiatric disorders.

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          Most cited references30

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          The adolescent brain.

          Adolescence is a developmental period characterized by suboptimal decisions and actions that are associated with an increased incidence of unintentional injuries, violence, substance abuse, unintended pregnancy, and sexually transmitted diseases. Traditional neurobiological and cognitive explanations for adolescent behavior have failed to account for the nonlinear changes in behavior observed during adolescence, relative to both childhood and adulthood. This review provides a biologically plausible model of the neural mechanisms underlying these nonlinear changes in behavior. We provide evidence from recent human brain imaging and animal studies that there is a heightened responsiveness to incentives and socioemotional contexts during this time, when impulse control is still relatively immature. These findings suggest differential development of bottom-up limbic systems, implicated in incentive and emotional processing, to top-down control systems during adolescence as compared to childhood and adulthood. This developmental pattern may be exacerbated in those adolescents prone to emotional reactivity, increasing the likelihood of poor outcomes.
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            Regional differences in synaptogenesis in human cerebral cortex.

            The formation of synaptic contacts in human cerebral cortex was compared in two cortical regions: auditory cortex (Heschl's gyrus) and prefrontal cortex (middle frontal gyrus). Synapse formation in both cortical regions begins in the fetus, before conceptual age 27 weeks. Synaptic density increases more rapidly in auditory cortex, where the maximum is reached near postnatal age 3 months. Maximum synaptic density in middle frontal gyrus is not reached until after age 15 months. Synaptogenesis occurs concurrently with dendritic and axonal growth and with myelination of the subcortical white matter. A phase of net synapse elimination occurs late in childhood, earlier in auditory cortex, where it has ended by age 12 years, than in prefrontal cortex, where it extends to midadolescence. Synaptogenesis and synapse elimination in humans appear to be heterochronous in different cortical regions and, in that respect, appears to differ from the rhesus monkey, where they are concurrent. In other respects, including overproduction of synaptic contacts in infancy, persistence of high levels of synaptic density to late childhood or adolescence, the absolute values of maximum and adult synaptic density, and layer specific differences, findings in the human resemble those in rhesus monkeys.
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              Synaptic density in human frontal cortex - developmental changes and effects of aging.

              Density of synaptic profiles in layer 3 of middle frontal gyrus was quantitated in 21 normal human brains ranging from newborn to age 90 years. Synaptic profiles could be reliably demonstrated by the phosphotungstic acid method (Bloom and Aghajanian) in tissue fixed up to 36 h postmortem. Synaptic density was constant throughout adult life (ages 16--72 years) with a mean of 11.05 X 10(8) synapses/cu.mm +/- 0.41 S.E.M. There was a slight decline in synaptic density in brains of the aged (ages 74--90 years) with a mean of 9.56 X 10(8) synapses/cu.mm +/- 0.28 S.E.M. in 4 samples (P less than 0.05). Synaptic density in neonatal brains was already high--in the range seen in adults. However, synaptic morphology differed; immature profiles had an irregular presynaptic dense band instead of the separate presynaptic projections seen in mature synapses. Synaptic density increased during infancy, reaching a maximum at age 1--2 years which was about 50% above the adult mean. The decline in synaptic density observed between ages 2--16 years was accompanied by a slight decrease in neuronal density. Human cerebral cortex is one of a number of neuronal systems in which loss of neurons and synapses appears to occur as a late developmental event.

                Author and article information

                Journal
                Front Syst Neurosci
                Front. Syst. Neurosci.
                Frontiers in Systems Neuroscience
                Frontiers Research Foundation
                1662-5137
                01 March 2010
                18 May 2010
                2010
                : 4
                : 10
                Affiliations
                [1] 1simpleDepartment of Psychiatry, Oregon Health and Science University Portland, OR, USA
                [2] 2simpleDepartment of Radiology, Washington University School of Medicine St. Louis, MO, USA
                [3] 3simpleDepartment of Behavioral Neuroscience, Oregon Health and Science University Portland, OR, USA
                Author notes

                Edited by: Lucina Q. Uddin, Stanford University, USA

                Reviewed by: Beatriz Luna, University of Pittsburgh, USA; Daniel Margulies, Max Planck Institute, Germany

                *Correspondence: Damien A. Fair, Department of Psychiatry, Oregon Health and Science University, 3181 SW Sam Jackson Park Road UHN80R1, Portland, OR 97239, USA. e-mail: damien.fair@ 123456aya.yale.edu ; Bonnie J. Nagel, Department of Psychiatry, Oregon Health and Science University, 3181 SW Sam Jackson Park Road DC7P, Portland, Oregon 97239, USA. e-mail: nagelb@ 123456ohsu.edu
                Article
                10.3389/fnsys.2010.00010
                2876871
                20514143
                efafeb8e-e2ae-4571-9ab9-6e7bec76130e
                Copyright © 2010 Fair, Bathula, Mills, Dias, Blythe, Zhang, Snyder, Raichle, Stevens, Nigg and Nagel.

                This is an open-access article subject to an exclusive license agreement between the authors and the Frontiers Research Foundation, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are credited.

                History
                : 05 February 2010
                : 06 April 2010
                Page count
                Figures: 4, Tables: 1, Equations: 0, References: 79, Pages: 10, Words: 8568
                Categories
                Neuroscience
                Original Research

                Neurosciences
                thalamus,mri,functional connectivity,fcmri,nuclei,development,subcortical
                Neurosciences
                thalamus, mri, functional connectivity, fcmri, nuclei, development, subcortical

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