Maturing Thalamocortical Functional Connectivity Across Development

Department of Psychiatry, Oregon Health and Science University Portland, OR, USA.
Frontiers in Systems Neuroscience 05/2010; 4(10):10. DOI: 10.3389/fnsys.2010.00010
Source: PubMed


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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Available from: Damien A Fair, Oct 07, 2015
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    • "Early in development, thalamic afferents play an important role in emerging functional specialization of cortical regions [O'Leary and Nakagawa, 2002]. There is also evidence of maturational changes in thalamocortical (TC) connectivity, with progressive strengthening of the frontal connections with dorsal/anterior subdivisions of the thalamus, but weakening of temporal lobe connectivity with ventral/midline/posterior subdivisions [Fair et al., 2010]. Growing interest in the thalamic roles beyond sensorimotor function has been fostered by evidence suggesting thalamic involvement in cognitive domains ranging from language and attention to executive functions and social motivation [Cabeza and Nyberg, 2000]. "
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    ABSTRACT: Preliminary evidence suggests aberrant (mostly reduced) thalamocortical (TC) connectivity in autism spectrum disorder (ASD), but despite the crucial role of thalamus in sensorimotor functions and its extensive connectivity with cerebral cortex, relevant evidence remains limited. We performed a comprehensive investigation of region-specific TC connectivity in ASD. Resting-state functional MRI and diffusion tensor imaging (DTI) data were acquired for 60 children and adolescents with ASD (ages 7–17 years) and 45 age, sex, and IQ-matched typically developing (TD) participants. We examined intrinsic functional connectivity (iFC) and anatomical connectivity (probabilistic tractography) with thalamus, using 68 unilateral cerebral cortical regions of interest (ROIs). For frontal and parietal lobes, iFC was atypically reduced in the ASD group for supramodal association cortices, but was increased for cingulate gyri and motor cortex. Temporal iFC was characterized by overconnectivity for auditory cortices, but underconnectivity for amygdalae. Occipital iFC was broadly reduced in the ASD group. DTI indices (such as increased radial diffusion) for regions with group differences in iFC further indicated compromised anatomical connectivity, especially for frontal ROIs, in the ASD group. Our findings highlight the regional specificity of aberrant TC connectivity in ASD. Their overall pattern can be largely accounted for by functional overconnectivity with limbic and sensorimotor regions, but underconnectivity with supramodal association cortices. This could be related to comparatively early maturation of limbic and sensorimotor regions in the context of early overgrowth in ASD, at the expense of TC connectivity with later maturing cortical regions. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc.
    Human Brain Mapping 08/2015; DOI:10.1002/hbm.22938 · 5.97 Impact Factor
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    • "Although the nature of the thalamic disruption in autism is unclear, there seems to be a dysregulation of the normal reciprocal synaptic relationship between the thalamus in the cortex that occurs during development (Fair et al., 2010; Righi et al., 2014). If MD afferent quantity is strictly coordinating PFC synaptic density, hypothetically, thalamic abnormalities could disrupt the normal developmental reduction in synapse number resulting in an over-pruning or under-pruning and compromising PFC function (see Figure 2). "
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    ABSTRACT: The mediodorsal thalamus (MD) represents a fundamental subcortical relay to the prefrontal cortex (PFC), and is thought to be highly implicated in modulation of cognitive performance. Additionally, it undergoes highly conserved developmental stages, which, when dysregulated, can have detrimental consequences. Embryonically, the MD experiences a tremendous surge in neurogenesis and differentiation, and disruption of this process may underlie the pathology in certain neurodevelopmental disorders. However, during the postnatal period, a vast amount of cell loss in the MD occurs. These together may represent an extended critical period for postnatal development, in which disturbances in the normal growth or reduction of the MD afferents to the PFC, can result in PFC-dependent cognitive, affective, or psychotic abnormalities. In this review, we explore the current knowledge supporting this hypothesis of a protracted critical period, and propose how developmental changes in the MD contribute to successful prefrontal cortical development and function. Specifically, we elaborate on the unique properties of MD-PFC connections compared with other thalamocortical afferents in sensory cortices, examine how MD-PFC innervation modulates synaptic transmission in the local prefrontal circuitry, and speculate on what occurs during postnatal development, particularly within the early neonatal stage, as well as juvenile and adolescent periods. Finally, we discuss the questions that remain and propose future experiments in order to provide perspective and novel insights into the cause of neuropsychiatric disorders associated with MD-PFC development.
    Frontiers in Human Neuroscience 01/2015; 8. DOI:10.3389/fnhum.2014.01027 · 2.99 Impact Factor
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    • "delman 2000 ) , autism ( Just et al . 2007 ) , Alzheimer ' s disease ( Greicius et al . 2004 ) , Tourette syndrome ( Church et al . 2007 ) , and adult ADHD ( Castellanos et al . 2008 ) . With regard to development , cortico – cortical interactions measured with rs - fcMRI have been investigated from birth through adulthood ( Supekar et al . 2009 ; Fair et al . 2007 , 2008 , 2009 , 2010a ; Kelly et al . 2009 ; Fransson et al . 2007 ) . It is largely believed that the changes in connectivity throughout development may contribute to the shift from reflexive , stimulus - bound behavior in childhood , to the goal - directed and more flexible functioning that is found in adulthood ."
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    ABSTRACT: Over the last two decades, there have been numerous technical and methodological advances available to clinicians and researchers to better understand attention deficit hyperactivity disorder (ADHD) and its etiology. Despite the growing body of literature investigating the disorder's pathophysiology, ADHD remains a complex psychiatric disorder to characterize. This chapter will briefly review the literature on ADHD, with a focus on its history, the current genetic insights, neurophysiologic theories, and the use of neuroimaging to further understand the etiology. We address some of the major concerns that remain unclear about ADHD, including subtype instability, heterogeneity, and the underlying neural correlates that define the disorder. We highlight that the field of ADHD is rapidly evolving; the descriptions provided here will hopefully provide a sturdy foundation for which to build and improve our understanding of the disorder.
    Current Topics in Behavioral Neurosciences 11/2013; 16. DOI:10.1007/7854_2013_249
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