Specialization and integration of functional thalamocortical connectivity in the human infant

Abstract

Connections between the thalamus and cortex develop rapidly before birth, and aberrant cerebral maturation during this period may underlie a number of neurodevelopmental disorders. To define functional thalamocortical connectivity at the normal time of birth, we used functional MRI (fMRI) to measure blood oxygen level-dependent (BOLD) signals in 66 infants, 47 of whom were at high risk of neurocognitive impairment because of birth before 33 wk of gestation and 19 of whom were term infants. We segmented the thalamus based on correlation with functionally defined cortical components using independent component analysis (ICA) and seed-based correlations. After parcellating the cortex using ICA and segmenting the thalamus based on dominant connections with cortical parcellations, we observed a near-facsimile of the adult functional parcellation. Additional analysis revealed that BOLD signal in heteromodal association cortex typically had more widespread and overlapping thalamic representations than primary sensory cortex. Notably, more extreme prematurity was associated with increased functional connectivity between thalamus and lateral primary sensory cortex but reduced connectivity between thalamus and cortex in the prefrontal, insular and anterior cingulate regions. This work suggests that, in early infancy, functional integration through thalamocortical connections depends on significant functional overlap in the topographic organization of the thalamus and that the experience of premature extrauterine life modulates network development, altering the maturation of networks thought to support salience, executive, integrative, and cognitive functions.resting-state fMRI | thalamus | preterm | functional connectivity | cortex T he formation of topographically organized neural connections between cerebral cortex and thalamus is necessary for normal cortical morphogenesis (1), and development of these connections requires thalamocortical projections to synapse transiently in the temporary cortical subplate before penetrating the cortical plate (2-4). In humans, the subplate is at maximal extent in the last trimester of gestation (5), a time of rapid growth for thalamocortical fibers and the cortical dendritic tree, particularly in heteromodal cortex (6, 7). This process has been shown to be disrupted by preterm birth (8). Premature delivery is associated with increased risk of neurocognitive impairment, and it is widely hypothesized that abnormal development of brain structure during this period is the cause of these problems and may also underlie the development of autistic spectrum disorders and attention deficit disorders in genetically predisposed individuals.During the last trimester of pregnancy, functional MRI (fMRI) detects the emergence of coordinated, spontaneous fluctuations in the blood oxygen level-dependent (BOLD) signals, which are closely linked with the development of electroencephalographic activity (9-11) and develop into a near-facsimile of the mature adult resting-state network architecture by the...

The emergence of functional architecture during early brain development

“…The notion that thalamocortical connectivity is established by the time of birth was recently illustrated in a rs-fMRI study, showing a high level of overlap between the distribution of thalamocortical projections in the thalamus in the neonatal brain and their topographical organization in the adult human brain (Toulmin et al, 2015). While axons continue to grow, facilitating major connections in the white matter to find their cortical targets, the overlying cortex transforms its relatively smooth surface into a highly convoluted mantle with secondary and tertiary sulci that resembles the adult human brain (Stiles and Jernigan, 2010;Striedter et al, 2014).…”

“…Most infants are scanned during natural sleep or after administering mild sedation (25-60 mg/kg oral chloral hydrate) (Doria et al, 2010a;Toulmin et al, 2015;van den Heuvel et al, 2014) and although appropriate measures are generally taken to reduce motion artifacts including feeding and swaddling (where infants are scanned during natural sleep), wrapping the infant in a vacuum fixation pillow and applying hearing protection devices to reduce exposure to acoustic noise, even subtle head movement remains a significant problem. Furthermore, the use of sedative medication -if administered -is generally confined to infants scanned in a clinical setting and may thus introduce a bias in terms of the effect of motion, as well as differences in physiological parameters and sleep state/level of consciousness between health and disease states.…”

“…However, alterations in the global framework of brain wiring have not been observed and are unlikely in the absence of major brain lesions (Bütefisch, 2004). The adverse effects of preterm birth have predominantly been noted to affect the quality of connections rather than their overall layout (Ball et al, , 2013Doria et al, 2010a;Scheinost et al, 2015;Smyser et al, 2010;Toulmin et al, 2015).…”

“…Both structural (Ball et al, , 2013 and functional deficits (Doria et al, 2010a;Smyser et al, 2010;Toulmin et al, 2015) have been reported. Disturbances in structural connectivity were revealed to be most widespread, involving thalamocortical connections distributed across frontal, temporal, occipital and parietal lobes (Ball et al, , 2013.…”

“…Historically, much of what we know about the intricate processes of early brain development came from post mortem studies in human fetuses, neonates, and non-human primates (Flechsig, 1920;Goldman-Rakic, 1987;Innocenti and Price, 2005;Kostovic, 2002;LaMantia and Rakic, 1990). With the increasing availability of high-quality neuroimaging techniques, including anatomical sequences customized to the developing neonatal and fetal brain, diffusion weighted imaging (DWI) and functional MRI, as well as electrophysiology recordings including electroencephalography (EEG), it has now become feasible to study early human brain development in unprecedented detail in vivo Counsell et al, 2007;Fransson et al, 2007;Huppi et al, 1998;Maas et al, 2004;Omidvarnia et al, 2014;Partridge et al, 2004;Smyser et al, 2001; Thomason et al, 2013;Toulmin et al, 2015;van den Heuvel et al, 2014). These advances have led to exciting new insights into both healthy and atypical macroscale brain network development and have paved the way to bridge the gap between the brain's neurobiological architecture and its behavioral repertoire.…”