Functional thalamocortical connectivity at term equivalent age and outcome at 2 years in infants born preterm.
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ABSTRACT:
SUBMITTER: Toulmin H
PROVIDER: S-EPMC7859832 | biostudies-literature | 2021 Feb
REPOSITORIES: biostudies-literature
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Functional thalamocortical connectivity at term equivalent age and outcome at 2 years in infants born preterm.
Toulmin Hilary H O'Muircheartaigh Jonathan J Counsell Serena J SJ Falconer Shona S Chew Andrew A Beckmann Christian F CF Edwards A David AD
Cortex; a journal devoted to the study of the nervous system and behavior 20201111
Infants born preterm are at high risk of long-term motor and neurocognitive deficits. In the majority of these infants structural MRI at the time of normal birth does not predict motor or cognitive outcomes accurately, and many infants without apparent brain lesions later develop motor and cognitive deficits. Thalamocortical connections are known to be necessary for normal brain function; they develop during late fetal life and are vulnerable to perinatal adversity. This study addressed the hypo ...[more]
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Project description:OBJECTIVES:To determine the functional network organization of the brain in infants born very preterm at term-equivalent age and to relate network alterations to known clinical risk factors for poor neurologic outcomes in prematurity. STUDY DESIGN:Resting-state functional magnetic resonance imaging data from 66 infants born very preterm (gestational age <32 weeks and birth weight <1500 g) and 66 healthy neonates born at full term, acquired as part of a prospective, cross-sectional study, were compared at term age using graph theory. Features of resting-state networks, including integration, segregation, and modularity, were derived from correlated hemodynamic activity arising from 93 cortical and subcortical regions of interest and compared between groups. RESULTS:Despite preserved small-world topology and modular organization, resting-state networks of infants born very preterm at term-equivalent age were less segregated and less integrated than those of infants born full term. Chronic respiratory illness (ie, bronchopulmonary dysplasia and the length of oxygen support) was associated with decreased global efficiency and increased path lengths (P < .05). In both cohorts, 4 functional modules with similar composition were observed (parietal/temporal, frontal, subcortical/limbic, and occipital). The density of connections in 3 of the 4 modules was decreased in the very preterm network (P < .01); however, in the occipital/visual cortex module, connectivity was increased in infants born very preterm relative to control infants (P < .0001). CONCLUSIONS:Early exposure to the ex utero environment is associated with altered resting-state network functional organization in infants born very preterm at term-equivalent age, likely reflecting disrupted brain maturational processes.
| S-EPMC6765421 | biostudies-literature
Project description:Cortical resting state networks have been consistently identified in infants using resting state-functional connectivity magnetic resonance imaging (rs-fMRI). Comparable studies in adults have demonstrated cerebellar components of well-established cerebral networks. However, there has been limited investigation of early cerebellar functional connectivity. We acquired non-sedated rs-fMRI data in the first week of life in 57 healthy, term-born infants and at term-equivalent postmenstrual age in 20 very preterm infants (mean birth gestational age 27 ± 2 weeks) without significant cerebral or cerebellar injury. Seed correlation analyses were performed using regions of interests spanning the cortical and subcortical gray matter and cerebellum. Parallel analyses were performed using rs-fMRI data acquired in 100 healthy adults. Our results demonstrate that cortico-cerebellar functional connectivity is well-established by term. Intra- and cortico-cerebellar functional connectivity were largely similar in infants and adults. However, infants showed more functional connectivity structure within the cerebellum, including stronger homotopic correlations and more robust anterior-posterior anticorrelations. Prematurity was associated with reduced correlation magnitudes, but no alterations in intra- and cortico-cerebellar functional connectivity topography. These results add to the growing evidence that the cerebellum plays an important role in shaping early brain development during infancy.
| S-EPMC6373668 | biostudies-literature
Project description:Preterm birth causes significant disruption in ongoing brain development, frequently resulting in adverse neurodevelopmental outcomes. Brain imaging using diffusion MRI may provide valuable insight into microstructural properties of the developing brain. The aim of this study was to establish whether the recently introduced fixel-based analysis method, with its associated measures of fibre density (FD), fibre bundle cross-section (FC), and fibre density and bundle cross-section (FDC), is suitable for the investigation of the preterm infant brain at term equivalent age. High-angular resolution diffusion weighted images (HARDI) of 55 preterm-born infants and 20 term-born infants, scanned around term-equivalent age, were included in this study (3?T, 64 directions, b?=?2000?s/mm2). Postmenstrual age at the time of MRI, and intracranial volume (FC and FDC only), were identified as confounding variables. Gestational age at birth was correlated with all fixel measures in the splenium of the corpus callosum. Compared to term-born infants, preterm infants showed reduced FD, FC, and FDC in a number of regions, including the corpus callosum, anterior commissure, cortico-spinal tract, optic radiations, and cingulum. Preterm infants with minimal macroscopic brain abnormality showed more extensive reductions than preterm infants without any macroscopic brain abnormality; however, little differences were observed between preterm infants with no and with minimal brain abnormality. FC showed significant reductions in preterm versus term infants outside regions identified with FD and FDC, highlighting the complementary role of these measures. Fixel-based analysis identified both microstructural and macrostructural abnormalities in preterm born infants, providing a more complete picture of early brain development than previous diffusion tensor imaging (DTI) based approaches.
| S-EPMC5984576 | biostudies-literature
Project description:BackgroundInfants born at 29-36 weeks gestational age (GA) are at risk of experiencing neurodevelopmental challenges. We hypothesize that cerebral hemodynamics and oxygen metabolism measured by bedside optical brain monitoring are potential biomarkers of brain development and are associated with neurological examination at term-equivalent age (TEA).MethodsPreterm infants (N = 133) born 29-36 weeks GA and admitted in the neonatal intensive care unit were enrolled in this prospective cohort study. Combined frequency-domain near infrared spectroscopy (FDNIRS) and diffuse correlation spectroscopy (DCS) were used from birth to TEA to measure cerebral hemoglobin oxygen saturation and an index of microvascular cerebral blood flow (CBF i ) along with peripheral arterial oxygen saturation (SpO2). In combination with hemoglobin concentration in the blood, these parameters were used to derive cerebral oxygen extraction fraction (OEF) and an index of cerebral oxygen metabolism (CMRO2i ). The Amiel-Tison and Gosselin Neurological Assessment was performed at TEA. Linear regression models were used to assess the associations between changes in FDNIRS-DCS parameters from birth to TEA and GA at birth. Logistic regression models were used to assess the associations between changes in FDNIRS-DCS parameters from birth to TEA and neurological examination at TEA.ResultsSteeper increases in CBF i (p < 0.0001) and CMRO2i (p = 0.0003) were associated with higher GA at birth. Changes in OEF, CBF i , and CMRO2i from birth to TEA were not associated with neurological examination at TEA.ConclusionIn this population, cerebral FDNIRS-DCS parameters were not associated with neurological examination at TEA. Larger increases in CBF i and CMRO2i from birth to TEA were associated with higher GA. Non-invasive bedside FDNIRS-DCS monitoring provides cerebral hemodynamic and metabolic parameters that may complement neurological examination to assess brain development in preterm infants.
| S-EPMC10017489 | biostudies-literature
Project description:Premature infants exhibit widespread insults and delays in white matter maturation that can be sensitively detected early using diffusion tensor imaging. Diffusion tensor tractography facilitates in vivo visualization of white matter tracts and has the potential to be more sensitive than simpler two-dimensional DTI-based measures. However, the reliability and reproducibility of performing tractography for major white matter tracts in preterm infants is not known. The main objective of our study was to develop highly reliable and repeatable methods for ten white matter tracts in extremely low birth weight infants (birth weight ? 1000 g) at term-equivalent age. To demonstrate clinical utility, we also compared fiber microstructural and macrostructural parameters between preterm and healthy term controls. Twenty-nine ELBW infants and a control group of 15 healthy term newborns were studied. A team of researchers experienced in neuroanatomy/neuroimaging established the manual segmentation protocol based on a priori anatomical knowledge and an extensive training period to identify sources of variability. Intra- and inter-rater reliability and repeatability was tested using intra-class correlation coefficient, within-subject standard deviation (SD), repeatability, and Dice similarity index. Our results support our primary goal of developing highly reliable and reproducible comprehensive methods for manual segmentation of 10 white matter tracts in ELBW infants. The within-subject SD was within 1-2% and repeatability within 3-7% of the mean values for all 10 tracts. The intra-rater Dice index was excellent with a range of 0.97 to 0.99, and as expected, the inter-rater Dice index was lower (range: 0.80 to 0.91), but still within a very good reliability range. ELBW infants exhibited fewer fiber numbers and/or abnormal microstructure in a majority of the ten quantified tracts, consistent with injury/delayed development. This protocol could serve as a valuable tool for prompt evaluation of the impact of neuroprotective therapies and as a prognostic biomarker for neurodevelopmental impairments.
| S-EPMC3901659 | biostudies-literature
Project description:Despite a growing body of research on perinatal sensory abilities, data on the extent of tactile sensitivity and more particularly passive touch (i.e. sensitivity to a stimulation imposed on the skin) are relatively limited, and the development and processing of tactile function are still thus little known. This question is particularly of high importance for infants with atypical early development such as those born prematurely who are exposed to many sensory (including tactile) stimulations (being in a hospital setting) during a critical period of brain development and those born at early term whose birth occurs at the precise time of cortical reorganization, in particular in the sensory areas. Some parents and health-care providers have for instance reported that children born prematurely exhibit atypical (e.g. higher) sensitivity to "benign" tactile stimuli. In the present study, we hypothesized that preterm and early-term infants may show altered tactile sensitivity. We compared the behavioral responses around term-equivalent age of infants born either pre-term, early-term or at term to the application of a light (0.008 grams) mechanical stimulus. We found that almost all preterm infants perceive this tactile stimulus, contrarily to the two other groups of infants. This extreme tactile sensitivity may be due to experiential, maturational or more likely both processes. We also compared the tactile sensitivity of these infants to that of adults. We found that adults were irresponsive to the light mechanical stimulus. This finding opens not only new insights in understanding development of tactile processing, but also new lines of thought about the particular sensory world of premature and early-term infants and hence about the potential impact of early care practices.
| S-EPMC7058305 | biostudies-literature
Project description:ObjectivesFirst, to apply a recently extended scoring system for preterm brain injury at term-equivalent age (TEA-)MRI in a regional extremely preterm cohort; second, to identify independent perinatal factors associated with this score; and third, to assess the prognostic value of this TEA-MRI score with respect to early neurodevelopmental outcome.Study design239 extremely preterm infants (median gestational age [range] in weeks: 26.6 [24.3-27.9]), admitted to the Wilhelmina Children's Hospital between 2006 and 2012 were included. Brain abnormalities in white matter, cortical and deep grey matter and cerebellum and brain growth were scored on T1- and T2-weighted TEA-MRI using the Kidokoro scoring system. Neurodevelopmental outcome was assessed at two years corrected age using the Bayley Scales of Infant and Toddler Development, third edition. The association between TEA-MRI and perinatal factors as well as neurodevelopmental outcome was evaluated using multivariable regression analysis.ResultsThe distribution of brain abnormalities and brain metrics in the Utrecht cohort differed from the original St. Louis cohort (p < .05). Mechanical ventilation >7 days (β [95% confidence interval, CI]: 1.3 [.5; 2.0]) and parenteral nutrition >21 days (2.2 [1.2; 3.2]) were independently associated with higher global brain abnormality scores (p < .001). Global brain abnormality scores were inversely associated with cognitive (β in composite scores [95% CI]: -.7 [-1.2; -.2], p = .004), fine motor (β in scaled scores [95% CI]: -.1 [-.3; -.0], p = .007) and gross motor outcome (β in scaled scores [95% CI]: -.2 [-.3; -.1], p < .001) at two years corrected age, although the explained variances were low (R2 ≤.219).ConclusionPatterns of brain injury differed between cohorts. Prolonged mechanical ventilation and parenteral nutrition were identified as independent perinatal risk factors. The prognostic value of the TEA-MRI score was rather limited in this well-performing cohort.
| S-EPMC5423624 | biostudies-literature
Project description:BackgroundRelative to full-term infants, very preterm infants exhibit disrupted white matter (WM) maturation and problems related to development, including motor, cognitive, social-emotional, and receptive and expressive language processing.ObjectiveThe present study aimed to determine whether regional abnormalities in the WM microstructure of very preterm infants, as defined relative to those of full-term infants at a near-term age, are associated with neurodevelopmental outcomes at the age of 18-22 months.MethodsWe prospectively enrolled 89 very preterm infants (birth weight < 1500 g) and 43 normal full-term control infants born between 2016 and 2018. All infants underwent a structural brain magnetic resonance imaging scan at near-term age. The diffusion tensor imaging (DTI) metrics of the whole-brain WM tracts were extracted based on the neonatal probabilistic WM pathway. The elastic net logistic regression model was used to identify altered WM tracts in the preterm brain. We evaluated the associations between the altered WM microstructure at near-term age and motor, cognitive, social-emotional, and receptive and expressive language developments at 18-22 months of age, as measured using the Bayley Scales of Infant Development, Third Edition.ResultsWe found that the elastic net logistic regression model could classify preterm and full-term neonates with an accuracy of 87.9% (corrected p < 0.008) using the DTI metrics in the pathway of interest with a 10% threshold level. The fractional anisotropy (FA) values of the body and splenium of the corpus callosum, middle cerebellar peduncle, left and right uncinate fasciculi, and right portion of the pathway between the premotor and primary motor cortices (premotor-PMC), as well as the mean axial diffusivity (AD) values of the left cingulum, were identified as contributive features for classification. Increased adjusted AD values in the left cingulum pathway were significantly correlated with language scores after false discovery rate (FDR) correction (r = 0.217, p = 0.043). The expressive language and social-emotional composite scores showed a significant positive correlation with the AD values in the left cingulum pathway (r = 0.226 [p = 0.036] and r = 0.31 [p = 0.003], respectively) after FDR correction.ConclusionOur approach suggests that the cingulum pathways of very preterm infants differ from those of full-term infants and significantly contribute to the prediction of the subsequent development of the language and social-emotional domains. This finding could improve our understanding of how specific neural substrates influence neurodevelopment at later ages, and individual risk prediction, thus helping to inform early intervention strategies that address developmental delay.
| S-EPMC7750449 | biostudies-literature
Project description:BackgroundRisk of morbidity differs between very preterm (VP; <32 weeks' gestational age (GA)), moderate preterm (MP; 32-33 weeks' GA), late preterm (LP; 34-36 weeks' GA), and full-term (FT; ≥37 weeks' GA) infants. However, brain structure at term-equivalent age (TEA; 38-44 weeks) remains to be characterised in all clinically important GA groups. We aimed to compare global and regional brain volumes, and regional white matter microstructure, between VP, MP, LP and FT groups at TEA, in order to establish the magnitude and anatomical locations of between-group differences.MethodsStructural images from 328 infants (91 VP, 63 MP, 104 LP and 70 FT) were segmented into white matter, cortical grey matter, cerebrospinal fluid (CSF), subcortical grey matter, brainstem and cerebellum. Global tissue volumes were analysed, and additionally, cortical grey matter and white matter volumes were analysed at the regional level using voxel-based morphometry. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) images from 361 infants (92 VP, 69 MP, 120 LP and 80 FT) were analysed using Tract-Based Spatial Statistics. Statistical analyses involved examining the overall effect of GA group on global volumes (using linear regressions) and regional volumes and microstructure (using non-parametric permutation testing), as well performing post-hoc comparisons between the GA sub-groups.ResultsOn global analysis, cerebrospinal fluid (CSF) volume was larger in all preterm sub-groups compared with the FT group. On regional analysis, volume was smaller in parts of the temporal cortical grey matter, and parts of the temporal white matter and corpus callosum, in all preterm sub-groups compared with the FT group. FA was lower, and RD and MD were higher in voxels located in much of the white matter in all preterm sub-groups compared with the FT group. The anatomical locations of group differences were similar for each preterm vs. FT comparison, but the magnitude and spatial extent of group differences was largest for the VP, followed by the MP, and then the LP comparison. Comparing within the preterm groups, the VP sub-group had smaller frontal and temporal grey and white matter volume, and lower FA and higher MD and RD within voxels in the approximate location of the corpus callosum compared with the MP sub-group. There were few volume and microstructural differences between the MP and LP sub-groups.ConclusionAll preterm sub-groups had atypical brain volume and microstructure at TEA when compared with a FT group, particularly for the CSF, temporal grey and white matter, and corpus callosum. In general, the groups followed a gradient, where the differences were most pronounced for the VP group, less pronounced for the MP group, and least pronounced for the LP group. The VP sub-group was particularly vulnerable compared with the MP and LP sub-groups.
| S-EPMC6411910 | biostudies-literature
Project description:BACKGROUND AND PURPOSE:Currently available MRI scoring systems of cerebral maturation in term and preterm infant at term equivalent age do not include the changes of transient fetal compartments that persist to term age. We studied the visibility and the pattern of these structures in healthy term newborns compared to preterm infants at term equivalent age in order to investigate if they can be included in a new MRI score system. We hypothesized that transient fetal compartments are different in both groups, and that these differences can be characterized using the clinical T2-weighted MRIs. MATERIALS AND METHODS:Using 3T MRI T2-weighted brain sequences of 21 full-term and 41 preterm infants (< 32 weeks), scanned at term equivalent age, 3 raters independently scored the maturation level of 3 transient fetal compartments: the periventricular crossroads, von Monakow segments of the white matter, and the subplate compartment. These 3 new items were included in a scoring system along with validated parameters of brain maturation (germinal matrix, bands of migration, subarachnoid space and quality of gyrification). A cumulative maturity score was calculated separately for both groups of newborns by adding together each item. More mature were the brain structures, higher was the cumulative maturity score. RESULTS:Cumulative maturity score distinguished full-term from preterm infants (mean score 41/60 ± 1.4 versus 37/60 ± 2.5 points, p < 0.001), with an increase of 0.5 points for each supplemental gestational week at birth (r?=?0.5, 95% CI 0.5 - 0.85). While a majority of transient fetal compartments were less mature in preterm group at term equivalent age, von Monakow segments of the white matter and subplate compartment presented a more advanced maturational stage in the preterm group compared to the term group. No subject had all scored items in the most mature state. Except a slight intra-rater agreement for von Monakow segment II, inter- and intra-rater agreements were moderate to excellent indicating the potential of the developed scoring system in routine clinical practice. CONCLUSION:Brain transient fetal structures can be assessed on regular T2-weighted MRI in newborns. Their appearance differs between term and preterm babies. However our results suggest a more complex situation, with both delayed and accelerated maturation pattern in preterm infants. It remains to be determined if these differences could be biomarkers of the future neurodevelopment of preterm infants.
| S-EPMC6838895 | biostudies-literature