Functional thalamocortical connectivity at term equivalent age and outcome at 2 years in infants born preterm.

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 hypothesis that abnormalities in the functional connectivity between cortex and thalamus underlie neurocognitive impairments seen after preterm birth. Using resting state functional connectivity magnetic resonance imaging (fMRI) in a group of 102 very preterm infants without major focal brain lesions, we used partial correlations between thalamus and functionally-derived cortical areas to determine significant connectivity between cortical areas and thalamus, and correlated the parameter estimates of these connections with standardised neurocognitive assessments in each infant at 20 months of age. Pre-motor association cortex connectivity to thalamus correlates with motor function, while connectivity between primary sensory-motor cortex and thalamus correlates with cognitive scores. These results demonstrate the importance and vulnerability of functional thalamocortical connectivity development in the perinatal period for later neurocognitive functioning.

Corticospinal Tract Injury Precedes Thalamic Volume Reduction in Preterm Infants with Cystic Periventricular Leukomalacia.

OBJECTIVES: To measure both fractional anisotropy (FA) values in the corticospinal tracts (CSTs) and volume of the thalami in preterm infants with cystic periventricular leukomalacia (c-PVL) and to compare these measurements with control infants. STUDY DESIGN: Preterm infants with c-PVL and controls with magnetic resonance imaging data acquired between birth and term equivalent age (TEA) were retrospectively identified in 2 centers. Tractography of the CST and segmentation of the thalamus were performed, and values from infants with c-PVL and controls were compared. RESULTS: Thirty-three subjects with c-PVL and 31 preterm controls were identified. All had at least 1 scan up to TEA, and multiple scans were performed in 31 infants. A significant difference in FA values of the CST was found between cases and controls on the scans both before and at TEA. Absolute thalamic volumes were significantly reduced at TEA but not on the earlier scans. Data acquired in infancy showed lower FA values in infants with c-PVL. CONCLUSIONS: Damage to the CST can be identified on the early scan and persists, whereas the changes in thalamic volume develop in the weeks between the early and term equivalent magnetic resonance imaging. This may reflect the difference between acute and remote effects of the extensive injury to the white matter caused by c-PVL.

Thalamocortical Connectivity Predicts Cognition in Children Born Preterm.

Thalamocortical connections are: essential for brain function, established early in development, and significantly impaired following preterm birth. Impaired cognitive abilities in preterm infants may be related to disruptions in thalamocortical connectivity. The aim of this study was to test the hypothesis: thalamocortical connectivity in the preterm brain at term-equivalent is correlated with cognitive performance in early childhood. We examined 57 infants who were born <35 weeks gestational age (GA) and had no evidence of focal abnormality on magnetic resonance imaging (MRI). Infants underwent diffusion MRI at term and cognitive performance at 2 years was assessed using the Bayley III scales of Infant and Toddler development. Cognitive scores at 2 years were correlated with structural connectivity between the thalamus and extensive cortical regions at term. Mean thalamocortical connectivity across the whole cortex explained 11% of the variance in cognitive scores at 2 years. The inclusion of GA at birth and parental socioeconomic group in the model explained 30% of the variance in subsequent cognitive performance. Identifying impairments in thalamocortical connectivity as early as term equivalent can help identify those infants at risk of subsequent cognitive delay and may be useful to assess efficacy of potential treatments at an early age.

White matter and cortical injury in hypoxic-ischemic encephalopathy: antecedent factors and 2-year outcome.

OBJECTIVE: To examine the spectrum of isolated white matter (WM)/cortical injury and its relation to outcomes in infants with hypoxic-ischemic encephalopathy (HIE) and normal appearing basal ganglia and thalami. STUDY DESIGN: From 1992-2007, 84 term infants with HIE and normal basal ganglia and thalami on neonatal magnetic resonance imaging were studied; WM/cortical lesions were classified by site and severity. Neurodevelopmental outcomes and head growth were documented at a median age of 2 years. RESULTS: The WM was normal or mildly abnormal in 33.5%, moderate in 40.5%, and severely abnormal in 26% of infants. Cortical involvement was not seen or was only mild in 75.5%, moderate in 13%, and severe in 12% of infants. WM and cortical injury severity were highly correlated (Spearman ρ = 0.74; P < .001). Infants with severe WM injury had more severe neonatal courses and a higher incidence of hypoglycemia. No infant died. Five infants (6%) developed cerebral palsy but all could walk independently. Cognitive, visual, language, behavioral, and seizure problems were highly prevalent and correlated significantly with the severity of WM injury and poor postnatal head growth. CONCLUSION: Infants with HIE and selective WM/cortical injury have a low prevalence of cerebral palsy but have a wide range of other problems, which occur more often with severe WM/cortical lesions.