White Matter Injury and General Movements in High-Risk Preterm Infants

BACKGROUND AND PURPOSE: Very preterm infants (birth weight, MATERIALS AND METHODS: In this prospective study of 47 preterm infants of 24-30 weeks' gestation, brain MR imaging was performed at term-equivalent age. Infants underwent T1- and T2-weighted imaging for volumetric analysis and DTI. General movements were assessed at 10-15 weeks' postterm age, and neurodevelopmental outcomes were evaluated at 2 years by using the Bayley Scales of Infant and Toddler Development Ill. RESULTS: Nine infants had aberrant general movements and were more likely to have adverse neurodevelopmental outcomes, compared with infants with normal movements. In infants with aberrant movements, Tract-Based Spatial Statistics analysis identified significantly lower fractional anisotropy in widespread white matter tracts, including the corpus callosum, inferior longitudinal and fronto-occipital fasciculi, internal capsule, and optic radiation. The subset of infants having both aberrant movements and abnormal neurodevelopmental outcomes in cognitive, language, and motor skills had significantly lower fractional anisotropy in specific brain regions. CONCLUSIONS: Aberrant general movements at 10-15 weeks' postterm are associated with adverse neurodevelopmental outcomes and specific white matter microstructure abnormalities for cognitive, language, and motor delays

Altered Neurocircuitry in the Dopamine Transporter Knockout Mouse Brain

The plasma membrane transporters for the monoamine neurotransmitters dopamine, serotonin, and norepinephrine modulate the dynamics of these monoamine neurotransmitters. Thus, activity of these transporters has significant consequences for monoamine activity throughout the brain and for a number of neurological and psychiatric disorders. Gene knockout (KO) mice that reduce or eliminate expression of each of these monoamine transporters have provided a wealth of new information about the function of these proteins at molecular, physiological and behavioral levels. In the present work we use the unique properties of magnetic resonance imaging (MRI) to probe the effects of altered dopaminergic dynamics on meso-scale neuronal circuitry and overall brain morphology, since changes at these levels of organization might help to account for some of the extensive pharmacological and behavioral differences observed in dopamine transporter (DAT) KO mice. Despite the smaller size of these animals, voxel-wise statistical comparison of high resolution structural MR images indicated little morphological change as a consequence of DAT KO. Likewise, proton magnetic resonance spectra recorded in the striatum indicated no significant changes in detectable metabolite concentrations between DAT KO and wild-type (WT) mice. In contrast, alterations in the circuitry from the prefrontal cortex to the mesocortical limbic system, an important brain component intimately tied to function of mesolimbic/mesocortical dopamine reward pathways, were revealed by manganese-enhanced MRI (MEMRI). Analysis of co-registered MEMRI images taken over the 26 hours after introduction of Mn^(2+) into the prefrontal cortex indicated that DAT KO mice have a truncated Mn^(2+) distribution within this circuitry with little accumulation beyond the thalamus or contralateral to the injection site. By contrast, WT littermates exhibit Mn^(2+) transport into more posterior midbrain nuclei and contralateral mesolimbic structures at 26 hr post-injection. Thus, DAT KO mice appear, at this level of anatomic resolution, to have preserved cortico-striatal-thalamic connectivity but diminished robustness of reward-modulating circuitry distal to the thalamus. This is in contradistinction to the state of this circuitry in serotonin transporter KO mice where we observed more robust connectivity in more posterior brain regions using methods identical to those employed here