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Reading is a learned skill that is likely influenced by both brain maturation and experience. Functional imaging studies have identified brain regions important for skilled reading, but the structural brain changes that co-occur with reading acquisition remain largely unknown. We investigated maturational volume changes in brain reading regions and their association with performance on reading measures. Sixteen typically developing children (5-15 years old, eight boys, mean age of sample=10.06 ± 3.29) received two MRI scans (mean interscan interval=2.19 years), and were administered a battery of cognitive measures. Volume changes between time points in five bilateral cortical regions of interest were measured, and assessed for relationships to three measures of reading. Better baseline performances on measures of word reading, fluency, and rapid naming, independent of age and total cortical gray matter volume change, were associated with volume decrease in the left inferior parietal cortex. Better baseline performance on a rapid naming measure was associated with volume decrease in the left inferior frontal region. These results suggest that children who are better readers, and who perhaps read more than less skilled readers, exhibit different development trajectories in brain reading regions. Understanding relationships between reading performance, reading experience, and brain maturation trajectories may help with the development and evaluation of targeted interventions.

Background: Quantitative MRI techniques have demonstrated thalamocortical abnormalities in idiopathic generalized epilepsy (IGE). However, there are few studies examining IGE early in its course and the neurodevelopmental course of this region is not adequately defined., Objective: We examined the 2-year developmental course of the thalamus and frontal lobes in pediatric new-onset IGE (i.e., within 12 months of diagnosis)., Methods: We performed whole-brain MRI in 22 patients with new-onset IGE and 36 age-matched healthy controls. MRI was repeated 24 months after baseline MRI. Quantitative volumetrics were used to examine thalamic and frontal lobe volumes., Results: The IGE group showed significant differences in thalamic volume within 1 year of seizure onset (baseline) and went on to show thalamic volume loss at a significantly faster rate than healthy control children over the 2-year interval. The control group also showed a significantly greater increase in frontal white matter expansion than the IGE group. In contrast, frontal lobe gray matter volume differences were moderate at baseline and persisted over time, indicating similar developmental trajectories with differences early in the disease process that are maintained., Conclusions: Brain tissue abnormalities in thalamic and frontal regions can be identified very early in the course of IGE and an abnormal trajectory of growth continues over a 2-year interval.

Neuronal dysfunctions in several neurodegenerative diseases such as Down syndrome (DS) have been linked to oxidative stress. In this study, we observed that lipid peroxidation, a marker of oxidative stress, is significantly increased in the frontal cortex of brains of individuals with DS as compared with control subjects. We report here that gelsolin levels are increased in the frontal cortex of individuals with DS as compared with controls during early developmental ages (5 to 13 y). Interestingly, the levels of gelsolin in the frontal cortex were increased as a function of age in both DS and control subjects. Because cytoplasmic gelsolin has 5 free thiol groups (cysteine), and its levels are increased in response to oxidative stress, we propose that gelsolin may serve as an antioxidant protein.

This study longitudinally compared activity in the frontal cortex during a spatial working memory task between 5-year-old and 7-year-old children using near-infrared spectroscopy. Eight children participated in this study twice, once at 5 years and once at 7 years of age. Behavioral analysis showed that older children performed the working memory task more precisely and more rapidly than younger children. Near-infrared spectroscopy analysis showed that right hemisphere dominance was observed in older children, whereas no hemispheric difference was apparent in younger children. Children with strengthened lateralization showed improved performance from 5 to 7 years. We therefore offer the first demonstration of the developmental changes in frontal cortical activation during spatial working memory tasks during the preschool period.

Objective: To investigate the effects of prematurity on sulcal formation., Methods: We evaluated the depth and volume of the primary olfactory sulcus (developed at 16 weeks' gestation) and the secondary orbital sulci (which start to develop at 28 weeks' gestation) in a sample of 22 adolescents with history of very-preterm birth (VPTB). We compared this preterm sample with a sample of subjects born at term and matched by age, gender, and sociocultural status. The Anatomist/BrainVISA 3.0.1 package was used to identify and quantify the sulci. In addition, voxel-based morphometry (VBM) was used to analyze possible reductions of gray and white matter in the orbitofrontal area., Results: Compared with controls, we found a significant reduction in the secondary sulci depth but not in the primary sulcus in the VPTB. VBM analysis showed reduced gray-matter volume in VPTB in the orbital region., Conclusions: Premature birth affects cerebral gyrification, and this impairment is not reversible during childhood. Identification of the specific factors involved in abnormal brain maturation may lead to effective interventions.

In this study, the neural mechanisms of novelty detection in children and adults were examined by means of novelty-elicited event-related potentials. The gross morphology of the event-related potentials elicited by complex, novel stimuli was similar in children and adults, suggesting that processing of novel acoustic information is essentially similar across the age groups. The more frontally distributed P3 components and the larger late frontal negativities in children than in adults suggest an age-related change in activity in the frontal part of the brain. This is consistent with the findings showing that the structural maturation of the frontal cortex does not appear to be completed until late adolescence.

The mismatch negativity (MMN) response of auditory ERPs in adults appears to result from several overlapping components involving both frontal and temporal brain areas. Our aim was to test whether a similar configuration could be observed in children, and to examine the maturation rates of the different components. MMN (standard tones: 1000 Hz, deviants: 1100 Hz) was recorded from 28 scalp electrodes in 24 healthy children aged from 5 to 10 and in eight adults for comparison. Scalp current density analysis revealed both temporal and frontal components in children of all ages as well as in adults. Moreover the amplitudes of the temporal components were significantly greater in children than in adults, whereas the frontal components were similar at all ages. The results strongly suggest that MMN is mediated by at least two separate neural systems, and that the frontal system matures earlier than the sensory-specific system.

Myelination is critical for the functional development of the brain, but the time course of myelination during childhood is not well known. Diffusion tensor MR imaging (DTI) provides a new method for estimating myelination in vivo. Myelin restricts diffusion of water transverse to the axons, causing diffusion to be anisotropic. By quantifying the anisotropy, the progressive myelination of axons can be studied. Central white matter of the frontal lobe was studied in seven children (mean age 10 years) and five adults (mean age 27 years). Anisotropy in the frontal white matter was significantly lower in children than in adults, suggesting less myelination in children. Measurement of the coherence of white matter revealed that the right frontal lobe had a more regular organization of axons than the left frontal lobe, in both children and adults. The results demonstrate that maturation of the frontal white matter continues into the second decade of life. The time course of prefrontal maturation makes it possible that myelination is a basis for the gradual development of prefrontal functions, such as increased working memory capacity.

The major androgen metabolizing enzymes, aromatase cytochrome P450 and 5 alpha-reductase play critical role(s) in the development of sexually dimorphic brain structures, the modulation of neuroendocrine function(s) and the regulation of sexual and non-sexual behaviors. Using established assays, we detected 5 alpha-reductase and aromatase enzymatic activities in amygdala and frontal cortical tissue from male and female rats during the perinatal interval (from gestational day (GD) 19 to postnatal day (PND) 6). The present findings indicate that 5 alpha-reductase and aromatase rates in the cortex display different enzyme profiles, while in the amygdala tissue site a similar pattern is seen for both enzymes during perinatal development. In general, there was a lack of sex differences in the enzymatic rates. The importance these enzyme systems play in generating androgen (and progesterone) steroid metabolites which influence neural development and function are discussed.

WE have investigated changes in inositol phospholipid turnover and membrane arachidonic acid concentration in the dentate gyrus and frontal cortex of animals aged 3-6 months, 14 months or 22 months which were trained in the Morris water maze. Ageing was associated with poorer performances in the behavioural test, characterized by increased variability in retention and acquisition amongst individuals, a decrease in membrane arachidonic acid concentration and increased unstimulated inositol phospholipid metabolism in synaptosomes prepared from frontal cortex and dentate gyrus. Arachidonic acid stimulated inositol phospholipid metabolism in synaptosomes, but in the older groups, stimulation was associated with good performance in the Morris water maze. In slices prepared from frontal cortex, responsiveness of inositol phospholipid metabolism to glutamate was also age- and performance-dependent. The findings highlight a correlation between age, inositol phospholipid metabolism and performance in the Morris water maze.

True Blue, a retrograde fluorescent tracer, was used to investigate axonal outgrowth after grafting embryonic forebrain cholinergic tissue into the cholinergically-deafferented rat frontal cortex. Unilateral deafferentation was achieved by injecting alpha-amino-3-OH-4-isoxozole propionic acid (AMPA) into the ipsilateral nucleus basalis magnocellularis. Grafting occurred 3 weeks after the lesion. Eight to 10 weeks later, True Blue was injected bilaterally into the cortex at a superficial site which, on the transplanted side, was located at least 2 mm away from the transplant. Forty-eight h later, retrogradely labelled fluorescent neurones could be seen in the deepest part of the transplants. Some of these neurones were shown to be ChAt-positive, providing evidence of axonal outgrowth from transplanted cholinergic neurones into cholinergically-deafferented frontal cortex.

Fetal frontal neocortex from 18-day-old rat embryonic brain was transplanted into cavities in 30-day-old host motor cortex. Sixty days after transplantation, 5 of 15 transplanted rats had surviving fetal transplants. The fetal cortex transplants were physically attached to the host brain, completely filled the original cavity, and had numerous surviving cells including pyramidal neurons. Cell lamination within the fetal transplant was abnormal. The (14C) 2-deoxyglucose uptake of all five of the fetal neocortex transplants was less than adjacent cortex and contralateral host motor-sensory cortex, but more than adjacent corpus callosum white matter. The results indicate that fetal frontal neocortex can be transplanted into damaged rat motor cortex. The metabolic rate of the transplants suggests they could be partially functional.

The incidence of motor and sensory, (nonfluent and fluent) aphasia was studied in 389 patients with a left-sided vascular lesion. The mean age of patients with motor aphasia was 45.3 years, and the mean age of patients with sensory aphasia was 56.5 years. The age difference was also found in a separate analysis of 50 cases of traumatic aphasia. Nonfluent aphasias predominate in early life in both males and females, but are more common in females in the third decade. The relationship between aphasia type and age, and sex, is explained by a process of regional specification of the left language areas that proceeds more slowly in females than males. It is hypothesized that this process reflects the effects of the sex hormones on protein synthesis and brain growth.