Disrupted fornix integrity in children with chromosome 22q11.2 deletion syndrome.

The fornix is the primary subcortical output fiber system of the hippocampal formation. In children with 22q11.2 deletion syndrome (22q11.2DS), hippocampal volume reduction has been commonly reported, but few studies as yet have evaluated the integrity of the fornix. Therefore, we investigated the fornix of 45 school-aged children with 22q11.2DS and 38 matched typically developing (TD) children. Probabilistic diffusion tensor imaging (DTI) tractography was used to reconstruct the body of the fornix in each child׳s brain native space. Compared with children, significantly lower fractional anisotropy (FA) and higher radial diffusivity (RD) was observed bilaterally in the body of the fornix in children with 22q11.2DS. Irregularities were especially prominent in the posterior aspect of the fornix where it emerges from the hippocampus. Smaller volumes of the hippocampal formations were also found in the 22q11.2DS group. The reduced hippocampal volumes were correlated with lower fornix FA and higher fornix RD in the right hemisphere. Our findings provide neuroanatomical evidence of disrupted hippocampal connectivity in children with 22q11.2DS, which may help to further understand the biological basis of spatial impairments, affective regulation, and other factors related to the ultra-high risk for schizophrenia in this population.

Frontostriatal white matter integrity mediates adult age differences in probabilistic reward learning.

Frontostriatal circuits have been implicated in reward learning, and emerging findings suggest that frontal white matter structural integrity and probabilistic reward learning are reduced in older age. This cross-sectional study examined whether age differences in frontostriatal white matter integrity could account for age differences in reward learning in a community life span sample of human adults. By combining diffusion tensor imaging with a probabilistic reward learning task, we found that older age was associated with decreased reward learning and decreased white matter integrity in specific pathways running from the thalamus to the medial prefrontal cortex and from the medial prefrontal cortex to the ventral striatum. Further, white matter integrity in these thalamocorticostriatal paths could statistically account for age differences in learning. These findings suggest that the integrity of frontostriatal white matter pathways critically supports reward learning. The findings also raise the possibility that interventions that bolster frontostriatal integrity might improve reward learning and decision making.

Visual feature-tolerance in the reading network.

A century of neurology and neuroscience shows that seeing words depends on ventral occipital-temporal (VOT) circuitry. Typically, reading is learned using high-contrast line-contour words. We explored whether a specific VOT region, the visual word form area (VWFA), learns to see only these words or recognizes words independent of the specific shape-defining visual features. Word forms were created using atypical features (motion-dots, luminance-dots) whose statistical properties control word-visibility. We measured fMRI responses as word form visibility varied, and we used TMS to interfere with neural processing in specific cortical circuits, while subjects performed a lexical decision task. For all features, VWFA responses increased with word-visibility and correlated with performance. TMS applied to motion-specialized area hMT+ disrupted reading performance for motion-dots, but not line-contours or luminance-dots. A quantitative model describes feature-convergence in the VWFA and relates VWFA responses to behavioral performance. These findings suggest how visual feature-tolerance in the reading network arises through signal convergence from feature-specialized cortical areas.

Bound pool fractions complement diffusion measures to describe white matter micro and macrostructure.

Diffusion imaging and bound pool fraction (BPF) mapping are two quantitative magnetic resonance imaging techniques that measure microstructural features of the white matter of the brain. Diffusion imaging provides a quantitative measure of the diffusivity of water in tissue. BPF mapping is a quantitative magnetization transfer (qMT) technique that estimates the proportion of exchanging protons bound to macromolecules, such as those found in myelin, and is thus a more direct measure of myelin content than diffusion. In this work, we combined BPF estimates of macromolecular content with measurements of diffusivity within human white matter tracts. Within the white matter, the correlation between BPFs and diffusivity measures such as fractional anisotropy and radial diffusivity was modest, suggesting that diffusion tensor imaging and bound pool fractions are complementary techniques. We found that several major tracts have high BPF, suggesting a higher density of myelin in these tracts. We interpret these results in the context of a quantitative tissue model.

COMT genotype affects prefrontal white matter pathways in children and adolescents.

Diffusion tensor imaging is widely used to evaluate the development of white matter. Information about how alterations in major neurotransmitter systems, such as the dopamine (DA) system, influence this development in healthy children, however, is lacking. Catechol-O-metyltransferase (COMT) is the major enzyme responsible for DA degradation in prefrontal brain structures, for which there is a corresponding genetic polymorphism (val158met) that confers either a more or less efficient version of this enzyme. The result of this common genetic variation is that children may have more or less available synaptic DA in prefrontal brain regions. In the present study we examined the relation between diffusion properties of frontal white matter structures and the COMT val158met polymorphism in 40 children ages 9-15. We found that the val allele was associated with significantly elevated fractional anisotropy values and reduced axial and radial diffusivities. These results indicate that the development of white matter in healthy children is related to COMT genotype and that alterations in white matter may be related to the differential availability of prefrontal DA. This investigation paves the way for further studies of how common functional variants in the genome might influence the development of brain white matter.

Differences in total and allergen specific IgE during pregnancy compared with 1 month and 1 year post partum.

BACKGROUND: Pregnancy alters the function of many body systems, including the immune system. However, little is known regarding the effect of pregnancy on maternal IgE levels or atopy. OBJECTIVE: To determine whether pregnancy consistently influences serum levels of total or allergen specific IgE. METHODS: Blood samples were obtained from 764 women during the third trimester of pregnancy and 1 month post partum. A third sample was obtained from 106 of these women 1 year post partum. Samples were analyzed for total and specific IgE to 8 regionally common allergens using a commercially available system. Sensitization was defined as an allergen specific IgE level of 0.35 kU of allergen per liter or higher to any allergen. RESULTS: Total IgE increased significantly post partum, both at 1 month (40.36 vs 35.37 IU/mL intrapartum; P = .001) and at 1 year (44.97 vs 37.00 IU/mL intrapartum; P = .005). Allergen specific IgE decreased significantly at 1 month for cat, dog, ragweed, timothy grass, and egg (P = .001 to P = .02) but not for dust mite, cockroach, or Alternaria (P = .15 to P = .90). Similar patterns of change in total and specific IgE were seen at 1 year. However, on average, only 3.5% of participants changed sensitization status to the individual allergens studied during the 1 year of observation. CONCLUSIONS: Compared with intrapartum levels, total IgE levels increased significantly at 1 month and 1 year post partum. Conversely, at the same time points, IgE levels specific for common allergens significantly declined to most but not all allergens. Few women changed their sensitization status over 1 year.

Reading impairment in a patient with missing arcuate fasciculus.

We describe the case of a child ("S") who was treated with radiation therapy at age 5 for a recurrent malignant brain tumor. Radiation successfully abolished the tumor but caused radiation-induced tissue necrosis, primarily affecting cerebral white matter. S was introduced to us at age 15 because of her profound dyslexia. We assessed cognitive abilities and performed diffusion tensor imaging (DTI) to measure cerebral white matter pathways. Diffuse white matter differences were evident in T1-weighted, T2-weighted, diffusion anisotropy, and mean diffusivity measures in S compared to a group of 28 normal female controls. In addition, we found specific white matter pathway deficits by comparing tensor-orientation directions in S's brain with those of the control brains. While her principal diffusion direction maps appeared consistent with those of controls over most of the brain, there were tensor-orientation abnormalities in the fiber tracts that form the superior longitudinal fasciculus (SLF) in both hemispheres. Tractography analysis indicated that the left and right arcuate fasciculus (AF), as well as other tracts within the SLF, were missing in S. Other major white matter tracts, such as the corticospinal and inferior occipitofrontal pathways, were intact. Functional MRI measurements indicated left-hemisphere dominance for language with a normal activation pattern. Despite the left AF abnormality, S had preserved oral language with average sentence repetition skills. In addition to profound dyslexia, S exhibited visuospatial, calculation, and rapid naming deficits and was impaired in both auditory and spatial working memory. We propose that the reading and visuospatial deficits were due to the abnormal left and right SLF pathways, respectively. These results advance our understanding of the functional significance of the SLF and are the first to link radiation necrosis with selective damage to a specific set of fiber tracts.

Socioeconomic disparities affect prefrontal function in children.

Social inequalities have profound effects on the physical and mental health of children. Children from low socioeconomic status (SES) backgrounds perform below children from higher SES backgrounds on tests of intelligence and academic achievement, and recent findings indicate that low SES (LSES) children are impaired on behavioral measures of prefrontal function. However, the influence of socioeconomic disparity on direct measures of neural activity is unknown. Here, we provide electrophysiological evidence indicating that prefrontal function is altered in LSES children. We found that prefrontal-dependent electrophysiological measures of attention were reduced in LSES compared to high SES (HSES) children in a pattern similar to that observed in patients with lateral prefrontal cortex (PFC) damage. These findings provide neurophysiological evidence that social inequalities are associated with alterations in PFC function in LSES children. There are a number of factors associated with LSES rearing conditions that may have contributed to these results such as greater levels of stress and lack of access to cognitively stimulating materials and experiences. Targeting specific prefrontal processes affected by socioeconomic disparity could be helpful in developing intervention programs for LSES children.