Teaching reading to children with neurofibromatosis type 1: a clinical trial with random assignment to different approaches.

AIM: Neurofibromatosis type 1 (NF1) is a genetic disorder with a cognitive profile that includes visual-spatial perception deficits and a high incidence of reading disability. There is a paucity of information about how this cognitively complex population responds to mainstream reading interventions. The clinical trial goals were to determine whether children and adolescents with NF1 and reading deficits (NF+RD) benefit from mainstream remedial reading programs and whether responsiveness varies with differences in program-related visual-spatial demands. METHOD: Forty-nine participants (28 males, 21 females; aged 8-14y) with either NF+RD (n=17, 11 males, six females) or idiopathic reading deficit (IRD) (n=32, 17 males, 15 females) were randomly assigned to intensive remedial teaching using one of two multisensory reading programs: one with greater kinesthetic demands and the other with greater visual-spatial demands. Two control groups - wait-list IRD (n=14, 11 males, three females) and typically developing readers (n=26, 13 males, 13 females) - received no treatment. Repeated measures and multivariate ANOVA analyses compared each group's growth in reading achievement from pre- to post-testing. RESULTS: Treated groups showed significant growth whereas untreated groups did not. Comparing treated groups, the IRD group responded equally well to both interventions, whereas the NF+RD group showed a better response to the more kinesthetic approach. INTERPRETATION: Results suggest that multisensory remedial reading teaching that emphasizes kinesthetic demands more than visual-spatial demands is suitable for students with NF+RD.

Not all reading disabilities are dyslexia: distinct neurobiology of specific comprehension deficits.

Although an extensive literature exists on the neurobiological correlates of dyslexia (DYS), to date, no studies have examined the neurobiological profile of those who exhibit poor reading comprehension despite intact word-level abilities (specific reading comprehension deficits [S-RCD]). Here we investigated the word-level abilities of S-RCD as compared to typically developing readers (TD) and those with DYS by examining the blood oxygenation-level dependent response to words varying on frequency. Understanding whether S-RCD process words in the same manner as TD, or show alternate pathways to achieve normal word-reading abilities, may provide insights into the origin of this disorder. Results showed that as compared to TD, DYS showed abnormal covariance during word processing with right-hemisphere homologs of the left-hemisphere reading network in conjunction with left occipitotemporal underactivation. In contrast, S-RCD showed an intact neurobiological response to word stimuli in occipitotemporal regions (associated with fast and efficient word processing); however, inferior frontal gyrus (IFG) abnormalities were observed. Specifically, TD showed a higher-percent signal change within right IFG for low-versus-high frequency words as compared to both S-RCD and DYS. Using psychophysiological interaction analyses, a coupling-by-reading group interaction was found in right IFG for DYS, as indicated by a widespread greater covariance between right IFG and right occipitotemporal cortex/visual word-form areas, as well as bilateral medial frontal gyrus, as compared to TD. For S-RCD, the context-dependent functional interaction anomaly was most prominently seen in left IFG, which covaried to a greater extent with hippocampal, parahippocampal, and prefrontal areas than for TD for low- as compared to high-frequency words. Given the greater lexical access demands of low frequency as compared to high-frequency words, these results may suggest specific weaknesses in accessing lexical-semantic representations during word recognition. These novel findings provide foundational insights into the nature of S-RCD, and set the stage for future investigations of this common, but understudied, reading disorder.

Learning disabilities and school failure.

After completing this article, readers should be able to:1. Articulate a systematic medical approach to the child who has school failure or suspected learning disability.2. Compare and contrast learning disability from other related conditions that may affect a child's school function.3. Identify key historic factors recognized during developmental surveillance for children who have learning disabilities.4. List key school and community resources for advising parents about the evaluation,treatment, and prognosis of a child who has a learning disability.5. Outline a medical home management plan for children who have learning disabilities.

Increased regional fractional anisotropy in highly screened attention-deficit hyperactivity disorder (ADHD).

Diffusion tensor imaging data were collected at 3.0 Tesla from 16 children with attention-deficit hyperactivity disorder (ADHD) and 16 typically developing controls, ages 9 to 14 years. Fractional anisotropy images were calculated and normalized by linear transformation. Voxel-wise and atlas-based region-of-interest analyses were performed. Using voxel-wise analysis, fractional anisotropy was found to be significantly increased in the attention-deficit hyperactivity disorder group in the right superior frontal gyrus and posterior thalamic radiation, and left dorsal posterior cingulate gyrus, lingual gyrus, and parahippocampal gyrus. No regions showed significantly decreased fractional anisotropy in attention-deficit hyperactivity disorder. Region-of-interest analysis revealed increased fractional anisotropy in the left sagittal stratum, that is, white matter that connects the temporal lobe to distant cortical regions. Only fractional anisotropy in the left sagittal stratum was significantly associated with attention-deficit hyperactivity disorder symptom severity. Several recent studies have reported pathological increases in fractional anisotropy in other conditions, highlighting the relevance of diffusion tensor imaging in identifying atypical white matter structure associated with neurodevelopmental processes.

White matter microstructural differences linked to left perisylvian language network in children with dyslexia.

Studies of dyslexia using diffusion tensor imaging (DTI) have reported fractional anisotropy (FA) differences in left inferior frontal gyrus (LIFG) and left temporo-parietal white matter, suggesting that impaired reading is associated with atypical white matter microstructure in these regions. These anomalies might reflect abnormalities in the left perisylvian language network, long implicated in dyslexia. While DTI investigations frequently report analyses on multiple tensor-derived measures (e.g., FA, orientation, tractography), it is uncommon to integrate analyses to examine the relationships between atypical findings. For the present study, semi-automated techniques were applied to DTI data in an integrated fashion to examine white matter microstructure in 14 children with dyslexia and 17 typically developing readers (ages 7-16 years). Correlations of DTI metrics (FA and fiber orientation) to reading skill (accuracy and speed) and to probabilistic tractography maps of the left perisylvian language tracts were examined. Consistent with previous reports, our findings suggest FA decreases in dyslexia in LIFG and left temporo-parietal white matter. The LIFG FA finding overlaps an area showing differences in fiber orientation in an anterior left perisylvian language pathway. Additionally, a positive correlation of FA to reading speed was found in a posterior circuit previously associated with activation on functional imaging during reading tasks. Overall, integrating results from several complementary semi-automated analyses reveals evidence linking atypical white matter microstructure in dyslexia to atypical fiber orientation in circuits implicated in reading including the left perisylvian language network.

Developmental sex differences in basic visuospatial processing: differences in strategy use?

Functional neuroimaging studies investigating sex differences in visuospatial processing traditionally focus on mental rotation tasks in adults, as it is a consistently robust finding, with a limited number of studies examining tasks tapping visuospatial skills at a more basic level. Furthermore, fewer studies have examined this issue in conjunction with investigating whether differences exist in younger populations. Therefore, functional neuroimaging was used to examine whether sex-based differences exist and/or develop during childhood. Thirty-two participants, matched on performance, participated in this study. Overall, both groups showed overlapping activation in bilateral superior parietal lobe, extrastriate cortex, and cerebellum; differences between the sexes showed that males had significantly greater activation in right lingual gyrus and cerebellum. Formal comparisons between age groups revealed that older males show engagement of left hemisphere regions, while females show greater bilateral (R>L) engagement of regions traditionally associated with visuospatial processing. Together, these results suggest that older males, as compared to younger males, may engage regions that are associated with a visuomotor network, whereas females utilize areas indicated in spatial attention and working memory. Furthermore, these results could also suggest that there may be differences in strategy use that are evident early on and may continue to develop over time evident by differential engagement of networks associated with visuospatial processing. Our data provide evidence for sex-based differences in the neural basis of visuospatial processing.

Visuospatial processing in children with neurofibromatosis type 1.

Neuroimaging studies investigating the neural network of visuospatial processing have revealed a right hemisphere network of activation including inferior parietal lobe, dorsolateral prefrontal cortex, and extrastriate regions. Impaired visuospatial processing, indicated by the Judgment of Line Orientation (JLO), is commonly seen in individuals with neurofibromatosis type 1 (NF-1). Nevertheless, few studies have examined the neural activity associated with visuospatial processing in NF-1, in particular, during a JLO task. This study used functional neuroimaging to explore differences in volume of activation in predefined regions of interest between 13 individuals with NF-1 and 13 controls while performing an analogue JLO task. We hypothesized that participants with NF-1 would show anomalous right hemisphere activation and therefore would recruit regions within the left hemisphere to complete the task. Multivariate analyses of variance were used to test for differences between groups in frontal, temporal, parietal, and occipital regions. Results indicate that, as predicted, controls utilized various right hemisphere regions to complete the task, while the NF-1 group tended to recruit left hemisphere regions. These results suggest that the NF-1 group has an inefficient right hemisphere network. An additional unexpected finding was that the NF-1 group showed decreased volume of activation in primary visual cortex (BA 17). Future studies are needed to examine whether the decrease in primary visual cortex is related to a deficit in basic visual processing; findings could ultimately lead to a greater understanding of the nature of deficits in NF-1 and have implications for remediation.

Atypical motor and sensory cortex activation in attention-deficit/hyperactivity disorder: a functional magnetic resonance imaging study of simple sequential finger tapping.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) has been shown to be associated with anomalous motor development, including excessive overflow movements. The neurological basis of these deficits has not been established. Functional magnetic resonance imaging (fMRI) was used to determine whether differences in brain activation during sequential finger tapping are present in children with ADHD compared with typically developing control subjects. METHODS: Twenty-two right-handed children between 8 and 12 years old, 11 with ADHD and 11 typically developing control subjects closely matched for age and gender, performed self-paced sequential finger tapping during fMRI acquisition. RESULTS: There were no significant between-group differences in speed of sequential finger tapping. The between-group whole-brain comparison showed greater magnitude of activation for control subjects than children with ADHD in the right superior parietal lobe during both right-handed and left-handed finger tapping. The region-of-interest analysis within Brodmann Area 4 revealed that children with ADHD showed a significantly smaller extent of fMRI activation in the primary motor cortex contralateral to the finger-sequencing hand. CONCLUSIONS: Despite similar speed of sequential finger tapping, children with ADHD showed decreased contralateral motor cortex and right parietal cortex activation during both right-handed finger sequencing (RHFS) and left-handed finger sequencing (LHFS). The fMRI findings suggest that children with ADHD have anomalous development of cortical systems necessary for execution of patterned movements.