Tami Katzir

A structural basis for reading fluency: White matter defects in a genetic brain malformation

Background: Multiple lines of evidence have suggested that developmental dyslexia may be associated with abnormalities of neuronal migration or axonal connectivity. In patients with periventricular nodular heterotopia—a rare genetic brain malformation characterized by misplaced nodules of gray matter along the lateral ventricles—a specific and unexpected reading disability is present, despite normal intelligence. We sought to investigate the cognitive and structural brain bases of this phenomenon. Methods: Ten adult subjects with heterotopia, 10 with dyslexia, and 10 normal controls were evaluated, using a battery of neuropsychometric measures. White matter integrity and fiber tract organization were examined in six heterotopia subjects, using diffusion tensor imaging methods. Results: Subjects with heterotopia and those with developmental dyslexia shared a common behavioral profile, with specific deficits in reading fluency. Individuals with dyslexia seemed to have a more prominent phonological impairment than heterotopia subjects. Periventricular nodular heterotopia was associated with specific, focal disruptions in white matter microstructure and organization in the vicinity of gray matter nodules. The degree of white matter integrity correlated with reading fluency in this population. Conclusions: We demonstrate that a genetic disorder of gray matter heterotopia shares behavioral characteristics with developmental dyslexia, and that focal white matter defects in this disorder may serve as the structural brain basis of this phenomenon. Our findings represent a potential model for the use of developmental brain malformations in the investigation of abnormal cognitive function.

Imaging phonology without print: Assessing the neural correlates of phonemic awareness using fMRI

Acquisition of phonological processing skills, such as the ability to segment words into corresponding speech sounds, is critical to the development of efficient reading. Prior neuroimaging studies of phonological processing have often relied on auditory stimuli or print-mediated tasks that may be problematic for various theoretical and empirical reasons. For the current study, we developed a task to evaluate phonological processing that used visual stimuli but did not require interpretation of orthographic forms. This task requires the subject to retrieve the names of objects and to compare their first sounds; then, the subject must indicate if the initial sounds of the names of the pictures are the same. The phonological analysis task was compared to both a baseline matching task and a more complex control condition in which the participants evaluated two different pictures and indicated whether they represented the same object. The complex picture-matching condition controls for the visual complexity of the stimuli but does not require phonological analysis of the names of the objects. While both frontal and ventral posterior areas were activated in response to phonological analysis of the names of pictures, only inferior and superior frontal gyrus exhibited differential sensitivity to the phonological comparison task as compared to the complex picture-matching control task. These findings suggest that phonological processing that is not mediated by print relies primarily on frontal language processing areas among skilled readers.

fMRI of syntactic processing in typically developing children: structural correlates in the inferior frontal gyrus

Development of syntactic processing was examined to evaluate maturational processes including left language lateralization functions and increased specialization of brain regions important for syntactic processing. We utilized multimodal methods, including indices of brain activity from fMRI during a syntactic processing task, cortical thickness measurements from structural MRI, and neuropsychological measures. To evaluate hypotheses about increasing lateralization and specialization with development, we examined relationships between cortical thickness and magnitude and spatial activation extent within the left inferior frontal gyrus (IFG) and its right hemisphere homologue. We predicted that increased activation in the left and decreased activation in the right IFG would be associated with increased syntactic proficiency. As predicted, a more mature pattern of increased thickness in the right pars triangularis was associated with decreased activation intensity and extent in the right IFG. These findings suggest a maturational shift towards decreased involvement of the right IFG for syntactic processing. Better syntactic skills were associated with increased activation in the left IFG independent from age, suggesting increased specialization of the left IFG with increased proficiency. Overall, our findings show relationships between structural and functional neurodevelopment that co-occur with improved syntactic processing in critical language regions of the IFG in typically developing children.

Abnormal structural and functional brain connectivity in gray matter heterotopia

Purpose:  Periventricular nodular heterotopia (PNH) is a malformation of cortical development associated with epilepsy and dyslexia. Evidence suggests that heterotopic gray matter can be functional in brain malformations and that connectivity abnormalities may be important in these disorders. We hypothesized that nodular heterotopia develop abnormal connections and systematically investigated the structural and functional connectivity of heterotopia in patients with PNH.

Predicting reading comprehension of narrative and expository texts among Hebrew-speaking readers with and without a reading disability.

The aim of this study was to investigate which cognitive and reading-related linguistic skills contribute to reading comprehension of narrative and expository texts. The study examined an Israeli national database of Hebrew-speaking readers in fourth grade, from which a subsample of 190 readers with a reading disability (RD) and 190 readers with no reading disability (NRD) was selected. IQ, text reading, reading comprehension, and various linguistic and cognitive skills were assessed. Structural equation modeling results suggested that both groups rely on lower level processes such as text reading accuracy and orthographic knowledge for reading comprehension of both genres. However, RD readers depend more heavily upon these lower level processes compared with NRD for whom higher level processes contribute more to reading comprehension. The various variables accounted for only 25–34% of reading comprehension variance, and possible explanations are discussed. Taken together, these findings highlight the variety of factors influencing reading comprehension and its multidimensional nature.

Are Confidence Ratings Test- or Trait-Driven? Individual Differences among High, Average, and Low Comprehenders in Fourth Grade

The aim of this study was to examine whether low, average, and high comprehenders (LC, AC, and HC, respectively) differed in their reading self-confidence and bias ratings, and whether confidence ratings were driven by reading ability or distributed evenly among diverse readers. Seventy fourth-graders with good decoding abilities were administered a battery of cognitive, linguistic, and self-evaluation measures. They were divided into high, average, and low comprehenders based on a measure of reading comprehension. The results demonstrated that compared to HC, LC exhibited over-confidence and low calibration scores. However, all three groups of readers showed a distribution of low, average, and high confidence ratings. Results support an interaction between test and trait in explaining confidence ratings and emphasize the importance of this interaction in reading comprehension theory and practice.

Integration of gray matter nodules into functional cortical circuits in periventricular heterotopia

Alterations in neuronal circuitry are recognized as an important substrate of many neurological disorders, including epilepsy. Patients with the developmental brain malformation of periventricular nodular heterotopia (PNH) often have both seizures and dyslexia, and there is evidence to suggest that aberrant neuronal connectivity underlies both of these clinical features. We used task-based functional MRI (fMRI) to determine whether heterotopic nodules of gray matter in this condition are integrated into functional cortical circuits. Blood oxygenation level-dependent (BOLD) fMRI was acquired in eight participants with PNH during the performance of reading-related tasks. Evidence of neural activation within heterotopic gray matter was identified, and regions of cortical coactivation were then mapped systematically. Findings were correlated with resting-state functional connectivity results and with performance on the fMRI reading-related tasks. Six participants (75%) demonstrated activation within at least one region of gray matter heterotopia. Cortical areas directly overlying the heterotopia were usually coactivated (60%), as were areas known to have functional connectivity to the heterotopia in the task-free resting state (73%). Six of seven (86%) primary task contrasts resulted in heterotopia activation in at least one participant. Activation was most commonly seen during rapid naming of visual stimuli, a characteristic impairment in this patient population. Our findings represent a systematic demonstration that heterotopic gray matter can be metabolically coactivated in a neuronal migration disorder associated with epilepsy and dyslexia. Gray matter nodules were most commonly coactivated with the anatomically overlying cortex and other regions with resting-state connectivity to heterotopia. These results have broader implications for understanding the network pathogenesis of both seizures and reading disabilities.

How research in the cognitive neuroscience sheds lights on subtypes of children with dyslexia: Implications for teachers

Department of Learning Disabilities, Faculty of Education, University of Haifa, Mount Carmel, Haifa, IsraelThe past decade has generated much excitement as well asskepticism about the applied value of neuroscience researchto educational problems (Katzir and Pare-Balagov, 2006). Onearea in which research in the cognitive neurosciences pro-vides important insights for clinical controversies is in thestudy of heterogeneity of children with dyslexia. Informingteachers about advances made in this area of research mayhelp them tailor their assessment and intervention for differ-ent subtypes of children with dyslexia.An estimated 10–20% of children are diagnosed with dys-lexia, a learning disability signaled by serious difficulty inreading, writing, and spelling (Lyon et al., 2003). A consider-able body of evidence indicates that dyslexic readers exhibitboth subtle structural differences, as well as differences inneural circuitry, when compared to non-impaired readers pri-marily, but not exclusively, in the neural circuitry of the lefthemisphere serving language (Berninger and Richards, 2002).However, there is no definitive brain marker, either structuralor functional, of dyslexia.

Gray matter volumes and cognitive ability in the epileptogenic brain malformation of periventricular nodular heterotopia

Periventricular nodular heterotopia (PNH) is a brain malformation clinically characterized by the triad of epilepsy, normal intelligence, and dyslexia. We investigated the structure-function relationship between cerebral volumes and cognitive ability in this disorder by studying 12 subjects with PNH and 6 controls using volumetric analysis of high-resolution anatomical MRI and neuropsychological testing. Total cerebral volumes and specific brain compartment volumes (gray matter, white matter, and cerebrospinal fluid) in subjects with PNH were comparable to those in controls. There was a negative correlation between heterotopic gray matter volume and cortical gray matter volume. Cerebral and cortical volumes in PNH did not correlate with Full Scale IQ, unlike in normal individuals. Our findings support the idea that heterotopic nodules contain misplaced neurons that would normally have migrated to the cortex, and suggest that structural correlates of normal cognitive ability may be different in the setting of neuronal migration failure.

Reading skill and structural brain development

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.