Gayle K. Deutsch

Neural deficits in children with dyslexia ameliorated by behavioral remediation: Evidence from functional MRI

Developmental dyslexia, characterized by unexplained difficulty in reading, is associated with behavioral deficits in phonological processing. Functional neuroimaging studies have shown a deficit in the neural mechanisms underlying phonological processing in children and adults with dyslexia. The present study examined whether behavioral remediation ameliorates these dysfunctional neural mechanisms in children with dyslexia. Functional MRI was performed on 20 children with dyslexia (8–12 years old) during phonological processing before and after a remediation program focused on auditory processing and oral language training. Behaviorally, training improved oral language and reading performance. Physiologically, children with dyslexia showed increased activity in multiple brain areas. Increases occurred in left temporo-parietal cortex and left inferior frontal gyrus, bringing brain activation in these regions closer to that seen in normal-reading children. Increased activity was observed also in right-hemisphere frontal and temporal regions and in the anterior cingulate gyrus. Children with dyslexia showed a correlation between the magnitude of increased activation in left temporo-parietal cortex and improvement in oral language ability. These results suggest that a partial remediation of language-processing deficits, resulting in improved reading, ameliorates disrupted function in brain regions associated with phonological processing and produces additional compensatory activation in other brain regions.

Disrupted neural responses to phonological and orthographic processing in dyslexic children: an fMRI study.

Developmental dyslexia, characterized by difficulty in reading, has been associated with phonological and orthographic processing deficits. fMRI was performed on dyslexic and normal-reading children (8–12 years old) during phonological and orthographic tasks of rhyming and matching visually presented letter pairs. During letter rhyming, both normal and dyslexic reading children had activity in left frontal brain regions, whereas only normal-reading children had activity in left temporo-parietal cortex. During letter matching, normal-reading children showed activity throughout extrastriate cortex, especially in occipito-parietal regions, whereas dyslexic children had little activity in extrastriate cortex during this task. These results indicate dyslexia may be characterized in childhood by disruptions in the neural bases of both phonological and orthographic processes important for reading.

Children's reading performance is correlated with white matter structure measured by diffusion tensor imaging

We investigated the white matter structure in children (n = 14) with a wide range of reading performance levels using diffusion tensor imaging (DTI), a form of magnetic resonance imaging. White matter structure in a left temporo-parietal region that had been previously described as covarying with reading skill in adult readers also differs between children who are normal and poor readers. Specifically, the white matter structure measured using fractional anisotropy (FA) and coherence index (CI) significantly correlated with behavioral measurements of reading, spelling, and rapid naming performance. In general, lower anisotropy and lower coherence were associated with lower performance scores. Although the magnitude of the differences in children are smaller than those in adults, the results support the hypothesis that the structure of left temporoparietal neural pathways is a significant component of the neural system needed to develop fluent reading.

Functional and morphometric brain dissociation between dyslexia and reading ability

In functional neuroimaging studies, individuals with dyslexia frequently exhibit both hypoactivation, often in the left parietotemporal cortex, and hyperactivation, often in the left inferior frontal cortex, but there has been no evidence to suggest how to interpret the differential relations of hypoactivation and hyperactivation to dyslexia. To address this question, we measured brain activation by functional MRI during visual word rhyme judgment compared with visual cross-hair fixation rest, and we measured gray matter morphology by voxel-based morphometry in dyslexic adolescents in comparison with (i) an age-matched group, and (ii) a reading-matched group younger than the dyslexic group but equal to the dyslexic group in reading performance. Relative to the age-matched group (n = 19; mean 14.4 years), the dyslexic group (n = 19; mean 14.4 years) exhibited hypoactivation in left parietal and bilateral fusiform cortices and hyperactivation in left inferior and middle frontal gyri, caudate, and thalamus. Relative to the reading-matched group (n = 12; mean 9.8 years), the dyslexic group (n = 12; mean 14.5 years) also exhibited hypoactivation in left parietal and fusiform regions but equal activation in all four areas that had exhibited hyperactivation relative to age-matched controls as well. In regions that exhibited atypical activation in the dyslexic group, only the left parietal region exhibited reduced gray matter volume relative to both control groups. Thus, areas of hyperactivation in dyslexia reflected processes related to the level of current reading ability independent of dyslexia. In contrast, areas of hypoactivation in dyslexia reflected functional atypicalities related to dyslexia itself, independent of current reading ability, and related to atypical brain morphology in dyslexia.

Temporal-callosal pathway diffusivity predicts phonological skills in children

The development of skilled reading requires efficient communication between distributed brain regions. By using diffusion tensor imaging, we assessed the interhemispheric connections in a group of children with a wide range of reading abilities. We segmented the callosal fibers into regions based on their likely cortical projection zones, and we measured diffusion properties in these segmented regions. Phonological awareness (a key factor in reading acquisition) was positively correlated with diffusivity perpendicular to the main axis of the callosal fibers that connect the temporal lobes. These results could be explained by several physiological properties. For example, good readers may have fewer but larger axons connecting left and right temporal lobes, or their axon membranes in these regions may be more permeable than the membranes of poor readers. These measurements are consistent with previous work suggesting that good readers have reduced interhemispheric connectivity and are better at processing rapidly changing visual and auditory stimuli.

Neural Basis of Dyslexia: A Comparison between Dyslexic and Nondyslexic Children Equated for Reading Ability

Adults and children with developmental dyslexia exhibit reduced parietotemporal activation in functional neuroimaging studies of phonological processing. These studies used age-matched and/or intelligence quotient-matched control groups whose reading ability and scanner task performance were often superior to that of the dyslexic group. It is unknown, therefore, whether differences in activation reflect simply poorer performance in the scanner, the underlying level of reading ability, or more specific neural correlates of dyslexia. To resolve this uncertainty, we conducted a functional magnetic resonance imaging study, with a rhyme judgment task, in which we compared dyslexic children with two control groups: age-matched children and reading-matched children (younger normal readers equated for reading ability or scanner-performance to the dyslexic children). Dyslexic children exhibited reduced activation relative to both age-matched and reading-matched children in the left parietotemporal cortex and five other regions, including the right parietotemporal cortex. The dyslexic children also exhibited reduced activation bilaterally in the parietotemporal cortex when compared with children equated for task performance during scanning. Nine of the 10 dyslexic children exhibited reduced left parietotemporal activation compared with their individually selected age-matched or reading-matched control children. Additionally, normal reading fifth graders showed more activation in the same bilateral parietotemporal regions than normal-reading third graders. These findings indicate that the activation differences seen in the dyslexic children cannot be accounted for by either current reading level or scanner task performance, but instead represent a distinct developmental atypicality in the neural systems that support learning to read.

Anatomical properties of the arcuate fasciculus predict phonological and reading skills in children

For more than a century, neurologists have hypothesized that the arcuate fasciculus carries signals that are essential for language function; however, the relevance of the pathway for particular behaviors is highly controversial. The primary objective of this study was to use diffusion tensor imaging to examine the relationship between individual variation in the microstructural properties of arcuate fibers and behavioral measures of language and reading skills. A second objective was to use novel fiber-tracking methods to reassess estimates of arcuate lateralization. In a sample of 55 children, we found that measurements of diffusivity in the left arcuate correlate with phonological awareness skills and arcuate volume lateralization correlates with phonological memory and reading skills. Contrary to previous investigations that report the absence of the right arcuate in some subjects, we demonstrate that new techniques can identify the pathway in every individual. Our results provide empirical support for the role of the arcuate fasciculus in the development of reading skills.

The development of cortical sensitivity to visual word forms

The ability to extract visual word forms quickly and efficiently is essential for using reading as a tool for learning. We describe the first longitudinal fMRI study to chart individual changes in cortical sensitivity to written words as reading develops. We conducted four annual measurements of brain function and reading skills in a heterogeneous group of children, initially 7–12 years old. The results show age-related increase in childrens cortical sensitivity to word visibility in posterior left occipito-temporal sulcus (LOTS), nearby the anatomical location of the visual word form area. Moreover, the rate of increase in LOTS word sensitivity specifically correlates with the rate of improvement in sight word efficiency, a measure of speeded overt word reading. Other cortical regions, including V1, posterior parietal cortex, and the right homologue of LOTS, did not demonstrate such developmental changes. These results provide developmental support for the hypothesis that LOTS is part of the cortical circuitry that extracts visual word forms quickly and efficiently and highlight the importance of developing cortical sensitivity to word visibility in reading acquisition.

Hippocampal CA1 apical neuropil atrophy and memory performance in Alzheimer's disease

Memory loss is often the first and most prominent symptom of Alzheimers disease (AD), coinciding with the spread of neurofibrillary pathology from the entorhinal cortex (ERC) to the hippocampus. The apical dendrites of hippocampal CA1 pyramidal neurons, in the stratum radiatum/stratum lacunosum-moleculare (SRLM), are among the earliest targets of this pathology, and atrophy of the CA1-SRLM is apparent in postmortem tissue from patients with mild AD. We previously demonstrated that CA1-SRLM thinning is also apparent in vivo, using ultra-high field 7-Tesla (7T) MRI to obtain high-resolution hippocampal microstructural imaging. Here, we hypothesized that CA1-SRLM thickness would correlate with episodic memory performance among patients with mild AD. We scanned nine patients, using an oblique coronal T2-weighted sequence through the hippocampal body with an in-plane resolution of 220 μm, allowing direct visual identification of subfields - dentate gyrus (DG)/CA3, CA2, CA1, and ERC - and hippocampal strata - SRLM and stratum pyramidale (SP). We present a novel semi-automated method of measuring stratal width that correlated well with manual measurements. We performed multi-domain neuropsychological evaluations that included three tests of episodic memory, yielding composite scores for immediate recall, delayed recall, and delayed recognition memory. Strong correlations occurred between delayed recall performance and the widths of CA1-SRLM (r(2)=0.69; p=0.005), CA1-SP (r(2)=0.5; p=0.034), and ERC (r(2)=0.62; p=0.012). The correlation between CA1-SRLM width and delayed recall lateralized to the left hemisphere. DG/CA3 size did not correlate significantly with any aspect of memory performance. These findings highlight a role for 7T hippocampal microstructural imaging in revealing focal structural pathology that correlates with the central cognitive feature of AD.

Frontoparietal white matter diffusion properties predict mental arithmetic skills in children

Functional MRI studies of mental arithmetic consistently report blood oxygen level–dependent signals in the parietal and frontal regions. We tested whether white matter pathways connecting these regions are related to mental arithmetic ability by using diffusion tensor imaging (DTI) to measure these pathways in 28 children (age 10–15 years, 14 girls) and assessing their mental arithmetic skills. For each child, we identified anatomically the anterior portion of the superior longitudinal fasciculus (aSLF), a pathway connecting parietal and frontal cortex. We measured fractional anisotropy in a core region centered along the length of the aSLF. Fractional anisotropy in the left aSLF positively correlates with arithmetic approximation skill, as measured by a mental addition task with approximate answer choices. The correlation is stable in adjacent core aSLF regions but lower toward the pathway endpoints. The correlation is not explained by shared variance with other cognitive abilities and did not pass significance in the right aSLF. These measurements used DTI, a structural method, to test a specific functional model of mental arithmetic.