The Role of Brain Activity in Characterizing Successful Reading Intervention in Children With Dyslexia.

Studies of reading intervention in dyslexia have shown changes in performance and in brain function. However, there is little consistency in the location of brain regions associated with successful reading gains in children, most likely due to variability/limitations in methodologies (study design, participant criteria, and neuroimaging procedures). Ultimately for the results to be meaningful, the intervention has to be successful, be assessed against a control, use rigorous statistics, and take biological variables (sex) into consideration. Using a randomized, crossover design, 31 children with dyslexia were assigned to a phonological- and orthographic-based tutoring period as well as a within-subjects control period to examine: (1) intervention-induced changes in behavior (reading performance) and in brain activity (during reading); and (2) behavioral and brain activity pre-intervention data that predicted intervention-induced gains in reading performance. We found gains in reading ability following the intervention, but not following the control period, with no effect of participants' sex. However, there were no changes in brain activity following the intervention (regardless of sex), suggesting that individual brain changes are too variable to be captured at the group level. Reading gains were not predicted by pre-intervention behavioral data, but were predicted by pre-intervention brain activity in bilateral supramarginal/angular gyri. Notably, some of this prediction was only found in females. Our results highlight the limitations of brain imaging in detecting the neural correlates of reading intervention in this age group, while providing further evidence for its utility in assessing eventual success of intervention, especially if sex is taken into consideration.

Cerebellar function in children with and without dyslexia during single word processing.

The cerebellar deficit hypothesis of dyslexia posits that dysfunction of the cerebellum is the underlying cause for reading difficulties observed in this common learning disability. The present study used functional magnetic resonance imaging (fMRI) and a single word processing task to test for differences in activity and connectivity in children with (n = 23) and without (n = 23) dyslexia. We found cerebellar activity in the control group when word processing was compared to fixation, but not when it was compared to the active baseline task designed to reveal activity specific to reading. In the group with dyslexia there was no cerebellar activity for either contrasts and there were no differences when they were compared to children without dyslexia. Turning to functional connectivity (FC) in the controls, background FC (i.e., not specific to reading) was predominately found between the cerebellum and the occipitaltemporal cortex. In the group with dyslexia, there was background FC between the cerebellum and several cortical regions. When comparing the two groups, they differed in background FC in connections between the seed region right crus I and three left-hemisphere perisylvian target regions. However, there was no task-specific FC for word processing in either group and no between-group differences. Together the results do not support the theory that the cerebellum is affected functionally during reading in children with dyslexia.

Functional neuroanatomy of arithmetic and word reading and its relationship to age.

Arithmetic and written language are uniquely human skills acquired during early schooling and used daily. While prior studies have independently characterized the neural bases for arithmetic and reading, here we examine both skills in a single study to capture their shared and unique cognitive mechanisms, as well as the role of age/experience in modulating their neural representations. We used functional MRI in 7- to 29-year-olds who performed single-digit subtraction, single-digit addition, and single-word reading. Using a factorial design, we examined the main effects of Task (subtraction, addition, reading) and Age (as a continuous variable), and their interactions. A main effect of Task revealed preferential activation for subtraction in bilateral intraparietal sulci and supramarginal gyri, right insula, inferior frontal gyrus, and cingulate. The right middle temporal gyrus and left superior temporal gyrus were preferentially active for both addition and reading, and left fusiform gyrus was preferentially active for reading. A main effect of Age revealed increased activity in older participants in right angular gyrus, superior temporal sulcus, and putamen, and less activity in left supplementary motor area, suggesting a left frontal to right temporo-parietal shift of activity with increasing age/experience across all tasks. Interactions for Task by Age were found in right hippocampus and left middle frontal gyrus, with older age invoking greater activity for addition and at the same time less activity for subtraction and reading. Together, in a study conducted in the same participants using similar task and acquisition parameters, the results reveal the neural substrates of these educationally relevant cognitive skills in typical participants in the context of age/experience.

Chinese Character and English Word processing in children's ventral occipitotemporal cortex: fMRI evidence for script invariance.

Learning to read is thought to involve the recruitment of left hemisphere ventral occipitotemporal cortex (OTC) by a process of "neuronal recycling", whereby object processing mechanisms are co-opted for reading. Under the same theoretical framework, it has been proposed that the visual word form area (VWFA) within OTC processes orthographic stimuli independent of culture and writing systems, suggesting that it is universally involved in written language. However, this "script invariance" has yet to be demonstrated in monolingual readers of two different writing systems studied under the same experimental conditions. Here, using functional magnetic resonance imaging (fMRI), we examined activity in response to English Words and Chinese Characters in 1st graders in the United States and China, respectively. We examined each group separately and found the readers of English as well as the readers of Chinese to activate the left ventral OTC for their respective native writing systems (using both a whole-brain and a bilateral OTC-restricted analysis). Critically, a conjunction analysis of the two groups revealed significant overlap between them for native writing system processing, located in the VWFA and therefore supporting the hypothesis of script invariance. In the second part of the study, we further examined the left OTC region responsive to each group's native writing system and found that it responded equally to Object stimuli (line drawings) in the Chinese-reading children. In English-reading children, the OTC responded much more to Objects than to English Words. Together, these results support the script invariant role of the VWFA and also support the idea that the areas recruited for character or word processing are rooted in object processing mechanisms of the left OTC.

The functional anatomy of single-digit arithmetic in children with developmental dyslexia.

Some arithmetic procedures, such as addition of small numbers, rely on fact retrieval mechanisms supported by left hemisphere perisylvian language areas, while others, such as subtraction, rely on procedural-based mechanisms subserved by bilateral parietal cortices. Previous work suggests that developmental dyslexia, a reading disability, is accompanied by subtle deficits in retrieval-based arithmetic, possibly because of compromised left hemisphere function. To test this prediction, we compared brain activity underlying arithmetic problem solving in children with and without dyslexia during addition and subtraction operations using a factorial design. The main effect of arithmetic operation (addition versus subtraction) for both groups combined revealed activity during addition in the left superior temporal gyrus and activity during subtraction in the bilateral intraparietal sulcus, the right supramarginal gyrus and the anterior cingulate, consistent with prior studies. For the main effect of diagnostic group (dyslexics versus controls), we found less activity in dyslexic children in the left supramarginal gyrus. Finally, the interaction analysis revealed that while the control group showed a strong response in the right supramarginal gyrus for subtraction but not for addition, the dyslexic group engaged this region for both operations. This provides physiological evidence in support of the theory that children with dyslexia, because of disruption to left hemisphere language areas, use a less optimal route for retrieval-based arithmetic, engaging right hemisphere parietal regions typically used by good readers for procedural-based arithmetic. Our results highlight the importance of language processing for mathematical processing and illustrate that children with dyslexia have impairments that extend beyond reading.

An investigation into the origin of anatomical differences in dyslexia.

Studies have converged in their findings of relatively less gray matter volume (GMV) in developmental dyslexia in bilateral temporoparietal and left occipitotemporal cortical regions. However, the interpretation of these results has been difficult. The reported neuroanatomical differences in dyslexia may be causal to the reading problems, following from, for example, neural migration errors that occurred during early human development and before learning to read. Alternatively, less GMV may represent the consequence of an impoverished reading experience, akin to the experience-dependent GMV differences attributed to illiterate compared with literate adults. Most likely, a combination of these factors is driving these observations. Here we attempt to disambiguate these influences by using a reading level-matched design, where dyslexic children were contrasted not only with age-matched controls, but also with younger controls who read at the same level as the dyslexics. Consistent with previous reports, dyslexics showed less GMV in multiple left and right hemisphere regions, including left superior temporal sulcus when compared with age-matched controls. However, not all of these differences emerged when dyslexics were compared with controls matched on reading abilities, with only right precentral gyrus GMV surviving this second analysis. When similar analyses were performed for white matter volume, no regions emerged from both comparisons. These results indicate that the GMV differences in dyslexia reported here and in prior studies are in large part the outcome of experience (e.g., disordered reading experience) compared with controls, with only a fraction of the differences being driven by dyslexia per se.

Sex-specific gray matter volume differences in females with developmental dyslexia.

Developmental dyslexia, characterized by unexpected reading difficulty, is associated with anomalous brain anatomy and function. Previous structural neuroimaging studies have converged in reports of less gray matter volume (GMV) in dyslexics within left hemisphere regions known to subserve language. Due to the higher prevalence of dyslexia in males, these studies are heavily weighted towards males, raising the question whether studies of dyslexia in females only and using the same techniques, would generate the same findings. In a replication study of men, we obtained the same findings of less GMV in dyslexics in left middle/inferior temporal gyri and right postcentral/supramarginal gyri as reported in the literature. However, comparisons in women with and without dyslexia did not yield left hemisphere differences, and instead, we found less GMV in right precuneus and paracentral lobule/medial frontal gyrus. In boys, we found less GMV in left inferior parietal cortex (supramarginal/angular gyri), again consistent with previous work, while in girls differences were within right central sulcus, spanning adjacent gyri, and left primary visual cortex. Our investigation into anatomical variants in dyslexia replicates existing studies in males, but at the same time shows that dyslexia in females is not characterized by involvement of left hemisphere language regions but rather early sensory and motor cortices (i.e., motor and premotor cortex, primary visual cortex). Our findings suggest that models on the brain basis of dyslexia, primarily developed through the study of males, may not be appropriate for females and suggest a need for more sex-specific investigations into dyslexia.

Developmental differences for word processing in the ventral stream.

The visual word form system (VWFS), located in the occipito-temporal cortex, is involved in orthographic processing of visually presented words (Cohen et al., 2002). Recent fMRI studies in children and adults have demonstrated a gradient of increasing word-selectivity along the posterior-to-anterior axis of this system (Vinckier et al., 2007), yet whether this pattern is modified by the increased reading experience afforded by age is still in question. In this study, we employed fMRI and an implicit word-processing task, and then used a region of interest analysis approach along the occipito-temporal cortex to test the prediction that the selectivity for words along the extent of the VWFS differs between older experienced and younger novice readers. Our results showed differences between children and adults during word processing in the anterior left occipito-temporal cortex, providing evidence of developmental refinement for word recognition along the VWFS.

Gray matter volume changes following reading intervention in dyslexic children.

Studies in children and adults with the reading disability developmental dyslexia have shown behavioral improvements after reading intervention. In another line of work, it has been shown that intensive training in a variety of cognitive and sensorimotor skills can result in changes in gray matter volume (GMV). This study examined changes in GMV following intensive reading intervention in children with dyslexia using voxel-based morphometry (VBM). Eleven dyslexic children underwent an eight week training focused on mental imagery, articulation and tracing of letters, groups of letters and words, which resulted in significant gains in reading skills. This was followed by an eight week null period (control) where no intervention was administered and no further significant gains in reading were observed. Structural scans were obtained before the intervention, after the intervention and after the null period. GMV increases between the first two time points were found in the left anterior fusiform gyrus/hippocampus, left precuneus, right hippocampus and right anterior cerebellum. However these areas did not change between time points two and three (control period), suggesting that the changes were specific to the intervention period. These results demonstrate for the first time that (1) training-induced changes in GMV can be observed in a pediatric sample and (2) reading improvements induced by intervention are accompanied by GMV changes.

Development of ventral stream representations for single letters.

Visual form recognition is mediated by the ventral extrastriate processing stream. Some regions of ventral stream cortex show preferential activity for specific stimulus categories, but little is known about how this regional specialization develops. Acquisition of letter-naming skill is of particular interest because letter recognition serves as the gateway to visual processing of words, and fluent letter naming predicts children's reading success. For this reason, we examined the school-age development of visual letter processing using fMRI. In a 2 x 2 design, we compared ventral stream BOLD activity in two groups, children (n= 22, age 6-11) and adults (n= 15, age 20-22), during two tasks: naming of single letters and naming of simple line drawings of objects. We hypothesized that, based on adults' greater experience with letters, the posterior left fusiform gyrus would be activated more in adults for letter naming than it would be in children. We found that bilateral areas of ventral stream cortex during letter naming were activated in both children and adults and that the midposterior areas of the fusiform gyrus in both hemispheres were activated to a greater degree in adults than in children. There were no areas within the ventral stream in either hemisphere that were activated preferentially for letters over line drawings, nor were there any significant differences in the developmental changes observed for letter naming compared to object naming. These findings indicate that visual processing of single letters continues to develop in both hemispheres during grade school. However, we found no evidence for development of areas specialized for single letter processing. Rather, our findings suggest that letter recognition is performed using the same general form recognition systems as are used to process other visually similar stimuli.

A meta-analysis of functional neuroimaging studies of dyslexia.

Reading and phonological processing deficits have been the primary focus of neuroimaging studies addressing the neurologic basis of developmental dyslexia, but to date there has been no objective assessment of the consistency of these findings. To address this issue, spatial coordinates reported in the literature were submitted to two parallel activation likelihood estimate (ALE) meta-analyses. First, a meta-analysis including 96 foci from nine publications identified regions where typical readers are likely to show greater activation than dyslexics: two left extrastriate areas within BA 37, precuneus, inferior parietal cortex, superior temporal gyrus, thalamus, and left inferior frontal gyrus. Right hemisphere ALE foci representing hypoactivity in dyslexia were found in the fusiform, postcentral, and superior temporal gyri. To identify regions in which dyslexic subjects reliably show greater activation than controls, 75 foci from six papers were entered into a second meta-analysis. Here ALE results revealed hyperactivity associated with dyslexia in right thalamus and anterior insula. These findings suggest that during the performance of a variety of reading tasks, normal readers activate left-sided brain areas more than dyslexic readers do, whereas dyslexia is associated with greater right-sided brain activity. The most robust result was in left extrastriate cortex, where hypoactivity associated with dyslexia was found. However, the ALE maps provided no support for cerebellar dysfunction, nor for hyperactivity in left frontal cortex in dyslexia, suggesting that these findings, unlike those described above, are likely to be more varied in terms of their reproducibility or spatial location.

A pianist's recovery from stroke.

OBJECTIVE: To determine alternative neural pathways for restitution of piano playing after right hemispheric infarction causing left arm and hand paralysis. DESIGN: Case report testing coordinated bimanual skills using structured motor skills tests and neuroimaging. SETTING: A professional pianist sustained a lacunar infarction in the posterior limb of his right internal capsule, which resulted in left hemiparesis with immobilized left-hand and -finger movements persisting for 13 weeks. After 6 months, he had recovered bimanual coordinated piano skills by "ignoring" his left hand while concentrating or discussing subjects other than music while playing. PATIENT: A 63-year-old, male professional pianist. INTERVENTION: Detailed neurological examination including computed cranial tomography, functional magnetic resonance imaging, and positron emission tomography. RESULTS: Functional magnetic resonance imaging activation patterns correlated with rapid movements of fingers in each hand separately and together demonstrating that subcortical and cerebellar pathways were activated during skilled motor function of his left hand. Contralateral cerebral and cerebellar activation occurred with both left- and right-hand movements. During tapping of the left fingers, there was bilateral cerebellar, parietal, and left premotor strip and left thalamic activation. CONCLUSION: Patterns of activation relate to task performance and they are not similar to subjects engaged in simpler tasks such as finger opposition.

Delayed detection of tonal targets in background noise in dyslexia.

Individuals with developmental dyslexia are often impaired in their ability to process certain linguistic and even basic non-linguistic auditory signals. Recent investigations report conflicting findings regarding impaired low-level binaural detection mechanisms associated with dyslexia. Binaural impairment has been hypothesized to stem from a general low-level processing disorder for temporally fine sensory stimuli. Here we use a new behavioral paradigm to address this issue. We compared the response times of dyslexic listeners and their matched controls in a tone-in-noise detection task. The tonal signals were either Huggins Pitch (HP), a stimulus requiring binaural processing to elicit a pitch percept, or a pure tone-perceptually similar but physically very different signals. The results showed no difference between the two groups specific to the processing of HP and thus no evidence for a binaural impairment in dyslexia. However, dyslexic subjects exhibited a general difficulty in extracting tonal objects from background noise, manifested by a globally delayed detection speed.

Altered temporal profile of visual-auditory multisensory interactions in dyslexia.

Recent studies have demonstrated that dyslexia is associated with deficits in the temporal encoding of sensory information. While most previous studies have focused on information processing within a single sensory modality, it is clear that the deficits seen in dyslexia span multiple sensory systems. Surprisingly, although the development of linguistic proficiency involves the rapid and accurate integration of auditory and visual cues, the capacity of dyslexic individuals to integrate information between the different senses has not been systematically examined. To test this, we studied the effects of task-irrelevant auditory information on the performance of a visual temporal-order-judgment (TOJ) task. Dyslexic subjects' performance differed significantly from that of control subjects, specifically in that they integrated the auditory and visual information over longer temporal intervals. Such a result suggests an extended temporal "window" for binding visual and auditory cues in dyslexic individuals. The potential deleterious effects of this finding for rapid multisensory processes such as reading are discussed.

Predictive assessment of reading.

Study 1 retrospectively analyzed neuropsychological and psychoeducational tests given to N=220 first graders, with follow-up assessments in third and eighth grade. Four predictor constructs were derived: (1) Phonemic Awareness, (2) Picture Vocabulary, (3) Rapid Naming, and (4) Single Word Reading. Together, these accounted for 88%, 76%, 69%, and 69% of the variance, respectively, in first, third, and eighth grade Woodcock Johnson Broad Reading and eighth grade Gates-MacGinitie. When Single Word Reading was excluded from the predictors, the remaining predictors still accounted for 71%, 65%, 61%, and 65% of variance in the respective outcomes. Secondary analyses of risk of low outcome showed sensitivities/specificities of 93.0/91.0, and 86.4/84.9, respectively, for predicting which students would be in the bottom 15% and 30% of actual first grade WJBR. Sensitivities/specificities were 84.8/83.3 and 80.2/81.3, respectively, for predicting the bottom 15% and 30% of actual third grade WJBR outcomes; eighth grade outcomes had sensitivities/specificities of 80.0/80.0 and 85.7/83.1, respectively, for the bottom 15% and 30% of actual eighth grade WJBR scores. Study 2 cross-validated the concurrent predictive validities in an N=500 geographically diverse sample of late kindergartners through third graders, whose ethnic and racial composition closely approximated the national early elementary school population. New tests of the same four predictor domains were used, together taking only 15 minutes to administer by teachers; the new Woodcock-Johnson III Broad Reading standard score was the concurrent criterion, whose testers were blind to the predictor results. This cross-validation showed 86% of the variance accounted for, using the same regression weights as used in Study 1. With these weights, sensitivity/specificity values for the 15% and 30% thresholds were, respectively, 91.3/88.0 and 94.1/89.1. These validities and accuracies are stronger than others reported for similar intervals in the literature.

Neural changes following remediation in adult developmental dyslexia.

Brain imaging studies have explored the neural mechanisms of recovery in adults following acquired disorders and, more recently, childhood developmental disorders. However, the neural systems underlying adult rehabilitation of neurobiologically based learning disabilities remain unexplored, despite their high incidence. Here we characterize the differences in brain activity during a phonological manipulation task before and after a behavioral intervention in adults with developmental dyslexia. Phonologically targeted training resulted in performance improvements in tutored compared to nontutored dyslexics, and these gains were associated with signal increases in bilateral parietal and right perisylvian cortices. Our findings demonstrate that behavioral changes in tutored dyslexic adults are associated with (1) increased activity in those left-hemisphere regions engaged by normal readers and (2) compensatory activity in the right perisylvian cortex. Hence, behavioral plasticity in adult developmental dyslexia involves two distinct neural mechanisms, each of which has previously been observed either for remediation of developmental or acquired reading disorders.

The neural basis of hyperlexic reading: an FMRI case study.

Children with autism spectrum disorders in very rare cases display surprisingly advanced "hyperlexic" reading skills. Using functional magnetic resonance imaging (fMRI), we studied the neural basis of this precocious reading ability in a 9-year-old hyperlexic boy who reads 6 years in advance of his age. During covert reading, he demonstrated greater activity in the left inferior frontal and superior temporal cortices than both chronological age- and reading age-matched controls. Activity in the right inferior temporal sulcus was greater when compared to reading age-matched controls. These findings suggest that precocious reading is brought about by simultaneously drawing on both left hemisphere phonological and right hemisphere visual systems, reconciling the two prevailing, but seemingly contradictory, single hemisphere theories of hyperlexia. Hyperlexic reading is therefore associated with hyperactivation of the left superior temporal cortex, much in the same way as developmental dyslexia is associated with hypoactivation of this area.

Development of neural mechanisms for reading.

The complexities of pediatric brain imaging have precluded studies that trace the neural development of cognitive skills acquired during childhood. Using a task that isolates reading-related brain activity and minimizes confounding performance effects, we carried out a cross-sectional functional magnetic resonance imaging (fMRI) study using subjects whose ages ranged from 6 to 22 years. We found that learning to read is associated with two patterns of change in brain activity: increased activity in left-hemisphere middle temporal and inferior frontal gyri and decreased activity in right inferotemporal cortical areas. Activity in the left-posterior superior temporal sulcus of the youngest readers was associated with the maturation of their phonological processing abilities. These findings inform current reading models and provide strong support for Orton's 1925 theory of reading development.