D. Lynn Flowers

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 Ortons 1925 theory of reading development.

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.

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.

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.

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.

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.

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.

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.