The neural basis of language development: Changes in lateralization over age.

We have long known that language is lateralized to the left hemisphere (LH) in most neurologically healthy adults. In contrast, findings on lateralization of function during development are more complex. As in adults, anatomical, electrophysiological, and neuroimaging studies in infants and children indicate LH lateralization for language. However, in very young children, lesions to either hemisphere are equally likely to result in language deficits, suggesting that language is distributed symmetrically early in life. We address this apparent contradiction by examining patterns of functional MRI (fMRI) language activation in children (ages 4 through 13) and adults (ages 18 through 29). In contrast to previous studies, we focus not on lateralization per se but rather on patterns of left-hemisphere (LH) and right-hemisphere (RH) activation across individual participants over age. Our analyses show significant activation not only in the LH language network but also in their RH homologs in all of the youngest children (ages 4 through 6). The proportion of participants showing significant RH activation decreases over age, with over 60% of adults lacking any significant RH activation. A whole-brain correlation analysis revealed an age-related decrease in language activation only in the RH homolog of Broca's area. This correlation was independent of task difficulty. We conclude that, while language is left-lateralized throughout life, the RH contribution to language processing is also strong early in life and decreases through childhood. Importantly, this early RH language activation may represent a developmental mechanism for recovery following early LH injury.

An fMRI study of finger tapping in children and adults.

Functional brain imaging studies have characterized the neural bases of voluntary movement for finger tapping in adults, but equivalent information for children is lacking. When contrasted to adults, one would expect children to have relatively greater activation, reflecting compensation for an underdeveloped motor system combined with less experience in the execution of voluntary movement. To test this hypothesis, we acquired functional magnetic resonance imaging (fMRI) data on 17 healthy right-handed children (7.48 ± 0.66 years) and 15 adults (24.9 ± 2.9 years) while they performed an irregularly paced finger-tapping task in response to a visual cue (left- and right-hand examined separately). Whole-brain within-group analyses revealed that finger tapping in either age group and for either hand activated contralateral SM1, SMA, ipsilateral anterior cerebellum, and occipital cortices. We used an ANOVA factorial design to test for main effects of Age Group (children vs adults), Hand (left vs. right), and their interactions. For main effects of Age Group, children showed relatively greater activity in left SM1 (extending into bilateral SMA), and, surprisingly, adults exhibited relatively greater activity in right pre-SMA/SMA (extending into left pre-SMA/SMA), right lateral globus pallidus, left putamen, and right anterior cerebellum. The interaction of Age Group × Hand revealed that while both groups activated right SM1 during left finger tapping and exhibited signal decreases (i.e., below fixation baseline) during right finger tapping, both these responses were attenuated in children relative to adults. These data provide an important foundation by which to study children with motor disorders.

Preliminary Report on Neuroanatomical Differences Among Reading Disabled, Nonverbally Gifted, and Gifted-Reading Disabled College Students.

Regional comparisons (cortical surface area and thickness) were performed on a well described sample of adults with reading disability alone (RD), nonverbal giftedness alone (G), and reading disability and nonverbal giftedness combined (GRD). These anatomical results are considered in relation to behavioral and functional work previously reported on this sample. GRD-RD regional differences were found in both hemispheres and were more common than GRD-G differences. Regional differences were found in the temporal, parietal, occipital and frontal lobes. While these data are preliminary given the small sample sizes, they suggest future avenues of research on the neurodevelopment of atypical samples.

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.

Neuroanatomical profiles of deafness in the context of native language experience.

The study of congenitally deaf adult humans provides an opportunity to examine neuroanatomical plasticity resulting from altered sensory experience. However, attributing the source of the brain's structural variance in the deaf is complicated by the fact that deaf individuals also differ in their language experiences (e.g., sign vs spoken), which likely influence brain anatomy independently. Although the majority of deaf individuals in the United States are born to hearing parents and are exposed to English, not American Sign Language (ASL) as their first language, most studies on deafness have been conducted with deaf native users of ASL (deaf signers). This raises the question of whether observations made in deaf signers can be generalized. Using a factorial design, we compared gray (GMV) and white (WMV) matter volume in deaf and hearing native users of ASL, as well as deaf and hearing native users of English. Main effects analysis of sensory experience revealed less GMV in the deaf groups combined (compared with hearing groups combined) in early visual areas and less WMV in a left early auditory region. The interaction of sensory experience and language experience revealed that deaf native users of English had fewer areas of anatomical differences than did deaf native users of ASL (each compared with their hearing counterparts). For deaf users of ASL specifically, WMV differences resided in language areas such as the left superior temporal and inferior frontal regions. Our results demonstrate that cortical plasticity resulting from deafness depends on language experience and that findings from native signers cannot be generalized.

An fMRI study of nonverbally gifted reading disabled adults: has deficit compensation effected gifted potential?

Neuroscience has advanced our understanding of the neurological basis of reading disability (RD). Yet, no functional imaging work has been reported on the twice-exceptional dyslexic: individuals exhibiting both non-verbal-giftedness and RD. We compared groups of reading-disabled (RD), non-verbally-gifted (G), non-verbally-gifted-RD (GRD), and control (C) adults on validated word-rhyming and spatial visualization fMRI tasks, and standardized psychometric tests, to ascertain if the neurological functioning of GRD subjects was similar to that of typical RD or G subjects, or perhaps some unique RD subtype. Results demonstrate that GRD adults resemble non-gifted RD adults in performance on paper-and-pencil reading, math and spatial tests, and in patterns of functional activation during rhyming and spatial processing. Data are consistent with what may be a shared etiology of RD and giftedness in GRD individuals that yields a lifespan interaction with reading compensation effects, modifying how their adult brain processes text and spatial stimuli.

Abnormal visual motion processing is not a cause of dyslexia.

Developmental dyslexia is a reading disorder, yet deficits also manifest in the magnocellular-dominated dorsal visual system. Uncertainty about whether visual deficits are causal or consequential to reading disability encumbers accurate identification and appropriate treatment of this common learning disability. Using fMRI, we demonstrate in typical readers a relationship between reading ability and activity in area V5/MT during visual motion processing and, as expected, also found lower V5/MT activity for dyslexic children compared to age-matched controls. However, when dyslexics were matched to younger controls on reading ability, no differences emerged, suggesting that weakness in V5/MT may not be causal to dyslexia. To further test for causality, dyslexics underwent a phonological-based reading intervention. Surprisingly, V5/MT activity increased along with intervention-driven reading gains, demonstrating that activity here is mobilized through reading. Our results provide strong evidence that visual magnocellular dysfunction is not causal to dyslexia but may instead be consequential to impoverished reading.

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.

Beyond phonological processing deficits in adult dyslexics: atypical FMRI activation patterns for spatial problem solving.

It is unclear the extent to which neurodevelopmental differences observed in reading disabled individuals are limited to traditional language processing areas. Some have suggested atypical processing of complex spatial problems in these individuals. Hitherto, research on this question has been limited to behavioral studies, yielding mixed results. Absence of related imaging studies is in stark contrast to the plethora examining functional neurology for verbal tasks. This study uses functional magnetic resonance imaging (fMRI) to examine how adult dyslexics perform when analyzing complex spatial material unrelated to the reading of text. We observed atypical functional neurology during spatial problem solving, which was not observed behaviorally.

Modeling hemodynamic responses in auditory cortex at 1.5 T using variable duration imaging acoustic noise.

A confound for functional magnetic resonance imaging (fMRI), especially for auditory studies, is the presence of imaging acoustic noise generated mainly as a byproduct of rapid gradient switching during volume acquisition and, to a lesser extent, the radiofrequency transmit. This work utilized a novel pulse sequence to present actual imaging acoustic noise for characterization of the induced hemodynamic responses and assessment of linearity in the primary auditory cortex with respect to noise duration. Results show that responses to brief duration (46 ms) imaging acoustic noise is highly nonlinear while responses to longer duration (>1 s) imaging acoustic noise becomes approximately linear, with the right primary auditory cortex exhibiting a higher degree of nonlinearity than the left for the investigated noise durations. This study also assessed the spatial extent of activation induced by imaging acoustic noise, showing that the use of modeled responses (specific to imaging acoustic noise) as the reference waveform revealed additional activations in the auditory cortex not observed with a canonical gamma variate reference waveform, suggesting an improvement in detection sensitivity for imaging acoustic noise-induced activity. Longer duration (1.5 s) imaging acoustic noise was observed to induce activity that expanded outwards from Heschl's gyrus to cover the superior temporal gyrus as well as parts of the middle temporal gyrus and insula, potentially affecting higher level acoustic processing.

Signal fluctuations induced by non-T1-related confounds in variable TR fMRI experiments.

PURPOSE: To assess and model signal fluctuations induced by non-T(1)-related confounds in variable repetition time (TR) functional magnetic resonance imaging (fMRI) and to develop a compensation procedure to correct for the non-T(1)-related artifacts. MATERIALS AND METHODS: Radiofrequency disabled volume gradient sequences were effected at variable offsets between actual image acquisitions, enabling perturbation of the measurement system without perturbing longitudinal magnetization, allowing the study of non-T(1)-related confounds that may arise in variable TR experiments. Three imaging sessions utilizing a daily quality assurance (DQA) phantom were conducted to assess the signal fluctuations, which were then modeled as a second-order system. A modified projection procedure was implemented to correct for signal fluctuations arising from non-T(1)-related confounds, and statistical analysis was performed to assess the significance of the artifacts with and without compensation. RESULTS: Assessment using phantom data reveals that the signal fluctuations induced by non-T(1)-related confounds was consistent in shape across the phantom and well-modeled by a second-order system. The phantom exhibited significant spurious detections (at P < 0.01) almost uniformly across the central slices of the phantom. CONCLUSION: Second-order system modeling and compensation of non-T(1)-related confounds achieves significant reduction of spurious detection of fMRI activity in a phantom.