The relationship between phonological processing and arithmetic in children with learning disabilities.

Phonological processing skills have not only been shown to be important for reading skills, but also for arithmetic skills. Specifically, previous research in typically developing children has suggested that phonological processing skills may be more closely related to arithmetic problems that are solved through fact retrieval (e.g., remembering the solution from memory) than procedural computation (e.g., counting). However, the relationship between phonological processing and arithmetic in children with learning disabilities (LDs) has not been investigated. Yet, understanding these relationships in children with LDs is especially important because it can help elucidate the cognitive underpinnings of math difficulties, explain why reading and math disabilities frequently co-occur, and provide information on which cognitive skills to target for interventions. In 63 children with LDs, we examined the relationship between different phonological processing skills (phonemic awareness, phonological memory, and rapid serial naming) and arithmetic. We distinguished between arithmetic problems that tend to be solved with fact retrieval versus procedural computation to determine whether phonological processing skills are differentially related to these two arithmetic processes. We found that phonemic awareness, but not phonological memory or rapid serial naming, was related to arithmetic fact retrieval. We also found no association between any phonological processing skills and procedural computation. These results converge with prior research in typically developing children and suggest that phonemic awareness is also related to arithmetic fact retrieval in children with LD. These results raise the possibility that phonemic awareness training might improve both reading and arithmetic fact retrieval skills. RESEARCH HIGHLIGHTS: Relationships between phonological processing and various arithmetic skills were investigated in children with learning disabilities (LDs) for the first time. We found phonemic awareness was related to arithmetic involving fact retrieval, but not to arithmetic involving procedural computation in LDs. The results suggest that phonemic awareness is not only important to skilled reading, but also to some aspects of arithmetic. These results raise the question of whether intervention in phonemic awareness might improve arithmetic fact retrieval skills.

Gray matter volume differences between early bilinguals and monolinguals: A study of children and adults.

Gray matter has been shown to be greater in early bilingual adults relative to monolingual adults in regions associated with language (Mechelli et al., 2004), and executive control (EC; Olulade et al., 2016). It is not known, however, if language experience-dependent differences in gray matter volume (GMV) exist in children. Further, any such differences are likely not to be the same as those observed in early bilingual adults, as children have had relatively shorter duration of dual-language exposure and/or less development of brain regions serving EC. We tested these predictions by comparing GMV in Spanish-English early bilingual and English monolingual children, and Spanish-English early bilingual and English monolingual adults (n = 122). Comparing only children revealed relatively more GMV in the bilinguals in bilateral frontal, right inferior frontal, and right superior parietal cortices (regions associated with EC). Bilinguals, however, had less GMV in left inferior parietal cortex (region associated with language). An ANOVA including these children with bilingual and monolingual adults revealed interactions of Language Background by Age Group. There were no regions of more GMV in bilinguals relative to monolinguals that were less pronounced in children than adults, despite the children's shorter dual-language experience. There were relative differences between bilingual and monolingual children that were more pronounced than those in adults in left precentral gyrus and right superior parietal lobule (close to, but not directly in areas associated with EC). Together, early bilingual children manifest relative differences in GMV, and, surprisingly, these do not diverge much from those observed in studies of bilingual adults.

Functional neuroanatomy of English word reading in early bilingual and monolingual adults.

Skilled reading is important in daily life. While the understanding of the neurofunctional organization of this uniquely human skill has advanced significantly, it does not take into consideration the common bilingual experiences around the world. To examine the role of early bilingualism on the neural substrates supporting English word processing, we compared brain activity, as well as functional connectivity, in Spanish-English early bilingual adults (N = 25) and English monolingual adults (N = 33) during single-word processing. Activation analysis revealed no significant differences between the two groups. A seed-to-voxel analysis using eight a priori selected seed-regions (placed in regions known to be involved in reading) revealed relatively stronger functional connectivity in bilinguals between two sets of regions: left superior temporal gyrus seed positively with left lingual gyrus and left middle frontal gyrus seed negatively with left anterior cingulate cortex. Together these results suggest that an early Spanish-English bilingual experience does not modulate local brain activity for English word reading. It does, however, have some influence on the functional intercommunication between brain regions during reading, specifically in two regions associated with reading, which are functionally connected to those inside and outside of the reading network. We conclude that brain regions involved in processing English words are not that different in Spanish-English early bilingual adults relative to monolingual adult users of English.

Functional neuroanatomy of arithmetic in monolingual and bilingual adults and children.

Prior studies on the brain bases of arithmetic have not focused on (or even described) their participants' language backgrounds. Yet, unlike monolinguals, early bilinguals have the capacity to solve arithmetic problems in both of their two languages. This raises the question whether this ability, or any other experience that comes with being bilingual, affects brain activity for arithmetic in bilinguals relative to monolinguals. Here, we used functional magnetic resonance imaging to compare brain activity in 44 English monolinguals and 44 Spanish-English early bilinguals, during the solving of arithmetic problems in English. We used a factorial design to test for a main effect of bilingual Language Experience. Based on the known modulating roles of arithmetic operation and age, we used two arithmetic tasks (addition and subtraction) and studied two age groups (adults and children). When collapsing across operations and age, we found broad bilateral activation for arithmetic in both the monolingual group and the bilingual group. However, an analysis of variance revealed that there was no effect of Language Experience, nor an interaction of Language Experience with Operation or Age Group. Bayesian analyses within regions of interest chosen for their role in arithmetic further supported the finding of no effect of Language Experience on brain activity underlying arithmetic. We conclude that early bilingualism does not influence the functional neuroanatomy of simple arithmetic.

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.

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.

Shared orthographic neuronal representations for spelling and reading.

A central question in the study of the neural basis of written language is whether reading and spelling utilize shared orthographic representations. While recent studies employing fMRI to test this question report that the left inferior frontal gyrus (IFG) and ventral occipitotemporal cortex (vOTC) are active during both spelling and reading in the same subjects (Purcell et al., 2011a; Rapp and Lipka, 2011), the spatial resolution of fMRI limits the interpretation of these findings. Specifically, it is unknown if the neurons which encode orthography for reading are also involved in spelling of the same words. Here we address this question by employing an event-related functional magnetic resonance imaging-adaptation (fMRI-A) paradigm designed to examine shared orthographic representations across spelling and reading. First, we identified areas that independently showed adaptation to reading, and adaptation to spelling. Then we identified spatial convergence for these two separate maps via a conjunction analysis. Consistent with previous studies (Purcell et al., 2011a; Rapp and Lipka, 2011), this analysis revealed the left dorsal IFG, vOTC and supplementary motor area. To further validate these observations, we then interrogated these regions using an across-task adaptation technique, and found adaptation across reading and spelling in the left dorsal IFG (BA 44/9). Our final analysis focused specifically on the Visual Word Form Area (VWFA) in the vOTC, whose variability in location among subjects requires the use of subject-specific identification mechanisms (Glezer and Riesenhuber, 2013). Using a functional localizer for reading, we defined the VWFA in each subject, and found adaptation effects for both within the spelling and reading conditions, respectively, as well as across spelling and reading. Because none of these effects were observed during a phonological/semantic control condition, we conclude that the left dorsal IFG and VWFA are involved in accessing the same orthography-specific representations for spelling and reading.

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.

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 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.

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.

Activation and functional connectivity of cerebellum during reading and during arithmetic in children with combined reading and math disabilities.

Background: Reading and math constitute important academic skills, and as such, reading disability (RD or developmental dyslexia) and math disability (MD or developmental dyscalculia) can have negative consequences for children's educational progress. Although RD and MD are different learning disabilities, they frequently co-occur. Separate theories have implicated the cerebellum and its cortical connections in RD and in MD, suggesting that children with combined reading and math disability (RD + MD) may have altered cerebellar function and disrupted functional connectivity between the cerebellum and cortex during reading and during arithmetic processing. Methods: Here we compared Control and RD + MD groups during a reading task as well as during an arithmetic task on (i) activation of the cerebellum, (ii) background functional connectivity, and (iii) task-dependent functional connectivity between the cerebellum and the cortex. Results: The two groups (Control, RD + MD) did not differ for either task (reading, arithmetic) on any of the three measures (activation, background functional connectivity, task-dependent functional connectivity). Conclusion: These results do not support theories that children's deficits in reading and math originate in the cerebellum.

A comparison of functional activation and connectivity of the cerebellum in adults and children during single word processing.

Meta-analyses on reading show cerebellar activation in adults, but not children, suggesting a possible age-dependent role of the cerebellum in reading. However, the few studies that compare adults and children during reading report mixed cerebellar activation results. Here, we studied (i) cerebellar activation during implicit word processing in adults and children and (ii) functional connectivity (FC) between the cerebellum and left cortical regions involved in reading. First, both groups activated bilateral cerebellum for word processing when compared to fixation, but not when compared to the active control. There were no differences between adults and children. Second, we found intrinsic FC between several cerebellar seed regions and cortical target regions in adults and children, as well as between-group differences. However, task-modulated FC specific to word processing revealed no within- nor between-group results. Together this study does not provide support for a role of the cerebellum in word processing at either age.

An fMRI study of finger movements in children with and without dyslexia.

Introduction: Developmental dyslexia is a language-based reading disability, yet some have reported motor impairments, usually attributed to cerebellar dysfunction. Methods: Using fMRI, we compared children with and without dyslexia during irregularly paced, left or right-hand finger tapping. Next, we examined seed-to-voxel intrinsic functional connectivity (iFC) using six seed regions of the motor system (left and right anterior lobe of the cerebellum, SM1 and SMA). Results: A whole-brain task-evoked analysis revealed relatively less activation in the group with dyslexia in right anterior cerebellum during right hand tapping. For iFC, we found the group with dyslexia to have greater iFC between the right SM1 seed and a medial aspect of right postcentral gyrus for left hand tapping; and greater iFC between the left SM1 seed and left thalamus, as well as weaker local iFC around the left SM1 seed region for right hand tapping. Lastly, extracted activity and connectivity values that had been identified in these between-group comparisons were not correlated with measures of reading. Discussion: We conclude that there are some aberrations in motor system function in children with dyslexia, but these are not tied to reading ability.

Cortical plasticity for visuospatial processing and object recognition in deaf and hearing signers.

Experience-dependent plasticity in deaf participants has been shown in a variety of studies focused on either the dorsal or ventral aspects of the visual system, but both systems have never been investigated in concert. Using functional magnetic resonance imaging (fMRI), we investigated functional plasticity for spatial processing (a dorsal visual pathway function) and for object processing (a ventral visual pathway function) concurrently, in the context of differing sensory (auditory deprivation) and language (use of a signed language) experience. During scanning, deaf native users of American Sign Language (ASL), hearing native ASL users, and hearing participants without ASL experience attended to either the spatial arrangement of frames containing objects or the identity of the objects themselves. These two tasks revealed the expected dorsal/ventral dichotomy for spatial versus object processing in all groups. In addition, the object identity matching task contained both face and house stimuli, allowing us to examine category-selectivity in the ventral pathway in all three participant groups. When contrasting the groups we found that deaf signers differed from the two hearing groups in dorsal pathway parietal regions involved in spatial cognition, suggesting sensory experience-driven plasticity. Group differences in the object processing system indicated that responses in the face-selective right lateral fusiform gyrus and anterior superior temporal cortex were sensitive to a combination of altered sensory and language experience, whereas responses in the amygdala were more closely tied to sensory experience. By selectively engaging the dorsal and ventral visual pathways within participants in groups with different sensory and language experiences, we have demonstrated that these experiences affect the function of both of these systems, and that certain changes are more closely tied to sensory experience, while others are driven by the combination of sensory and language experience.

Neural basis of single-word reading in Spanish-English bilinguals.

Brain imaging studies have identified a left-lateralized network of regions that are engaged when monolinguals read. However, for individuals who are native speakers of two languages, it is unclear whether this pattern of activity is maintained across both languages or if it deviates according to language-specific properties. We used functional magnetic resonance imaging to investigate single-word processing in Spanish and in English in 12 proficient early Spanish-English bilinguals matched in skill level in both languages. Word processing in Spanish engaged the left inferior frontal and left middle temporal gyri. Word processing in English activated the left inferior frontal, middle frontal, and fusiform gyri extending to inferior temporal gyrus and the right middle temporal gyrus extending into superior temporal sulcus. The comparison of reading in Spanish greater than reading in English revealed involvement of the left middle temporal gyrus extending into the superior temporal sulcus. English greater than Spanish, however, demonstrated greater engagement of the left middle frontal gyrus extending into the superior frontal gyrus. We conclude that although word processing in either language activates classical areas associated with reading, there are language-specific differences, which can be attributed to the disparity in orthographic transparency. English, an orthographically deep language, may require greater engagement of the frontal regions for phonological coding, whereas Spanish allows increased access to semantic processing via the left middle temporal areas. Together, these results suggest that bilinguals will show adjustments to the typical neural representation of reading as necessitated by the demands of the orthography.

Harnessing neuroplasticity for clinical applications.

Neuroplasticity can be defined as the ability of the nervous system to respond to intrinsic or extrinsic stimuli by reorganizing its structure, function and connections. Major advances in the understanding of neuroplasticity have to date yielded few established interventions. To advance the translation of neuroplasticity research towards clinical applications, the National Institutes of Health Blueprint for Neuroscience Research sponsored a workshop in 2009. Basic and clinical researchers in disciplines from central nervous system injury/stroke, mental/addictive disorders, paediatric/developmental disorders and neurodegeneration/ageing identified cardinal examples of neuroplasticity, underlying mechanisms, therapeutic implications and common denominators. Promising therapies that may enhance training-induced cognitive and motor learning, such as brain stimulation and neuropharmacological interventions, were identified, along with questions of how best to use this body of information to reduce human disability. Improved understanding of adaptive mechanisms at every level, from molecules to synapses, to networks, to behaviour, can be gained from iterative collaborations between basic and clinical researchers. Lessons can be gleaned from studying fields related to plasticity, such as development, critical periods, learning and response to disease. Improved means of assessing neuroplasticity in humans, including biomarkers for predicting and monitoring treatment response, are needed. Neuroplasticity occurs with many variations, in many forms, and in many contexts. However, common themes in plasticity that emerge across diverse central nervous system conditions include experience dependence, time sensitivity and the importance of motivation and attention. Integration of information across disciplines should enhance opportunities for the translation of neuroplasticity and circuit retraining research into effective clinical therapies.

Dorsal visual stream activity during coherent motion processing is not related to math ability or dyscalculia.

Math disability (MD) or developmental dyscalculia is a highly prevalent learning disability involving deficits in computation and arithmetic fact retrieval and is associated with dysfunction of parietal and prefrontal cortices. It has been suggested that dyscalculia (and other learning disabilities and developmental disorders) can be viewed in terms of a broader 'dorsal stream vulnerability,' which could explain a range of dorsal visual stream function deficits, including poor coherent visual motion perception. Behavioral evidence from two studies in typical children has linked performance on visual motion perception to math ability, and a third behavioral study reported poorer visual motion perception in a small group of children with MD compared to controls. Visual motion perception relies on the magnocellular-dominated dorsal stream, particularly its constituent area V5/MT. Here we used functional MRI to measure brain activity in area V5/MT during coherent visual motion processing to test its relationship with math ability. While we found bilateral activation in V5/MT in 66 children/adolescents with varied math abilities, we found no relationships between V5/MT activity and standardized math measures. Next, we selected a group of children/adolescents with MD (n = 23) and compared them to typically developing controls (n = 18), but found no differences in activity in V5/MT or elsewhere in the brain. We followed these frequentist statistics with Bayesian analyses, which favored null models in both studies. We conclude that dorsal stream function subserving visual motion processing in area V5/MT is not related to math ability, nor is it altered in those with the math disability dyscalculia.

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.