Joel Talcott - Academia.edu (original) (raw)
Papers by Joel Talcott
Phonological tasks are highly predictive of reading development but their complexity obscures the... more Phonological tasks are highly predictive of reading development but their complexity obscures the underlying mechanisms driving this association. There are three key components hypothesised to drive the relationship between phonological tasks and reading; (a) the linguistic nature of the stimuli, (b) the phonological complexity of the stimuli, and (c) the production of a verbal response. We isolated the contribution of the stimulus and response components separately through the creation of latent variables to represent specially designed tasks that were matched for procedure. These tasks were administered to 570 6 to 7-year-old children along with standardised tests of regular word and non-word reading. A structural equation model, where tasks were grouped according to stimulus, revealed that the linguistic nature and the phonological complexity of the stimulus predicted unique variance in decoding, over and above matched comparison tasks without these components. An alternative model, grouped according to response mode, showed that the production of a verbal response was a unique predictor of decoding beyond matched tasks without a verbal response. In summary, we found that multiple factors contributed to reading development, supporting multivariate models over those that prioritize single factors. More broadly, we demonstrate the value of combining matched task designs with latent variable modelling to deconstruct the components of complex tasks.
Purpose: Phonological accounts of reading implicate three aspects of phonological awareness tasks... more Purpose: Phonological accounts of reading implicate three aspects of phonological awareness tasks that underlie the relationship with reading; a) the language-based nature of the stimuli (words or nonwords), b) the verbal nature of the response, and c) the complexity of the stimuli (words can be segmented into units of speech). Yet, it is uncertain which task characteristics are most important as they are typically confounded. By systematically varying response-type and stimulus complexity across speech and non-speech stimuli, the current study seeks to isolate the characteristics of phonological awareness tasks that drive the prediction of early reading. Method: Four sets of tasks were created; tone stimuli (simple non-speech) requiring a non-verbal response, phonemes (simple speech) requiring a non-verbal response, phonemes requiring a verbal response, and nonwords (complex speech) requiring a verbal response. Tasks were administered to 570 2nd grade children along with standardized tests of reading and non-verbal IQ. Results: Three structural equation models comparing matched sets of tasks were built. Each model consisted of two 'task' factors with a direct link to a reading factor. The following factors predicted unique variance in reading: a) simple speech and non-speech stimuli, b) simple speech requiring a verbal response but not simple speech requiring a non-verbal-response, and c) complex and simple speech stimuli. Conclusions: Results suggest that the prediction of reading by phonological tasks is driven by the verbal nature of the response and not the complexity or 'speechness' of the stimuli. Findings highlight the importance of phonological output processes to early reading.
Child Development
Handedness has been studied for association with language‐related disorders because of its link w... more Handedness has been studied for association with language‐related disorders because of its link with language hemispheric dominance. No clear pattern has emerged, possibly because of small samples, publication bias, and heterogeneous criteria across studies. Non‐right‐handedness (NRH) frequency was assessed in N = 2503 cases with reading and/or language impairment and N = 4316 sex‐matched controls identified from 10 distinct cohorts (age range 6–19 years old; European ethnicity) using a priori set criteria. A meta‐analysis (Ncases = 1994) showed elevated NRH % in individuals with language/reading impairment compared with controls (OR = 1.21, CI = 1.06–1.39, p = .01). The association between reading/language impairments and NRH could result from shared pathways underlying brain lateralization, handedness, and cognitive functions.
Psychological Medicine
Background It is unknown how much variation in adult mental health problems is associated with di... more Background It is unknown how much variation in adult mental health problems is associated with differences between societal/cultural groups, over and above differences between individuals. Methods To test these relative contributions, a consortium of indigenous researchers collected Adult Self-Report (ASR) ratings from 16 906 18- to 59-year-olds in 28 societies that represented seven culture clusters identified in the Global Leadership and Organizational Behavioral Effectiveness study (e.g. Confucian, Anglo). The ASR is scored on 17 problem scales, plus a personal strengths scale. Hierarchical linear modeling estimated variance accounted for by individual differences (including measurement error), society, and culture cluster. Multi-level analyses of covariance tested age and gender effects. Results Across the 17 problem scales, the variance accounted for by individual differences ranged from 80.3% for DSM-oriented anxiety problems to 95.2% for DSM-oriented avoidant personality (mea...
Noninvasive Assessment of the Visual System, 1993
Translational Psychiatry
Reading Disability (RD) is often characterized by difficulties in the phonology of the language. ... more Reading Disability (RD) is often characterized by difficulties in the phonology of the language. While the molecular mechanisms underlying it are largely undetermined, loci are being revealed by genome-wide association studies (GWAS). In a previous GWAS for word reading (Price, 2020), we observed that top single-nucleotide polymorphisms (SNPs) were located near to or in genes involved in neuronal migration/axon guidance (NM/AG) or loci implicated in autism spectrum disorder (ASD). A prominent theory of RD etiology posits that it involves disturbed neuronal migration, while potential links between RD-ASD have not been extensively investigated. To improve power to identify associated loci, we up-weighted variants involved in NM/AG or ASD, separately, and performed a new Hypothesis-Driven (HD)–GWAS. The approach was applied to a Toronto RD sample and a meta-analysis of the GenLang Consortium. For the Toronto sample (n = 624), no SNPs reached significance; however, by gene-set analysis,...
Proceedings of the National Academy of Sciences
The use of spoken and written language is a fundamental human capacity. Individual differences in... more The use of spoken and written language is a fundamental human capacity. Individual differences in reading- and language-related skills are influenced by genetic variation, with twin-based heritability estimates of 30 to 80% depending on the trait. The genetic architecture is complex, heterogeneous, and multifactorial, but investigations of contributions of single-nucleotide polymorphisms (SNPs) were thus far underpowered. We present a multicohort genome-wide association study (GWAS) of five traits assessed individually using psychometric measures (word reading, nonword reading, spelling, phoneme awareness, and nonword repetition) in samples of 13,633 to 33,959 participants aged 5 to 26 y. We identified genome-wide significant association with word reading (rs11208009, P = 1.098 × 10 −8 ) at a locus that has not been associated with intelligence or educational attainment. All five reading-/language-related traits showed robust SNP heritability, accounting for 13 to 26% of trait varia...
Worldwide, the majority of people prefer using the right hand for most motor tasks, including wri... more Worldwide, the majority of people prefer using the right hand for most motor tasks, including writing. Because of the link between handedness and language hemispheric dominance, handedness has been studied for association with language-related disorders. No clear pattern has emerged from these studies, and inconsistencies have been attributed to small sample sizes, publication bias, and heterogeneous criteria for the definition of handedness and disorders.Here, we assessed the frequency of non-right handedness (NRH) in 10 distinct cohorts not analysed before in this context. We identified N = 2,499 cases with reading and/or language impairment and N = 4,428 unique controls on the basis of a priori defined criteria. Overall, NRH was more frequent and more variable in the cases (8-24%) than in the controls (8-16%). Meta-analysis in the eight cohorts that met the inclusion criteria showed an increase of NRH in individuals with language/reading impairment compared to controls (OR = 1.21...
Pediatric Transplantation, 2011
PURPOSE: Polyunsaturated Fatty Acids (PUFAs) serve important structural and functional roles in t... more PURPOSE: Polyunsaturated Fatty Acids (PUFAs) serve important structural and functional roles in the central nervous system, which may modulate cognitive function. This study used a liver disease and transplant (Tx) model to evaluate whether sub-optimal concentrations of PUFAs, as a result of fat malabsorption or dependence on inadequate dietary sources, is associated with PUFA deficiency and deficits in cognitive abili.METHOD: In 28 paediatric patients (14 pre-Tx, mean age 12.1; 14 post-Tx, mean age 15.0) and 11 healthy controls (mean age 12.2), erythrocyte biomarkers of fatty acid status, including the major omega-6 (linoleic and arachidonic), omega-3 (docosohexaenoic and eicosapentaenoic) fatty acids and defciency markers (osbond and mead acid), were quantifiedusing standard gas chromatography-mass spectrometry. Full-scale IQ (FSIQ) and Information Processing Speed (IPS) were assessed using standard Wechsler psychometric assessment batteries.RESULTS: Compared to controls, no signs...
Molecular Psychiatry, 2020
Developmental dyslexia (DD) is a learning disorder affecting the ability to read, with a heritabi... more Developmental dyslexia (DD) is a learning disorder affecting the ability to read, with a heritability of 40–60%. A notable part of this heritability remains unexplained, and large genetic studies are warranted to identify new susceptibility genes and clarify the genetic bases of dyslexia. We carried out a genome-wide association study (GWAS) on 2274 dyslexia cases and 6272 controls, testing associations at the single variant, gene, and pathway level, and estimating heritability using single-nucleotide polymorphism (SNP) data. We also calculated polygenic scores (PGSs) based on large-scale GWAS data for different neuropsychiatric disorders and cortical brain measures, educational attainment, and fluid intelligence, testing them for association with dyslexia status in our sample. We observed statistically significant (p < 2.8 × 10−6) enrichment of associations at the gene level, forLOC388780(20p13; uncharacterized gene), and forVEPH1(3q25), a gene implicated in brain development. ...
ABSTRACTReading and writing are crucial for many aspects of modern life but up to 1 in 10 childre... more ABSTRACTReading and writing are crucial for many aspects of modern life but up to 1 in 10 children are affected by dyslexia [1, 2], which can persist into adulthood. Family studies of dyslexia suggest heritability up to 70% [3, 4], yet no convincing genetic markers have been found due to limited study power [5]. Here, we present a genome-wide association study representing a 20-fold increase in sample size from prior work, with 51,800 adults self-reporting a dyslexia diagnosis and 1,087,070 controls. We identified 42 independent genome-wide significant loci: 17 are in genes linked to or pleiotropic with cognitive ability/educational attainment; 25 are novel and may be more specifically associated with dyslexia. Twenty-three loci (12 novel) were validated in independent cohorts of Chinese and European ancestry. We confirmed a similar genetic aetiology of dyslexia between sexes, and found genetic covariance with many traits, including ambidexterity, but not neuroanatomical measures of...
Developmental Science, 2020
We reconcile competing theories of the role of phonological memory in reading development, by unc... more We reconcile competing theories of the role of phonological memory in reading development, by uncovering their dynamic relationship during the first 5 years of school. Phonological memory, reading and phoneme awareness were assessed in 780 phonics‐educated children at age 4, 5, 6 and 9. Confirmatory factor analyses demonstrated that phonological memory loaded onto two factors: verbal short‐term memory (verbal STM; phonological tasks that loaded primarily on serial order memory) and nonword repetition. Using longitudinal structural equation models, we found that verbal STM directly predicted early word‐level reading from age 4 to 6, reflecting the importance of serial‐order memory for letter‐by‐letter decoding. In contrast, reading had no reciprocal influence on the development of verbal STM. The relationship between nonword repetition and reading was bidirectional across the 5 years of study: nonword repetition and reading predicted each other both directly and indirectly (via phone...
Experimental brain research, 2003
Tests of postural stability have provided some evidence of a link between deficits in gross motor... more Tests of postural stability have provided some evidence of a link between deficits in gross motor skills and developmental dyslexia. The ordinal-level scales used previously, however, have limited measurement sensitivity, and no studies have investigated motor performance during walking in participants with dyslexia. The purpose of this study was to investigate if continuous-scaled measures of standing balance and gait could discriminate between groups of impaired and normal readers when investigators were blind to group membership during testing. Children with dyslexia ( n=22) and controls ( n=18), aged 10-12 years, performed walking tests at four different speeds (slow-preferred-fast-very fast) on an even and an uneven surface, and tests of unperturbed and perturbed body sway during standing. Body movements were registered by a triaxial accelerometer over the lower trunk, and measures of reaction time, body sway, walking speed, step length and cadence were calculated. Results were...
The Lancet, 1998
Neurological and physiological deficits have been reported in the brain in developmental dyslexia... more Neurological and physiological deficits have been reported in the brain in developmental dyslexia. The temporoparietal cortex has been directly implicated in dyslexic dysfunction, and substantial indirect evidence suggests that the cerebellum is also implicated. We wanted to find out whether the neurological and physiological deficits manifested as biochemical changes in the brain. We obtained localised proton magnetic resonance spectra bilaterally from the temporo-parietal cortex and cerebellum of 14 well-defined dyslexic men and 15 control men of similar age. We found biochemical differences between dyslexic men and controls in the left temporo-parietal lobe (ratio of choline-containing compounds [Cho] to N-acetylaspartate [NA] p&amp;lt; or =0.01) and right cerebellum (Cho/NA, p&amp;lt; or = 0.01; creatine [Cre] to NA p&amp;lt; or =0.05; (not significant). We found lateral biochemical differences in dyslexic men in both these brain regions (Cho/NA in temporo-parietal lobe, left vs right, p&amp;lt; or =0.01; Cre/NA in cerebellum, left vs right, p&amp;lt; or =0.001). We found no such lateral differences in controls. There was no significant relation between the degree of contralateral chemical difference and handedness in dyslexic or control men. We suggest that the observed differences reflect changes in cell density in the temporo-parietal lobe in developmental dyslexia and that the altered cerebral structural symmetry in dyslexia is associated with abnormal development of cells or intracellular connections or both. The cerebellum is biochemically asymmetric in dyslexic men, indicating altered development of this organ. These differences provide direct evidence of the involvement of the cerebellum in dyslexic dysfunction.
Phonological tasks are highly predictive of reading development but their complexity obscures the... more Phonological tasks are highly predictive of reading development but their complexity obscures the underlying mechanisms driving this association. There are three key components hypothesised to drive the relationship between phonological tasks and reading; (a) the linguistic nature of the stimuli, (b) the phonological complexity of the stimuli, and (c) the production of a verbal response. We isolated the contribution of the stimulus and response components separately through the creation of latent variables to represent specially designed tasks that were matched for procedure. These tasks were administered to 570 6 to 7-year-old children along with standardised tests of regular word and non-word reading. A structural equation model, where tasks were grouped according to stimulus, revealed that the linguistic nature and the phonological complexity of the stimulus predicted unique variance in decoding, over and above matched comparison tasks without these components. An alternative model, grouped according to response mode, showed that the production of a verbal response was a unique predictor of decoding beyond matched tasks without a verbal response. In summary, we found that multiple factors contributed to reading development, supporting multivariate models over those that prioritize single factors. More broadly, we demonstrate the value of combining matched task designs with latent variable modelling to deconstruct the components of complex tasks.
Purpose: Phonological accounts of reading implicate three aspects of phonological awareness tasks... more Purpose: Phonological accounts of reading implicate three aspects of phonological awareness tasks that underlie the relationship with reading; a) the language-based nature of the stimuli (words or nonwords), b) the verbal nature of the response, and c) the complexity of the stimuli (words can be segmented into units of speech). Yet, it is uncertain which task characteristics are most important as they are typically confounded. By systematically varying response-type and stimulus complexity across speech and non-speech stimuli, the current study seeks to isolate the characteristics of phonological awareness tasks that drive the prediction of early reading. Method: Four sets of tasks were created; tone stimuli (simple non-speech) requiring a non-verbal response, phonemes (simple speech) requiring a non-verbal response, phonemes requiring a verbal response, and nonwords (complex speech) requiring a verbal response. Tasks were administered to 570 2nd grade children along with standardized tests of reading and non-verbal IQ. Results: Three structural equation models comparing matched sets of tasks were built. Each model consisted of two 'task' factors with a direct link to a reading factor. The following factors predicted unique variance in reading: a) simple speech and non-speech stimuli, b) simple speech requiring a verbal response but not simple speech requiring a non-verbal-response, and c) complex and simple speech stimuli. Conclusions: Results suggest that the prediction of reading by phonological tasks is driven by the verbal nature of the response and not the complexity or 'speechness' of the stimuli. Findings highlight the importance of phonological output processes to early reading.
Child Development
Handedness has been studied for association with language‐related disorders because of its link w... more Handedness has been studied for association with language‐related disorders because of its link with language hemispheric dominance. No clear pattern has emerged, possibly because of small samples, publication bias, and heterogeneous criteria across studies. Non‐right‐handedness (NRH) frequency was assessed in N = 2503 cases with reading and/or language impairment and N = 4316 sex‐matched controls identified from 10 distinct cohorts (age range 6–19 years old; European ethnicity) using a priori set criteria. A meta‐analysis (Ncases = 1994) showed elevated NRH % in individuals with language/reading impairment compared with controls (OR = 1.21, CI = 1.06–1.39, p = .01). The association between reading/language impairments and NRH could result from shared pathways underlying brain lateralization, handedness, and cognitive functions.
Psychological Medicine
Background It is unknown how much variation in adult mental health problems is associated with di... more Background It is unknown how much variation in adult mental health problems is associated with differences between societal/cultural groups, over and above differences between individuals. Methods To test these relative contributions, a consortium of indigenous researchers collected Adult Self-Report (ASR) ratings from 16 906 18- to 59-year-olds in 28 societies that represented seven culture clusters identified in the Global Leadership and Organizational Behavioral Effectiveness study (e.g. Confucian, Anglo). The ASR is scored on 17 problem scales, plus a personal strengths scale. Hierarchical linear modeling estimated variance accounted for by individual differences (including measurement error), society, and culture cluster. Multi-level analyses of covariance tested age and gender effects. Results Across the 17 problem scales, the variance accounted for by individual differences ranged from 80.3% for DSM-oriented anxiety problems to 95.2% for DSM-oriented avoidant personality (mea...
Noninvasive Assessment of the Visual System, 1993
Translational Psychiatry
Reading Disability (RD) is often characterized by difficulties in the phonology of the language. ... more Reading Disability (RD) is often characterized by difficulties in the phonology of the language. While the molecular mechanisms underlying it are largely undetermined, loci are being revealed by genome-wide association studies (GWAS). In a previous GWAS for word reading (Price, 2020), we observed that top single-nucleotide polymorphisms (SNPs) were located near to or in genes involved in neuronal migration/axon guidance (NM/AG) or loci implicated in autism spectrum disorder (ASD). A prominent theory of RD etiology posits that it involves disturbed neuronal migration, while potential links between RD-ASD have not been extensively investigated. To improve power to identify associated loci, we up-weighted variants involved in NM/AG or ASD, separately, and performed a new Hypothesis-Driven (HD)–GWAS. The approach was applied to a Toronto RD sample and a meta-analysis of the GenLang Consortium. For the Toronto sample (n = 624), no SNPs reached significance; however, by gene-set analysis,...
Proceedings of the National Academy of Sciences
The use of spoken and written language is a fundamental human capacity. Individual differences in... more The use of spoken and written language is a fundamental human capacity. Individual differences in reading- and language-related skills are influenced by genetic variation, with twin-based heritability estimates of 30 to 80% depending on the trait. The genetic architecture is complex, heterogeneous, and multifactorial, but investigations of contributions of single-nucleotide polymorphisms (SNPs) were thus far underpowered. We present a multicohort genome-wide association study (GWAS) of five traits assessed individually using psychometric measures (word reading, nonword reading, spelling, phoneme awareness, and nonword repetition) in samples of 13,633 to 33,959 participants aged 5 to 26 y. We identified genome-wide significant association with word reading (rs11208009, P = 1.098 × 10 −8 ) at a locus that has not been associated with intelligence or educational attainment. All five reading-/language-related traits showed robust SNP heritability, accounting for 13 to 26% of trait varia...
Worldwide, the majority of people prefer using the right hand for most motor tasks, including wri... more Worldwide, the majority of people prefer using the right hand for most motor tasks, including writing. Because of the link between handedness and language hemispheric dominance, handedness has been studied for association with language-related disorders. No clear pattern has emerged from these studies, and inconsistencies have been attributed to small sample sizes, publication bias, and heterogeneous criteria for the definition of handedness and disorders.Here, we assessed the frequency of non-right handedness (NRH) in 10 distinct cohorts not analysed before in this context. We identified N = 2,499 cases with reading and/or language impairment and N = 4,428 unique controls on the basis of a priori defined criteria. Overall, NRH was more frequent and more variable in the cases (8-24%) than in the controls (8-16%). Meta-analysis in the eight cohorts that met the inclusion criteria showed an increase of NRH in individuals with language/reading impairment compared to controls (OR = 1.21...
Pediatric Transplantation, 2011
PURPOSE: Polyunsaturated Fatty Acids (PUFAs) serve important structural and functional roles in t... more PURPOSE: Polyunsaturated Fatty Acids (PUFAs) serve important structural and functional roles in the central nervous system, which may modulate cognitive function. This study used a liver disease and transplant (Tx) model to evaluate whether sub-optimal concentrations of PUFAs, as a result of fat malabsorption or dependence on inadequate dietary sources, is associated with PUFA deficiency and deficits in cognitive abili.METHOD: In 28 paediatric patients (14 pre-Tx, mean age 12.1; 14 post-Tx, mean age 15.0) and 11 healthy controls (mean age 12.2), erythrocyte biomarkers of fatty acid status, including the major omega-6 (linoleic and arachidonic), omega-3 (docosohexaenoic and eicosapentaenoic) fatty acids and defciency markers (osbond and mead acid), were quantifiedusing standard gas chromatography-mass spectrometry. Full-scale IQ (FSIQ) and Information Processing Speed (IPS) were assessed using standard Wechsler psychometric assessment batteries.RESULTS: Compared to controls, no signs...
Molecular Psychiatry, 2020
Developmental dyslexia (DD) is a learning disorder affecting the ability to read, with a heritabi... more Developmental dyslexia (DD) is a learning disorder affecting the ability to read, with a heritability of 40–60%. A notable part of this heritability remains unexplained, and large genetic studies are warranted to identify new susceptibility genes and clarify the genetic bases of dyslexia. We carried out a genome-wide association study (GWAS) on 2274 dyslexia cases and 6272 controls, testing associations at the single variant, gene, and pathway level, and estimating heritability using single-nucleotide polymorphism (SNP) data. We also calculated polygenic scores (PGSs) based on large-scale GWAS data for different neuropsychiatric disorders and cortical brain measures, educational attainment, and fluid intelligence, testing them for association with dyslexia status in our sample. We observed statistically significant (p < 2.8 × 10−6) enrichment of associations at the gene level, forLOC388780(20p13; uncharacterized gene), and forVEPH1(3q25), a gene implicated in brain development. ...
ABSTRACTReading and writing are crucial for many aspects of modern life but up to 1 in 10 childre... more ABSTRACTReading and writing are crucial for many aspects of modern life but up to 1 in 10 children are affected by dyslexia [1, 2], which can persist into adulthood. Family studies of dyslexia suggest heritability up to 70% [3, 4], yet no convincing genetic markers have been found due to limited study power [5]. Here, we present a genome-wide association study representing a 20-fold increase in sample size from prior work, with 51,800 adults self-reporting a dyslexia diagnosis and 1,087,070 controls. We identified 42 independent genome-wide significant loci: 17 are in genes linked to or pleiotropic with cognitive ability/educational attainment; 25 are novel and may be more specifically associated with dyslexia. Twenty-three loci (12 novel) were validated in independent cohorts of Chinese and European ancestry. We confirmed a similar genetic aetiology of dyslexia between sexes, and found genetic covariance with many traits, including ambidexterity, but not neuroanatomical measures of...
Developmental Science, 2020
We reconcile competing theories of the role of phonological memory in reading development, by unc... more We reconcile competing theories of the role of phonological memory in reading development, by uncovering their dynamic relationship during the first 5 years of school. Phonological memory, reading and phoneme awareness were assessed in 780 phonics‐educated children at age 4, 5, 6 and 9. Confirmatory factor analyses demonstrated that phonological memory loaded onto two factors: verbal short‐term memory (verbal STM; phonological tasks that loaded primarily on serial order memory) and nonword repetition. Using longitudinal structural equation models, we found that verbal STM directly predicted early word‐level reading from age 4 to 6, reflecting the importance of serial‐order memory for letter‐by‐letter decoding. In contrast, reading had no reciprocal influence on the development of verbal STM. The relationship between nonword repetition and reading was bidirectional across the 5 years of study: nonword repetition and reading predicted each other both directly and indirectly (via phone...
Experimental brain research, 2003
Tests of postural stability have provided some evidence of a link between deficits in gross motor... more Tests of postural stability have provided some evidence of a link between deficits in gross motor skills and developmental dyslexia. The ordinal-level scales used previously, however, have limited measurement sensitivity, and no studies have investigated motor performance during walking in participants with dyslexia. The purpose of this study was to investigate if continuous-scaled measures of standing balance and gait could discriminate between groups of impaired and normal readers when investigators were blind to group membership during testing. Children with dyslexia ( n=22) and controls ( n=18), aged 10-12 years, performed walking tests at four different speeds (slow-preferred-fast-very fast) on an even and an uneven surface, and tests of unperturbed and perturbed body sway during standing. Body movements were registered by a triaxial accelerometer over the lower trunk, and measures of reaction time, body sway, walking speed, step length and cadence were calculated. Results were...
The Lancet, 1998
Neurological and physiological deficits have been reported in the brain in developmental dyslexia... more Neurological and physiological deficits have been reported in the brain in developmental dyslexia. The temporoparietal cortex has been directly implicated in dyslexic dysfunction, and substantial indirect evidence suggests that the cerebellum is also implicated. We wanted to find out whether the neurological and physiological deficits manifested as biochemical changes in the brain. We obtained localised proton magnetic resonance spectra bilaterally from the temporo-parietal cortex and cerebellum of 14 well-defined dyslexic men and 15 control men of similar age. We found biochemical differences between dyslexic men and controls in the left temporo-parietal lobe (ratio of choline-containing compounds [Cho] to N-acetylaspartate [NA] p&amp;lt; or =0.01) and right cerebellum (Cho/NA, p&amp;lt; or = 0.01; creatine [Cre] to NA p&amp;lt; or =0.05; (not significant). We found lateral biochemical differences in dyslexic men in both these brain regions (Cho/NA in temporo-parietal lobe, left vs right, p&amp;lt; or =0.01; Cre/NA in cerebellum, left vs right, p&amp;lt; or =0.001). We found no such lateral differences in controls. There was no significant relation between the degree of contralateral chemical difference and handedness in dyslexic or control men. We suggest that the observed differences reflect changes in cell density in the temporo-parietal lobe in developmental dyslexia and that the altered cerebral structural symmetry in dyslexia is associated with abnormal development of cells or intracellular connections or both. The cerebellum is biochemically asymmetric in dyslexic men, indicating altered development of this organ. These differences provide direct evidence of the involvement of the cerebellum in dyslexic dysfunction.