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1.  Assessment of Cerebral Lateralization in Children using Functional Transcranial Doppler Ultrasound (fTCD) 
There are many unanswered questions about cerebral lateralization. In particular, it remains unclear which aspects of language and nonverbal ability are lateralized, whether there are any disadvantages associated with atypical patterns of cerebral lateralization, and whether cerebral lateralization develops with age. In the past, researchers interested in these questions tended to use handedness as a proxy measure for cerebral lateralization, but this is unsatisfactory because handedness is only a weak and indirect indicator of laterality of cognitive functions1. Other methods, such as fMRI, are expensive for large-scale studies, and not always feasible with children2.
Here we will describe the use of functional transcranial Doppler ultrasound (fTCD) as a cost-effective, non-invasive and reliable method for assessing cerebral lateralization. The procedure involves measuring blood flow in the middle cerebral artery via an ultrasound probe placed just in front of the ear. Our work builds on work by Rune Aaslid, who co-introduced TCD in 1982, and Stefan Knecht, Michael Deppe and their colleagues at the University of Münster, who pioneered the use of simultaneous measurements of left- and right middle cerebral artery blood flow, and devised a method of correcting for heart beat activity. This made it possible to see a clear increase in left-sided blood flow during language generation, with lateralization agreeing well with that obtained using other methods3.
The middle cerebral artery has a very wide vascular territory (see Figure 1) and the method does not provide useful information about localization within a hemisphere. Our experience suggests it is particularly sensitive to tasks that involve explicit or implicit speech production. The 'gold standard' task is a word generation task (e.g. think of as many words as you can that begin with the letter 'B') 4, but this is not suitable for young children and others with limited literacy skills. Compared with other brain imaging methods, fTCD is relatively unaffected by movement artefacts from speaking, and so we are able to get a reliable result from tasks that involve describing pictures aloud5,6. Accordingly, we have developed a child-friendly task that involves looking at video-clips that tell a story, and then describing what was seen.
doi:10.3791/2161
PMCID: PMC3346060  PMID: 20972398
Neuroscience;  Issue 43;  functional transcranial Doppler ultrasound;  cerebral lateralization;  language;  child
2.  Developmental cognitive genetics: How psychology can inform genetics and vice versa 
Developmental neuropsychology is concerned with uncovering the underlying basis of developmental disorders such as specific language impairment (SLI), developmental dyslexia, and autistic disorder. Twin and family studies indicate that genetic influences play an important part in the aetiology of all of these disorders, yet progress in identifying genes has been slow. One way forward is to cut loose from conventional clinical criteria for diagnosing disorders and to focus instead on measures of underlying cognitive mechanisms. Psychology can inform genetics by clarifying what the key dimensions are for heritable phenotypes. However, it is not a one-way street. By using genetically informative designs, one can gain insights about causal relationships between different cognitive deficits. For instance, it has been suggested that low-level auditory deficits cause phonological problems in SLI. However, a twin study showed that, although both types of deficit occur in SLI, they have quite different origins, with environmental factors more important for auditory deficit, and genes more important for deficient phonological short-term memory. Another study found that morphosyntactic deficits in SLI are also highly heritable, but have different genetic origins from impairments of phonological short-term memory. A genetic perspective shows that a search for the underlying cause of developmental disorders may be misguided, because they are complex and heterogeneous and are associated with multiple risk factors that only cause serious disability when they occur in combination.
doi:10.1080/17470210500489372
PMCID: PMC2409179  PMID: 16769616
3.  Forty years on: Uta Frith's contribution to research on autism and dyslexia, 1966–2006 
Uta Frith has made a major contribution to our understanding of developmental disorders, especially autism and dyslexia. She has studied the cognitive and neurobiological bases of both disorders and demonstrated distinctive impairments in social cognition and central coherence in autism, and in phonological processing in dyslexia. In this enterprise she has encouraged psychologists to work in a theoretical framework that distinguishes between observed behaviour and the underlying cognitive and neurobiological processes that mediate that behaviour.
doi:10.1080/17470210701508665
PMCID: PMC2409181  PMID: 18038335
4.  Problems with tense marking in children with specific language impairment: not how but when 
Many children with specific language impairment (SLI) have persisting problems in the correct use of verb tense, but there has been disagreement as to the underlying reason. When we take into account studies using receptive as well as expressive language tasks, the data suggest that the difficulty for children with SLI is in knowing when to inflect verbs for tense, rather than how to do so. This is perhaps not surprising when we consider that tense does not have a transparent semantic interpretation, but depends on complex relationships between inflections and hierarchically organized clauses. An explanation in terms of syntactic limitations contrasts with a popular morpho-phonological account, the Words and Rules model. This model, which attributes problems to difficulties with applying a rule to generate regular inflected forms, has been widely applied to adult-acquired disorders. There are striking similarities in the pattern of errors in adults with anterior aphasia and children with SLI, suggesting that impairments in appreciation of when to mark tense may apply to acquired as well as developmental disorders.
doi:10.1098/rstb.2012.0401
PMCID: PMC3866428  PMID: 24324242
specific language impairment; grammar; past tense; morphology; aphasia; inflections
5.  When words fail us: insights into language processing from developmental and acquired disorders 
Acquired disorders of language represent loss of previously acquired skills, usually with relatively specific impairments. In children with developmental disorders of language, we may also see selective impairment in some skills; but in this case, the acquisition of language or literacy is affected from the outset. Because systems for processing spoken and written language change as they develop, we should beware of drawing too close a parallel between developmental and acquired disorders. Nevertheless, comparisons between the two may yield new insights. A key feature of connectionist models simulating acquired disorders is the interaction of components of language processing with each other and with other cognitive domains. This kind of model might help make sense of patterns of comorbidity in developmental disorders. Meanwhile, the study of developmental disorders emphasizes learning and change in underlying representations, allowing us to study how heterogeneity in cognitive profile may relate not just to neurobiology but also to experience. Children with persistent language difficulties pose challenges both to our efforts at intervention and to theories of learning of written and spoken language. Future attention to learning in individuals with developmental and acquired disorders could be of both theoretical and applied value.
doi:10.1098/rstb.2012.0403
PMCID: PMC3866430  PMID: 24324244
aphasia; dyslexia; specific language impairment; cognitive neuropsychology; connectionist models; development
6.  Preface 
doi:10.1098/rstb.2013.0564
PMCID: PMC3866433  PMID: 24324247
7.  Children with Specific Language Impairment are not impaired in the acquisition and retention of Pavlovian delay and trace conditioning of the eyeblink response☆ 
Brain and Language  2013;127(3):428-439.
Highlights
•We tested the integrity of small regions of the cerebellum and hippocampal formation in children with SLI.•Pavlovian delay conditioning engages elements of the procedural memory system.•Pavlovian trace conditioning engages procedural and declarative memory systems.•Children with Specific Language Impairment learned to delay and trace conditioning.•Brain regions engaged in eyeblink conditioning are normal in children with SLI.
Three converging lines of evidence have suggested that cerebellar abnormality is implicated in developmental language and literacy problems. First, some brain imaging studies have linked abnormalities in cerebellar grey matter to dyslexia and specific language impairment (SLI). Second, theoretical accounts of both dyslexia and SLI have postulated impairments of procedural learning and automatisation of skills, functions that are known to be mediated by the cerebellum. Third, motor learning has been shown to be abnormal in some studies of both disorders. We assessed the integrity of face related regions of the cerebellum using Pavlovian eyeblink conditioning in 7–11 year-old children with SLI. We found no relationship between oral language skills or literacy skills with either delay or trace conditioning in the children. We conclude that this elementary form of associative learning is intact in children with impaired language or literacy development.
doi:10.1016/j.bandl.2013.08.001
PMCID: PMC3847270  PMID: 24139661
Specific Language Impairment; SLI; Pavlovian; Classical; Conditioning; Eyeblink; Delay; Trace; Cerebellum; Procedural
8.  Fine motor deficits in reading disability and language impairment: same or different? 
PeerJ  2013;1:e217.
Several studies have found evidence of motor deficits in poor readers. There is no obvious reason for motor and literacy skills to go together, and it has been suggested that both deficits could be indicative of an underlying problem with cerebellar function and/or procedural learning. However, the picture is complicated by the fact that reading problems often co-occur with oral language impairments, which have also been linked with motor deficits. This raises the question of whether motor deficits characterise poor readers when language impairment has been accounted for – and vice versa. We considered these questions by assessing motor deficits associated with reading disability (RD) and language impairment (LI). A large community sample provided a subset of 9- to 10-year-olds, selected to oversample children with reading and/or language difficulties, to give 37 children with comorbid LI + RD, 67 children with RD only, 32 children with LI only, and 117 typically-developing (TD) children with neither type of difficulty. These children were given four motor tasks that taxed speed, sequence, and imitation abilities to differing extents. Different patterns of results were found for the four motor tasks. There was no effect of RD or LI on two speeded fingertip tapping tasks, one of which involved sequencing of movements. LI, but not RD, was associated with problems in imitating hand positions and slowed performance on a speeded peg-moving task that required a precision grip. Fine motor deficits in poor readers may be more a function of language impairment than literacy problems.
doi:10.7717/peerj.217
PMCID: PMC3845870  PMID: 24349898
Reading disability; Specific language impairment; Dyslexia; Motor; Imitation; Speed; Dexterity; Comorbidity
9.  Associations between Handedness and Cerebral Lateralisation for Language: A Comparison of Three Measures in Children 
PLoS ONE  2013;8(5):e64876.
It has been known for many years that hand preference is associated with cerebral lateralisation for language, but the relationship is weak and indirect. It has been suggested that quantitative measures of differential hand skill or reaching preference may provide more valid measures than traditional inventories, but to date these have not been validated against direct measures of cerebral lateralisation. We investigated the associations of three different handedness assessments; 1) a hand preference inventory, 2) a measure of relative hand skill, and 3) performance on a reaching task; with cerebral lateralisation for language function as derived from functional transcranial Doppler ultrasound during a language production task, in a group of 57 typically developing children aged from 6 to 16 years. Significant correlations between cerebral lateralisation for language production and handedness were found for a short version of the inventory and for performance on the reaching task. However, confidence intervals for the correlations overlapped and no one measure emerged as clearly superior to the others. The best handedness measures accounted for only 8–16% of the variance in cerebral lateralisation. These findings indicate that researchers should not rely on handedness as an indicator of cerebral lateralisation for language. They also imply that lateralisation of language and motor functions in the human brain show considerable independence from one another.
doi:10.1371/journal.pone.0064876
PMCID: PMC3667815  PMID: 23738006
10.  The Genetic and Environmental Foundation of the Simple View of Reading in Chinese 
PLoS ONE  2012;7(10):e47872.
The Simple View of Reading (SVR) in Chinese was examined in a genetically sensitive design. A total of 270 pairs of Chinese twins (190 pairs of monozygotic twins and 80 pairs of same-sex dizygotic twins) were tested on Chinese vocabulary and word reading at the mean age 7.8 years and reading comprehension of sentences and passages one year later. Results of behavior-genetic analyses showed that both vocabulary and word reading had significant independent genetic influences on reading comprehension, and the two factors together accounted for most but not all of the genetic influences on reading comprehension. In addition, sentence comprehension had a stronger genetic correlation with word reading while passage comprehension showed a trend of stronger genetic overlap with vocabulary. These findings suggest that the genetic foundation of the SVR in Chinese is largely supported in that language comprehension and decoding are two core skills for reading comprehension in nonalphabetic as well as alphabetic written languages.
doi:10.1371/journal.pone.0047872
PMCID: PMC3480450  PMID: 23112862
12.  Delayed Retention of New Word-Forms Is Better in Children than Adults Regardless of Language Ability: A Factorial Two-Way Study 
PLoS ONE  2012;7(5):e37326.
Background
Nonword repetition, the ability to retain and repeat unfamiliar sequences of phonemes is usually impaired in children with specific language impairment (SLI), but it is unclear whether this explains slow language learning. Traditional nonword repetition tests involve a single presentation of nonwords for immediate repetition. Here we considered whether rate of learning of novel phonological sequences was impaired when the same items were presented repeatedly.
Methodology/Principal Findings
Three complex nonwords were each presented for repetition five times in two sessions (A and B) separated by one hour. We studied both adults and children from (i) families with a child with SLI and (ii) families whose children did not have SLI. This gave a 2×2 design with familial SLI as one factor, and age (up to or above 18 years) as the other. Overall, participants from families with SLI were poorer at nonword repetition than their peers from typical-language families, and there was a trend for children with SLI to show less within-session learning than typically developing children. However, between-session retention, measured as the difference between the last trial from session 1 and the first trial of session 2, showed a significant age effect, η2 = .139, p = .004, regardless of family SLI status. Adult participants showed a decrease in score from the last trial of session A to the first trial of session B, whereas children maintained their level of performance, regardless of whether or not they had SLI.
Conclusions/Significance
Poor nonword repetition in SLI appears to reflect inadequate encoding of phonological information, rather than problems retaining encoded information. Furthermore, the nonword learning task is consistent with the notion of a sensitive period in language learning: Children show better retention over a delay for new phonological sequences than adults, regardless of overall level of language ability.
doi:10.1371/journal.pone.0037326
PMCID: PMC3353950  PMID: 22615979
13.  Does cerebral lateralization develop? A study using functional transcranial Doppler ultrasound assessing lateralization for language production and visuospatial memory 
Brain and Behavior  2012;2(3):256-269.
In the majority of people, language production is lateralized to the left cerebral hemisphere and visuospatial skills to the right. However, questions remain as to when, how, and why humans arrive at this division of labor. In this study, we assessed cerebral lateralization for language production and for visuospatial memory using functional transcranial Doppler ultrasound in a group of 60 typically developing children between the ages of six and 16 years. The typical pattern of left-lateralized activation for language production and right-lateralized activation for visuospatial memory was found in the majority of the children (58%). No age-related change in direction or strength of lateralization was found for language production. In contrast, the strength of lateralization (independent of direction) for visuospatial memory function continued to increase with age. In addition, boys showed a trend for stronger right-hemisphere lateralization for visuospatial memory than girls, but there was no gender effect on language laterality. We tested whether having language and visuospatial functions in the same hemisphere was associated with poor cognitive performance and found no evidence for this “functional crowding” hypothesis. We did, however, find that children with left-lateralized language production had higher vocabulary and nonword reading age-adjusted standard scores than other children, regardless of the laterality of visuospatial memory. Thus, a link between language function and left-hemisphere lateralization exists, and cannot be explained in terms of maturational change.
doi:10.1002/brb3.56
PMCID: PMC3381631  PMID: 22741100
Cerebral lateralization; development; functional transcranial Doppler ultrasonography; language production; left hemisphere; right hemisphere; visuospatial memory
14.  Lateralised visual attention is unrelated to language lateralisation, and not influenced by task difficulty – A functional transcranial Doppler study 
Neuropsychologia  2012;50(5-3):810-815.
Graphical abstract
Highlights
► fTCD gives a reliable index of cerebral lateralisation for visuospatial attention. ► Task difficulty has no effect on the laterality index in the visuospatial paradigm. ► Visuospatial and language lateralisation are not correlated within subjects. ► The results challenge single-factor theories of hemispheric specialisation.
Historically, most theoretical accounts of hemispheric specialisation have proposed a single underlying factor that leads to left hemisphere language and right hemisphere visuospatial processing in the majority of people. More recently empirical evidence has started to challenge this view, suggesting lateralisation of language and visuospatial attention are independent. However, so far studies did not control for a possible confound, task difficulty. For this study, 20 healthy right-handed volunteers underwent functional laterality assessment using functional transcranial Doppler ultrasound (fTCD). We assessed laterality using both a word generation task and a novel variation of the visuospatial landmark task that can be adjusted along two dimensions of difficulty (temporal and spatial). The visuospatial laterality measures were highly intercorrelated and unaffected by task difficulty. Furthermore, there was no correlation between visuospatial and verbal lateralisation within individuals – neither qualitatively (in direction of lateralisation), nor quantitatively (in laterality index size). These results substantiate a growing body of evidence suggesting multiple independent biases leading to the hemispheric lateralisation of different cognitive domains, thus further questioning previously accepted models of laterality development and evolution.
doi:10.1016/j.neuropsychologia.2012.01.015
PMCID: PMC3334833  PMID: 22285903
Cerebral laterality; Difficulty; Functional transcranial Doppler ultrasound (fTCD); Landmark task; Visuospatial attention; Verbal fluency; Word generation task
15.  dopOSCCI: A functional transcranial Doppler ultrasonography summary suite for the assessment of cerebral lateralization of cognitive function 
Journal of Neuroscience Methods  2012;204(2-2):383-388.
Highlights
► We present a new functional transcranial Doppler ultrasongraphy toolbox for Matlab. ► The basic features include multi-file summaries and laterality index calculation. ► Advanced features include behavioural and multi-session summaries. ► The toolbox is freely available under the GNU GPL license.
We present a description of a new software package, ‘dopOSCCI’, which summarises data from experimental studies where functional transcranial Doppler ultrasonography (fTCD) is used to compare hemispheric rates of blood flow in order to assess lateralization of a cognitive process. The software provides a graphical user interface to summarise analogue and digital data collected using Multi-Dop Doppler Ultrasound devices (DWL Multidop T2: manufacturer, DWL Elektronische Systeme, Singen, Germany). The unique aspects of dopOSCCI allow multi-file processing, multi-event marker processing, behavioural and multi-session summaries, image file data visualization, and tab-delimited output files which includes split-half, single-trial summaries and data quality variables. The Matlab based software is available under the GNU GPL license and can be accessed online at https://databank.ora.ox.ac.uk/general/datasets/dopOSCCI, the Oxford University DataBank.
doi:10.1016/j.jneumeth.2011.11.018
PMCID: PMC3314978  PMID: 22120689
Functional transcranial Doppler ultrasonography; Imaging; Blood flow velocity; Methods; Matlab
16.  Co-localisation of abnormal brain structure and function in specific language impairment 
Brain and Language  2012;120(3-4):310-320.
Graphical abstract
Highlights
► Compared brain structure and function in SLI, unaffected siblings, and typical peers. ► More grey matter in SLI in the left inferior frontal cortex. ► Less grey matter in SLI in the right caudate nucleus and superior temporal cortex bilaterally. ► Functional activation was examined with an auditory covert naming task. ► Functionally, SLI had reduced activation of the left inferior frontal cortex and the superior temporal cortex bilaterally.
We assessed the relationship between brain structure and function in 10 individuals with specific language impairment (SLI), compared to six unaffected siblings, and 16 unrelated control participants with typical language. Voxel-based morphometry indicated that grey matter in the SLI group, relative to controls, was increased in the left inferior frontal cortex and decreased in the right caudate nucleus and superior temporal cortex bilaterally. The unaffected siblings also showed reduced grey matter in the caudate nucleus relative to controls. In an auditory covert naming task, the SLI group showed reduced activation in the left inferior frontal cortex, right putamen, and in the superior temporal cortex bilaterally. Despite spatially coincident structural and functional abnormalities in frontal and temporal areas, the relationships between structure and function in these regions were different. These findings suggest multiple structural and functional abnormalities in SLI that are differently associated with receptive and expressive language processing.
doi:10.1016/j.bandl.2011.10.006
PMCID: PMC3315677  PMID: 22137677
Developmental disorders; Voxel-based morphometry; Functional magnetic resonance imaging; Language specialisation; Lateralisation
17.  Adult psychosocial outcomes of children with specific language impairment, pragmatic language impairment and autism 
Background: The few studies that have tracked children with developmental language disorder to adulthood have found that these individuals experience considerable difficulties with psychosocial adjustment (for example, academic, vocational and social aptitude). Evidence that some children also develop autistic symptomatology over time has raised suggestions that developmental language disorder may be a high-functioning form of an autism spectrum disorder (ASD). It is not yet clear whether these outcomes vary between individuals with different subtypes of language impairment.
Aims: To compare the adult psychosocial outcomes of children with specific language impairment (SLI), pragmatic language impairment (PLI) and ASD.
Methods & Procedures: All participants took part in research as children. In total, there were 19 young adults with a childhood history of Specific Language Impairment (M age = 24;8), seven with PLI (M age = 22;3), 11 with high functioning ASD (M age = 21;9) and 12 adults with no history of developmental disorder (Typical; n = 12; M age = 21;6). At follow-up, participants and their parents were interviewed to elicit information about psychosocial outcomes.
Outcomes & Results: Participants in the SLI group were most likely to pursue vocational training and work in jobs not requiring a high level of language/literacy ability. The PLI group tended to obtain higher levels of education and work in ‘skilled’ professions. The ASD participants had lower levels of independence and more difficulty obtaining employment than the PLI and SLI participants. All groups had problems establishing social relationships, but these difficulties were most prominent in the PLI and ASD groups. A small number of participants in each group were found to experience affective disturbances. The PLI and SLI groups showed lower levels of autistic symptomatology than the ASD group.
Conclusions & Implications: The between-group differences in autistic symptomatology provide further evidence that SLI, PLI, and ASD are related disorders that vary along qualitative dimensions of language structure, language use and circumscribed interests. Childhood diagnosis showed some relation to adult psychosocial outcome. However, within-group variation highlights the importance of evaluating children on a case-by-case basis.
doi:10.1080/13682820802708098
PMCID: PMC2835860  PMID: 19340628
specific language impairment; pragmatic language impairment; autism; longitudinal; psychosocial; outcome
18.  Qualitative aspects of developmental language impairment relate to language and literacy outcome in adulthood 
Background: Developmental language disorder is a heterogeneous diagnostic category. Little research has compared the long-term outcomes of children with different subtypes of language impairment.
Aims: To determine whether the pattern of language impairment in childhood related to language and literacy outcomes in adulthood.
Methods & Procedures: Adults who took part in previous studies as children were traced. There were four groups of participants, each with a different childhood diagnosis: specific language impairment (SLI; n = 19, mean age at follow-up = 24;8), pragmatic language impairment (PLI; n = 7, mean age at follow-up = 22;3), autism spectrum disorder (ASD; n = 11; mean age at follow-up = 21;9), and no childhood diagnosis (typical; n = 12; mean age at follow-up = 21;6). Participants were administered a battery of language and literacy tests.
Outcomes & Results: Adults with a history of SLI had persisting language impairment as well as considerable literacy difficulties. Pragmatic deficits also appeared to develop over time in these individuals. The PLI group had enduring difficulties with language use, but presented with relatively intact language and literacy skills. Although there were some similarities in the language profile of the PLI and ASD groups, the ASD group was found to have more severe pragmatic deficits and parent-reported linguistic difficulties in conversational speech.
Conclusions & Implications: The pattern of deficits observed in different subtypes of developmental language disorder persists into adulthood. The findings highlight the importance of a wide-ranging clinical assessment in childhood, which may provide an indication of outcome in adulthood.
doi:10.1080/13682820802708080
PMCID: PMC2892753  PMID: 19343569
specific language impairment; pragmatic language impairment; autism; language; literacy; outcome
19.  Grammatical Difficulties in Children with Specific Language Impairment: Is Learning Deficient? 
Human development  2011;53(5):264-277.
Theoretical accounts of grammatical limitations in specific language impairment (SLI) have been polarized between those that postulate problems with domain-specific grammatical knowledge, and those that regard grammatical deficits as downstream consequences of perceptual or memory limitations. Here we consider an alternative view that grammatical deficits arise when the learning system is biased towards memorization of exemplars, and is poor at extracting statistical dependencies from the input. We examine evidence that SLI involves deficits in extracting nonadjacent dependencies from input, leading to reliance on rote learning, and consider how far this may be part of a limitation of procedural learning, or a secondary consequence of memory limitations.
doi:10.1159/000321289
PMCID: PMC3191529  PMID: 22003258
Grammar; Specific language impairment; Statistical learning
20.  Autism, language and communication in children with sex chromosome trisomies 
Archives of disease in childhood  2010;96(10):954-959.
Purpose
Sex chromosome trisomies (SCTs) are found on amniocentesis in 2.3–3.7 per 1000 same-sex births, yet there is a limited database on which to base a prognosis. Autism has been described in postnatally diagnosed cases of Klinefelter syndrome (XXY karyotype), but the prevalence in non-referred samples, and in other trisomies, is unclear. The authors recruited the largest sample including all three SCTs to be reported to date, including children identified on prenatal screening, to clarify this issue.
Design
Parents of children with a SCT were recruited either via prenatal screening or via a parental support group, to give a sample of 58 XXX, 19 XXY and 58 XYY cases. Parents were interviewed using the Vineland Adaptive Behavior Scales and completed questionnaires about the communicative development of children with SCTs and their siblings (42 brothers and 26 sisters).
Results
Rates of language and communication problems were high in all three trisomies. Diagnoses of autism spectrum disorder (ASD) were found in 2/19 cases of XXY (11%) and 11/58 XYY (19%). After excluding those with an ASD diagnosis, communicative profiles indicative of mild autistic features were common, although there was wide individual variation.
Conclusions
Autistic features have not previously been remarked upon in studies of non-referred samples with SCTs, yet the rate is substantially above population levels in this sample, even when attention is restricted to early-identified cases. The authors hypothesise that X-linked and Y-linked neuroligins may play a significant role in the aetiology of communication impairments and ASD.
doi:10.1136/adc.2009.179747
PMCID: PMC3182523  PMID: 20656736
21.  Where were those rabbits? A new paradigm to determine cerebral lateralisation of visuospatial memory function in children 
Neuropsychologia  2011;49(12):3265-3271.
Highlights
► A child-friendly fTCD task to measure cerebral lateralisation of visuospatial memory. ► Strong positive correlations were found between the child and adult versions. ► No associations between lateralisation and task performance were found. ► It was a valid measure of cerebral lateralisation for visuospatial memory in children.
In the majority of people, functional differences are observed between the two cerebral hemispheres: language production is typically subserved by the left hemisphere and visuospatial skills by the right hemisphere. The development of this division of labour is not well understood and lateralisation of visuospatial function has received little attention in children. In this study we devised a child-friendly version of a paradigm to assess lateralisation of visuospatial memory using functional transcranial Doppler ultrasound (fTCD). In a group of 24 adults we found this child-friendly version gave similar results to the original version of the task. In addition, fourteen children aged 6–8 years successfully completed the child-friendly fTCD task, showing a negative lateralisation index, indicating right hemispheric specialisation at the group level. Additionally, we assessed effects of task accuracy and reaction time on the lateralisation index. No effects were found, at the group level or at the level of single trials, in either the adult or the child group. We conclude that this new task reliably assesses lateralisation of visuospatial memory function in children as young as 6 years of age, using fTCD. As such, it holds promise for investigating development of lateralisation of visuospatial function in typically and atypically developing children.
doi:10.1016/j.neuropsychologia.2011.07.031
PMCID: PMC3198251  PMID: 21843539
Cerebral lateralisation; Visuospatial; Right hemisphere; Functional transcranial Doppler ultrasonography; Children
22.  DCDC2, KIAA0319 and CMIP Are Associated with Reading-Related Traits 
Biological Psychiatry  2011;70(3):237-245.
Background
Several susceptibility genes have been proposed for dyslexia (reading disability; RD) and specific language impairment (SLI). RD and SLI show comorbidity, but it is unclear whether a common genetic component is shared.
Methods
We have investigated whether candidate genes for RD and SLI affect specific cognitive traits or have broad effect on cognition. We have analyzed common risk variants within RD (MRPL19/C2ORF3, KIAA0319, and DCDC2) and language impairment (CMIP and ATP2C2) candidate loci in the Avon Longitudinal Study of Parents and Children cohort (n = 3725), representing children born in southwest England in the early 1990s.
Results
We detected associations between reading skills and KIAA0319, DCDC2, and CMIP. We show that DCDC2 is specifically associated with RD, whereas variants in CMIP and KIAA0319 are associated with reading skills across the ability range. The strongest associations were restricted to single-word reading and spelling measures, suggesting that these genes do not extend their effect to other reading and language-related skills. Inclusion of individuals with comorbidity tends to strengthen these associations. Our data do not support MRPL19/C2ORF3 as a locus involved in reading abilities nor CMIP/ATP2C2 as genes regulating language skills.
Conclusions
We provide further support for the role of KIAA0319 and DCDC2 in contributing to reading abilities and novel evidence that the language-disorder candidate gene CMIP is also implicated in reading processes. Additionally, we present novel data to evaluate the prevalence and comorbidity of RD and SLI, and we recommend not excluding individuals with comorbid RD and SLI when designing genetic association studies for RD.
doi:10.1016/j.biopsych.2011.02.005
PMCID: PMC3139836  PMID: 21457949
ALSPAC; association study; dyslexia; language; reading abilities; specific language impairment (SLI)
23.  Pragmatic tolerance: Implications for the acquisition of informativeness and implicature 
Cognition  2011;120(1):67-81.
Recent investigations of the acquisition of scalar implicature report that young children do not reliably reject a sentence with a weak scalar term, e.g. ‘some of the books are red’, when it is used as a description of a situation where a stronger statement is true, e.g. where all the books are red. This is taken as evidence that children do not interpret the sentence with the implicature that the stronger statement does not hold. We propose that (a) these tasks cannot differentiate between actual implicature derivation and mere sensitivity to violations of informativeness; and that (b) children’s apparent failure is not due to lack of competence (whether with informativeness or implicature) but due to their tolerance of pragmatic violations. We report three studies with 5-to-6-year-old English-speaking children and adults employing utterances involving scalar and non-scalar expressions. These show that both age-groups are competent with informativeness, but also tolerant of pragmatic infelicity. These findings have implications for the well-established literature on whether children are aware of ambiguity in referential communication tasks.
doi:10.1016/j.cognition.2011.02.015
PMCID: PMC3104140  PMID: 21429481
Pragmatics; Acquisition; Informativeness; Implicature; Ambiguity
24.  Auditory Development between 7 and 11 Years: An Event-Related Potential (ERP) Study 
PLoS ONE  2011;6(5):e18993.
Background
There is considerable uncertainty about the time-course of central auditory maturation. On some indices, children appear to have adult-like competence by school age, whereas for other measures development follows a protracted course.
Methodology
We studied auditory development using auditory event-related potentials (ERPs) elicited by tones in 105 children on two occasions two years apart. Just over half of the children were 7 years initially and 9 years at follow-up, whereas the remainder were 9 years initially and 11 years at follow-up. We used conventional analysis of peaks in the auditory ERP, independent component analysis, and time-frequency analysis.
Principal Findings
We demonstrated maturational changes in the auditory ERP between 7 and 11 years, both using conventional peak measurements, and time-frequency analysis. The developmental trajectory was different for temporal vs. fronto-central electrode sites. Temporal electrode sites showed strong lateralisation of responses and no increase of low-frequency phase-resetting with age, whereas responses recorded from fronto-central electrode sites were not lateralised and showed progressive change with age. Fronto-central vs. temporal electrode sites also mapped onto independent components with differently oriented dipole sources in auditory cortex. A global measure of waveform shape proved to be the most effective method for distinguishing age bands.
Conclusions/Significance
The results supported the idea that different cortical regions mature at different rates. The ICC measure is proposed as the best measure of ‘auditory ERP age’.
doi:10.1371/journal.pone.0018993
PMCID: PMC3090390  PMID: 21573058
25.  Genetic and Environmental Influences on Chinese Language and Reading Abilities 
PLoS ONE  2011;6(2):e16640.
This study investigated the etiology of individual differences in Chinese language and reading skills in 312 typically developing Chinese twin pairs aged from 3 to 11 years (228 pairs of monozygotic twins and 84 pairs of dizygotic twins; 166 male pairs and 146 female pairs). Children were individually given tasks of Chinese word reading, receptive vocabulary, phonological memory, tone awareness, syllable and rhyme awareness, rapid automatized naming, morphological awareness and orthographic skills, and Raven's Coloured Progressive Matrices. All analyses controlled for the effects of age. There were moderate to substantial genetic influences on word reading, tone awareness, phonological memory, morphological awareness and rapid automatized naming (estimates ranged from .42 to .73), while shared environment exerted moderate to strong effects on receptive vocabulary, syllable and rhyme awareness and orthographic skills (estimates ranged from .35 to .63). Results were largely unchanged when scores were adjusted for nonverbal reasoning as well as age. Findings of this study are mostly similar to those found for English, a language with very different characteristics, and suggest the universality of genetic and environmental influences across languages.
doi:10.1371/journal.pone.0016640
PMCID: PMC3037369  PMID: 21347359

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