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1.  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
2.  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
3.  Preface 
doi:10.1098/rstb.2013.0564
PMCID: PMC3866433  PMID: 24324247
4.  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
5.  Which Neurodevelopmental Disorders Get Researched and Why? 
PLoS ONE  2010;5(11):e15112.
Aim
There are substantial differences in the amount of research concerned with different disorders. This paper considers why.
Methods
Bibliographic searches were conducted to identify publications (1985–2009) concerned with 35 neurodevelopmental disorders: Developmental dyslexia, Developmental dyscalculia, Developmental coordination disorder, Speech sound disorder, Specific language impairment, Attention deficit hyperactivity disorder, Autistic spectrum disorder, Tourette syndrome, Intellectual disability, Angelman syndrome, Cerebral palsy, Cornelia de Lange syndrome, Cri du chat syndrome, Down syndrome, Duchenne muscular dystrophy, Fetal alcohol syndrome, Fragile X syndrome, Galactosaemia, Klinefelter syndrome, Lesch-Nyhan syndrome, Lowe syndrome, Marfan syndrome, Neurofibromatosis type 1, Noonan syndrome, Phenylketonuria, Prader-Willi syndrome, Rett syndrome, Rubinstein-Taybi syndrome, Trisomy 18, Tuberous sclerosis, Turner syndrome, Velocardiofacial syndrome, Williams syndrome, XXX and XYY. A publication index reflecting N publications relative to prevalence was derived.
Results
The publication index was higher for rare than common conditions. However, this was partly explained by the tendency for rare disorders to be more severe.
Interpretation
Although research activity is predictable from severity and prevalence, there are exceptions. Low rates of research, and relatively low levels of NIH funding, characterise conditions that are the domain of a single discipline with limited research resources. Growth in research is not explained by severity, and was exceptionally steep for autism and ADHD.
doi:10.1371/journal.pone.0015112
PMCID: PMC2994844  PMID: 21152085
6.  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
7.  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
8.  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
9.  Training understanding of reversible sentences: a study comparing language-impaired children with age-matched and grammar-matched controls 
PeerJ  2014;2:e656.
Introduction. Many children with specific language impairment (SLI) have problems with language comprehension, and little is known about how to remediate these. We focused here on errors in interpreting sentences such as “the ball is above the cup”, where the spatial configuration depends on word order. We asked whether comprehension of such short reversible sentences could be improved by computerized training, and whether learning by children with SLI resembled that of younger, typically-developing children.
Methods. We trained 28 children with SLI aged 6–11 years, 28 typically-developing children aged from 4 to 7 years who were matched to the SLI group for raw scores on a test of receptive grammar, and 20 typically-developing children who were matched to the SLI group on chronological age. A further 20 children with SLI were given pre- and post-test assessments, but did not undergo training. Those in the trained groups were given training on four days using a computer game adopting an errorless learning procedure, during which they had to select pictures to correspond to spoken sentences such as “the cup is above the drum” or “the bird is below the hat”. Half the trained children heard sentences using above/below and the other half heard sentences using before/after (with a spatial interpretation). A total of 96 sentences was presented over four sessions. Half the sentences were unique, whereas the remainder consisted of 12 repetitions of each of four sentences that became increasingly familiar as training proceeded.
Results. Age-matched control children performed near ceiling (≥ 90% correct) in the first session and were excluded from the analysis. Around half the trained SLI children also performed this well. Training effects were examined in 15 SLI and 16 grammar-matched children who scored less than 90% correct on the initial training session. Overall, children’s scores improved with training. Memory span was a significant predictor of improvement, even after taking into account performance on training session 1. Unlike the grammar-matched controls, children with SLI showed greater accuracy with repeated sentences compared with unique sentences. Training did not improve children’s performance on a standardized test of receptive grammar.
Discussion. Overall, these results indicate that a subset of children with SLI perform well below ceiling on reversible sentences with three key words and simple syntactic structure. For these children, weak verbal short-term memory appears to impair comprehension of spoken sentences. In contrast to the general finding that rule-learning benefits from variable input, these children seem to do best if given repeated exposure to the same nouns used with a given sentence frame. Generalisation to other sentences using the same syntactic frame may be more effective if preceded by such item-specific learning.
doi:10.7717/peerj.656
PMCID: PMC4226637  PMID: 25392757
Specific language impairment; Child; Language; Intervention; Grammar; Receptive language; Comprehension; Verbal memory; Procedural learning; Speech and language therapy
10.  No population bias to left-hemisphere language in 4-year-olds with language impairment 
PeerJ  2014;2:e507.
Background. An apparent paradox in the field of neuropsychology is that people with atypical cerebral lateralization do not appear to suffer any cognitive disadvantage, yet atypical cerebral lateralization is more common in children and adults with developmental language disorders. This study was designed to explore possible reasons for this puzzling pattern of results.
Methods. We used functional transcranial Doppler ultrasound (fTCD) to assess cerebral blood flow during language production in 57 four-year-olds, including 15 children who had been late-talkers when first seen at 20 months of age. We categorized cerebral lateralization as left, right or bilateral, and compared proportions with each type of laterality with those seen in a previously tested sample of children aged 6–16 years. We also compared language scores at 4 years for those with typical and atypical lateralization, and then looked at the association the opposite way: comparing those with typical or impaired language in terms of their cerebral lateralization.
Results. The distribution of types of cerebral lateralization was similar for 4-year-olds to that seen in older children. Overall, cerebral lateralization was not predictive of language level. However, for children who had language difficulties at 20 months and/or 4 years (N = 21), there was no population bias to left-hemisphere language activation, whereas children without language problems at either age showed a pronounced bias to left-sided language lateralization. Nevertheless, many children with right hemisphere language had no indications of language difficulties, confirming that atypical cerebral asymmetry is not a direct cause of problems.
Conclusions. We suggest that atypical lateralization at the individual level is not associated with language impairment. However, lack of lateralization at the population level is a marker of risk for language impairment, which could be due to genetic or non-genetic causes.
doi:10.7717/peerj.507
PMCID: PMC4137668  PMID: 25165624
Language impairment; Cerebral lateralization; Transcranial functional Doppler ultrasound; Child; Asymmetry
11.  Cerebral asymmetry and language development: cause, correlate or consequence? 
Science (New York, N.Y.)  2013;340(6138):1230531.
In most people language is processed predominantly by the left hemisphere, but we don’t know how or why. A popular view is that developmental language disorders result from a poorly lateralized brain, but until recently evidence has been weak and indirect. Modern neuroimaging methods have made it possible to study normal and abnormal development of lateralized function in the developing brain and have confirmed links with language and literacy impairments. However, there is little evidence that weak cerebral lateralization has common genetic origins with language/literacy impairments. Our understanding of the association between atypical language lateralization and developmental disorders may benefit if we reconceptualise the nature of cerebral asymmetry to recognize its multidimensional nature and to take into account variation in lateralization over developmental time. Contrary to popular belief, cerebral lateralization may not be a highly heritable, stable characteristic of individuals; rather, weak lateralization may be a consequence of impaired language learning.
doi:10.1126/science.1230531
PMCID: PMC4031634  PMID: 23766329
12.  Sequence-specific Procedural Learning Deficits in Children with Specific Language Impairment 
Developmental science  2014;17(3):352-365.
This study tested the procedural deficit hypothesis of specific language impairment (SLI) by comparing children’s performance in two motor procedural learning tasks and an implicit verbal sequence learning task. Participants were 7- to 11-year-old children with SLI (n= 48), typically-developing age-matched children (N = 20) and younger typically-developing children matched for receptive grammar (N = 28). In a serial reaction time task, the children with SLI performed at the same level as the grammar-matched children, but poorer than age-match controls in learning motor sequences. When tested with a motor procedural learning task that did not involve learning sequential relationships between discrete elements (i.e., pursuit rotor), the children with SLI performed comparably with age-matched children and better than younger grammar-matched controls. In addition, poor implicit learning of word sequences in a verbal memory task (Hebb effect) was found in the children with SLI. Together, these findings suggest that SLI might be characterized by deficits in learning sequence-specific information, rather than generally weak procedural learning.
doi:10.1111/desc.12125
PMCID: PMC4031743  PMID: 24410990
procedural learning; sequence learning; SLI
13.  A Spotlight on Preschool: The Influence of Family Factors on Children’s Early Literacy Skills 
PLoS ONE  2014;9(4):e95255.
Rationale
Phonological awareness, letter knowledge, oral language (including sentence recall) and rapid automatised naming are acknowledged within-child predictors of literacy development. Separate research has identified family factors including socio-economic status, parents’ level of education and family history. However, both approaches have left unexplained significant amounts of variance in literacy outcomes. This longitudinal study sought to improve prospective classification accuracy for young children at risk of literacy failure by adding two new family measures (parents’ phonological awareness and parents’ perceived self-efficacy), and then combining the within-child and family factors.
Method
Pre-literacy skills were measured in 102 four year olds (46 girls and 56 boys) at the beginning of Preschool, and then at the beginning and end of Kindergarten, when rapid automatised naming was also measured. Family factors data were collected at the beginning of Preschool, and children’s literacy outcomes were measured at the end of Year 1 (age 6–7 years).
Results
Children from high-risk backgrounds showed poorer literacy outcomes than low-risk students, though three family factors (school socio-economic status, parents’ phonological awareness, and family history) typically accounted for less Year 1 variance than the within-child factors. Combining these family factors with the end of Kindergarten within-child factors provided the most accurate classification (i.e., sensitivity = .85; specificity = .90; overall correct = .88).
Implications
Our approach would identify at-risk children for intervention before they began to fail. Moreover, it would be cost-effective because although few at-risk children would be missed, allocation of unnecessary educational resources would be minimised.
doi:10.1371/journal.pone.0095255
PMCID: PMC3994054  PMID: 24751691
14.  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
15.  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
16.  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
17.  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
19.  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
20.  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
21.  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
22.  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
23.  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
24.  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
25.  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

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