Syntactic complexity in the comprehension of wh-questions and relative clauses in typical language development and autism

This study investigates effects of syntactic complexity operationalised in terms of movement, intervention and (NP) feature similarity in the development of A’ dependencies in 4-, 6-, and 8-year old typically developing (TD) French children and children with Autism Spectrum Disorders (ASD). Children completed an off-line comprehension task testing eight syntactic structures classified in four levels of complexity: Level 0: No Movement; Level 1: Movement without (configurational) Intervention; Level 2: Movement with Intervention from an element which is maximally different or featurally ‘disjoint’ (mismatched in both lexical NP restriction and number); Level 3: Movement with Intervention from an element similar in one feature or featurally ‘intersecting’ (matched in lexical NP restriction, mismatched in number). The results show that syntactic complexity affects TD children across the three age groups, but also indicate developmental differences between these groups. Movement affected all three groups in a similar way, but intervention effects in intersection cases were stronger in younger than older children, with NP feature similarity affecting only 4-year olds. Complexity effects created by the similarity in lexical restriction of an intervener thus appear to be overcome early in development, arguably thanks to other differences of this intervener (which was mismatched in number). Children with ASD performed less well than the TD children although they were matched on non-verbal reasoning. Overall, syntactic complexity affected their performance in a similar way as in their TD controls, but their performance correlated with non-verbal abilities rather than age, suggesting that their grammatical development does not follow the smooth relation to age that is found in TD children.

Developmental changes in presynaptic muscarinic modulation of excitatory and inhibitory neurotransmission in rat piriform cortex in vitro: relevance to epileptiform bursting susceptibility

Suppression of depolarizing postsynaptic potentials and isolated GABA-A receptor-mediated fast inhibitory postsynaptic potentials by the muscarinic acetylcholine receptor agonist, oxotremorine-M (10 microM), was investigated in adult and immature (P14-P30) rat piriform cortical (PC) slices using intracellular recording. Depolarizing postsynaptic potentials evoked by layers II-III stimulation underwent concentration-dependent inhibition in oxotremorine-M that was most likely presynaptic and M2 muscarinic acetylcholine receptor-mediated in immature, but M1-mediated in adult (P40-P80) slices; percentage inhibition was smaller in immature than in adult piriform cortex. In contrast, compared with adults, layer Ia-evoked depolarizing postsynaptic potentials in immature piriform cortex slices in oxotremorine-M, showed a prolonged multiphasic depolarization with superimposed fast transients and spikes, and an increased 'all-or-nothing' character. Isolated N-methyl-d-aspartate receptor-mediated layer Ia depolarizing postsynaptic potentials (although significantly larger in immature slices) were however, unaffected by oxotremorine-M, but blocked by dl-2-amino-5-phosphonovaleric acid. Fast inhibitory postsynaptic potentials evoked by layer Ib or layers II-III-fiber stimulation in immature slices were significantly smaller than in adults, despite similar estimated mean reversal potentials ( approximately -69 and -70 mV respectively). In oxotremorine-M, only layer Ib-fast inhibitory postsynaptic potentials were suppressed; suppression was again most likely presynaptic M2-mediated in immature slices, but M1-mediated in adults. The degree of fast inhibitory postsynaptic potential suppression was however, greater in immature than in adult piriform cortex. Our results demonstrate some important physiological and pharmacological differences between excitatory and inhibitory synaptic systems in adult and immature piriform cortex that could contribute toward the increased susceptibility of this region to muscarinic agonist-induced epileptiform activity in immature brain slices.

Understanding and production of prosody in children with Williams syndrome: A developmental trajectory approach

This study investigated the development of three aspects of linguistic prosody in a group of children with Williams syndrome compared to typically developing children. The prosodic abilities investigated were: (1) the ability to understand and use prosody to make specific words or syllables stand out in an utterance (focus); (2) the ability to understand and use prosody to disambiguate complex noun phrases (chunking); (3) the ability to understand and use prosody to regulate conversational behaviour (turn-end). The data were analysed using a cross-sectional developmental trajectory approach. The results showed that, relative to chronological age, there was a delayed onset in the development of the ability of children with WS to use prosody to signal the most important word in an utterance (the focus function). Delayed rate of development was found for all the other aspects of expressive and receptive prosody under investigation. However, when non-verbal mental age was taken into consideration, there were no differences between the children with WS and the controls neither with the onset nor with the rate of development for any of the prosodic skills under investigation apart from the ability to use prosody in order to regulate conversational behaviour. We conclude that prosody is not a ‘preserved’ cognitive skill in WS. The genetic factors, development in other cognitive domains and environmental influences affect developmental pathways and as a result, development proceeds along an atypical trajectory.

Differences between naïve and expert observers’ vergence and accommodative responses to a range of targets

Purpose: Vergence and accommodation studies often use adult participants with experience of vision science. Reports of infant and clinical responses are generally more variable and of lower gain, with the implication that differences lie in immaturity or sub-optimal clinical characteristics but expert/naïve differences are rarely considered or quantified. Methods: Sixteen undergraduates, naïve to vision science, were individually matched by age, visual acuity, refractive error, heterophoria, stereoacuity and near point of accommodation to second- and third-year orthoptics and optometry undergraduates (‘experts’). Accommodation and vergence responses were assessed to targets moving between 33 cm, 50 cm, 1 m and 2 m using a haploscopic device incorporating a PlusoptiX SO4 autorefractor. Disparity, blur and looming cues were separately available or minimised in all combinations. Instruction set was minimal. Results: In all cases, vergence and accommodation response slopes (gain) were steeper and closer to 1.0 in the expert group (p = 0.001), with the largest expert/naïve differences for both vergence and accommodation being for near targets (p = 0.012). For vergence, the differences between expert and naïve response slopes increased with increasingly open-loop targets (linear trend p = 0.025). Although we predicted that proximal cues would drive additional response in the experts, the proximity-only cue was the only condition that showed no statistical effect of experience. Conclusions: Expert observers provide more accurate responses to near target demand than closely matched naïve observers. We suggest that attention, practice, voluntary and proprioceptive effects may enhance responses in experienced participants when compared to a more typical general population. Differences between adult reports and the developmental and clinical literature may partially reflect expert/naïve effects, as well as developmental change. If developmental and clinical studies are to be compared to adult normative data, uninstructed naïve adult data should be used.

Developmental programming: Deficits in reproductive hormone dynamics and ovulatory outcomes in prenatal, testosterone-treated sheep

Prenatal testosterone excess leads to neuroendocrine, ovarian, and metabolic disruptions, culminating in reproductive phenotypes mimicking that of women with polycystic ovary syndrome (PCOS). The objective of this study was to determine the consequences of prenatal testosterone treatment on periovulatory hormonal dynamics and ovulatory outcomes. To generate prenatal testosterone-treated females, pregnant sheep were injected intramuscularly (days 30-90 of gestation, term = 147 days) with 100 mg of testosterone-propionate in cottonseed oil semi-weekly. Female offspring born to untreated control females and prenatal testosterone-treated females were then studied during their first two breeding seasons. Sheep were given two injections of prostaglandin F-2alpha 11 days apart, and blood samples were collected at 2-h intervals for 120 h, 10-min intervals for 8 h during the luteal phase (first breeding season only), and daily for an additional 15 days to characterize changes in reproductive hormonal dynamics. During the first breeding season, prenatal testosterone-treated females manifested disruptions in the timing and magnitude of primary gonadotropin surges, luteal defects, and reduced responsiveness to progesterone negative feedback. Disruptions in the periovulatory sequence of events during the second breeding season included: 1) delayed but increased preovulatory estradiol rise, 2) delayed and severely reduced primary gonadotropin surge in prenatal testosterone-treated females having an LH surge, 3) tendency for an amplified secondary FSH surge and a shift in the relative balance of FSH regulatory proteins, and 4) luteal responses that ranged from normal to anovulatory. These outcomes are likely to be of relevance to developmental origin of infertility disorders and suggest that differences in fetal exposure or fetal susceptibility to testosterone may account for the variability in reproductive phenotypes.

Problems in the coupling of eye and hand in the sequential movements of children with developmental coordination disorder

Background: Shifting gaze and attention ahead of the hand is a natural component in the performance of skilled manual actions. Very few studies have examined the precise co-ordination between the eye and hand in children with Developmental Coordination Disorder (DCD). Methods This study directly assessed the maturity of eye-hand co-ordination in children with DCD. A double-step pointing task was used to investigate the coupling of the eye and hand in 7-year-old children with and without DCD. Sequential targets were presented on a computer screen, and eye and hand movements were recorded simultaneously. Results There were no differences between typically developing (TD) and DCD groups when completing fast single-target tasks. There were very few differences in the completion of the first movement in the double-step tasks, but differences did occur during the second sequential movement. One factor appeared to be the propensity for the DCD children to delay their hand movement until some period after the eye had landed on the target. This resulted in a marked increase in eye-hand lead during the second movement, disrupting the close coupling and leading to a slower and less accurate hand movement among children with DCD. Conclusions In contrast to skilled adults, both groups of children preferred to foveate the target prior to initiating a hand movement if time allowed. The TD children, however, were more able to reduce this foveation period and shift towards a feedforward mode of control for hand movements. The children with DCD persevered with a look-then-move strategy, which led to an increase in error. For the group of DCD children in this study, there was no evidence of a problem in speed or accuracy of simple movements, but there was a difficulty in concatenating the sequential shifts of gaze and hand required for the completion of everyday tasks or typical assessment items.

Polymorphisms in dopamine system genes are associated with individual differences in attention in infancy

Knowledge about the functional status of the frontal cortex in infancy is limited. This study investigated the effects of polymorphisms in four dopamine system genes on performance in a task developed to assess such functioning, the Freeze-Frame task, at 9 months of age. Polymorphisms in the catechol-O-methyltransferase (COMT) and the dopamine D4 receptor (DRD4) genes are likely to impact directly on the functioning of the frontal cortex, whereas polymorphisms in the dopamine D2 receptor (DRD2) and dopamine transporter (DAT1) genes might influence frontal cortex functioning indirectly via strong frontostriatal connections. A significant effect of the COMT valine158methionine (Val158Met) polymorphism was found. Infants with the Met/Met genotype were significantly less distractible than infants with the Val/Val genotype in Freeze-Frame trials presenting an engaging central stimulus. In addition, there was an interaction with the DAT1 3′ variable number of tandem repeats polymorphism; the COMT effect was present only in infants who did not have two copies of the DAT1 10-repeat allele. These findings indicate that dopaminergic polymorphisms affect selective aspects of attention as early as infancy and further validate the Freeze-Frame task as a frontal cortex task.

Disrupted white matter in language and motor tracts in developmental stuttering

White matter tractsc onnecting areas involved in speech and motor control were examined using diffusion-tensor imagingingin a sample of peoplewhostutter (n=29) who were heterogeneous with respect to age, sex, handedness and stuttering severity. The goals were to replicate previous findings in developmental stuttering and to extend ourknowledge by evaluating the relationship between white matter differences in people who stutter and factors such as age, sex, handedness and stuttering severity. We replicated previous findings that showed reduced integrity in white matter underlying ventral premotorcortex, cerebral peduncles and posteriorcorpus callosum in people who stutter, relative to controls. Tractography analysis additionally revealed significantly reduced white matter integrity in the arcuate fasciculus bilaterally and the left corticospinal tract and significantly reduced connectivity within theleft corticobulbar tract in people who stutter. Region-of-interest analyses revealed reduced white matter integrity in people whostutter in the three pairs ocerebellar peduncles thatcarry the afferent and efferent fibers of the cerebellum. Within thegroup of people who stutter, the higher the stuttering severity index, the lower the white matter integrity in the leftangular gyrus but the greater the white matter connectivity in theleft corticobulbartract. Also,in people who stutter, handedness and age predicted the integrity of the corticospinal tract and peduncles, respectively. Further studies are needed to determine which of these white matter differences relate to the neural basis of stuttering and which reflect experience-dependent plasticity.

Children and adolescents referred for treatment of anxiety disorders: differences in clinical characteristics

Background: Reports of the clinical characteristics of children and adolescents with anxiety disorders are typically based on community populations or from clinical samples with exclusion criterion applied. Little is known about the clinical characteristics of children and adolescents routinely referred for treatment for anxiety disorders. Furthermore, children and adolescents are typically treated as one homogeneous group although they may differ in ways that are clinically meaningful. Methods: A consecutive series of children (n = 100, aged 6-12 years) and adolescents (n = 100, aged 13-18 years), referred to a routine clinical service, were assessed for anxiety and comorbid disorders, school refusal and parental symptoms of psychopathology. Results: Children were significantly more likely to be diagnosed with separation anxiety disorder than adolescents. Adolescents with a primary anxiety disorder had significantly higher self and clinician rated anxiety symptoms and had more frequent primary diagnoses of social anxiety disorder, diagnoses and symptoms of mood disorders, and irregular school attendance. Limitations: Childhood and adolescence were considered categorically as distinct, developmental periods; in reality changes would be unlikely to occur in such a discrete manner. Conclusions: The finding that children and adolescents with anxiety disorders have distinct clinical characteristics has clear implications for treatment. Simply adapting treatments designed for children to make the materials more ‘adolescent-friendly’ is unlikely to sufficiently meet the needs of adolescents.

Sex/gender differences and autism: setting the scene for future research

Objective The relationship between sex/gender differences and autism has attracted a variety of research ranging from clinical, neurobiological to etiological, stimulated by the male bias in autism prevalence. Findings are complex and do not always relate to each other in a straightforward manner. Distinct but interlinked questions on the relationship between sex/gender differences and autism remain under addressed. To better understand the implications from existing research and to help design future studies, we propose a four-level conceptual framework to clarify the embedded themes. Method We searched PubMed for publications before September 2014 using search terms “‘sex OR gender OR females’ AND autism.” 1,906 citations were screened for relevance, along with publications identified via additional literature reviews, resulting in 329 reports that were reviewed. Results Level 1 “Nosological and diagnostic challenges” concerns the question “How should autism be defined and diagnosed in males and females?” Level 2 “Sex/gender-independent and sex/gender-dependent characteristics” addresses the question “What are the similarities and differences between males and females with autism?” Level 3 “General models of etiology: liability and threshold” asks the question “How is the liability for developing autism linked to sex/gender?” Level 4 “Specific etiological-developmental mechanisms” focuses on the question “What etiological-developmental mechanisms of autism are implicated by sex/gender and/or sexual/gender differentiation?” Conclusions Using this conceptual framework, findings can be more clearly summarized, and the implications of the links between findings from different levels can become clearer. Based on this four-level framework, we suggest future research directions, methodology, and specific topics in sex/gender differences and autism.

Neuroanatomy of individual differences in language in adult males with autism

One potential source of heterogeneity within autism spectrum conditions (ASC) is language development and ability. In 80 high-functioning male adults with ASC, we tested if variations in developmental and current structural language are associated with current neuroanatomy. Groups with and without language delay differed behaviorally in early social reciprocity, current language, but not current autistic features. Language delay was associated with larger total gray matter (GM) volume, smaller relative volume at bilateral insula, ventral basal ganglia, and right superior, middle, and polar temporal structures, and larger relative volume at pons and medulla oblongata in adulthood. Despite this heterogeneity, those with and without language delay showed significant commonality in morphometric features when contrasted with matched neurotypical individuals (n = 57). In ASC, better current language was associated with increased GM volume in bilateral temporal pole, superior temporal regions, dorsolateral fronto-parietal and cerebellar structures, and increased white matter volume in distributed frontal and insular regions. Furthermore, current language–neuroanatomy correlation patterns were similar across subgroups with or without language delay. High-functioning adult males with ASC show neuroanatomical variations associated with both developmental and current language characteristics. This underscores the importance of including both developmental and current language as specifiers for ASC, to help clarify heterogeneity.

Interpretation of ambiguity: differences between children and adolescents with and without an anxiety disorder

Background: Theory and treatment of anxiety disorders in young people are commonly based on the premise that interpretation biases found in anxious adults are also found in children and adolescents. Although there is some evidence that this may be the case, studies have not typically taken age into account, which is surprising given the normative changes in cognition that occur throughout childhood. The aim of the current study was to identify whether associations between anxiety disorder status and interpretation biases differed in children and adolescents. Methods: The responses of children (7-10 years) and adolescents (13-16 years) with and without anxiety disorders (n = 120) were compared on an ambiguous scenarios task. Results: Children and adolescents with an anxiety disorder showed significantly higher levels of threat interpretation and avoidant strategies than non-anxious children and adolescents. However, age significantly moderated the effect of anxiety disorder status on interpretation of ambiguity, in that adolescents with anxiety disorders showed significantly higher levels of threat interpretation and associated negative emotion than non-anxious adolescents, but a similar relationship was not observed among children. Conclusions: The findings suggest that theoretical accounts of interpretation biases in anxiety disorders in children and adolescents should distinguish between different developmental periods. For both ages, treatment that targets behavioral avoidance appears warranted. However, while adolescents are likely to benefit from treatment that addresses interpretation biases, there may be limited benefit for children under the age of ten.