Children's Pronoun Interpretation Problems Are Related to Theory of Mind and Inhibition, But Not Working Memory

In several languages, including English and Dutch, children’s acquisition of the interpretation of object pronouns (e.g., him) is delayed compared to that of reflexives (e.g., himself). Various syntactic and pragmatic explanations have been proposed to account for this delay in children’s acquisition of pronoun interpretation. This study aims to provide more insight into this delay by investigating potential cognitive mechanisms underlying this delay. Dutch-speaking children between 6 and 12 years old with autism spectrum disorder (ASD; n = 47), attention-deficit/hyperactivity disorder (ADHD; n = 36) or typical development (TD; n = 38) were tested on their interpretation and production of object pronouns and reflexives and on theory of mind, working memory, and response inhibition. It was found that all three groups of children had difficulty with pronoun interpretation and that their performance on pronoun interpretation was associated with theory of mind and inhibition. These findings support an explanation of object pronoun interpretation in terms of perspective taking, according to which listeners need to consider the speaker’s perspective in order to block coreference between the object pronoun and the subject of the same sentence. Unlike what is predicted by alternative theoretical accounts, performance on pronoun interpretation was not associated with working memory, and the children made virtually no errors in their production of object pronouns. As the difficulties with pronoun interpretation were similar for children with ASD, children with ADHD and typically developing children, this suggests that certain types of perspective taking are unaffected in children with ASD and ADHD

Disorder-specific cognitive profiles in major depressive disorder and generalized anxiety disorder

BACKGROUND: This investigation examines differences in cognitive profiles in subjects with major depressive disorder (MDD) and generalized anxiety disorder (GAD). METHODS: Data were used from subjects with current MDD (n = 655), GAD (n = 107) and comorbid MDD/GAD (n = 266) diagnosis from the Netherlands Study of Depression and Anxiety (NESDA). The Composite Interview Diagnostic Instrument was used to diagnose MDD and GAD. Cognitive profiles were measured using the Leiden Index of Depression Sensitivity, the Anxiety Sensitivity Index, and the Penn State Worry Questionnaire. RESULTS: Results showed that differences in cognitive profiles between single MDD and single GAD subjects were present: scores on hopelessness/suicidality and rumination were significantly higher in MDD than GAD, whereas anxiety sensitivity for physical concerns and pathological worry were higher in GAD than MDD. The cognitive profile of comorbid MDD/GAD showed more extreme depression cognitions compared to single disorders, and a similar anxiety profile compared to single GAD subjects. CONCLUSIONS: Despite the commonalities in cognitive profiles in MDD and GAD, there are differences suggesting that MDD and GAD have disorder-specific cognitive profiles. Findings of this investigation give support for models like the cognitive content-specificity model and the tripartite model and could provide useful handles for treatment focus

Low-dose cyclophosphamide synergizes with dendritic cell-based immunotherapy in antitumor activitys

Clinical immunotherapy trials like dendritic cell-based vaccinations are hampered by the tumor's offensive repertoire that suppresses the incoming effector cells. Regulatory T cells are instrumental in suppressing the function of cytotoxic T cells. We studied the effect of low-dose cyclophosphamide on the suppressive function of regulatory T cells and investigated if the success rate of dendritic cell immunotherapy could be improved. For this, mesothelioma tumor-bearing mice were treated with dendritic cell-based immunotherapy alone or in combination with low-dose of cyclophosphamide.

Measuring emotional support in family networks: Adapting the Family Network Method for individuals with a mild intellectual disability.

Informal supportive networks of individuals with intellectual disability have become increasingly important. The aim of this paper is to describe how the Family Network Method - Intellectual Disability (FNM-ID) offers a way to gather the perspective of people with mild intellectual disability on their family support. The FNM is designed to explore how individuals define their family contexts, and more specifically how they perceive existing supportive relationships in these contexts. By carefully piloting ways of questioning people with mild intellectual disability, systematic adaptations were made to the original FNM. Data obtained by the FNM-ID can be analysed using social network analysis. Thereby, the FNM-ID provides rich, theoretically significant information on emotional support in the family networks of individuals with mild intellectual disability. The FNM-ID is a useful and successfully adapted tool for other researchers and professionals to systematically explore the family support experiences of individuals with mild intellectual disability

Combining gamma with Alpha and Beta power modulation for enhanced cortical mapping in patients with focal epilepsy

About one third of patients with epilepsy have seizures refractory to the medical treatment. Electrical stimulation mapping (ESM) is the gold standard for the identification of "eloquent" areas prior to resection of epileptogenic tissue. However, it is time-consuming and may cause undesired side effects. Broadband gamma activity (55-200 Hz) recorded with extraoperative electrocorticography (ECoG) during cognitive tasks may be an alternative to ESM but until now has not proven of definitive clinical value. Considering their role in cognition, the alpha (8-12 Hz) and beta (15-25 Hz) bands could further improve the identification of eloquent cortex. We compared gamma, alpha and beta activity, and their combinations for the identification of eloquent cortical areas defined by ESM. Ten patients with intractable focal epilepsy (age: 35.9 ± 9.1 years, range: 22-48, 8 females, 9 right handed) participated in a delayed-match-to-sample task, where syllable sounds were compared to visually presented letters. We used a generalized linear model (GLM) approach to find the optimal weighting of each band for predicting ESM-defined categories and estimated the diagnostic ability by calculating the area under the receiver operating characteristic (ROC) curve. Gamma activity increased more in eloquent than in non-eloquent areas, whereas alpha and beta power decreased more in eloquent areas. Diagnostic ability of each band was close to 0.7 for all bands but depended on multiple factors including the time period of the cognitive task, the location of the electrodes and the patient's degree of attention to the stimulus. We show that diagnostic ability can be increased by 3-5% by combining gamma and alpha and by 7.5-11% when gamma and beta were combined. We then show how ECoG power modulation from cognitive testing can be used to map the probability of eloquence in individual patients and how this probability map can be used in clinical settings to optimize ESM planning. We conclude that the combination of gamma and beta power modulation during cognitive testing can contribute to the identification of eloquent areas prior to ESM in patients with refractory focal epilepsy.info:eu-repo/semantics/publishedVersio

Neuronal differentiation of hair-follicle-bulge-derived stem cells co-cultured with mouse cochlear modiolus explants

Stem-cell-based repair of auditory neurons may represent an attractive therapeutic option to restore sensorineural hearing loss. Hair-follicle-bulge-derived stem cells (HFBSCs) are promising candidates for this type of therapy, because they (1) have migratory properties, enabling migration after transplantation, (2) can differentiate into sensory neurons and glial cells, and (3) can easily be harvested in relatively high numbers. However, HFBSCs have never been used for this purpose. We hypothesized that HFBSCs can be used for cell-based repair of the auditory nerve and we have examined their migration and incorporation into cochlear modiolus explants and their subsequent differentiation. Modiolus explants obtained from adult wild-type mice were cultured in the presence of EF1α-copGFP-transduced HFBSCs, constitutively expressing copepod green fluorescent protein (copGFP). Also, modiolus explants without hair cells were co-cultured with DCX-copGFP-transduced HFBSCs, which demonstrate copGFP upon doublecortin expression during neuronal differentiation. Velocity of HFBSC migration towards modiolus explants was calculated, and after two weeks, co-cultures were fixed and processed for immunohistochemical staining. EF1α-copGFP HFBSC migration velocity was fast: 80.5 ± 6.1 μm/h. After arrival in the explant, the cells formed a fascicular pattern and changed their phenotype into an ATOH1-positive neuronal cell type. DCX-copGFP HFBSCs became green-fluorescent after integration into the explants, confirming neuronal differentiation of the cells. These results show that HFBSC-derived neuronal progenitors are migratory and can integrate into cochlear modiolus explants, while adapting their phenotype depending on this micro-environment. Thus, HFBSCs show potential to be employed in cell-based therapies for auditory nerve repair

The phenotype of floating-harbor syndrome:clinical characterization of 52 individuals with mutations in exon 34 of SRCAP

Background\ud Floating-Harbor syndrome (FHS) is a rare condition characterized by short stature, delays in expressive language, and a distinctive facial appearance. Recently, heterozygous truncating mutations in SRCAP were determined to be disease-causing. With the availability of a DNA based confirmatory test, we set forth to define the clinical features of this syndrome.\ud \ud Methods and results\ud Clinical information on fifty-two individuals with SRCAP mutations was collected using standardized questionnaires. Twenty-four males and twenty-eight females were studied with ages ranging from 2 to 52 years. The facial phenotype and expressive language impairments were defining features within the group. Height measurements were typically between minus two and minus four standard deviations, with occipitofrontal circumferences usually within the average range. Thirty-three of the subjects (63%) had at least one major anomaly requiring medical intervention. We did not observe any specific phenotype-genotype correlations.\ud \ud Conclusions\ud This large cohort of individuals with molecularly confirmed FHS has allowed us to better delineate the clinical features of this rare but classic genetic syndrome, thereby facilitating the development of management protocols.The authors would like to thank the families for their cooperation and permission to publish these findings. SdM would like to thank Barto Otten. Funding was provided by the Government of Canada through Genome Canada, the Canadian Institutes of Health Research (CIHR) and the Ontario Genomics Institute (OGI-049), by Genome Québec and Genome British Columbia, and the Manton Center for Orphan Disease Research at Children’s Hospital Boston. KMB is supported by a Clinical Investigatorship Award from the CIHR Institute of Genetics. AD is supported by NIH grant K23HD073351. BBAdV and HGB were financially supported by the AnEUploidy project (LSHG-CT-2006-37627). This work was selected for study by the FORGE Canada Steering Committee, which consists of K. Boycott (University of Ottawa), J. Friedman (University of British Columbia), J. Michaud (University of Montreal), F. Bernier (University of Calgary), M. Brudno (University of Toronto), B. Fernandez (Memorial University), B. Knoppers (McGill University), M. Samuels (Université de Montréal), and S. Scherer (University of Toronto). We thank the Galliera Genetic Bank - “Telethon Genetic Biobank Network” supported by Italian Telethon grants (project no. GTB07001) for providing us with specimens

The phenotype of Floating-Harbor syndrome: Clinical characterization of 52 individuals with mutations in exon 34 of SRCAP

Background: Floating-Harbor syndrome (FHS) is a rare condition characterized by short stature, delays in expressive language, and a distinctive facial appearance. Recently, heterozygous truncating mutations in SRCAP were determined to be disease-causing. With the availability of a DNA based confirmatory test, we set forth to define the clinical features of this syndrome. Methods and results. Clinical information on fifty-two individuals with SRCAP mutations was collected using standardized questionnaires. Twenty-four males and twenty-eight females were studied with ages ranging from

Narrative Production in Children With Autism Spectrum Disorder (ASD) and Children With Attention-Deficit/Hyperactivity Disorder (ADHD):Similarities and Differences

The present study focuses on the similarities and differences in language production between children with autism spectrum disorder (ASD) and children with attention-deficit/hyperactivity disorder (ADHD). In addition, we investigated whether Theory of Mind (ToM), working memory, and response inhibition are associated with language production. Narratives, produced by 106 Dutch-speaking children (36 with ASD, 34 with ADHD, and 36 typically developing) aged 6 to 12 during ADOS assessment, were examined on several linguistic measures: verbal productivity, speech fluency, syntactic complexity, lexical semantics, and discourse pragmatics. Children were tested on ToM, working memory, and response inhibition and parents filled in the Children's Communication Checklist (CCC-2). Gold-standard diagnostic measures (Autism Diagnostic Observation Schema [ADOS], Autism Diagnostic Interview Revised [ADI-R], and the Parent Interview for Child Symptoms [PICS]) were administered to all children to confirm diagnosis. Regarding similarities, both clinical groups showed impairments in narrative performance relative to typically developing children. These were confirmed by the CCC-2. These impairments were not only present on pragmatic measures, such as the inability to produce a narrative in a coherent and cohesive way, but also on syntactic complexity and their production of repetitions. As for differences, children with ADHD but not children with ASD showed problems in their choice of referring expressions and speech fluency. ToM and working memory performance but not response inhibition were associated with many narrative skills, suggesting that these cognitive mechanisms explain some of the impairments in language production. We conclude that children with ASD and children with ADHD manifest multiple and diverse language production problems, which may partly relate to their problems in ToM and working memory. General Scientific Summary This study on narrative production shows that children with autism spectrum disorder (ASD) and children with attention-deficit/hyperactivity disorder (ADHD) manifest multiple and diverse language production problems, which may partly relate to their problems in Theory of Mind and working memory. The results of the present study emphasize the need to investigate language abilities not only of children with ASD, but also of children with ADHD

Mean Scores (Standard Deviations) of age, clinical interviews, WISC-III, PPVT, Theory of Mind task, n-back task, Stop task per Participant Group.

<p>* = <i>p</i> < .05;</p><p>** = <i>p</i> < .01;</p><p>*** = <i>p</i> < .001;</p><p>n.s. = non-significant.</p><p>^a Number of participants may vary per task, since some children did not finish all tasks (see Procedure).</p><p>^b Five children in the ADHD group scored on the ADI-R above the cut-off for ASD (on the basis of Risi et al.’s criteria [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0132408#pone.0132408.ref040" target="_blank">40</a>]).</p><p>^c Two children in the ADHD group scored above the ADOS criteria for ASD.</p><p>^d Seven children in the ASD group scored within our criteria for ADHD on the PICS (above or one point below the cut-off on the PICS).</p><p>Mean Scores (Standard Deviations) of age, clinical interviews, WISC-III, PPVT, Theory of Mind task, n-back task, Stop task per Participant Group.</p