Exploring Associations between Language and Working Memory Abilities in Children with Specific or Combined Impairments in Language and Working Memory

Children with disproportionate deficits in language, known as Specific Language Impairment (SLI), often demonstrate deficits in nonverbal cognitive abilities, such as working memory. Such findings have prompted much debate on the association between language and working memory functioning. The primary aim of this thesis was to examine the connection between working memory and language abilities among children with specific or combined impairments in these domains. Study 1 examined the potential of narrative retell performance to indicate impairment in language or working memory among 17 children with specific or combined impairment in language or working memory as well as 9 controls. Quantitative analysis using logistic regression revealed that language impairment was predicted best by the interaction between mean length of utterance, percent grammatical utterances, and age, whereas working memory impairment was best predicted by the interaction between events recalled and subordinate clauses per utterance. Exploratory qualitative analysis using qualitative descriptors differentiated narratives of children with and without impairment and revealed clusters of descriptors that identified contrasting speaking styles. Study 2 tested domain-specific interventions in language or working memory using a single subject design. Chapter 3 reports the effects of a narrative-based language intervention for 10 children with language impairment with or without working memory impairment. Results showed gains on narrative ability for most participants, and broader linguistic gains for half of the participants. Intervention effects on related domains (i.e., working memory, reading, math) were evident for some participants as well. Chapter 4 reports the effects of a working memory training program for 7 children with working memory impairment with or without language impairment. Results showed training effects on working memory tasks similar to training tasks for all participants. Transfer to language ability was seen for 4 participants, and transfer to reading or math was evident for 3 participants. Responder analyses for Study 2 showed associations between intervention effectiveness and baseline cognitive abilities, age, speaking style, and intervention intensity. Results support the view that working memory and language are separable but closely related cognitive processes. Responder analyses highlight the importance of considering heterogeneity among children with impairments in research and clinical settings

Cognitive and linguistic effects of narrative-based language intervention in children with Developmental Language Disorder

Background and aims: Narrative-based language intervention provides a naturalistic context for targeting overall story structure and specific syntactic goals in children with Developmental Language Disorder (DLD). Given the cognitive demands of narratives, narrative-based language intervention also has the potential to positively impact related abilities such as working memory and academic skills. Methods: Ten children (8–11 years old) with DLD completed 15 sessions of narrative-based language intervention. Results: Results of single subject data revealed gains in language for five participants, four of whom improved on a probe tapping working memory. An additional four participants improved on a working memory probe only. On standardized measures, clinically significant gains were noted for one additional participant on a language measure and one additional participant on a visuospatial working memory. Carry over to reading was noted for three participants and to math for one participant. Across measures, gains in both verbal and visuospatial working memory were common. A responder analysis revealed that improvement in language may be associated with higher verbal short-term memory and receptive language at baseline. Those with working memory impairments were among those showing the fewest improvements across measures. Conclusions: Narrative-based language intervention impacted verbal skills in different ways across individual children with DLD. Implications: Further research is needed to gain an understanding of who benefits most from narrative-based language intervention

Cognitive and Linguistic Effects of Working Memory Training in Children With Corresponding Deficits

Working memory training has been found to result in improvements on tasks similar to those involved in the training (near transfer) but show limited impact on everyday skills such as language or academic abilities (far transfer). Previous research has largely focused on those with a broad range of skills, and examined group level responses. This study uses a single subject design to examine the effect of working memory training on both working memory and related domains in children with working memory impairment. Seven children (8–11 years old) with a working memory impairment completed 20 sessions of computerized working memory intervention. Data revealed near transfer for all participants. Evidence of far transfer to improvements in language, reading, or math was observed for approximately half of the participants on individual measures. Three participants showed convincing but modest training effects across multiple measures. A combination of factors appeared to influence far transfer including age, training intensity, and baseline measures

Analysis of protein-coding genetic variation in 60,706 humans

Large-scale reference data sets of human genetic variation are critical for the medical and functional interpretation of DNA sequence changes. We describe the aggregation and analysis of high-quality exome (protein-coding region) sequence data for 60,706 individuals of diverse ethnicities generated as part of the Exome Aggregation Consortium (ExAC). This catalogue of human genetic diversity contains an average of one variant every eight bases of the exome, and provides direct evidence for the presence of widespread mutational recurrence. We have used this catalogue to calculate objective metrics of pathogenicity for sequence variants, and to identify genes subject to strong selection against various classes of mutation; identifying 3,230 genes with near-complete depletion of truncating variants with 72% having no currently established human disease phenotype. Finally, we demonstrate that these data can be used for the efficient filtering of candidate disease-causing variants, and for the discovery of human “knockout” variants in protein-coding genes

Analysis of shared common genetic risk between amyotrophic lateral sclerosis and epilepsy

Because hyper-excitability has been shown to be a shared pathophysiological mechanism, we used the latest and largest genome-wide studies in amyotrophic lateral sclerosis (n = 36,052) and epilepsy (n = 38,349) to determine genetic overlap between these conditions. First, we showed no significant genetic correlation, also when binned on minor allele frequency. Second, we confirmed the absence of polygenic overlap using genomic risk score analysis. Finally, we did not identify pleiotropic variants in meta-analyses of the 2 diseases. Our findings indicate that amyotrophic lateral sclerosis and epilepsy do not share common genetic risk, showing that hyper-excitability in both disorders has distinct origins

Combined searches for the production of supersymmetric top quark partners in proton-proton collisions at root s=13 TeV

A combination of searches for top squark pair production using proton-proton collision data at a center-of-mass energy of 13 TeV at the CERN LHC, corresponding to an integrated luminosity of 137 fb(-1) collected by the CMS experiment, is presented. Signatures with at least 2 jets and large missing transverse momentum are categorized into events with 0, 1, or 2 leptons. New results for regions of parameter space where the kinematical properties of top squark pair production and top quark pair production are very similar are presented. Depending on themodel, the combined result excludes a top squarkmass up to 1325 GeV for amassless neutralino, and a neutralinomass up to 700 GeV for a top squarkmass of 1150 GeV. Top squarks with masses from 145 to 295 GeV, for neutralino masses from 0 to 100 GeV, with a mass difference between the top squark and the neutralino in a window of 30 GeV around the mass of the top quark, are excluded for the first time with CMS data. The results of theses searches are also interpreted in an alternative signal model of dark matter production via a spin-0 mediator in association with a top quark pair. Upper limits are set on the cross section for mediator particle masses of up to 420 GeV

Search for new particles in events with energetic jets and large missing transverse momentum in proton-proton collisions at root s=13 TeV

A search is presented for new particles produced at the LHC in proton-proton collisions at root s = 13 TeV, using events with energetic jets and large missing transverse momentum. The analysis is based on a data sample corresponding to an integrated luminosity of 101 fb(-1), collected in 2017-2018 with the CMS detector. Machine learning techniques are used to define separate categories for events with narrow jets from initial-state radiation and events with large-radius jets consistent with a hadronic decay of a W or Z boson. A statistical combination is made with an earlier search based on a data sample of 36 fb(-1), collected in 2016. No significant excess of events is observed with respect to the standard model background expectation determined from control samples in data. The results are interpreted in terms of limits on the branching fraction of an invisible decay of the Higgs boson, as well as constraints on simplified models of dark matter, on first-generation scalar leptoquarks decaying to quarks and neutrinos, and on models with large extra dimensions. Several of the new limits, specifically for spin-1 dark matter mediators, pseudoscalar mediators, colored mediators, and leptoquarks, are the most restrictive to date.Peer reviewe

Probing effective field theory operators in the associated production of top quarks with a Z boson in multilepton final states at root s=13 TeV

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Search for lepton-flavor violating decays of the Higgs boson in the mu tau and e tau final states in proton-proton collisions at root s=13 TeV

A search is presented for lepton-flavor violating decays of the Higgs boson to mu t and et. The dataset corresponds to an integrated luminosity of 137 fb(-1) collected at the LHC in proton-proton collisions at a center-of-mass energy of 13 TeV. No significant excess has been found, and the results are interpreted in terms of upper limits on lepton-flavor violating branching fractions of the Higgs boson. The observed (expected) upper limits on the branching fractions are, respectively, B(H -> mu t) e tau) < 0.22(0.16)% at 95% confidence level.Peer reviewe

Search for Physics beyond the Standard Model in Events with Overlapping Photons and Jets

Results are reported from a search for new particles that decay into a photon and two gluons, in events with jets. Novel jet substructure techniques are developed that allow photons to be identified in an environment densely populated with hadrons. The analyzed proton-proton collision data were collected by the CMS experiment at the LHC, in 2016 at root s = 13 TeV, and correspond to an integrated luminosity of 35.9 fb(-1). The spectra of total transverse hadronic energy of candidate events are examined for deviations from the standard model predictions. No statistically significant excess is observed over the expected background. The first cross section limits on new physics processes resulting in such events are set. The results are interpreted as upper limits on the rate of gluino pair production, utilizing a simplified stealth supersymmetry model. The excluded gluino masses extend up to 1.7 TeV, for a neutralino mass of 200 GeV and exceed previous mass constraints set by analyses targeting events with isolated photons.Peer reviewe