Structural connectivity of the brain in autism spectrum disorder

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterised by social communication deficits and restricted and repetitive interests. It mostly affects males, and has a range of severities and presentations. The causes of ASD are, as yet, unknown, though research indicates that a combination of genetic and environmental factors contribute to aberrant brain structure and function. The structure of the brain can be non-invasively assessed in vivo using magnetic resonance imaging (MRI). The MRI method diffusion tensor imaging (DTI) can be used to reconstruct the brain’s white matter tracts and quantify their microstructural health. The aim of this thesis is to investigate white matter microstructure in ASD, and comprises of four studies: an investigation of the association between white matter microstructure and the spectrum of ASD traits; a study of amygdala connections and their association with ASD symptomatology; a graph theory approach to investigate the structural networks of the brain; a study of sex-based differences in brain structure in ASD, and unaffected siblings of probands. White matter microstructure was associated with ASD traits across a spectrum that incorporated healthy controls through to those with clinically-diagnosed autism. Associations between the microstructure of amygdala–cortical connections and ASD symptoms were dependent upon the brain region and ASD trait of interest. The ASD structural network was similar to that of controls, which indicates that the macromolecular arrangement of the ASD brain is relatively conserved. There were some sex-based differences in white matter microstructure in ASD, though fewer than anticipated. In conclusion, DTI techniques provide evidence that brain microstructure is compromised in ASD, and that the severity of the structural deficits is correlated with symptom severity in a specific fashion. Brain topology is relatively conserved, indicating that ASD arises from deficits in the quality of brain connections, rather than their overall arrangement

Structural connectivity of the amygdala in young adults with autism spectrum disorder

Autism spectrum disorder (ASD) is characterized by impairments in social cognition, a function associated with the amygdala. Subdivisions of the amygdala have been identified which show specificity of structure, connectivity, and function. Little is known about amygdala connectivity in ASD. The aim of this study was to investigate the microstructural properties of amygdala-cortical connections and their association with ASD behaviours, and whether connectivity of specific amygdala subregions is associated with particular ASD traits. The brains of 51 high-functioning young adults (25 with ASD; 26 controls) were scanned using MRI. Amygdala volume was measured, and amygdala-cortical connectivity estimated using probabilistic tractography. An iterative 'winner takes all' algorithm was used to parcellate the amygdala based on its primary cortical connections. Measures of amygdala connectivity were correlated with clinical scores. In comparison with controls, amygdala volume was greater in ASD (F(1,94) = 4.19; p = .04). In white matter (WM) tracts connecting the right amygdala to the right cortex, ASD subjects showed increased mean diffusivity (t = 2.35; p = .05), which correlated with the severity of emotion recognition deficits (rho = -0.53; p = .01). Following amygdala parcellation, in ASD subjects reduced fractional anisotropy in WM connecting the left amygdala to the temporal cortex was associated with with greater attention switching impairment (rho = -0.61; p = .02). This study demonstrates that both amygdala volume and the microstructure of connections between the amygdala and the cortex are altered in ASD. Findings indicate that the microstructure of right amygdala WM tracts are associated with overall ASD severity, but that investigation of amygdala subregions can identify more specific associations

White matter microstructure correlates with autism trait severity in a combined clinical-control sample of high-functioning adults

Diffusion tensor imaging (DTI) studies have demonstrated white matter (WM) abnormalities in tracts involved in emotion processing in autism spectrum disorder (ASD), but little is known regarding the nature and distribution of WM anomalies in relation to ASD trait severity in adults. Increasing evidence suggests that ASD occurs at the extreme of a distribution of social abilities. We aimed to examine WM microstructure as a potential marker for ASD symptom severity in a combined clinical-neurotypical population. SIENAX was used to estimate whole brain volume. Tract-based spatial statistics (TBSS) was used to provide a voxel-wise comparison of WM microstructure in 50 high-functioning young adults: 25 ASD and 25 neurotypical. The severity of ASD traits was measured by autism quotient (AQ); we examined regressions between DTI markers of WM microstructure and ASD trait severity. Cognitive abilities, measured by intelligence quotient, were well-matched between the groups and were controlled in all analyses. There were no significant group differences in whole brain volume. TBSS showed widespread regions of significantly reduced fractional anisotropy (FA) and increased mean diffusivity (MD) and radial diffusivity (RD) in ASD compared with controls. Linear regression analyses in the combined sample showed that average whole WM skeleton FA was negatively influenced by AQ (p = 0.004), whilst MD and RD were positively related to AQ (p = 0.002; p = 0.001). Regression slopes were similar within both groups and strongest for AQ social, communication and attention switching scores. In conclusion, similar regression characteristics were found between WM microstructure and ASD trait severity in a combined sample of ASD and neurotypical adults. WM anomalies were relatively more severe in the clinically diagnosed sample. Both findings suggest that there is a dimensional relationship between WM microstructure and severity of ASD traits from neurotypical subjects through to clinical ASD, with reduced coherence of WM associated with greater ASD symptoms. General cognitive abilities were independent of the relationship between WM indices and ASD traits

Measurement of the cross-section of high transverse momentum vector bosons reconstructed as single jets and studies of jet substructure in pp collisions at √s = 7 TeV with the ATLAS detector

This paper presents a measurement of the cross-section for high transverse momentum W and Z bosons produced in pp collisions and decaying to all-hadronic final states. The data used in the analysis were recorded by the ATLAS detector at the CERN Large Hadron Collider at a centre-of-mass energy of √s = 7 TeV;{\rm Te}{\rm V}$and correspond to an integrated luminosity of$4.6\;{\rm f}{{{\rm b}}^{-1}}$. The measurement is performed by reconstructing the boosted W or Z bosons in single jets. The reconstructed jet mass is used to identify the W and Z bosons, and a jet substructure method based on energy cluster information in the jet centre-of-mass frame is used to suppress the large multi-jet background. The cross-section for events with a hadronically decaying W or Z boson, with transverse momentum${{p}_{{\rm T}}}\gt 320\;{\rm Ge}{\rm V}$and pseudorapidity$|\eta |\lt 1.9$, is measured to be${{\sigma }_{W+Z}}=8.5\pm 1.7$ pb and is compared to next-to-leading-order calculations. The selected events are further used to study jet grooming techniques

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

Search for the neutral Higgs bosons of the minimal supersymmetric standard model in pp collisions at root s=7 TeV with the ATLAS detector

A search for neutral Higgs bosons of the Minimal Supersymmetric Standard Model (MSSM) is reported. The analysis is based on a sample of proton-proton collisions at a centre-of-mass energy of 7TeV recorded with the ATLAS detector at the Large Hadron Collider. The data were recorded in 2011 and correspond to an integrated luminosity of 4.7 fb-1 to 4.8 fb-1. Higgs boson decays into oppositely-charged muon or τ lepton pairs are considered for final states requiring either the presence or absence of b-jets. No statistically significant excess over the expected background is observed and exclusion limits at the 95% confidence level are derived. The exclusion limits are for the production cross-section of a generic neutral Higgs boson, φ, as a function of the Higgs boson mass and for h/A/H production in the MSSM as a function of the parameters mA and tan β in the mhmax scenario for mA in the range of 90GeV to 500 GeV. Copyright CERN

Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at s√=8 TeV with the ATLAS detector

The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton–proton collision data at √s = 8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t˜→tχ˜01 or t˜→ bχ˜±1 →bW(∗)χ˜01 , where χ˜01 (χ˜±1 ) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t˜ → tχ˜01 . For a branching fraction of 100%, top squark masses in the range 270–645 GeV are excluded for χ˜01 masses below 30 GeV. For a branching fraction of 50% to either t˜ → tχ˜01 or t˜ → bχ˜±1 , and assuming the χ˜±1 mass to be twice the χ˜01 mass, top squark masses in the range 250–550 GeV are excluded for χ˜01 masses below 60 GeV

Search for pair-produced long-lived neutral particles decaying to jets in the ATLAS hadronic calorimeter in ppcollisions at √s=8TeV

The ATLAS detector at the Large Hadron Collider at CERN is used to search for the decay of a scalar boson to a pair of long-lived particles, neutral under the Standard Model gauge group, in 20.3fb−1of data collected in proton–proton collisions at √s=8TeV. This search is sensitive to long-lived particles that decay to Standard Model particles producing jets at the outer edge of the ATLAS electromagnetic calorimeter or inside the hadronic calorimeter. No significant excess of events is observed. Limits are reported on the product of the scalar boson production cross section times branching ratio into long-lived neutral particles as a function of the proper lifetime of the particles. Limits are reported for boson masses from 100 GeVto 900 GeV, and a long-lived neutral particle mass from 10 GeVto 150 GeV