Development of cognitive flexibility in late adolescence: investigating behavioral performance and neural activation in a task-switching paradigm

Successful cognitive control relies on both the ability to instantiate higher-order cognitive functions and the ability to flexibly switch between them in service of changing task demands, i.e. cognitive flexibility. While a wealth of important work on the development of cognitive control in adolescence has focused on the development of executive functions, there has been a relative lack of work on the development of cognitive flexibility. Here we address this limitation by investigating the development of cognitive flexibility using a task-switching paradigm in a large sample of adolescents and young adults (ages 14-32, n = 82). For a subset of subjects that had usable fMRI data (n=56), we assessed task-switching performance and analyzed fMRI data collected in-scanner while they performed the task-switching paradigm. We observed that successful task-switching was associated with widespread activation of frontoparietal and visual processing brain areas. A component of this larger task-switching system, the left inferior parietal cortex, showed age-related reductions in neural activation specifically during task-switching into trials that taxed inhibitory control. These neural findings occurred in parallel with age-related improvements in successful task-switching performance in the same context. This pattern of results suggests that task-switching into the most cognitively demanding contexts follows a protracted development that extends through adolescence and young adulthood. Further, the age-related reduction in parietal cortex activation suggests that adolescents have greater reliance on the frontoparietal system, which has been implicated in transient aspects of cognitive control, to achieve adult-like performance. Taken together, our results suggest that a key aspect of cognitive maturation in adulthood is the ability to flexibly switch between cognitive tasks with limited cost to performance and a decreasing reliance on frontoparietal regions across adolescence

In Between Breaths: Memories, Stories, and Otherwise Design Histories

Decolonial approaches foreground the necessity for design historians to rethink their methodologies and terms of debate to recognize the impact of colonial legacies. Only then is it possible to make changes toward social and cognitive justice. This piece explores new models for working collectively with history and memory across oral registers to include the colloquial and moments of pause, of taking breath. In mid-2020, four design historians teamed up to develop experimental, multimedia methods of working to explore new critical design histories. By using “otherwise” methods to look, listen, and read closely, this piece foregrounds the making of space for new interpretations of thinking and writing. The tensions between memories, stories, and histories are interpreted and challenged using concepts such as breath, voice, palimpsest, circle and rhythm. Exploring translation, opacity, embodiment, positionality, and nonlinearity emerged as crucial to questioning the terms under which design history can be transformed

Low Cost MR Compatible Haptic Stimulation with Application to fMRI Neurofeedback

The most common feedback displays in the fMRI environment are visual, e.g., in which participants try to increase or decrease the level of a thermometer. However, haptic feedback is increasingly valued in computer interaction tasks, particularly for real-time fMRI feedback. fMRI-neurofeedback is a clinical intervention that has not yet taken advantage of this trend. Here we describe a low-cost, user-friendly, MR-compatible system that can provide graded haptic vibrotactile stimulation in an initial application to fMRI neurofeedback. We also present a feasibility demonstration showing that we could successfully set up the system and obtain data in the context of a neurofeedback paradigm. We conclude that vibrotactile stimulation using this low-cost system is a viable method of feedback presentation, and encourage neurofeedback researchers to incorporate this type of feedback into their studies

Identification of Glycochenodeoxycholate 3-O-glucuronide and Glycodeoxycholate 3-O-glucuronide as Highly Sensitive and Specific OATP1B1 Biomarkers

The aim of this study was to investigate the sensitivity and specificity of endogenous glycochenodeoxycholate and glycodeoxycholate 3-O-glucuronides (GCDCA-3G and GDCA-3G) as substrates for organic anion transporting polypeptide 1B1 (OATP1B1) in humans. We measured fasting levels of plasma GCDCA-3G and GDCA-3G using liquid chromatography-tandem mass spectrometry in 356 healthy volunteers. The mean plasma levels of both compounds were similar to 50% lower in women than in men (P = 2.25 x 10(-18) and P = 4.73 x 10(-9)). In a microarray-based genome-wide association study, theSLCO1B1rs4149056 (c.521T>C, p.Val174Ala) variation showed the strongest association with the plasma GCDCA-3G (P = 3.09 x 10(-30)) and GDCA-3G (P = 1.60 x 10(-17)) concentrations. The mean plasma concentration of GCDCA-3G was 9.2-fold (P = 8.77 x 10(-31)) and that of GDCA-3G was 6.4-fold (P = 2.45x10(-13)) higher in individuals with theSLCO1B1c.521C/C genotype than in those with the c.521T/T genotype. No other variants showed independent genome-wide significant associations with GCDCA-3G or GDCA-3G. GCDCA-3G was highly efficacious in detecting theSLCO1B1c.521C/C genotype with an area under the receiver operating characteristic curve of 0.996 (P <0.0001). The sensitivity (98-99%) and specificity (100%) peaked at a cutoff value of 180 ng/mL for men and 90 ng/mL for women. In a haplotype-based analysis,SLCO1B1*5and*15were associated with reduced, andSLCO1B1*1B, *14, and *35with increased OATP1B1 function.In vitro, both GCDCA-3G and GDCA-3G showed at least 6 times higher uptake by OATP1B1 than OATP1B3 or OATP2B1. These data indicate that the hepatic uptake of GCDCA-3G and GDCA-3G is predominantly mediated by OATP1B1. GCDCA-3G, in particular, is a highly sensitive and specific OATP1B1 biomarker in humans.Peer reviewe

Reduction of hRNase H2 activity in Aicardi-Goutières syndrome cells leads to replication stress and genome instability

Aicardi-Gouti\ue8res syndrome (AGS) is an inflammatory encephalopathy caused by defective nucleic acids metabolism. Over 50% of AGS mutations affect RNase H2 the only enzyme able to remove single ribonucleotidemonophosphates (rNMPs) embedded in DNA. Ribonucleotide triphosphates (rNTPs) are incorporated into genomic DNA with relatively high frequency during normal replication making DNA more susceptible to strand breakage and mutations. Here we demonstrate that human cells depleted of RNase H2 show impaired cell cycle progression associated with chronic activation of post-replication repair (PRR) and genome instability. We identify a similar phenotype in cells derived from AGS patients, which indeed accumulate rNMPs in genomic DNA and exhibit markers of constitutive PRR and checkpoint activation. Our data indicate that in human cells RNase H2 plays a crucial role in correcting rNMPs misincorporation, preventing DNA damage. Such protective function is compromised in AGS patients and may be linked to unscheduled immune responses. These findings may be relevant to shed further light on the mechanisms involved in AGS pathogenesis

Shadow monochromatic backlighting: Large-field high resolution X-ray shadowgraphy with improved spectral tunability

The shadow monochromatic backlighting (SMB) scheme, a modification of the well-known soft X-ray monochromatic backlighting scheme, is proposed. It is based on a spherical crystal as the dispersive element and extends the traditional scheme by allowing one to work with a wide range of Bragg angles and thus in a wide spectral range. The advantages of the new scheme are demonstrated experimentally and supported numerically by ray-tracing simulations. In the experiments, the X-ray backlighter source is a laser-produced plasma, created by the interaction of an ultrashort pulse, Ti:Sapphire laser (120 fs, 3–5 mJ, 1016 W/cm2 on target) or a short wavelength XeCl laser (10 ns, 1–2 J, 1013 W/cm2 on target) with various solid targets (Dy, Ni + Cr, BaF2). In both experiments, the X-ray sources are well localized spatially (∼20 μm) and are spectrally tunable in a relatively wide wavelength range (λ = 8–15 Å). High quality monochromatic (δλ/λ ∼ 10−5–10−3) images with high spatial resolution (up to ∼4 μm) over a large field of view (a few square millimeters) were obtained. Utilization of spherically bent crystals to obtain high-resolution, large field, monochromatic images in a wide range of Bragg angles (35° < Θ < 90°) is demonstrated for the first time

ACCURATE WAVELENGTH MEASUREMENTS AND MODELING OF Fe XV TO Fe XIX SPECTRA RECORDED IN HIGH-DENSITY PLASMAS BETWEEN 13.5 AND 17 A

Iron spectra have been recorded from plasmas created at three different laser plasma facilities: the Tor Vergata University laser in Rome (Italy), the Hercules laser at ENEA in Frascati (Italy), and the Compact Multipulse Terawatt (COMET) laser at LLNL in California (USA). The measurements provide a means of identifying dielectronic satellite lines from Fe XVI and Fe XV in the vicinity of the strong 2p → 3d transitions of Fe XVII. About 80 Δn ≥ 1 lines of Fe XV (Mg-like) to Fe XIX (O-like) were recorded between 13.8 and 17.1 A with a high spectral resolution (λ/Δλ ≈ 4000); about 30 of these lines are from Fe XVI and Fe XV. The laser-produced plasmas had electron temperatures between 100 and 500 eV and electron densities between 1020 and 1022 cm-3. The Hebrew University Lawrence Livermore Atomic Code (HULLAC) was used to calculate the atomic structure and atomic rates for Fe XV-XIX. HULLAC was used to calculate synthetic line intensities at Te = 200 eV and ne = 1021 cm-3 for three different conditions to illustrate the role of opacity: optically thin plasmas with no excitation-autoionization/dielectronic recombination (EA/DR) contributions to the line intensities, optically thin plasmas that included EA/DR contributions to the line intensities, and optically thick plasmas (optical depth ≈200 μm) that included EA/DR contributions to the line intensities. The optically thick simulation best reproduced the recorded spectrum from the Hercules laser. However, some discrepancies between the modeling and the recorded spectra remain

VID22 counteracts G-quadruplex-induced genome instability

Genome instability is a condition characterized by the accumulation of genetic alterations and is a hallmark of cancer cells. To uncover new genes and cellular pathways affecting endogenous DNA damage and genome integrity, we exploited a Synthetic Genetic Array (SGA)-based screen in yeast. Among the positive genes, we identified VID22, reported to be involved in DNA double-strand break repair. vid22Δ cells exhibit increased levels of endogenous DNA damage, chronic DNA damage response activation and accumulate DNA aberrations in sequences displaying high probabilities of forming G-quadruplexes (G4-DNA). If not resolved, these DNA secondary structures can block the progression of both DNA and RNA polymerases and correlate with chromosome fragile sites. Vid22 binds to and protects DNA at G4-containing regions both in vitro and in vivo. Loss of VID22 causes an increase in gross chromosomal rearrangement (GCR) events dependent on G-quadruplex forming sequences. Moreover, the absence of Vid22 causes defects in the correct maintenance of G4-DNA rich elements, such as telomeres and mtDNA, and hypersensitivity to the G4-stabilizing ligand TMPyP4. We thus propose that Vid22 is directly involved in genome integrity maintenance as a novel regulator of G4 metabolism.Associazione Italiana per la Ricerca sul Cancro (AIRC) [15631, 21806 to M.M.F.]; MIUR [PRIN 2015-2015SJLMB9; PRIN 2017-2017KSZZJW to M.M.F.]; Telethon [GGP15227 to M.M.F.]; F.L. was supported by the University of Milano: ‘‘Piano di Sviluppo dell’Ateneo per la Ricerca. Linea B: Supporto per i Giovani Ricercatori’’; M.C.B. was supported by Fondazione Veronesi; Research at the laboratory of A.A. was funded by the Spanish Ministry of Economy and Competitiveness [BFU2016-75058-P]; B.G.G. was funded by the Spanish Association Against Cancer; MIUR [PRIN2017-2017Z55KC to T.B.]; M.C., D.S.H. are supported by MIUR [PRIN 2017] and CNRbiomics [PIR01_00017]; H2020 Projects ELIXIR-EXCELERATE, EOSC-Life, EOSC-Pillar and Elixir-IIB; G.W.B. was supported by the Canadian Institutes of Health Research[FDN-159913]. Funding for open access charge: Associazione Italiana per la Ricerca sul Cancro (AIRC) [21806]

X-ray radiation from ions with K-shell vacancies

Abstract New types of space resolved X-ray spectra produced in light matter experiments with high intensity lasers have been investigated experimentally and theoretically. This type of spectra is characterised by the disappearance of distinct resonance line emission and the appearance of very broad emission structures due to the dielectronic satellite transitions associated to the resonance lines. Atomic data calculations have shown, that rather exotic states with K-shell vacancies are involved. For quantitative spectra interpretation we developed a model for dielectronic satellite accumulation (DSA-model) in cold dense optically thick plasmas which are tested by rigorous comparison with space resolved spectra from ns-lasers. In experiments with laser intensities up to 10 19 W/cm 2 focused into nitrogen gas targets, hollow ion configurations are observed by means of soft X-ray spectroscopy. It is shown that transitions in hollow ions can be used for plasma diagnostic. The determination of the electron temperature in the long lasting recombining regime is demonstrated. In Light-matter interaction experiments with extremely high contrast (up to 10 10 ) short pulse (400 fs) lasers electron densities of n e ≈3×10 23 cm −3 at temperatures between kT e =200–300 eV have been determined by means of spectral simulations developed previously for ns-laser produced plasmas. Expansion velocities are determined analysing asymmetric optically thick line emission. Further, the results are checked by observing the spectral windows involving the region about the He α -line and the region from the He β -line to the He-like continuum. Finally, plasmas of solid density are characteristic in experiments with heavy ion beams heating massive targets. We report the first spectroscopic investigations in plasmas of this type with results on solid neon heated by Ar-ions. A spectroscopic method for the determination of the electron temperature in extreme optically thick plasmas is developed

Azimuthal anisotropy of charged jet production in root s(NN)=2.76 TeV Pb-Pb collisions

We present measurements of the azimuthal dependence of charged jet production in central and semi-central root s(NN) = 2.76 TeV Pb-Pb collisions with respect to the second harmonic event plane, quantified as nu(ch)(2) (jet). Jet finding is performed employing the anti-k(T) algorithm with a resolution parameter R = 0.2 using charged tracks from the ALICE tracking system. The contribution of the azimuthal anisotropy of the underlying event is taken into account event-by-event. The remaining (statistical) region-to-region fluctuations are removed on an ensemble basis by unfolding the jet spectra for different event plane orientations independently. Significant non-zero nu(ch)(2) (jet) is observed in semi-central collisions (30-50% centrality) for 20 <p(T)(ch) (jet) <90 GeV/c. The azimuthal dependence of the charged jet production is similar to the dependence observed for jets comprising both charged and neutral fragments, and compatible with measurements of the nu(2) of single charged particles at high p(T). Good agreement between the data and predictions from JEWEL, an event generator simulating parton shower evolution in the presence of a dense QCD medium, is found in semi-central collisions. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe