109 research outputs found

    Examining individual differences in language learning: A neurocognitive model of language aptitude

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    A common practice in the cognitive neurosciences is to investigate population-typical phenomena, treating individuals as equal except for a few outliers that are usually discarded from analyses or that disappear on group-level patterns. Only a few studies to date have captured the heterogeneity of language processing across individuals as so-called “individual differences”; fewer have explicitly researched language aptitude, which designates an individual’s ability for acquiring foreign languages. Existing studies show that, relative to average learners, very gifted language learners display different task-related patterns of functional activation and connectivity during linguistic tasks, and structural differences in white and grey matter morphology, and in white matter connectivity. Despite growing interest in language aptitude, there is no recent comprehensive review, nor a theoretical model to date that includes the neural level. To fill this gap, we review neuroscientific research on individual differences in language learning and language aptitude and present a first, preliminary neurocognitive model of language aptitude. We suggest that language aptitude could arise from an advantageous neurocognitive profile, which leads to high intrinsic motivation and proactive engagement in language learning activities. On the neural level, interindividual differences in the morphology of the bilateral auditory cortex constrain individual neural plasticity, as is evident in the speed and efficiency of language learning. We suggest that language learning success is further dependent upon highly efficient auditory-motor connections (speech-motor networks) and the structural characteristics of dorsal and ventral fibre tracts during language learning

    The human 'pitch center' responds differently to iterated noise and Huggins pitch

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    A magnetoencephalographic marker for pitch analysis (the pitch onset response) has been reported for different types of pitch-evoking stimuli, irrespective of whether the acoustic cues for pitch are monaurally or binaurally produced. It is claimed that the pitch onset response reflects a common cortical representation for pitch, putatively in lateral Heschl's gyrus. The result of this functional MRI study sheds doubt on this assertion. We report a direct comparison between iterated ripple noise and Huggins pitch in which we reveal a different pattern of auditory cortical activation associated with each pitch stimulus, even when individual variability in structure-function relations is accounted for. Our results suggest it may be premature to assume that lateral Heschl's gyrus is a universal pitch center

    Short-term plasticity of neuro-auditory processing induced by musical active listening training

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    Although there is strong evidence for the positive effects of musical training on auditory perception, processing, and training-induced neuroplasticity, there is still little knowledge on the auditory and neurophysiological short-term plasticity through listening training. In a sample of 37 adolescents (20 musicians and 17 nonmusicians) that was compared to a control group matched for age, gender, and musical experience, we conducted a 2-week active listening training (AULOS: Active IndividUalized Listening OptimizationS). Using magnetoencephalography and psychoacoustic tests, the short-term plasticity of auditory evoked fields and auditory skills were examined in a pre-post design, adapted to the individual neuro-auditory profiles. We found bilateral, but more pronounced plastic changes in the right auditory cortex. Moreover, we observed synchronization of the auditory evoked P1, N1, and P2 responses and threefold larger amplitudes of the late P2 response, similar to the reported effects of musical long-term training. Auditory skills and thresholds benefited largely from the AULOS training. Remarkably, after training, the mean thresholds improved by 12 dB for bone conduction and by 3–4 dB for air conduction. Thus, our findings indicate a strong positive influence of active listening training on neural auditory processing and perception in adolescence, when the auditory system is still developing

    Modeling Mechanisms of In Vivo Variability in Methotrexate Accumulation and Folate Pathway Inhibition in Acute Lymphoblastic Leukemia Cells

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    Methotrexate (MTX) is widely used for the treatment of childhood acute lymphoblastic leukemia (ALL). The accumulation of MTX and its active metabolites, methotrexate polyglutamates (MTXPG), in ALL cells is an important determinant of its antileukemic effects. We studied 194 of 356 patients enrolled on St. Jude Total XV protocol for newly diagnosed ALL with the goal of characterizing the intracellular pharmacokinetics of MTXPG in leukemia cells; relating these pharmacokinetics to ALL lineage, ploidy and molecular subtype; and using a folate pathway model to simulate optimal treatment strategies. Serial MTX concentrations were measured in plasma and intracellular MTXPG concentrations were measured in circulating leukemia cells. A pharmacokinetic model was developed which accounted for the plasma disposition of MTX along with the transport and metabolism of MTXPG. In addition, a folate pathway model was adapted to simulate the effects of treatment strategies on the inhibition of de novo purine synthesis (DNPS). The intracellular MTXPG pharmacokinetic model parameters differed significantly by lineage, ploidy, and molecular subtypes of ALL. Folylpolyglutamate synthetase (FPGS) activity was higher in B vs T lineage ALL (p<0.005), MTX influx and FPGS activity were higher in hyperdiploid vs non-hyperdiploid ALL (p<0.03), MTX influx and FPGS activity were lower in the t(12;21) (ETV6-RUNX1) subtype (p<0.05), and the ratio of FPGS to Îł-glutamyl hydrolase (GGH) activity was lower in the t(1;19) (TCF3-PBX1) subtype (p<0.03) than other genetic subtypes. In addition, the folate pathway model showed differential inhibition of DNPS relative to MTXPG accumulation, MTX dose, and schedule. This study has provided new insights into the intracellular disposition of MTX in leukemia cells and how it affects treatment efficacy

    3D urban subsurface modelling and visualisation : a review of good practices and techniques to ensure optimal use of geological information in urban planning

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    This report is the result of COST Action TU1206 Working Group 2, Work package 2.3, and focusses on 3D urban subsurface modelling and visualisation. The major aims of this report are: 1) evaluating current techniques and identify good practices / best efforts in 3D geological modelling and visualisation of the urban subsurface, based on case studies, and 2) co-developing (subsurface specialists & model users) requirements for optimal use of 3D geological modelling information in specific planning and policy contexts. Three major topics have been considered: ‱ Constructing and maintaining 3D urban geological models ‱ Modelling man-made ground ‱ Visualising 3D urban subsurface model results To improve the use of subsurface modelling in urban planning in the future, the following challenges have been identified: ‱ The complexity of the urban subsurface, including man-made ground, combined with the level of detail of information asked for in many urban planning issues demand that geologists look beyond their traditional data sources. ‱ Combined 3D property modelling of the small-scale heterogeneity of man-made deposits and natural deposits requires new modelling approaches. ‱ Management of the shallow urban subsurface requires model tools that can be frequently updated to reflect the frequently changing properties and functions of the urban subsurface. ‱ There is a need for dynamic (4D) urban subsurface models that can be used for real-time monitoring and incorporation of time-series data on subsurface properties. ‱ It would be cost-effective to have an actively maintained, scalable geological framework model of a city available that forms a common basis for the various kinds of dedicated models of parts of the city. ‱ To give subsurface information a firm position in urban planning and management, geological information will have to be presented in the right format, and at the right time. It is absolutely necessary to include the subsurface infrastructure and to combine the model with above-ground information

    Sensitivity of the human auditory cortex to acoustic degradation of speech and non-speech sounds

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    The perception of speech is usually an effortless and reliable process even in highly adverse listening conditions. In addition to external sound sources, the intelligibility of speech can be reduced by degradation of the structure of speech signal itself, for example by digital compression of sound. This kind of distortion may be even more detrimental to speech intelligibility than external distortion, given that the auditory system will not be able to utilize sound source-specific acoustic features, such as spatial location, to separate the distortion from the speech signal. The perceptual consequences of acoustic distortions on speech intelligibility have been extensively studied. However, the cortical mechanisms of speech perception in adverse listening conditions are not well known at present, particularly in situations where the speech signal itself is distorted. The aim of this thesis was to investigate the cortical mechanisms underlying speech perception in conditions where speech is less intelligible due to external distortion or as a result of digital compression. In the studies of this thesis, the intelligibility of speech was varied either by digital compression or addition of stochastic noise. Cortical activity related to the speech stimuli was measured using magnetoencephalography (MEG). The results indicated that degradation of speech sounds by digital compression enhanced the evoked responses originating from the auditory cortex, whereas addition of stochastic noise did not modulate the cortical responses. Furthermore, it was shown that if the distortion was presented continuously in the background, the transient activity of auditory cortex was delayed. On the perceptual level, digital compression reduced the comprehensibility of speech more than additive stochastic noise. In addition, it was also demonstrated that prior knowledge of speech content enhanced the intelligibility of distorted speech substantially, and this perceptual change was associated with an increase in cortical activity within several regions adjacent to auditory cortex. In conclusion, the results of this thesis show that the auditory cortex is very sensitive to the acoustic features of the distortion, while at later processing stages, several cortical areas reflect the intelligibility of speech. These findings suggest that the auditory system rapidly adapts to the variability of the auditory environment, and can efficiently utilize previous knowledge of speech content in deciphering acoustically degraded speech signals.Puheen havaitseminen on useimmiten vaivatonta ja luotettavaa myös erittÀin huonoissa kuunteluolosuhteissa. Puheen ymmÀrrettÀvyys voi kuitenkin heikentyÀ ympÀristön hÀiriölÀhteiden lisÀksi myös silloin, kun puhesignaalin rakennetta muutetaan esimerkiksi pakkaamalla digitaalista ÀÀntÀ. TÀllainen hÀiriö voi heikentÀÀ ymmÀrrettÀvyyttÀ jopa ulkoisia hÀiriöitÀ voimakkaammin, koska kuulojÀrjestelmÀ ei pysty hyödyntÀmÀÀn ÀÀnilÀhteen ominaisuuksia, kuten ÀÀnen tulosuuntaa, hÀiriön erottelemisessa puheesta. Akustisten hÀiriöiden vaikutuksia puheen havaitsemiseen on tutkttu laajalti, mutta havaitsemiseen liittyvÀt aivomekanismit tunnetaan edelleen melko puutteelisesti etenkin tilanteissa, joissa itse puhesignaali on laadultaan heikentynyt. TÀmÀn vÀitöskirjan tavoitteena oli tutkia puheen havaitsemisen aivomekanismeja tilanteissa, joissa puhesignaali on vaikeammin ymmÀrrettÀvissÀ joko ulkoisen ÀÀnilÀhteen tai digitaalisen pakkauksen vuoksi. VÀitöskirjan neljÀssÀ osatutkimuksessa lyhyiden puheÀÀnien ja jatkuvan puheen ymmÀrrettÀvyyttÀ muokattiin joko digitaalisen pakkauksen kautta tai lisÀÀmÀllÀ puhesignaaliin satunnaiskohinaa. PuheÀrsykkeisiin liittyvÀÀ aivotoimintaa tutkittiin magnetoenkefalografia-mittauksilla. Tutkimuksissa havaittiin, ettÀ kuuloaivokuorella syntyneet herÀtevasteet voimistuivat, kun puheÀÀntÀ pakattiin digitaalisesti. Sen sijaan puheÀÀniin lisÀtty satunnaiskohina ei vaikuttanut herÀtevasteisiin. Edelleen, mikÀli puheÀÀnien taustalla esitettiin jatkuvaa hÀiriötÀ, kuuloaivokuoren aktivoituminen viivÀstyi hÀiriön intensiteetin kasvaessa. Kuuntelukokeissa havaittiin, ettÀ digitaalinen pakkaus heikentÀÀ puheÀÀnien ymmÀrrettÀvyyttÀ voimakkaammin kuin satunnaiskohina. LisÀksi osoitettiin, ettÀ aiempi tieto puheen sisÀllöstÀ paransi merkittÀvÀsti hÀiriöisen puheen ymmÀrrettÀvyyttÀ, mikÀ heijastui aivotoimintaan kuuloaivokuoren viereisillÀ aivoalueilla siten, ettÀ ymmÀrrettÀvÀ puhe aiheutti suuremman aktivaation kuin heikosti ymmÀrrettÀvÀ puhe. VÀitöskirjan tulokset osoittavat, ettÀ kuuloaivokuori on erittÀin herkkÀ puheÀÀnien akustisille hÀiriöille, ja myöhemmissÀ prosessoinnin vaiheissa useat kuuloaivokuoren viereiset aivoalueet heijastavat puheen ymmÀrrettÀvyyttÀ. Tulosten mukaan voi olettaa, ettÀ kuulojÀrjestelmÀ mukautuu nopeasti ÀÀniympÀristön vaihteluihin muun muassa hyödyntÀmÀllÀ aiempaa tietoa puheen sisÀllöstÀ tulkitessaan hÀiriöistÀ puhesignaalia

    Insights on the Neuromagnetic Representation of Temporal Asymmetry in Human Auditory Cortex.

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    Communication sounds are typically asymmetric in time and human listeners are highly sensitive to this short-term temporal asymmetry. Nevertheless, causal neurophysiological correlates of auditory perceptual asymmetry remain largely elusive to our current analyses and models. Auditory modelling and animal electrophysiological recordings suggest that perceptual asymmetry results from the presence of multiple time scales of temporal integration, central to the auditory periphery. To test this hypothesis we recorded auditory evoked fields (AEF) elicited by asymmetric sounds in humans. We found a strong correlation between perceived tonal salience of ramped and damped sinusoids and the AEFs, as quantified by the amplitude of the N100m dynamics. The N100m amplitude increased with stimulus half-life time, showing a maximum difference between the ramped and damped stimulus for a modulation half-life time of 4 ms which is greatly reduced at 0.5 ms and 32 ms. This behaviour of the N100m closely parallels psychophysical data in a manner that: i) longer half-life times are associated with a stronger tonal percept, and ii) perceptual differences between damped and ramped are maximal at 4 ms half-life time. Interestingly, differences in evoked fields were significantly stronger in the right hemisphere, indicating some degree of hemispheric specialisation. Furthermore, the N100m magnitude was successfully explained by a pitch perception model using multiple scales of temporal integration of auditory nerve activity patterns. This striking correlation between AEFs, perception, and model predictions suggests that the physiological mechanisms involved in the processing of pitch evoked by temporal asymmetric sounds are reflected in the N100m

    Auditory temporal processing in healthy aging: a magnetoencephalographic study

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    <p>Abstract</p> <p>Background</p> <p>Impaired speech perception is one of the major sequelae of aging. In addition to peripheral hearing loss, central deficits of auditory processing are supposed to contribute to the deterioration of speech perception in older individuals. To test the hypothesis that auditory temporal processing is compromised in aging, auditory evoked magnetic fields were recorded during stimulation with sequences of 4 rapidly recurring speech sounds in 28 healthy individuals aged 20 – 78 years.</p> <p>Results</p> <p>The decrement of the N1m amplitude during rapid auditory stimulation was not significantly different between older and younger adults. The amplitudes of the middle-latency P1m wave and of the long-latency N1m, however, were significantly larger in older than in younger participants.</p> <p>Conclusion</p> <p>The results of the present study do not provide evidence for the hypothesis that auditory temporal processing, as measured by the decrement (short-term habituation) of the major auditory evoked component, the N1m wave, is impaired in aging. The differences between these magnetoencephalographic findings and previously published behavioral data might be explained by differences in the experimental setting between the present study and previous behavioral studies, in terms of speech rate, attention, and masking noise. Significantly larger amplitudes of the P1m and N1m waves suggest that the cortical processing of individual sounds differs between younger and older individuals. This result adds to the growing evidence that brain functions, such as sensory processing, motor control and cognitive processing, can change during healthy aging, presumably due to experience-dependent neuroplastic mechanisms.</p

    The search for the 'next' euphoric non-fentanil novel synthetic opioids on the illicit drugs market: current status and horizon scanning

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    Purpose: A detailed review on the chemistry and pharmacology of non-fentanil novel synthetic opioid receptor agonists, particularly N-substituted benzamides and acetamides (known colloquially as U-drugs) and 4-aminocyclohexanols, developed at the Upjohn Company in the 1970s and 1980s is presentedMethod: Peer-reviewed literature, patents, professional literature, data from international early warning systems and drug user fora discussion threads have been used to track their emergence as substances of abuse.Results: In terms of impact on drug markets, prevalence and harm, the most significant compound of this class to date has been U-47700 (trans-3,4-dichloro-N-[2-(dimethylamino)cyclohexyl]-N-methylbenzamide), reported by users to give short-lasting euphoric effects and a desire to re-dose. Since U-47700 was internationally controlled in 2017, a range of related compounds with similar chemical structures, adapted from the original patented compounds, have appeared on the illicit drugs market. Interest in a structurally unrelated opioid developed by the Upjohn Company and now known as BDPC/bromadol appears to be increasing and should be closely monitored.Conclusions: International early warning systems are an essential part of tracking emerging psychoactive substances and allow responsive action to be taken to facilitate the gathering of relevant data for detailed risk assessments. Pre-emptive research on the most likely compounds to emerge next, so providing drug metabolism and pharmacokinetic data to ensure that new substances are detected early in toxicological samples is recommended. As these compounds are chiral compounds and stereochemistry has a large effect on their potency, it is recommended that detection methods consider the determination of configuration
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