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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Taylor, JSH; Davis, Matthew H; Rastle, Kathleen;

    Reading involves transforming arbitrary visual symbols into sounds and meanings. This study interrogated the neural representations in ventral occipitotemporal cortex (vOT) that support this transformation process. Twenty-four adults learned to read 2 sets of 24 novel words that shared phonemes and semantic categories but were written in different artificial orthographies. Following 2 wk of training, participants read the trained words while neural activity was measured with functional MRI. Representational similarity analysis on item pairs from the same orthography revealed that right vOT and posterior regions of left vOT were sensitive to basic visual similarity. Left vOT encoded letter identity and representations became more invariant to position along a posterior-to-anterior hierarchy. Item pairs that shared sounds or meanings, but were written in different orthographies with no letters in common, evoked similar neural patterns in anterior left vOT. These results reveal a hierarchical, posterior-to-anterior gradient in vOT, in which representations of letters become increasingly invariant to position and are transformed to convey spoken language information. Significance Learning to read is the most important milestone in a child’s education. However, controversies remain regarding how readers’ brains transform written words into sounds and meanings. We address these by combining artificial language learning with neuroimaging to reveal how the brain represents written words. Participants learned to read new words written in 2 different alphabets. Following 2 wk of training, we found a hierarchy of brain areas that support reading. Letter position is represented more flexibly from lower to higher visual regions. Furthermore, higher visual regions encode information about word sounds and meanings. These findings advance our understanding of how the brain comprehends language from arbitrary visual symbols.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Apollo
    Article . 2020
    License: CC BY
    Data sources: Datacite
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Apollo
    Other literature type . 2019
    License: CC BY
    Data sources: Apollo
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Proceedings of the National Academy of Sciences
    Article . 2019 . Peer-reviewed
    License: CC BY
    Data sources: Crossref
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
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      Apollo
      Article . 2020
      License: CC BY
      Data sources: Datacite
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      Apollo
      Other literature type . 2019
      License: CC BY
      Data sources: Apollo
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      Proceedings of the National Academy of Sciences
      Article . 2019 . Peer-reviewed
      License: CC BY
      Data sources: Crossref
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Michael E. Rule; David Schnoerr; Matthias H. Hennig; Guido Sanguinetti;

    Large-scale neural recording methods now allow us to observe large populations of identified single neurons simultaneously, opening a window into neural population dynamics in living organisms. However, distilling such large-scale recordings to build theories of emergent collective dynamics remains a fundamental statistical challenge. The neural field models of Wilson, Cowan, and colleagues remain the mainstay of mathematical population modeling owing to their interpretable, mechanistic parameters and amenability to mathematical analysis. Inspired by recent advances in biochemical modeling, we develop a method based on moment closure to interpret neural field models as latent state-space point-process models, making them amenable to statistical inference. With this approach we can infer the intrinsic states of neurons, such as active and refractory, solely from spiking activity in large populations. After validating this approach with synthetic data, we apply it to high-density recordings of spiking activity in the developing mouse retina. This confirms the essential role of a long lasting refractory state in shaping spatiotemporal properties of neonatal retinal waves. This conceptual and methodological advance opens up new theoretical connections between mathematical theory and point-process state-space models in neural data analysis. Author summary Developing statistical tools to connect single-neuron activity to emergent collective dynamics is vital for building interpretable models of neural activity. Neural field models relate single-neuron activity to emergent collective dynamics in neural populations, but integrating them with data remains challenging. Recently, latent state-space models have emerged as a powerful tool for constructing phenomenological models of neural population activity. The advent of high-density multi-electrode array recordings now enables us to examine large-scale collective neural activity. We show that classical neural field approaches can yield latent state-space equations and demonstrate that this enables inference of the intrinsic states of neurons from recorded spike trains in large populations.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ bioRxivarrow_drop_down
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    PLoS Computational Biology
    Article . Preprint
    License: CC BY
    Data sources: UnpayWall
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    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    PLoS Computational Biology
    Article . 2019 . Peer-reviewed
    License: CC BY
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    Apollo
    Article . 2019
    License: CC BY
    Data sources: Datacite
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Apollo
    Other literature type . 2019
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    Data sources: Apollo
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ bioRxivarrow_drop_down
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
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      PLoS Computational Biology
      Article . Preprint
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      PLoS Computational Biology
      Article . 2019 . Peer-reviewed
      License: CC BY
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      Apollo
      Article . 2019
      License: CC BY
      Data sources: Datacite
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
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      Apollo
      Other literature type . 2019
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Jerusalem, A; Al-Rekabi, Z; Chen, H; Ercole, A; +4 Authors

    The current understanding of the role of the cell membrane is in a state of flux. Recent experiments show that conventional models, considering only electrophysiological properties of a passive membrane, are incomplete. The neuronal membrane is an active structure with mechanical properties that modulate electrophysiology. Protein transport, lipid bilayer phase, membrane pressure and stiffness can all influence membrane capacitance and action potential propagation. A mounting body of evidence indicates that neuronal mechanics and electrophysiology are coupled, and together shape the membrane potential in tight coordination with other physical properties. In this review, we summarise recent updates concerning electrophysiological-mechanical coupling in neuronal function. In particular, we aim at making the link with two relevant yet often disconnected fields with strong clinical potential: the use of mechanical vibrations-ultrasound-to alter the electrophysiogical state of neurons, e.g., in neuromodulation, and the theories attempting to explain the action of general anaesthetics. STATEMENT OF SIGNIFICANCE: General anaesthetics revolutionised medical practice; now an apparently unrelated technique, ultrasound neuromodulation-aimed at controlling neuronal activity by means of ultrasound-is poised to achieve a similar level of impact. While both technologies are known to alter the electrophysiology of neurons, the way they achieve it is still largely unknown. In this review, we argue that in order to explain their mechanisms/effects, the neuronal membrane must be considered as a coupled mechano-electrophysiological system that consists of multiple physical processes occurring concurrently and collaboratively, as opposed to sequentially and independently. In this framework the behaviour of the cell membrane is not the result of stereotypical mechanisms in isolation but instead emerges from the integrative behaviour of a complexly coupled multiphysics system.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Oxford University Re...arrow_drop_down
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    Oxford University Research Archive
    Other literature type . 2019
    License: CC BY
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    Apollo
    Other literature type . 2019
    License: CC BY
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    Apollo
    Article . 2019
    License: CC BY
    Data sources: Datacite
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    Acta Biomaterialia
    Article . 2019 . Peer-reviewed
    License: CC BY
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Oxford University Re...arrow_drop_down
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      Oxford University Research Archive
      Other literature type . 2019
      License: CC BY
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      Apollo
      Other literature type . 2019
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      Apollo
      Article . 2019
      License: CC BY
      Data sources: Datacite
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      Acta Biomaterialia
      Article . 2019 . Peer-reviewed
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Konrad Wagstyl; Kirstie Whitaker; Armin Raznahan; Jakob Seidlitz; +63 Authors

    OBJECTIVE: Drug-resistant focal epilepsy is often caused by focal cortical dysplasias (FCDs). The distribution of these lesions across the cerebral cortex and the impact of lesion location on clinical presentation and surgical outcome are largely unknown. We created a neuroimaging cohort of patients with individually mapped FCDs to determine factors associated with lesion location and predictors of postsurgical outcome. METHODS: The MELD (Multi-centre Epilepsy Lesion Detection) project collated a retrospective cohort of 580 patients with epilepsy attributed to FCD from 20 epilepsy centers worldwide. Magnetic resonance imaging-based maps of individual FCDs with accompanying demographic, clinical, and surgical information were collected. We mapped the distribution of FCDs, examined for associations between clinical factors and lesion location, and developed a predictive model of postsurgical seizure freedom. RESULTS: FCDs were nonuniformly distributed, concentrating in the superior frontal sulcus, frontal pole, and temporal pole. Epilepsy onset was typically before the age of 10 years. Earlier epilepsy onset was associated with lesions in primary sensory areas, whereas later epilepsy onset was associated with lesions in association cortices. Lesions in temporal and occipital lobes tended to be larger than frontal lobe lesions. Seizure freedom rates varied with FCD location, from around 30% in visual, motor, and premotor areas to 75% in superior temporal and frontal gyri. The predictive model of postsurgical seizure freedom had a positive predictive value of 70% and negative predictive value of 61%. SIGNIFICANCE: FCD location is an important determinant of its size, the age at epilepsy onset, and the likelihood of seizure freedom postsurgery. Our atlas of lesion locations can be used to guide the radiological search for subtle lesions in individual patients. Our atlas of regional seizure freedom rates and associated predictive model can be used to estimate individual likelihoods of postsurgical seizure freedom. Data-driven atlases and predictive models are essential for evidence-based, precision medicine and risk counseling in epilepsy. Funder: National Institute for Health Research (NIHR) GOSH BRC

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    Epilepsia
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    Epilepsia
    Article . 2021 . Peer-reviewed
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      Epilepsia
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      Epilepsia
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    Authors: Ramanan, Siddharth; Halai, Ajay D; Garcia-Penton, Lorna; Perry, Alistair G; +10 Authors

    Abstract Background Clinical variants of primary progressive aphasia (PPA) are diagnosed based on characteristic patterns of language deficits, supported by corresponding neural changes on brain imaging. However, there is (i) considerable phenotypic variability within and between each diagnostic category with partially overlapping profiles of language performance between variants and (ii) accompanying non-linguistic cognitive impairments that may be independent of aphasia magnitude and disease severity. The neurobiological basis of this cognitive-linguistic heterogeneity remains unclear. Understanding the relationship between these variables would improve PPA clinical/research characterisation and strengthen clinical trial and symptomatic treatment design. We address these knowledge gaps using a data-driven transdiagnostic approach to chart cognitive-linguistic differences and their associations with grey/white matter degeneration across multiple PPA variants. Methods Forty-seven patients (13 semantic, 15 non-fluent, and 19 logopenic variant PPA) underwent assessment of general cognition, errors on language performance, and structural and diffusion magnetic resonance imaging to index whole-brain grey and white matter changes. Behavioural data were entered into varimax-rotated principal component analyses to derive orthogonal dimensions explaining the majority of cognitive variance. To uncover neural correlates of cognitive heterogeneity, derived components were used as covariates in neuroimaging analyses of grey matter (voxel-based morphometry) and white matter (network-based statistics of structural connectomes). Results Four behavioural components emerged: general cognition, semantic memory, working memory, and motor speech/phonology. Performance patterns on the latter three principal components were in keeping with each variant’s characteristic profile, but with a spectrum rather than categorical distribution across the cohort. General cognitive changes were most marked in logopenic variant PPA. Regardless of clinical diagnosis, general cognitive impairment was associated with inferior/posterior parietal grey/white matter involvement, semantic memory deficits with bilateral anterior temporal grey/white matter changes, working memory impairment with temporoparietal and frontostriatal grey/white matter involvement, and motor speech/phonology deficits with inferior/middle frontal grey matter alterations. Conclusions Cognitive-linguistic heterogeneity in PPA closely relates to individual-level variations on multiple behavioural dimensions and grey/white matter degeneration of regions within and beyond the language network. We further show that employment of transdiagnostic approaches may help to understand clinical symptom boundaries and reveal clinical and neural profiles that are shared across categorically defined variants of PPA.

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    Alzheimer’s Research & Therapy
    Article . 2023 . Peer-reviewed
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      Alzheimer’s Research & Therapy
      Article . 2023 . Peer-reviewed
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    Authors: Chan, Dennis; Shafto, Meredith; Kievit, Rogier; Matthews, Fiona; +4 Authors

    AbstractIntroductionThis study tested the hypothesis that mid-life intellectual, physical and social activities contribute to cognitive reserve (CR).Methods205 individuals (196 with MRI) aged 66-88 from the Cambridge Centre for Ageing and Neuroscience (www.cam-can.com) were studied, with cognitive ability and structural brain health measured as fluid IQ and total grey matter volume, respectively. Mid-life activities were measured using the Lifetime of Experiences Questionnaire.ResultsMultivariable linear regression found that mid-life activities (MA) made a unique contribution to late-life cognitive ability independent of education, occupation and late-life activities. Crucially, MA moderated the relationship between late-life cognitive ability and brain structure, with the cognitive ability of people with higher MA less dependent on their brain structure, consistent with the concept of CR.Conclusions. Mid-life intellectual, physical and social activities contribute uniquely to CR. The modifiability of these activities has implications for public health initiatives aimed at dementia prevention.

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    Apollo
    Article . 2019
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    Europe PubMed Central
    Other literature type . 2018
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    https://www.biorxiv.org/conten...
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    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    Neurobiology of Aging
    Other literature type . Article . 2018 . Peer-reviewed
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      Article . 2019
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      Europe PubMed Central
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
      Neurobiology of Aging
      Other literature type . Article . 2018 . Peer-reviewed
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      Article . 2018
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    Authors: Maura Malpetti; Luca Passamonti; P.S. Jones; Duncan Street; +8 Authors

    IntroductionIn addition to tau pathology and neuronal loss, neuroinflammation occurs in progressive supranuclear palsy (PSP). However, the prognostic value of the in vivo imaging markers for these processes in PSP remains unclear. We test the primary hypothesis that baseline in vivo imaging assessment of neuroinflammation in subcortical regions predicts clinical progression in patients with PSP.MethodsSeventeen patients with PSP–Richardson’s syndrome underwent a baseline multimodal imaging assessment, including [11C]PK11195 positron emission tomography (PET) to index microglial activation, [18F]AV-1451 PET for tau pathology and structural MRI. Disease severity was measured at baseline and serially up to 4 years with the Progressive Supranuclear Palsy Rating Scale (PSPRS) (average interval of 5 months). Regional grey-matter volumes and PET ligand binding potentials were summarised by three principal component analyses (PCAs). A linear mixed-effects model was applied to the longitudinal PSPRS scores. Single-modality imaging predictors were regressed against the individuals’ estimated rate of progression to identify the prognostic value of baseline imaging markers.ResultsPCA components reflecting neuroinflammation and tau burden in the brainstem and cerebellum correlated with the subsequent annual rate of change in the PSPRS. PCA-derived PET markers of neuroinflammation and tau pathology correlated with regional brain volume in the same regions. However, MRI volumes alone did not predict the rate of clinical progression.ConclusionsMolecular imaging with PET for microglial activation and tau pathology can predict clinical progression in PSP. These data encourage the evaluation of immunomodulatory approaches to disease-modifying therapies in PSP and the potential for PET to stratify patients in early phase clinical trials.

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    Europe PubMed Central
    Article . 2021 . Peer-reviewed
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    Article . 2021
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    Journal of Neurology Neurosurgery & Psychiatry
    Article . 2021 . Peer-reviewed
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    Journal of Neurology Neurosurgery & Psychiatry
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    https://pubmed.ncbi.nlm.nih.go...
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      Europe PubMed Central
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      Journal of Neurology Neurosurgery & Psychiatry
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      Journal of Neurology Neurosurgery & Psychiatry
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    Authors: Duka, Theodora; Nikolaou, Kyriaki; King, Sarah L.; Banaschewski, Tobias; +17 Authors

    Variations in genes encoding several GABAA receptors have been associated with human drug and alcohol abuse. Among these, a number of human studies have suggested an association between GABRB1, the gene encoding GABAA receptor β1 subunits, with Alcohol dependence (AD), both on its own and comorbid with other substance dependence and psychiatric illnesses. In the present study, we hypothesized that the GABRB1 genetically-associated increased risk for developing alcoholism may be associated with impaired behavioral control and altered sensitivity to reward, as a consequence of altered brain function. Exploiting the IMAGEN database (Schumann et al., 2010), we explored in a human adolescent population whether possession of the minor (T) variant of the single nucleotide polymorphism (SNP) rs2044081 is associated with performance of tasks measuring aspects of impulsivity, and reward sensitivity that are implicated in drug and alcohol abuse. Allelic variation did not associate with altered performance in either a stop-signal task (SST), measuring one aspect of impulsivity, or a monetary incentive delay (MID) task assessing reward anticipation. However, increased functional magnetic resonance imaging (fMRI) blood-oxygen-level dependent (BOLD) response in the right hemisphere inferior frontal gyrus (IFG), left hemisphere caudate/insula and left hemisphere inferior temporal gyrus (ITG) during MID performance was higher in the minor (T) allelic group. In contrast, during SST performance, the BOLD response found in the right hemisphere supramarginal gyrus, right hemisphere lingual and left hemisphere inferior parietal gyrus indicated reduced responses in the minor genotype. We suggest that β1-containing GABAA receptors may play a role in excitability of brain regions important in controlling reward-related behavior, which may contribute to susceptibility to addictive behavior.

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    Apollo
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    Frontiers in Behavioral Neuroscience
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    Frontiers in Behavioral Neuroscience
    Article . 2017 . Peer-reviewed
    https://doi.org/10.17169/refub...
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      Frontiers in Behavioral Neuroscience
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    Authors: Taylor, J. S. H.; Davis, Matthew H.; Rastle, Kathleen;

    There is strong scientific consensus that emphasizing print-to-sound relationships is critical when learning to read alphabetic languages. Nevertheless, reading instruction varies across English-speaking countries, from intensive phonic training to multicuing environments that teach sound- and meaning-based strategies. We sought to understand the behavioral and neural consequences of these differences in relative emphasis. We taught 24 English-speaking adults to read 2 sets of 24 novel words (e.g., /buv/, /sig/), written in 2 different unfamiliar orthographies. Following pretraining on oral vocabulary, participants learned to read the novel words over 8 days. Training in 1 language was biased toward print-to-sound mappings while training in the other language was biased toward print-to-meaning mappings. Results showed striking benefits of print-sound training on reading aloud, generalization, and comprehension of single words. Univariate analyses of fMRI data collected at the end of training showed that print-meaning relative to print-sound relative training increased neural effort in dorsal pathway regions involved in reading aloud. Conversely, activity in ventral pathway brain regions involved in reading comprehension was no different following print-meaning versus print-sound training. Multivariate analyses validated our artificial language approach, showing high similarity between the spatial distribution of fMRI activity during artificial and English word reading. Our results suggest that early literacy education should focus on the systematicities present in print-to-sound relationships in alphabetic languages, rather than teaching meaning-based strategies, in order to enhance both reading aloud and comprehension of written words. (PsycINFO Database Record

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    Journal of Experimental Psychology General
    Article . 2017 . Peer-reviewed
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      Journal of Experimental Psychology General
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    Authors: Vamvakopoulou, Ioanna A; Fonville, Leon; Hayes, Alexandra; McGonigle, John; +13 Authors

    INTRODUCTION: Negative affective states contribute to the chronic-relapsing nature of addiction. Mesolimbic dopamine D3 receptors are well placed to modulate emotion and are dysregulated in substance dependence. Selective antagonists might restore dopaminergic hypofunction, thus representing a potential treatment target. We investigated the effects of selective D3 antagonist, GSK598809, on the neural response to negative emotional processing in substance dependent individuals and healthy controls. METHODOLOGY: Functional MRI BOLD response was assessed during an evocative image task, 2 h following acute administration of GSK598809 (60 mg) or placebo in a multi-site, double-blind, pseudo-randomised, cross-over design. Abstinent drug dependent individuals (DD, n = 36) comprising alcohol-only (AO, n = 19) and cocaine-alcohol polydrug (PD, n = 17) groups, and matched controls (n = 32) were presented with aversive and neutral images in a block design (contrast of interest: aversive > neutral). Whole-brain mixed-effects and a priori ROI analyses tested for group and drug effects, with identical models exploring subgroup effects. RESULTS: No group differences in task-related BOLD signal were identified between DD and controls. However, subgroup analysis revealed greater amygdala/insular BOLD signal in PD compared with AO groups. Following drug administration, GSK598809 increased BOLD response across HC and DD groups in thalamus, caudate, putamen, and pallidum, and reduced BOLD response in insular and opercular cortices relative to placebo. Multivariate analyses in a priori ROIs revealed differential effects of D3 antagonism according to subgroup in substantia nigra; GSK598809 increased BOLD response in AO and decreased response in PD groups. CONCLUSION: Acute GSK598809 modulates the BOLD response to aversive image processing, providing evidence that D3 antagonism may impact emotional regulation. Enhanced BOLD response within D3-rich mesolimbic regions is consistent with its pharmacology and with attenuation of substance-related hypodopaminergic function. However, the lack of group differences in task-related BOLD response and the non-specific effect of GSK598809 between groups makes it difficult to ascertain whether D3 antagonism is likely to be normalising or restorative in our abstinent populations. The suggestion of differential D3 modulation between AO and PD subgroups is intriguing, raising the possibility of divergent treatment responses. Further study is needed to determine whether D3 antagonism should be recommended as a treatment target in substance dependence. Acknowledgements: We wish to thank our volunteers and all the recruitment partners who assisted with participant identification and referrals; Imperial College Healthcare NHS Trust, Central North West London NHS Foundation trust, Camden and Islington NHS trust, Cambridge University Hospitals NHS Foundation Trust, Norfolk and Suffolk NHS Foundation Trust, Cambridge and Peterborough NHS Foundation Trust, South Staffordshire and Shropshire NHS Foundation Trust, Manchester Mental Health NHS and Social Care Trust, Greater Manchester West NHS Foundation Trust, Pennine Care NHS Foundation Trust, Salford Royal NHS Foundation Trust, Addaction, Foundation 66 and CRI (Crime Reduction Initiative). We also wish to thank our ICCAM Consortium collaborators David Nutt, Anne Lingford-Hughes, Louise Paterson, John McGonigle, Remy Flechais, Csaba Orban, Bill Deakin, Rebecca Elliott, Anna Murphy, Eleanor Taylor, Trevor Robbins, Karen Ersche, John Suckling, Dana Smith, Laurence Reed, Filippo Passetti, Luca Faravelli, David Erritzoe, Inge Mick, Nicola Kalk, Adam Waldman, Liam Nestor, Shankar Kuchibatla, Venkataramana Boyapati, Antonio Metastasio, Yetunde Faluyi, Emilio Fernandez-Egea, Sanja Abbott, Barbara Sahakian, Valerie Voon, and Ilan Rabiner. Peer reviewed: True

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    Frontiers in Psychiatry
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      Frontiers in Psychiatry
      Article . 2022 . Peer-reviewed
      License: CC BY
      Data sources: Crossref
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      Apollo
      Article . 2022
      License: CC BY
      Data sources: Datacite
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      Apollo
      Other literature type . 2022
      Data sources: Apollo
      Apollo
      Article . 2022
      Data sources: Datacite
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