المؤلفون: Aznarez-Sanado, Maite, Romero García, Rafael, Li, Chao, Morris, Rob C., Price, Stephen J., Manly, Thomas, Santarius, Thomas, Erez, Yaara, Hart, Michael G., Suckling, John

المساهمون: Cancer Research UK, Brain Tumour Charity, Ministerio de Universidades (España), Junta de Andalucía, National Institute for Health and Care Research (US)

مصطلحات موضوعية: Tumour microstructure, Brain tumors, Diffusion MRI, Microstructure, Neurosurgery

الوصف: Brain tumour microstructure is potentially predictive of changes following treatment to cognitive functions subserved by the functional networks in which they are embedded. To test this hypothesis, intra-tumoural microstructure was quantified from diffusion-weighted MRI to identify which tumour subregions (if any) had a greater impact on participants' cognitive recovery after surgical resection. Additionally, we studied the role of tumour microstructure in the functional interaction between the tumour and the rest of the brain. Sixteen patients (22-56 years, 7 females) with brain tumours located in or near speech-eloquent areas of the brain were included in the analyses. Two different approaches were adopted for tumour segmentation from a multishell diffusion MRI acquisition: the first used a two-dimensional four group partition of feature space, whilst the second used data-driven clustering with Gaussian mixture modelling. For each approach, we assessed the capability of tumour microstructure to predict participants' cognitive outcomes after surgery and the strength of association between the BOLD signal of individual tumour subregions and the global BOLD signal. With both methodologies, the volumes of partially overlapped subregions within the tumour significantly predicted cognitive decline in verbal skills after surgery. We also found that these particular subregions were among those that showed greater functional interaction with the unaffected cortex. Our results indicate that tumour microstructure measured by MRI multishell diffusion is associated with cognitive recovery after surgery. ; This research was supported by the Guarantors of Brain; Cancer Research UK Cambridge Centre (ref: A25117); The Brain Tumour Charity; the Ministerio de Universidades (marco del Programa Estatal de Promoción del Talento y su Empleabilidad en I + D + i, Subprograma Estatal de Movilidad, del Plan Estatal de Investigación Científica y Técnica y de Innovación 2017–2020); the EMERGIA Junta de Andalucia program; (EMERGIA20_00139) ...

وصف الملف: application/pdf

العلاقة: #PLACEHOLDER_PARENT_METADATA_VALUE#; info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-122853OA-I00/ES/NEUROIMAGEN GENETICA PARA LA CARACTERIZACION DE TRAYECTORIAS DE NEURODESARROLLO ATIPICAS EN PSICOSIS/; Publisher's version; The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI 10.1038/s41598-024-55130-5; https://doi.org/10.1038/s41598-024-55130-5Test; Sí; Scientific Reports 14: 5646 (2024); http://hdl.handle.net/10261/359934Test; 2-s2.0-85187182834; https://api.elsevier.com/content/abstract/scopus_id/85187182834Test

الإتاحة: https://doi.org/10.1038/s41598-024-55130-5Test
http://hdl.handle.net/10261/359934Test
https://api.elsevier.com/content/abstract/scopus_id/85187182834Test

المؤلفون: Dorfschmidt, Lena, Bethlehem, Richard A., Seidlitz, Jakob, Váša, , František, White, Simon R., Romero García, Rafael, Bullmore, Edward T.

المساهمون: Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica

مصطلحات موضوعية: Sexuality, Adolescence, Depression

الوصف: Sexual differences in human brain development could be relevant to sex differences in the incidence of depres- sion during adolescence. We tested for sex differences in parameters of normative brain network development using fMRI data on N = 298 healthy adolescents, aged 14 to 26 years, each scanned one to three times. Sexually divergent development of functional connectivity was located in the default mode network, limbic cortex, and subcortical nuclei. Females had a more “disruptive” pattern of development, where weak functional connectivity at age 14 became stronger during adolescence. This fMRI-derived map of sexually divergent brain network devel- opment was robustly colocated with i prior loci of reward-related brain activation ii a map of functional dysconnec- tivity in major depressive disorder (MDD), and iii an adult brain gene transcriptional pattern enriched for genes on the X chromosome, neurodevelopmental genes, and risk genes for MDD. We found normative sexual divergence in adolescent development of a cortico-subcortical brain functional network that is relevant to depression.

العلاقة: science advance, 8 (21), eabm7825.; https://idus.us.es/handle//11441/154850Test

الإتاحة: https://idus.us.es/handle//11441/154850Test

المؤلفون: Assem, Moataz, Hart, Michael G., Coelho, Pedro, Romero García, Rafael, McDonald, Alexa, Woodberry, Emma

المساهمون: Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica, Universidad de Sevilla. Instituto de Biomedicina de Sevilla (IBIS)

مصطلحات موضوعية: Cognitive control, High gamma, Fronto-parietal, Intraoperative, Electrocorticography, ECoG, Intracranial, EEG, iEEG, fMRI

الوصف: Though the lateral frontal cortex is broadly implicated in cognitive control, functional MRI (fMRI) studies suggest fine-grained distinctions within this region. To examine this question electrophysiologically, we placed electrodes on the lateral frontal cortex in patients undergoing awake craniotomy for tumor resection. Patients performed verbal tasks with a manipulation of attentional switching, a canonical control demand. Power in the high gamma range (70e250 Hz) distinguished electrodes based on their location within a highresolution fMRI network parcellation of the frontal lobe. Electrodes within the canonical fronto-parietal control network showed increased power in the switching condition, a result absent in electrodes within default mode, language and somato-motor networks. High gamma results contrasted with spatially distributed power decreases in the beta range (12e30 Hz). These results confirm the importance of fine-scale functional distinctions within the human frontal lobe, and pave the way for increased precision of functional mapping in tumor surgeries.

العلاقة: Cortex, 159, 286-298.; https://www.sciencedirect.com/science/article/pii/S0010945222003380?via%3DihubTest; https://idus.us.es/handle//11441/154436Test

الإتاحة: https://idus.us.es/handle//11441/154436Test

المؤلفون: Azevedo, Tiago, Campbell, Alexander, Romero García, Rafael, Passamonti, Luca, Bethlehem, Richard A. I., Liò, Pietro, Toschi, Nicola

المساهمون: Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica, Universidad de Sevilla. Instituto de Biomedicina de Sevilla (IBIS)

مصطلحات موضوعية: Deep learning, Graph neural networks, UK Biobank, Time series, Temporal convolutional network, Rs-fMRI, Spatio-temporal dynamics

الوصف: Resting-state functional magnetic resonance imaging (rs-fMRI) has been successfully employed to understand the organisation of the human brain. Typically, the brain is parcellated into regions of interest (ROIs) and modelled as a graph where each ROI represents a node and association measures between ROI-specific blood-oxygen-level-dependent (BOLD) time series are edges. Recently, graph neural networks (GNNs) have seen a surge in popularity due to their success in modelling unstructured relational data. The latest developments with GNNs, however, have not yet been fully exploited for the analysis of rs-fMRI data, particularly with regards to its spatio-temporal dynamics. In this paper, we present a novel deep neural network architecture which combines both GNNs and temporal convolutional networks (TCNs) in order to learn from both the spatial and temporal components of rs-fMRI data in an end-to-end fashion. In particular, this corresponds to intra-feature learning (i.e., learning temporal dynamics with TCNs) as well as inter-feature learning (i.e., leveraging interactions between ROI-wise dynamics with GNNs). We evaluate our model with an ablation study using 35,159 samples from the UK Biobank rs-fMRI database, as well as in the smaller Human Connectome Project (HCP) dataset, both in a unimodal and in a multimodal fashion. We also demonstrate that out architecture contains explainability-related features which easily map to realistic neurobiological insights. We suggest that this model could lay the groundwork for future deep learning architectures focused on leveraging the inherently and inextricably spatio-temporal nature of rs-fMRI data.

العلاقة: Medical Image Analysis, 79, 102477.; https://www.sciencedirect.com/science/article/pii/S1361841522001189?via%3DihubTest; https://idus.us.es/handle//11441/154435Test

الإتاحة: https://idus.us.es/handle//11441/154435Test

المؤلفون: Mandal, Ayan S., Wiener, Chemda, Assem, Moataz, Romero-Garcia, Rafael, Coelho, Pedro, McDonald, Alexa, Woodberry, Emma, Morris, Robert C., Price, Stephen J., Duncan, John, Santarius, Thomas, Suckling, John, Hart, Michael G., Erez, Yaara

المساهمون: The Royal Society, Guarantors Of Brain, Brain Tumor Charity, Cambridge Commonwealth European and International Trust, The Applebaum Foundation Inc, UKRI Medical Research Council, National Institute for Health and Care Research, Bill & Melinda Gates Foundation

المصدر: Cortex ; volume 173, page 1-15 ; ISSN 0010-9452

مصطلحات موضوعية: Cognitive Neuroscience, Experimental and Cognitive Psychology, Neuropsychology and Physiological Psychology

الإتاحة: https://doi.org/10.1016/j.cortex.2024.01.004Test
https://api.elsevier.com/content/article/PII:S0010945224000224?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0010945224000224?httpAccept=text/plainTest

المؤلفون: Romero García, Rafael, Mandal, Ayan, Bethlehem, Richard A. I., Crespo-Facorro, Benedicto, Hart, Michael G., Suckling, John

المساهمون: Junta de Andalucía, Cancer Research UK, Universidad de Sevilla, Romero Garcia, Rafael, Mandal, Ayan

مصطلحات موضوعية: Connectomic, Gene expression, Glioma, Transcriptomic

الوصف: Unravelling the complex events driving grade-specific spatial distribution of brain tumour occurrence requires rich datasets from both healthy individuals and patients. Here, we combined open-access data from The Cancer Genome Atlas, the UK Biobank and the Allen Brain Human Atlas to disentangle how the different spatial occurrences of glioblastoma multiforme and low-grade gliomas are linked to brain network features and the normative transcriptional profiles of brain regions. From MRI of brain tumour patients, we first constructed a grade-related frequency map of the regional occurrence of low-grade gliomas and the more aggressive glioblastoma multiforme. Using associated mRNA transcription data, we derived a set of differential gene expressions from glioblastoma multiforme and low-grade gliomas tissues of the same patients. By combining the resulting values with normative gene expressions from post-mortem brain tissue, we constructed a grade-related expression map indicating which brain regions express genes dysregulated in aggressive gliomas. Additionally, we derived an expression map of genes previously associated with tumour subtypes in a genome-wide association study (tumour-related genes). There were significant associations between grade-related frequency, grade-related expression and tumour-related expression maps, as well as functional brain network features (specifically, nodal strength and participation coefficient) that are implicated in neurological and psychiatric disorders. These findings identify brain network dynamics and transcriptomic signatures as key factors in regional vulnerability for glioblastoma multiforme and low-grade glioma occurrence, placing primary brain tumours within a well established framework of neurological and psychiatric cortical alterations. ; R.R.-G. is funded by a non-clinical post-doctoral Brain fellowship, the EMERGIA Junta de Andalucía program (EMERGIA20_00139) and Cancer Research UK Cambridge Centre (grant ref. A25117) and the Plan Propio of the University of ...

وصف الملف: application/pdf

العلاقة: Publisher's version; Romero Garcia, Rafael; Mandal, Ayan; Bethlehem, Richard, A. I.; Crespo-Facorro, Benedicto; Hart, Michael G.; Suckling, John; 2023; Transcriptomic and connectomic correlates of differential spatial patterning among gliomas Supplementary Material [Dataset]; Oxford University Press; https://doi.org/10.1093/brain/awac378Test; https://doi.org/10.1093/brain/awac378Test; Sí; Brain 146(3): 1200-1211 (2023); http://hdl.handle.net/10261/340125Test; http://dx.doi.org/10.13039/100009042Test; http://dx.doi.org/10.13039/501100000289Test; http://dx.doi.org/10.13039/501100011011Test; 2-s2.0-85149185577; https://api.elsevier.com/content/abstract/scopus_id/85149185577Test

الإتاحة: https://doi.org/10.1093/brain/awac37810.13039/10000904210.13039/50110000028910.13039/501100011011Test
http://hdl.handle.net/10261/340125Test
https://api.elsevier.com/content/abstract/scopus_id/85149185577Test

المؤلفون: Mandal, Ayan, Romero García, Rafael, Hart, Michael G., Suckling, John

المساهمون: Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica, Universidad de Sevilla. CTS1086: Psiquiatría Traslacional

مصطلحات موضوعية: Neuro-oncology, Gliomagenesis, Connectomics, Imaging-transcriptomics

الوصف: For decades, it has been known that gliomas follow a non-random spatial distribution, appearing more often in some brain regions (e.g. the insula) compared to others (e.g. the occipital lobe). A better understanding of the localization patterns of gliomas could provide clues to the origins of these types of tumours, and consequently inform treatment targets. Following hypotheses derived from prior research into neuropsychiatric disease and cancer, gliomas may be expected to localize to brain regions characterized by functional hubness, stem-like cells, and transcription of genetic drivers of gliomagenesis. We combined neuroimaging data from 335 adult patients with high- and low-grade glioma to form a replicable tumour frequency map. Using this map, we demonstrated that glioma frequency is elevated in association cortex and correlated with multiple graph-theoretical metrics of high functional connectedness. Brain regions populated with putative cells of origin for glioma, neural stem cells and oligodendrocyte precursor cells, exhibited a high glioma frequency. Leveraging a human brain atlas of post-mortem gene expression, we found that gliomas were localized to brain regions enriched with expression of genes associated with chromatin organization and synaptic signalling. A set of glioma proto-oncogenes was enriched among the transcriptomic correlates of glioma distribution. Finally, a regression model incorporating connectomic, cellular, and genetic factors explained 58% of the variance in glioma frequency. These results add to previous literature reporting the vulnerability of hub regions to neurological disease, as well as provide support for cancer stem cell theories of glioma. Our findings illustrate how factors of diverse scale, from genetic to connectomic, can independently in fluence the anatomic localization of brain dysfunction. ; Bill and Melinda Gates Foundation OPP1144 ; Brain fellowship ; Gates Cambridge Scholarship ; Medical Research Council (MRC) MR/M009041/1 ; MRC MR/M009041/1

العلاقة: Brain, 143 (11), 3294-3307.; https://idus.us.es/handle//11441/147025Test

الإتاحة: https://idus.us.es/handle//11441/147025Test

المؤلفون: Vása, Frantisek, Romero García, Rafael, Kitzbichler, Manfred G., Seidlitz, Jakob, Whitaker, Kristie J., Vaghi, Matilde M., Bullmore, Edward T.

المساهمون: Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica

مصطلحات موضوعية: Neurodevelopment, Connectome, MRI, Allen Human Brain Atlas, Head movement

الوصف: Adolescent changes in human brain function are not entirely understood. Here, we used multiecho functional MRI (fMRI) to measure developmental change in functional connectivity (FC) of resting-state oscillations between pairs of 330 cortical regions and 16 subcortical regions in 298 healthy adolescents scanned 520 times. Participants were aged 14 to 26 y and were scanned on 1 to 3 occasions at least 6 mo apart. We found 2 distinct modes of age-related change in FC: “conservative” and “disruptive.” Conservative development was characteristic of primary cortex, which was strongly connected at 14 y and became even more connected in the period from 14 to 26 y. Disruptive development was characteristic of association cortex and subcortical regions, where connectivity was remodeled: connections that were weak at 14 y became stronger during adolescence, and connections that were strong at 14 y became weaker. These modes of development were quantified using the maturational index (MI), estimated as Spearman’s correlation between edgewise baseline FC (at 14 y, FC14) and adolescent change in FC (∆FC14−26), at each region. Disruptive systems (with negative MI) were activated by social cognition and autobiographical memory tasks in prior fMRI data and significantly colocated with prior maps of aerobic glycolysis (AG), AG-related gene expression, postnatal cortical surface expansion, and adolescent shrinkage of cortical thickness. The presence of these 2 modes of development was robust to numerous sensitivity analyses. We conclude that human brain organization is disrupted during adolescence by remodeling of FC between association cortical and subcortical areas. ; University College London ; EPSRC EP/N510129/1 ; Gates Cambridge Trust ; King's College London - Engineering and Physical Sciences Research Council (EPSRC) EP/N510129/1 ; King's College London - Engineering and Physical Sciences Research Council (EPSRC) NF-SI-0514-10157 ; Medical Research Council (MRC) MR/K020706/1 ; Medical Research Council (MRC) MQF17/24

العلاقة: PNAS, 117 (6), 3248-3253.; https://idus.us.es/handle//11441/149679Test

الإتاحة: https://idus.us.es/handle//11441/149679Test

المؤلفون: Bethlehem, Richard A. I., Seidlitz, Jakob, Romero García, Rafael, Trakoshis, Stavros, Dumas, Guillaume, Lombardo, Michael V.

المساهمون: Universidad de Sevilla.Departamento de Fisiología Médica y Biofísica

مصطلحات موضوعية: Autism spectrum disorders (ASD), Heterogeneity, Cortical thickness (CT), Typically-developing (TD) age-related norms

الوصف: Understanding heterogeneity is an important goal on the path to precision medicine for autism spectrum disorders (ASD). We examined how cortical thickness (CT) in ASD can be parameterized as an individualized metric of atypicality relative to typically-developing (TD) age-related norms. Across a large sample (n = 870 per group) and wide age range (5–40 years), we applied normative modelling resulting in individualized whole-brain maps of age-related CT atypicality in ASD and isolating a small subgroup with highly age-atypical CT. Age-normed CT scores also highlights on-average differentiation, and associations with behavioural symptomatology that is separate from insights gleaned from traditional case-control approaches. This work showcases an individualized approach for understanding ASD heterogeneity that could potentially further prioritize work on a subset of individuals with cortical pathophysiology represented in age-related CT atypicality. Only a small subset of ASD individuals are actually highly atypical relative to age-norms. driving small on-average case-control differences. ; Autism Research Trust ; British Academy Post-Doctoral Fellowship ; European Research Council (ERC) Starting Grant 755816 ; Guarantors of Brain ; MRC MR/M009041/1 ; MRC research infrastructure award MR/M009041/1 ; National Institutes of Health Oxford-Cambridge Scholars Program ; NIHR Cambridge Biomedical Research Centre

العلاقة: Communications Biology, 3 (1), 1-10.; https://idus.us.es/handle//11441/149371Test

الإتاحة: https://idus.us.es/handle//11441/149371Test

المؤلفون: Romero García, Rafael, Seidlitz, Jakob, Whitaker, Kristie J., Morgan, Sarah, Fonagy, Peter, Dolan, Raymond J., Jones, Peter B., Goodyer, Ian, Suckling, John

المساهمون: Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica

مصطلحات موضوعية: Adolescence, Allen Human Brain Atlas, Development, Fast-spiking GABAergic interneurons, Multiparameter MRI mapping, Myelination, Schizophrenia

الوصف: Background: Genetic risk is thought to drive clinical variation on a spectrum of schizophrenia-like traits, but the underlying changes in brain structure that mechanistically link genomic variation to schizotypal experience and behavior are unclear. Methods: We assessed schizotypy using a self-reported questionnaire and measured magnetization transfer as a putative microstructural magnetic resonance imaging marker of intracortical myelination in 68 brain regions in 248 healthy young people (14–25 years of age). We used normative adult brain gene expression data and partial least squares analysis to find the weighted gene expression pattern that was most colocated with the cortical map of schizotypy-related magnetization. Results: Magnetization was significantly correlated with schizotypy in the bilateral posterior cingulate cortex and precuneus (and for disorganized schizotypy, also in medial prefrontal cortex; all false discovery rate–corrected ps < .05), which are regions of the default mode network specialized for social and memory functions. The genes most positively weighted on the whole-genome expression map colocated with schizotypy-related magnetization were enriched for genes that were significantly downregulated in two prior case-control histological studies of brain gene expression in schizophrenia. Conversely, the most negatively weighted genes were enriched for genes that were transcriptionally upregulated in schizophrenia. Positively weighted (downregulated) genes were enriched for neuronal, specifically interneuronal, affiliations and coded a network of proteins comprising a few highly interactive “hubs” such as parvalbumin and calmodulin. Conclusions: Microstructural magnetic resonance imaging maps of intracortical magnetization can be linked to both the behavioral traits of schizotypy and prior histological data on dysregulated gene expression in schizophrenia. ; Alan Turing Institute under the Engineering and Physical Sciences Research Council EP/N510129/1 ; MQ fellowship Grant MQF17_24 ...

العلاقة: Biological Psychiatry, 88 (3), 248-259.; https://idus.us.es/handle//11441/149448Test

الإتاحة: https://idus.us.es/handle//11441/149448Test