RESUMEN
The anatomy of the brain necessarily constrains its function, but precisely how remains unclear. The classical and dominant paradigm in neuroscience is that neuronal dynamics are driven by interactions between discrete, functionally specialized cell populations connected by a complex array of axonal fibres1-3. However, predictions from neural field theory, an established mathematical framework for modelling large-scale brain activity4-6, suggest that the geometry of the brain may represent a more fundamental constraint on dynamics than complex interregional connectivity7,8. Here, we confirm these theoretical predictions by analysing human magnetic resonance imaging data acquired under spontaneous and diverse task-evoked conditions. Specifically, we show that cortical and subcortical activity can be parsimoniously understood as resulting from excitations of fundamental, resonant modes of the brain's geometry (that is, its shape) rather than from modes of complex interregional connectivity, as classically assumed. We then use these geometric modes to show that task-evoked activations across over 10,000 brain maps are not confined to focal areas, as widely believed, but instead excite brain-wide modes with wavelengths spanning over 60 mm. Finally, we confirm predictions that the close link between geometry and function is explained by a dominant role for wave-like activity, showing that wave dynamics can reproduce numerous canonical spatiotemporal properties of spontaneous and evoked recordings. Our findings challenge prevailing views and identify a previously underappreciated role of geometry in shaping function, as predicted by a unifying and physically principled model of brain-wide dynamics.
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Mapeo Encefálico , Encéfalo , Humanos , Axones/fisiología , Encéfalo/anatomía & histología , Encéfalo/citología , Encéfalo/fisiología , Imagen por Resonancia Magnética , Neuronas/fisiologíaRESUMEN
Gender inequality across the world has been associated with a higher risk to mental health problems and lower academic achievement in women compared to men. We also know that the brain is shaped by nurturing and adverse socio-environmental experiences. Therefore, unequal exposure to harsher conditions for women compared to men in gender-unequal countries might be reflected in differences in their brain structure, and this could be the neural mechanism partly explaining women's worse outcomes in gender-unequal countries. We examined this through a random-effects meta-analysis on cortical thickness and surface area differences between adult healthy men and women, including a meta-regression in which country-level gender inequality acted as an explanatory variable for the observed differences. A total of 139 samples from 29 different countries, totaling 7,876 MRI scans, were included. Thickness of the right hemisphere, and particularly the right caudal anterior cingulate, right medial orbitofrontal, and left lateral occipital cortex, presented no differences or even thicker regional cortices in women compared to men in gender-equal countries, reversing to thinner cortices in countries with greater gender inequality. These results point to the potentially hazardous effect of gender inequality on women's brains and provide initial evidence for neuroscience-informed policies for gender equality.
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Encéfalo , Equidad de Género , Masculino , Adulto , Humanos , Femenino , Encéfalo/diagnóstico por imagen , Factores SexualesRESUMEN
Voxel-based morphometry (VBM) and surface-based morphometry (SBM) are two widely used neuroimaging techniques for investigating brain anatomy. These techniques rely on statistical inferences at individual points (voxels or vertices), clusters of points, or a priori regions-of-interest. They are powerful tools for describing brain anatomy, but offer little insights into the generative processes that shape a particular set of findings. Moreover, they are restricted to a single spatial resolution scale, precluding the opportunity to distinguish anatomical variations that are expressed across multiple scales. Drawing on concepts from classical physics, here we develop an approach, called mode-based morphometry (MBM), that can describe any empirical map of anatomical variations in terms of the fundamental, resonant modes-eigenmodes-of brain anatomy, each tied to a specific spatial scale. Hence, MBM naturally yields a multiscale characterization of the empirical map, affording new opportunities for investigating the spatial frequency content of neuroanatomical variability. Using simulated and empirical data, we show that the validity and reliability of MBM are either comparable or superior to classical vertex-based SBM for capturing differences in cortical thickness maps between two experimental groups. Our approach thus offers a robust, accurate, and informative method for characterizing empirical maps of neuroanatomical variability that can be directly linked to a generative physical process.
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Encéfalo , Neuroanatomía , Humanos , Reproducibilidad de los Resultados , Encéfalo/diagnóstico por imagen , Cabeza , NeuroimagenRESUMEN
Deficits in effective executive function, including inhibitory control are associated with risk for a number of psychiatric disorders and significantly impact everyday functioning. These complex traits have been proposed to serve as endophenotypes, however, their genetic architecture is not yet well understood. To identify the common genetic variation associated with inhibitory control in the general population we performed the first trans-ancestry genome wide association study (GWAS) combining data across 8 sites and four ancestries (N = 14,877) using cognitive traits derived from the stop-signal task, namely - go reaction time (GoRT), go reaction time variability (GoRT SD) and stop signal reaction time (SSRT). Although we did not identify genome wide significant associations for any of the three traits, GoRT SD and SSRT demonstrated significant and similar SNP heritability of 8.2%, indicative of an influence of genetic factors. Power analyses demonstrated that the number of common causal variants contributing to the heritability of these phenotypes is relatively high and larger sample sizes are necessary to robustly identify associations. In Europeans, the polygenic risk for ADHD was significantly associated with GoRT SD and the polygenic risk for schizophrenia was associated with GoRT, while in East Asians polygenic risk for schizophrenia was associated with SSRT. These results support the potential of executive function measures as endophenotypes of neuropsychiatric disorders. Together these findings provide the first evidence indicating the influence of common genetic variation in the genetic architecture of inhibitory control quantified using objective behavioural traits derived from the stop-signal task.
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Estudio de Asociación del Genoma Completo , Esquizofrenia , Humanos , Estudio de Asociación del Genoma Completo/métodos , Esquizofrenia/genética , Función Ejecutiva , Herencia Multifactorial/genética , Endofenotipos , Polimorfismo de Nucleótido Simple/genética , Predisposición Genética a la Enfermedad/genéticaRESUMEN
Dysfunction of fronto-striato-thalamic (FST) circuits is thought to contribute to dopaminergic dysfunction and symptom onset in psychosis, but it remains unclear whether this dysfunction is driven by aberrant bottom-up subcortical signalling or impaired top-down cortical regulation. We used spectral dynamic causal modelling of resting-state functional MRI to characterize the effective connectivity of dorsal and ventral FST circuits in a sample of 46 antipsychotic-naïve first-episode psychosis patients and 23 controls and an independent sample of 36 patients with established schizophrenia and 100 controls. We also investigated the association between FST effective connectivity and striatal 18F-DOPA uptake in an independent healthy cohort of 33 individuals who underwent concurrent functional MRI and PET. Using a posterior probability threshold of 0.95, we found that midbrain and thalamic connectivity were implicated as dysfunctional across both patient groups. Dysconnectivity in first-episode psychosis patients was mainly restricted to the subcortex, with positive symptom severity being associated with midbrain connectivity. Dysconnectivity between the cortex and subcortical systems was only apparent in established schizophrenia patients. In the healthy 18F-DOPA cohort, we found that striatal dopamine synthesis capacity was associated with the effective connectivity of nigrostriatal and striatothalamic pathways, implicating similar circuits to those associated with psychotic symptom severity in patients. Overall, our findings indicate that subcortical dysconnectivity is evident in the early stages of psychosis, that cortical dysfunction may emerge later in the illness, and that nigrostriatal and striatothalamic signalling are closely related to striatal dopamine synthesis capacity, which is a robust marker for psychosis.
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Trastornos Psicóticos , Esquizofrenia , Humanos , Dopamina/metabolismo , Trastornos Psicóticos/diagnóstico por imagen , Esquizofrenia/diagnóstico por imagen , Esquizofrenia/metabolismo , Dihidroxifenilalanina , Imagen por Resonancia Magnética , Vías Nerviosas/fisiologíaRESUMEN
Schizophrenia is a debilitating neuropsychiatric disorder whose underlying correlates remain unclear despite decades of neuroimaging investigation. One contentious topic concerns the role of global signal (GS) fluctuations and how they affect more focal functional changes. Moreover, it has been difficult to pinpoint causal mechanisms of circuit disruption. Here, we analyzed resting-state fMRI data from 47 schizophrenia patients and 118 age-matched healthy controls and used dynamical analyses to investigate how global fluctuations and other functional metastable states are affected by this disorder. We found that brain dynamics in the schizophrenia group were characterized by an increased probability of globally coherent states and reduced recurrence of a substate dominated by coupled activity in the default mode and limbic networks. We then used the in silico perturbation of a whole-brain model to identify critical areas involved in the disease. Perturbing a set of temporo-parietal sensory and associative areas in a model of the healthy brain reproduced global pathological dynamics. Healthy brain dynamics were instead restored by perturbing a set of medial fronto-temporal and cingulate regions in the model of pathology. These results highlight the relevance of GS alterations in schizophrenia and identify a set of vulnerable areas involved in determining a shift in brain state.
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Esquizofrenia , Humanos , Encéfalo , Mapeo Encefálico , Giro del Cíngulo , Neuroimagen Funcional/métodos , Imagen por Resonancia Magnética/métodosRESUMEN
OBJECTIVE: Reward-based eating drives are putative mechanisms of uncontrolled eating implicated in obesity and disordered eating (e.g., binge eating). Uncovering the genetic and environmental contributions to reward-related eating, and their genetic correlation with BMI, could shed light on key mechanisms underlying eating and weight-related disorders. METHOD: We conducted a classical twin study to examine how much variance in uncontrolled eating phenotypes and body mass index (BMI) was explained by genetic factors, and the extent that these phenotypes shared common genetic factors. 353 monozygotic twins and 128 dizygotic twins completed the Reward-based Eating Drive 13 scale, which measures three distinct uncontrolled eating phenotypes (loss of control over eating, preoccupation with thoughts about food, and lack of satiety), and a demographic questionnaire which included height and weight for BMI calculation. We estimated additive genetic (A), common environmental (C), and unique environmental (E) factors for each phenotype, as well as their genetic correlations, with a multivariate ACE model. A common pathway model also estimated whether genetic variance in the uncontrolled eating phenotypes was better explained by a common latent uncontrolled eating factor. RESULTS: There were moderate genetic correlations between uncontrolled eating phenotypes and BMI (.26-.41). Variance from the uncontrolled eating phenotypes was also best explained by a common latent uncontrolled eating factor that was explained by additive genetic factors (52%). DISCUSSION: These results suggest that uncontrolled eating phenotypes are heritable traits that also share genetic variance with BMI. This has implications for understanding the cognitive mechanisms that underpin obesity and disordered eating. PUBLIC SIGNIFICANCE: Our study clarifies the degree to which uncontrolled eating phenotypes and BMI are influenced by shared genetics and shows that vulnerability to uncontrolled eating traits is impacted by common genetic factors.
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Índice de Masa Corporal , Fenotipo , Humanos , Femenino , Masculino , Adulto , Conducta Alimentaria , Gemelos Monocigóticos/genética , Trastornos de Alimentación y de la Ingestión de Alimentos/genética , Gemelos Dicigóticos/genética , Recompensa , Persona de Mediana Edad , Encuestas y Cuestionarios , Obesidad/genéticaRESUMEN
Neuroanatomical abnormalities have been reported along a continuum from at-risk stages, including high schizotypy, to early and chronic psychosis. However, a comprehensive neuroanatomical mapping of schizotypy remains to be established. The authors conducted the first large-scale meta-analyses of cortical and subcortical morphometric patterns of schizotypy in healthy individuals, and compared these patterns with neuroanatomical abnormalities observed in major psychiatric disorders. The sample comprised 3004 unmedicated healthy individuals (12-68 years, 46.5% male) from 29 cohorts of the worldwide ENIGMA Schizotypy working group. Cortical and subcortical effect size maps with schizotypy scores were generated using standardized methods. Pattern similarities were assessed between the schizotypy-related cortical and subcortical maps and effect size maps from comparisons of schizophrenia (SZ), bipolar disorder (BD) and major depression (MDD) patients with controls. Thicker right medial orbitofrontal/ventromedial prefrontal cortex (mOFC/vmPFC) was associated with higher schizotypy scores (r = 0.067, pFDR = 0.02). The cortical thickness profile in schizotypy was positively correlated with cortical abnormalities in SZ (r = 0.285, pspin = 0.024), but not BD (r = 0.166, pspin = 0.205) or MDD (r = -0.274, pspin = 0.073). The schizotypy-related subcortical volume pattern was negatively correlated with subcortical abnormalities in SZ (rho = -0.690, pspin = 0.006), BD (rho = -0.672, pspin = 0.009), and MDD (rho = -0.692, pspin = 0.004). Comprehensive mapping of schizotypy-related brain morphometry in the general population revealed a significant relationship between higher schizotypy and thicker mOFC/vmPFC, in the absence of confounding effects due to antipsychotic medication or disease chronicity. The cortical pattern similarity between schizotypy and schizophrenia yields new insights into a dimensional neurobiological continuity across the extended psychosis phenotype.
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Trastorno Bipolar , Trastornos Psicóticos , Esquizofrenia , Trastorno de la Personalidad Esquizotípica , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Trastornos Psicóticos/diagnóstico por imagen , Trastorno de la Personalidad Esquizotípica/diagnóstico por imagenRESUMEN
Goal-directed behavior is dependent upon the ability to detect errors and implement appropriate posterror adjustments. Accordingly, several studies have explored the neural activity underlying error-monitoring processes, identifying the insula cortex as crucial for error awareness and reporting mixed findings with respect to the anterior cingulate cortex (ACC). Variable patterns of activation have previously been attributed to insufficient statistical power. We therefore sought to clarify the neural correlates of error awareness in a large event-related functional magnetic resonance imaging (fMRI) study. Four hundred and two healthy participants undertook the error awareness task, a motor Go/No-Go response inhibition paradigm in which participants were required to indicate their awareness of commission errors. Compared to unaware errors, aware errors were accompanied by significantly greater activity in a network of regions, including the insula cortex, supramarginal gyrus (SMG), and midline structures, such as the ACC and supplementary motor area (SMA). Error awareness activity was related to indices of task performance and dimensional measures of psychopathology in selected regions, including the insula, SMG, and SMA. Taken together, we identified a robust and reliable neural network associated with error awareness.
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Giro del Cíngulo , Imagen por Resonancia Magnética , Humanos , Lóbulo Parietal , Análisis y Desempeño de Tareas , Inhibición Psicológica , Concienciación/fisiologíaRESUMEN
Adverse life events can inflict substantial long-term damage, which, paradoxically, has been posited to stem from initially adaptative responses to the challenges encountered in one's environment. Thus, identification of the mechanisms linking resilience against recent stressors to longer-term psychological vulnerability is key to understanding optimal functioning across multiple timescales. To address this issue, our study tested the relevance of neuro-reproductive maturation and senescence, respectively, to both resilience and longer-term risk for pathologies characterised by accelerated brain aging, specifically, Alzheimer's Disease (AD). Graph theoretical and partial least squares analyses were conducted on multimodal imaging, reported biological aging and recent adverse experience data from the Lifespan Human Connectome Project (HCP). Availability of reproductive maturation/senescence measures restricted our investigation to adolescent (N = 178) and middle-aged (N = 146) females. Psychological resilience was linked to age-specific brain senescence patterns suggestive of precocious functional development of somatomotor and control-relevant networks (adolescence) and earlier aging of default mode and salience/ventral attention systems (middle adulthood). Biological aging showed complementary associations with the neural patterns relevant to resilience in adolescence (positive relationship) versus middle-age (negative relationship). Transcriptomic and expression quantitative trait locus data analyses linked the neural aging patterns correlated with psychological resilience in middle adulthood to gene expression patterns suggestive of increased AD risk. Our results imply a partially antagonistic relationship between resilience against proximal stressors and longer-term psychological adjustment in later life. They thus underscore the importance of fine-tuning extant views on successful coping by considering the multiple timescales across which age-specific processes may unfold.
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Conectoma , Resiliencia Psicológica , Adolescente , Adulto , Envejecimiento/fisiología , Encéfalo/fisiología , Femenino , Humanos , Persona de Mediana Edad , TranscriptomaRESUMEN
Large-scale dynamics of the brain are routinely modelled using systems of nonlinear dynamical equations that describe the evolution of population-level activity, with distinct neural populations often coupled according to an empirically measured structural connectivity matrix. This modelling approach has been used to generate insights into the neural underpinnings of spontaneous brain dynamics, as recorded with techniques such as resting state functional MRI (fMRI). In fMRI, researchers have many degrees of freedom in the way that they can process the data and recent evidence indicates that the choice of pre-processing steps can have a major effect on empirical estimates of functional connectivity. However, the potential influence of such variations on modelling results are seldom considered. Here we show, using three popular whole-brain dynamical models, that different choices during fMRI preprocessing can dramatically affect model fits and interpretations of findings. Critically, we show that the ability of these models to accurately capture patterns in fMRI dynamics is mostly driven by the degree to which they fit global signals rather than interesting sources of coordinated neural dynamics. We show that widespread deflections can arise from simple global synchronisation. We introduce a simple two-parameter model that captures these fluctuations and performs just as well as more complex, multi-parameter biophysical models. From our combined analyses of data and simulations, we describe benchmarks to evaluate model fit and validity. Although most models are not resilient to denoising, we show that relaxing the approximation of homogeneous neural populations by more explicitly modelling inter-regional effective connectivity can improve model accuracy at the expense of increased model complexity. Our results suggest that many complex biophysical models may be fitting relatively trivial properties of the data, and underscore a need for tighter integration between data quality assurance and model development.
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Conectoma , Imagen por Resonancia Magnética , Encéfalo/diagnóstico por imagen , Conectoma/métodos , Exactitud de los Datos , Humanos , Imagen por Resonancia Magnética/métodos , Modelos EstadísticosRESUMEN
KEY POINTS: TMS is commonly used to study excitatory/inhibitory neurotransmission in cortical circuits. Changes in cortical excitability following TMS are typically measured from hand (using EMG; limited to motor cortex) or scalp (using EEG); however, it is unclear whether these two measures represent the same activity when assessing motor cortex. We found that TMS-EMG and TMS-EEG measures of motor cortex excitability are differentially affected by sensory confounds at different time points, masking any actual relationship between them in the time domain. In the frequency domain, local high-frequency oscillations in EEG recordings were minimally confounded by sensory artefacts and demonstrated strong correlations with EMG measures of cortical excitability across time, regardless of TMS intensity or waveform. Therefore, despite the effects of sensory artefacts, the two measures of motor cortex excitability share a response component, suggesting that they index a similar cortical activity and perhaps the same neuronal population. ABSTRACT: Transcranial magnetic stimulation (TMS) is a powerful tool for investigating cortical circuits. Changes in cortical excitability following TMS are typically assessed by measuring changes in either conditioned motor-evoked potentials (MEPs) following paired-pulse TMS over motor cortex or evoked potentials measured with electroencephalography following single-pulse TMS (TEPs). However, it is unclear whether these two measures of cortical excitability index the same cortical response. Twenty-four healthy participants received local and interhemispheric paired-pulse TMS over motor cortex with eight inter-pulse intervals, sub- and suprathreshold conditioning intensities, and two different pulse waveforms, while MEPs were recorded from a hand muscle. TEPs were also recorded in response to single-pulse TMS using the conditioning pulse alone. The relationships between TEPs and conditioned-MEPs were evaluated using metrics sensitive to both their magnitude at each time point and their overall shape across time. The impacts of undesired sensory potentials resulting from TMS pulse and muscle contractions were also assessed on both measures. Both conditioned-MEPs and TEPs were sensitive to re-afferent somatosensory activity following motor-evoked responses, but over different post-stimulus time points. Moreover, the amplitude of low-frequency oscillations in TEPs was strongly correlated with the sensory potentials, whereas early and local high-frequency responses showed minimal relationships. Accordingly, conditioned-MEPs did not correlate with TEPs in the time domain but showed high shape similarity with the amplitude of high-frequency oscillations in TEPs. Therefore, despite the effects of sensory confounds, the TEP and MEP measures share a response component, suggesting that they index a similar cortical response and perhaps the same neuronal populations.
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Corteza Motora , Estimulación Magnética Transcraneal , Electroencefalografía , Potenciales Evocados , Potenciales Evocados Motores , HumanosRESUMEN
The integration of modern neuroimaging methods with genetically informative designs and data can shed light on the molecular mechanisms underlying the structural and functional organization of the human connectome. Here, we review studies that have investigated the genetic basis of human brain network structure and function through three complementary frameworks: (1) the quantification of phenotypic heritability through classical twin designs; (2) the identification of specific DNA variants linked to phenotypic variation through association and related studies; and (3) the analysis of correlations between spatial variations in imaging phenotypes and gene expression profiles through the integration of neuroimaging and transcriptional atlas data. We consider the basic foundations, strengths, limitations, and discoveries associated with each approach. We present converging evidence to indicate that anatomical connectivity is under stronger genetic influence than functional connectivity and that genetic influences are not uniformly distributed throughout the brain, with phenotypic variation in certain regions and connections being under stronger genetic control than others. We also consider how the combination of imaging and genetics can be used to understand the ways in which genes may drive brain dysfunction in different clinical disorders.
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Encéfalo/diagnóstico por imagen , Conectoma/métodos , Variación Biológica Poblacional , Humanos , Neuroimagen , Fenotipo , Transcriptoma , GemelosRESUMEN
The structure of the adult brain is the result of complex physical mechanisms acting in three-dimensional space through development. Consequently, the brain's spatial embedding plays a key role in its organization, including the gradient-like patterning of gene expression that encodes the molecular underpinning of functional specialization. However, we do not yet understand how changes in brain shape and size that occur across development influence the brain's transcriptional architecture. Here we investigate the spatial embedding of transcriptional patterns of over 1800 genes across seven time points through mouse-brain development using data from the Allen Developing Mouse Brain Atlas. We find that transcriptional similarity decreases exponentially with separation distance across all developmental time points, with a correlation length scale that follows a power-law scaling relationship with a linear dimension of brain size. This scaling suggests that the mouse brain achieves a characteristic balance between local molecular similarity (homogeneous gene expression within a specialized brain area) and longer-range diversity (between functionally specialized brain areas) throughout its development. Extrapolating this mouse developmental scaling relationship to the human cortex yields a prediction consistent with the value measured from microarray data. We introduce a simple model of brain growth as spatially autocorrelated gene-expression gradients that expand through development, which captures key features of the mouse developmental data. Complementing the well-known exponential distance rule for structural connectivity, our findings characterize an analogous exponential distance rule for transcriptional gradients that scales across mouse brain development, providing new understanding of spatial constraints on the brain's molecular patterning.
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Encéfalo , Corteza Cerebral/fisiología , Expresión Génica/fisiología , Tamaño de los Órganos/fisiología , Animales , Encéfalo/crecimiento & desarrollo , Encéfalo/fisiología , Mapeo Encefálico/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Ratones Endogámicos C57BLRESUMEN
Brain function relies on a precisely coordinated and dynamic balance between the functional integration and segregation of distinct networks. Characterizing the way in which brain regions reconfigure their interactions to give rise to distinct but hidden brain states remains an open challenge. In this paper, we propose a Bayesian method for characterizing community structure-based latent brain states and showcase a novel strategy based on posterior predictive discrepancy using the latent block model to detect transitions between community structures in blood oxygen level-dependent (BOLD) time series. The set of estimated parameters in the model includes a latent label vector that assigns network nodes to communities, and also block model parameters that reflect the weighted connectivity within and between communities. Besides extensive in-silico model evaluation, we also provide empirical validation (and replication) using the Human Connectome Project (HCP) dataset of 100 healthy adults. Our results obtained through an analysis of task-fMRI data during working memory performance show appropriate lags between external task demands and change-points between brain states, with distinctive community patterns distinguishing fixation, low-demand and high-demand task conditions.
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Encéfalo/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Teorema de Bayes , Cognición , Simulación por Computador , Conectoma , Técnicas Histológicas , Humanos , Saturación de Oxígeno , Factores de TiempoRESUMEN
Numerous neuroimaging techniques have been used to identify biomarkers of disease progression in Huntington's disease (HD). To date, the earliest and most sensitive of these is caudate volume; however, it is becoming increasingly evident that numerous changes to cortical structures, and their interconnected networks, occur throughout the course of the disease. The mechanisms by which atrophy spreads from the caudate to these cortical regions remains unknown. In this review, the neuroimaging literature specific to T1-weighted and diffusion-weighted magnetic resonance imaging is summarized and new strategies for the investigation of cortical morphometry and the network spread of degeneration in HD are proposed. This new avenue of research may enable further characterization of disease pathology and could add to a suite of biomarker/s of disease progression for patient stratification that will help guide future clinical trials.
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Enfermedad de Huntington , Atrofia/patología , Encéfalo/patología , Progresión de la Enfermedad , Humanos , Enfermedad de Huntington/diagnóstico por imagen , Enfermedad de Huntington/patología , Imagen por Resonancia Magnética , NeuroimagenRESUMEN
OBJECTIVE: Synthetic cannabinoids (SCs) have become increasingly popular in recent years, especially among adolescents. The first aim of the current study was to examine resting-state functional connectivity (rsFC) in SC users compared to controls. Our second aim was to examine the influence of comorbid attention-deficit/hyperactivity disorder (ADHD) symptomatology on rsFC changes in SC users compared to controls. METHODS: Resting-state functional magnetic resonance imaging (fMRI) analysis included 25 SC users (14 without ADHD and 11 with ADHD combined type) and 12 control subjects. RESULTS: We found (i) higher rsFC between the default mode network (DMN) and salience network, dorsal attention network and cingulo-opercular network, and (ii) lower rsFC within the DMN and between the DMN and visual network in SC users compared to controls. There were no significant differences between SC users with ADHD and controls, nor were there any significant differences between SC users with and without ADHD. CONCLUSIONS: We found the first evidence of abnormalities within and between resting state networks in adolescent SC users without ADHD. In contrast, SC users with ADHD showed no differences compared to controls. These results suggest that comorbidity of ADHD and substance dependence may show different rsFC alterations than substance use alone.
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Trastorno por Déficit de Atención con Hiperactividad , Cannabinoides , Adolescente , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico por imagen , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Cannabinoides/efectos adversos , Humanos , Imagen por Resonancia Magnética/métodos , Vías Nerviosas/diagnóstico por imagenRESUMEN
One of the most controversial procedures in the analysis of resting-state functional magnetic resonance imaging (rsfMRI) data is global signal regression (GSR): the removal, via linear regression, of the mean signal averaged over the entire brain. On one hand, the global mean signal contains variance associated with respiratory, scanner-, and motion-related artifacts, and its removal via GSR improves various quality-control metrics, enhances the anatomical specificity of functional-connectivity patterns, and can increase the behavioral variance explained by such patterns. On the other hand, GSR alters the distribution of regional signal correlations in the brain, can induce artifactual anticorrelations, may remove real neural signal, and can distort case-control comparisons of functional-connectivity measures. Global signal fluctuations can be identified visually from a matrix of colour-coded signal intensities, called a carpet plot, in which rows represent voxels and columns represent time. Prior to GSR, large, periodic bands of coherent signal changes that affect most of the brain are often apparent; after GSR, these apparently global changes are greatly diminished. Here, using three independent datasets, we show that reordering carpet plots to emphasize cluster structure in the data reveals a greater diversity of spatially widespread signal deflections (WSDs) than previously thought. Their precise form varies across time and participants, and GSR is only effective in removing specific kinds of WSDs. We present an alternative, iterative correction method called Diffuse Cluster Estimation and Regression (DiCER), that identifies representative signals associated with large clusters of coherent voxels. DiCER is more effective than GSR at removing diverse WSDs as visualized in carpet plots, reduces correlations between functional connectivity and head-motion estimates, reduces inter-individual variability in global correlation structure, and results in comparable or improved identification of canonical functional-connectivity networks. Using task fMRI data across 47 contrasts from 7 tasks in the Human Connectome Project, we also present evidence that DiCER is more successful than GSR in preserving the spatial structure of expected task-related activation patterns. Our findings indicate that care must be exercised when examining WSDs (and their possible removal) in rsfMRI data, and that DiCER is a viable alternative to GSR for removing anatomically widespread and temporally coherent signals. All code for implementing DiCER and replicating our results is available at https://github.com/BMHLab/DiCER.
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Artefactos , Encéfalo/fisiología , Conectoma/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , HumanosRESUMEN
Numerous studies have investigated grey matter (GM) volume changes in diverse patient groups. Reports of disorder-related GM reductions are common in such work, but many studies also report evidence for GM volume increases in patients. It is unclear whether these GM increases and decreases are independent or related in some way. Here, we address this question using a novel meta-analytic network mapping approach. We used a coordinate-based meta-analysis of 64 voxel-based morphometry studies of psychiatric disorders to calculate the probability of finding a GM increase or decrease in one region given an observed change in the opposite direction in another region. Estimating this co-occurrence probability for every pair of brain regions allowed us to build a network of concurrent GM changes of opposing polarity. Our analysis revealed that disorder-related GM increases and decreases are not independent; instead, a GM change in one area is often statistically related to a change of opposite polarity in other areas, highlighting distributed yet coordinated changes in GM volume as a function of brain pathology. Most regions showing GM changes linked to an opposite change in a distal area were located in salience, executive-control and default mode networks, as well as the thalamus and basal ganglia. Moreover, pairs of regions showing coupled changes of opposite polarity were more likely to belong to different canonical networks than to the same one. Our results suggest that regional GM alterations in psychiatric disorders are often accompanied by opposing changes in distal regions that belong to distinct functional networks.
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Red en Modo Predeterminado , Sustancia Gris , Trastornos Mentales , Metaanálisis como Asunto , Red Nerviosa , Neuroimagen , Red en Modo Predeterminado/diagnóstico por imagen , Red en Modo Predeterminado/patología , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Humanos , Trastornos Mentales/diagnóstico por imagen , Trastornos Mentales/patología , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/patologíaRESUMEN
Head motion is a major confounding factor in neuroimaging studies. While numerous studies have investigated how motion impacts estimates of functional connectivity, the effects of motion on structural connectivity measured using diffusion MRI have not received the same level of attention, despite the fact that, like functional MRI, diffusion MRI relies on elaborate preprocessing pipelines that require multiple choices at each step. Here, we report a comprehensive analysis of how these choices influence motion-related contamination of structural connectivity estimates. Using a healthy adult sample (N = 294), we evaluated 240 different preprocessing pipelines, devised using plausible combinations of different choices related to explicit head motion correction, tractography propagation algorithms, track seeding methods, track termination constraints, quantitative metrics derived for each connectome edge, and parcellations. We found that an approach to motion correction that includes outlier replacement and within-slice volume correction led to a dramatic reduction in cross-subject correlations between head motion and structural connectivity strength, and that motion contamination is more severe when quantifying connectivity strength using mean tract fractional anisotropy rather than streamline count. We also show that the choice of preprocessing strategy can significantly influence subsequent inferences about network organization, with the location of network hubs varying considerably depending on the specific preprocessing steps applied. Our findings indicate that the impact of motion on structural connectivity can be successfully mitigated using recent motion-correction algorithms that include outlier replacement and within-slice motion correction.