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Corbetta, M.

Publications and source records attributed to Corbetta, M..

At least 37 records · Page 2Linked to original sources

Deep Learning disconnectomes to accelerate and improve long-term predictions for post-stroke symptoms

Deep learning as a truly transformative force is revolutionizing a wide range of fields, making a significant difference in medical imaging, where recent advancements have yielded some truly remarkable outcomes. In a connected brain, maps of white matter damage -- otherwise known as disconnectomes -- are essential for capturing the effects of focal lesions. However, the current tools for obtaining such information are prohibitively slow and not admitted for clinical usage. Here, we have explored the potential of deep-learning models to accurately generate disconnectomes in a population of stroke survivors. We trained a 3D U-Net algorithm to produce deep-disconnectomes from binary lesion masks. This artificial neural network was able to capture most information obtained in conventional disconnectomes, i.e., statistical maps filtering normative white-matter networks, but output a deep-disconnectome 170 times faster - compared to disconnectome computation with the state-of-the-art BCBToolkit software. Moreover, the deep-disconnectomes were challenged to predict cognitive and behavioral outcomes one-year post-stroke. In an additional cohort of N=139 stroke survivors, N=86 neuropsychological scores were predicted from deep-disconnectomes achieving, on average, 85.2% of accuracy and R2= 0.208. The deep-disconnectomes predictivity power outperformed the conventional disconnectome predictions for clinical scores. In summary, we have achieved a significant milestone for clinical neuroimaging by accelerating and ameliorating the creation of disconnectome maps using deep learning. By integrating deep learning into the management of stroke, one of the most prevailing catalysts for acquired disabilities, we deepen our understanding of its impact on the brain. This novel approach may offer potential avenues for acute intervention, ultimately enhancing patients overall quality of life.

neuroscience↗

Encoding manual dexterity through modulation of intrinsic alpha band connectivity

Using hands proficiently implies consolidated motor skills, yet malleable to task demands. How the brain realizes this balance between stability and flexibility is unknown. At rest, in absence of overt input or behavior, the communication within the brain may represent a neural prior of stored memories. This magnetoencephalography study addresses how the modulation of such stable connectivity, induced by motor tasks, relates to proficient behavior. To this aim, we estimated functional connectivity from 51 participants of the Human Connectome Project during rest and finger tapping in alpha and beta bands. We identified two groups of participants characterized by opposite patterns of connectivity strength and topology. High and low performers showed distributed decreases and increases of connectivity, respectively. However, while dexterous individuals also show modulations of the motor network, low performers exhibited a stability of such connections. Furthermore, in dexterous individuals, an increased segregation was observed through an increment of network modularity and decrease of nodal centrality. Instead, low performers show a dysfunctional increased integration. Our findings reveal that the balance between stability and flexibility is not fixed; rather it constrains proficient behavior.

neuroscience↗

Controlling target brain regions by optimal selection of input nodes

The network control theory framework holds great potential to inform neurostimulation experiments aimed at inducing desired activity states in the brain. However, the current applicability of the framework is limited by inaccurate modeling of brain dynamics, and an overly ambitious focus on whole-brain activity control. In this work, we leverage recent progress in linear modeling of brain dynamics (effective connectivity) and we exploit the concept of target controllability to focus on the control of a single region or a small subnetwork of nodes. We discuss when control may be possible with a reasonably low energy cost and few stimulation loci, and give general predictions on where to stimulate depending on the subset of regions one wishes to control. Importantly, using the robustly asymmetric effective connectome instead of the symmetric structural connectome (as in previous research), we highlight the fundamentally different roles in- and out-hubs have in the control problem, and the relevance of inhibitory connections. The large degree of inter-individual variation in the effective connectome implies that the control problem is best formulated at the individual level, but we discuss to what extent group results may still prove useful.

neuroscience↗

A new framework for metabolic connectivity mapping using bolus FDG PET and kinetic modelling

PurposeMetabolic connectivity (MC) has been previously proposed as the covariation of static [18F]FDG PET images across participants, which we call across-individual MC (ai-MC). In few cases, MC has also been inferred from dynamic [18F]FDG signals, similarly to fMRI functional connectivity (FC), which we term within-individual MC (wi-MC). The validity and interpretability of both MC approaches is an important open issue. Here we reassess this topic, aiming to 1) develop a novel methodology for wi-MC estimation; 2) compare ai-MC maps obtained using different [18F]FDG parameters (K1, i.e. tracer transport rate, k3, i.e. phosphorylation rate, Ki, i.e. tracer uptake rate, and the standardized uptake value ratio, SUVR); 3) assess the interpretability of ai-MC and wi-MC in comparison to structural and functional connectivity (FC) measures. MethodsWe analyzed dynamic [18F]FDG data from 54 healthy adults using kinetic modelling to quantify the macro- and microparameters describing the tracer behavior (i.e. Ki, K1, k3). We also calculated SUVR. From the across-individual correlation of SUVR, Ki, K1, k3, we obtained four different ai-MC matrices. A new approach based on Euclidean distance was developed to calculate wi-MC from PET time-activity curves. ResultsWe identified Euclidean similarity as the most appropriate metric to calculate wi-MC. ai-MC networks changed with different [18F]FDG parameters (k3 MC vs. SUVR MC, r = 0.44). We found that wi-MC and ai-MC matrices are dissimilar (maximum r = 0.37), and that the match with FC is higher for wi-MC (Dice similarity: 0.47-0.63) than for ai-MC (0.24-0.39). ConclusionOur data demonstrate that individual-level MC from dynamic [18F]FDG data using Euclidean similarity is feasible and yields interpretable matrices that bear similarity to resting-state fMRI FC measures.

bioengineering↗

A low dimensional cognitive-network space in Alzheimer's disease and frontotemporal dementia

Network neuroscience is a promising approach to explore cognitive processes in neurological disorders. Alzheimers disease (AD) and frontotemporal dementia (FTD) show network dysfunctions linked with cognitive deficits. Within this framework, network abnormalities between AD and FTD show both convergent and divergent patterns. However, these functional patterns are far from being established and their relevance to cognitive processes remains to be elucidated. In this study, we aimed to investigate the relationship between cognition and functional connectivity of major cognitive networks in these diseases. Twenty-three bvFTD (age: 71{+/-}10), 22 AD (age: 72{+/-}6) and 20 controls (age: 72{+/-}6) underwent cognitive evaluation and resting-state functional MRI. Principal component analysis was used to describe cognitive variance across participants. Brain network connectivity was estimated with connectome analysis. Connectivity matrices were created assessing correlations between parcels within each functional network. The following cognitive networks were considered: default mode (DMN), dorsal attention (DAN), ventral attention (VAN) and frontoparietal (FPN) networks. The relationship between cognition and connectivity was assessed using a robust convergent correlation-wise and interaction analyses. Three principal cognitive components explained more than 80% of the cognitive variance: the first component (cogPC1) loaded on memory, the second component (cogPC2) loaded on emotion and language, the third component (cogPC3) loaded on the visuo-spatial and attentional domains. Compared to HC, AD and bvFTD showed impairment in all cogPCs (p<0.002), and bvFTD scored worse than AD in cogPC2 (p=0.031). At the network level, the DMN showed a robust association in the whole group with cogPC1 and cogPC2, and the VAN with cogPC2. By contrast, DAN and FPN showed a divergent pattern between diagnosis and connectivity for cogPC2. We confirmed these results by means of a multivariate analysis (canonical correlation). These results suggest that a low-dimensional representation can account for a large variance in cognitive scores in the continuum from normal to pathological aging. Moreover, cognitive components showed both convergent and divergent patterns with connectivity across AD and bvFTD. The convergent pattern was observed across the networks primarily involved in these diseases (i.e., the DMN and VAN), while a divergent FC-cognitive pattern was mainly observed between attention/executive networks and the language/emotion cognitive component, suggesting the co-existence of compensatory and detrimental mechanisms underlying these components.

neuroscience↗

A visual representation of the hand in the resting somatomotor regions of the human brain

Hands are regularly in sight in everyday life. This visibility affects motor control, perception, and attention, as visual information is integrated into an internal model of sensorimotor control. Spontaneous brain activity, i.e., ongoing activity in the absence of an active task (rest), is correlated among somatomotor regions that are jointly activated during motor tasks1. Moreover, recent studies suggest that spontaneous activity patterns do not only replay at rest task activation patterns, but also maintain a model of the statistical regularities (priors) of the body and environment, which may be used to predict upcoming behavior2-4. Here we test whether spontaneous activity in the human somatomotor cortex is modulated by visual stimuli that display hands vs. non-hand stimuli, and by the use/action they represent. We analyzed activity with fMRI and multivariate pattern analysis to examine the similarity between spontaneous (rest) activity patterns and task-evoked patterns to the presentation of natural hands, robot hands, gloves, or control stimuli (food). In the left somatomotor cortex we observed a stronger (multi-voxel) spatial correlation between resting-state activity and natural hand picture patterns, as compared to other stimuli. A trend analysis showed that task-rest pattern similarity was influenced by inferred visual and motor attributes (i.e., correlation for hand>robot>glove>food). We did not observe any task-rest similarity in the visual cortex. We conclude that somatomotor brain regions code at rest for visual representations of hand stimuli and their inferred use.

neuroscience↗

Stroke-related alterations in inter-areal communication revealed via Granger causality analysis

Beyond causing local ischemia and cell damage at the site of injury, stroke strongly affects long-range anatomical connections, perturbing the functional organization of brain networks. Several studies reported functional connectivity abnormalities parallelling both behavioral deficits and functional recovery across different cognitive domains. FC alterations suggest that long-range communication in the brain is altered after stroke. However, standard FC analyses cannot reveal the directionality and time scale of inter-areal information transfer. We used resting-state fMRI and covariance-based Granger causality analysis to quantify network-level information transfer and its alteration in stroke. Two main large-scale anomalies were observed in stroke patients. First, inter-hemispheric information transfer was significantly decreased with respect to healthy controls. Second, stroke caused inter-hemispheric asymmetries, as information transfer within the affected hemisphere and from the affected to the intact hemisphere was significantly reduced. Both anomalies were more prominent in resting-state networks related to attention and language, and they correlated with impaired performance in several behavioral domains. Overall, our findings support the hypothesis that stroke provokes asymmetries between the affected and spared hemisphere, with different functional consequences depending on which hemisphere is lesioned.

neuroscience↗

Recovery of neural dynamics criticality in personalized whole brain models of stroke

The critical brain hypothesis states that biological neuronal networks, because of their structural and functional architecture, work near phase transitions for optimal response to internal and external inputs. Criticality thus provides optimal function and behavioral capabilities. We test this hypothesis by examining the influence of brain injury (strokes) on the criticality of neural dynamics estimated at the level of single participants using directly measured individual structural connectomes and whole-brain models. Lesions engender a sub-critical state that recovers over time in parallel with behavior. The improvement of criticality is associated with the re-modeling of specific white matter connections. We show that personalized whole-brain dynamical models poised at criticality track neural dynamics, alteration post-stroke, and behavior at the level of single participants.

neuroscience↗

Spontaneous emergence of behaviorally relevant motifs in human motor cortex

Spontaneous neural activity has been shown to preserve the inter-regional structure of cortical activity evoked by a task. It is unclear, however, whether patterns of spontaneous activity within a cortical region comprise representations associated with specific behaviors or mental states. The current study investigated the hypothesis that spontaneous neural activity in human motor cortex represents motor responses that commonly occur in daily life. To test this hypothesis 15 healthy participants were scanned in a 3T fMRI scanner while performing four simple hand movements differing by their daily life relevance, and while not performing any specific task (resting-state scans). Using the task data, we identified cortical patterns in a motor ROI corresponding to the different hand movements. These task-defined patterns were compared to spontaneous cortical activity patterns in the same motor ROI. The results indicated a higher similarity of the spontaneous patterns to the most common hand movement than to the least common hand movement. This finding provides the first evidence that spontaneous activity in human cortex forms fine-scale, patterned representations associated with behaviors that frequently occur in daily life.

neuroscience↗

Lesion Quantification Toolkit: A MATLAB software tool for estimating grey matter damage and white matter disconnections in patients with focal brain lesions

Lesion studies are an important tool for cognitive neuroscientists and neurologists. However, while brain lesion studies have traditionally aimed to localize neurological symptoms to specific anatomical loci, a growing body of evidence indicates that neurological diseases such as stroke are best conceptualized as brain network disorders. While researchers in the fields of neuroscience and neurology are therefore increasingly interested in quantifying the effects of focal brain lesions on the white matter connections that form the brains structural connectome, few dedicated tools exist to facilitate this endeavor. Here, we present the Lesion Quantification Toolkit, a publicly available MATLAB software package for quantifying the structural impacts of focal brain lesions. The Lesion Quantification Toolkit uses atlas-based approaches to estimate parcel-level grey matter lesion loads and multiple measures of white matter disconnection severity that include tract-level disconnection measures, voxel-wise disconnection maps, and parcel-wise disconnection matrices. The toolkit also estimates lesion-induced increases in the lengths of the shortest structural paths between parcel pairs, which provide information about changes in higher-order structural network topology. We describe in detail each of the different measures produced by the toolkit, discuss their applications and considerations relevant to their use, and perform example analyses using real behavioral data collected from sub-acute stroke patients. We show that analyses performed using the different measures produced by the toolkit produce results that are highly consistent with results that have been reported in the prior literature, and we demonstrate the consistency of results obtained from analyses conducted using the different disconnection measures produced by the toolkit. We anticipate that the Lesion Quantification Toolkit will empower researchers to address research questions that would be difficult or impossible to address using traditional lesion analyses alone, and ultimately, lead to advances in our understanding of how white matter disconnections contribute to the cognitive, behavioral, and physiological consequences of focal brain lesions.

neuroscience↗

Structural disconnections contribute to lesion-induced brain functional connectivity disruptions via direct and indirect mechanisms

Focal brain lesions disrupt resting-state functional connectivity, but the underlying structural mechanisms are unclear. Here, we examined the direct and indirect effects of structural disconnections on resting-state functional connectivity in a large sample of sub-acute stroke patients with heterogeneous brain lesions. We defined direct disconnections as the loss of direct structural connections between two regions, and indirect disconnections as increases in the shortest structural path length between two regions that lack direct structural connections. On average, nearly 20% of all region pairs suffered either a direct or indirect disconnection by the lesions in our sample. Importantly, both directly and indirectly disconnected region pairs showed more severe functional connectivity disruptions than region pairs with spared direct and indirect connections, respectively, although functional connectivity disruptions tended to be most severe between region pairs that sustained direct structural disconnections. Together, these results emphasize the widespread impacts of focal brain lesions on the structural connectome, and show that these impacts are reflected by disruptions of the functional connectome. Further, they indicate that in addition to direct structural disconnections, lesion-induced increases in the structural shortest path lengths between indirectly structurally connected region pairs provide information about the remote functional disruptions caused by focal brain lesions.

neuroscience↗

Structural disconnections explain brain network dysfunction after stroke

SummaryFunctional connectivity (FC) studies have identified physiological signatures of stroke that correlate with behavior. Using structural and functional MRI data from 114 stroke patients, 24 matched controls, and the Human Connectome Project, we tested the hypothesis that structural disconnection, not damage to critical regions, underlies FC disruptions. Disconnection severity outperformed damage to putative FC connector nodes for explaining reductions in system modularity, and multivariate models based on disconnection outperformed damage models for explaining FC disruptions within and between systems. Across patients, disconnection and FC patterns exhibited a low-dimensional covariance dominated by a single axis linking interhemispheric disconnections to reductions in FC measures of interhemispheric system integration, ipsilesional system segregation, and system modularity, and that correlated with multiple behavioral deficits. These findings clarify the structural basis of FC disruptions in stroke patients and demonstrate a low-dimensional link between perturbations of the structural connectome, disruptions of the functional connectome, and behavioral deficits.

neuroscience↗

MOU-EC: model-based whole-brain effective connectivity to extract biomarkers for brain dynamics from fMRI data and study distributed cognition

Neuroimaging techniques are increasingly used to study brain cognition in humans. Beyond their individual activation, the functional associations between brain areas have become a standard proxy to describe how information is distributed across the brain network. Among the many analysis tools available, dynamic models of brain activity have been developed to overcome the limitations of original connectivity measures such as functional connectivity. In particular, much effort has been devoted to the assessment of directional interactions between brain areas from their observed activity. This paper summarizes our recent approach to analyze fMRI data based on our whole-brain effective connectivity referred to as MOU-EC, while discussing the pros and cons of its underlying assumptions with respect to other established approaches. Once tuned, the model provides a connectivity measure that reflects the dynamical state of BOLD activity obtained using fMRI, which can be used to explore the brain cognition. We focus on two important applications. First, as a connectivity measure, MOU-EC can be used to extract biomarkers for task-specific brain coordination, understood as the patterns of areas exchanging information. The multivariate nature of connectivity measures raises several challenges for whole-brain analysis, for which machine-learning tools presents some advantages over statistical testing. Second, we show how to interpret changes in MOU-EC connections in a collective and model-based manner, bridging with network analysis. To illustrate our framework, we use a dataset where subjects were recorded in two conditions, watching a movie and a black screen (referred to as rest). Our framework provides a comprehensive set of tools that open exciting perspectives for the study of distributed cognition, as well as neuropathologies.

neuroscience↗

Resting multivoxel activity patterns in human visual cortex are linked to patterns evoked by preferred visual stimuli

The function of spontaneous brain activity is an important issue in neuroscience. Here we test the hypothesis that patterns of spontaneous activity code representational patterns evoked by stimuli and tasks. We compared in human visual cortex multi-vertex patterns of spontaneous activity to patterns evoked by ecological visual stimuli (faces, bodies, scenes) and low-level visual features (e.g. phase-scrambled faces). Specifically, we identified regions that preferred particular stimulus categories during localizer scans (e.g. extra-striate body area for bodies), measured multi-vertex patterns for each category during event-related task scans, and then correlated over vertices these stimulus-evoked patterns to the pattern measured on each frame of resting-state scans. The mean correlation coefficient was essentially zero for all regions/stimulus categories, indicating that resting multi-vertex patterns were not biased toward particular stimulus-evoked patterns. However, the spread of correlation coefficients between stimulus-evoked and resting patterns, i.e. both positive and negative, was significantly greater for the preferred stimulus category of an ROI (e.g. body category in body-preferring ROIs). The relationship between spontaneous and stimulus-evoked multi-vertex patterns also governed the temporal correlation or functional connectivity of patterns of spontaneous activity between individual regions (pattern-based functional connectivity). Resting patterns related to an object category fluctuated preferentially between ROIs preferring the same category, and patterns related to different categories fluctuated independently within their respective preferred ROIs (e.g. body- and scene-related multi-vertex patterns within body- and scene-preferring ROIs). These results support the general proposal that spontaneous multi-vertex activity patterns are linked to stimulus-evoked patterns, consistent with a representational function for spontaneous activity.

neuroscience↗

Architecture of functional lateralisation in the human brain

Functional lateralisation is a fundamental principle of the human brain. However, a comprehensive taxonomy of functional lateralisation and its organisation in the brain is missing. We report the first complete map of functional hemispheric asymmetries in the human brain, reveal its low dimensional structure, and its relationship with structural inter-hemispheric connectivity. Our results suggest that the lateralisation of brain functions is distributed along four functional axes: symbolic communication, perception/action, emotion, and decision-making, and that cortical regions showing asymmetries in task-evoked activity have reduced connections with the opposite hemisphere.

neuroscience↗

Comparison of stimulus-evoked BOLD responses in human and monkey visual cortex

We characterized the blood oxygenation level dependent (BOLD) signal in humans and macaque monkeys by comparing the response in visual cortex to a single checkerboard or two checkerboards, spaced 1.5, 3.0, or 4.5 s apart. We found that the magnitude and shape of the BOLD response to a single checkerboard was similar in the two species. In addition, we found that the BOLD responses summed similarly, and that at an inter-stimulus interval (ISI) of 4.5 sec BOLD summation was nearly linear in both species. When comparing the ratio of the amplitude of the response to the second checkerboard at the 4.5 sec ISI with that of the single checkerboard between subjects in both species, the results from both monkey subjects fell within one standard deviation of the mean human results (human mean (n=12): .95 +/- .31 second/single response amplitude; monkey 1: 1.16; monkey 2: .86). At the shorter ISIs, both species demonstrated increased suppression of the BOLD response to the second checkerboard. These findings indicate that the magnitude of the BOLD response to events separated by 4.5 seconds can be accurately measured in and compared between human and monkey visual cortex.

neuroscience↗

Topographic Organization of Extraoccipital Visual Processing Areas in the Macaque

The macaque visual system has long been used as a model for investigating the processing of incoming visual stimuli results from the coordinated work of a distributed network of areas interacting at many different levels (Felleman and Van Essen, 1991). While much is known about the organization and layout of the occipital visual areas, there are still substantial gaps in our understanding of layout and organization of the higher-level areas. The goal of this study is to describe the whole brain functional anatomy using BOLD-fMRI in macaques performing a series of demanding visuospatial attention tasks. We wish to study the spatial specificity of visual responses in terms of contralateral preference, i.e. stronger responses to contralateral visual stimuli, as well as retinotopic organization both in terms of polar angle and eccentricity. We found that most visuospatial processing areas only respond to contralaterally presented stimuli; ipsilaterally presented stimuli evoked little or no activity in these areas. Additionally, we found that LIP, MT, and possibly PITd contained polar-angle maps of the contralateral hemifield. These same areas, plus FEF and area 46, appear to have separate representations of the fovea and periphery. When compared to previous human fMRI studies, these results indicate that there may be significant differences between macaque visual processing areas and their putative human homologues.

neuroscience↗

Attentional Modulation of Macaque Visual Processing Areas

Introduction Introduction Materials and Methods Results Discussion References The visual expectation that an object will appear at a certain location or time may increase the accuracy and speed of its detection (Eriksen and Hoffman, 1974; Posner, 1980; Carrasco et al., 2000; Dosher and Z-L., 2000). The ability to use prior information to enhance the processing of visual stimuli at a specific location is critical for quickly sorting through the myriad of incoming stimuli and making decisions regarding future actions. This selection process, known as visual attention, appears to be fundamental to our ability to navigate and interact with the environment, and accordingly has been the focus of innumerable psychological and neurobiological studies (Pa ...

neuroscience↗