brainlife.io: a decentralized and open-source cloud platform to support neuroscience research.

Neuroscience is advancing standardization and tool development to support rigor and transparency. Consequently, data pipeline complexity has increased, hindering FAIR (findable, accessible, interoperable and reusable) access. brainlife.io was developed to democratize neuroimaging research. The platform provides data standardization, management, visualization and processing and automatically tracks the provenance history of thousands of data objects. Here, brainlife.io is described and evaluated for validity, reliability, reproducibility, replicability and scientific utility using four data modalities and 3,200 participants.

Intra-V1 functional networks and classification of observed stimuli.

Introduction: Previous studies suggest that co-fluctuations in neural activity within V1 (measured with fMRI) carry information about observed stimuli, potentially reflecting various cognitive mechanisms. This study explores the neural sources shaping this information by using different fMRI preprocessing methods. The common response to stimuli shared by all individuals can be emphasized by using inter-subject correlations or de-emphasized by deconvolving the fMRI with hemodynamic response functions (HRFs) before calculating the correlations. The latter approach shifts the balance towards participant-idiosyncratic activity. Methods: Here, we used multivariate pattern analysis of intra-V1 correlation matrices to predict the Level or Shape of observed Navon letters employing the types of correlations described above. We assessed accuracy in inter-subject prediction of specific conjunctions of properties, and attempted intra-subject cross-classification of stimulus properties (i.e., prediction of one feature despite changes in the other). Weight maps from successful classifiers were projected onto the visual field. A control experiment investigated eye-movement patterns during stimuli presentation. Results: All inter-subject classifiers accurately predicted the Level and Shape of specific observed stimuli. However, successful intra-subject cross-classification was achieved only for stimulus Level, but not Shape, regardless of preprocessing scheme. Weight maps for successful Level classification differed between inter-subject correlations and deconvolved correlations. The latter revealed asymmetries in visual field link strength that corresponded to known perceptual asymmetries. Post-hoc measurement of eyeball fMRI signals did not find differences in gaze between stimulus conditions, and a control experiment (with derived simulations) also suggested that eye movements do not explain the stimulus-related changes in V1 topology. Discussion: Our findings indicate that both inter-subject common responses and participant-specific activity contribute to the information in intra-V1 co-fluctuations, albeit through distinct sub-networks. Deconvolution, that enhances subject-specific activity, highlighted interhemispheric links for Global stimuli. Further exploration of intra-V1 networks promises insights into the neural basis of attention and perceptual organization.

Cognitive modelling of concepts in the mental lexicon with multilayer networks: Insights, advancements, and future challenges.

The mental lexicon is a complex cognitive system representing information about the words/concepts that one knows. Over decades psychological experiments have shown that conceptual associations across multiple, interactive cognitive levels can greatly influence word acquisition, storage, and processing. How can semantic, phonological, syntactic, and other types of conceptual associations be mapped within a coherent mathematical framework to study how the mental lexicon works? Here we review cognitive multilayer networks as a promising quantitative and interpretative framework for investigating the mental lexicon. Cognitive multilayer networks can map multiple types of information at once, thus capturing how different layers of associations might co-exist within the mental lexicon and influence cognitive processing. This review starts with a gentle introduction to the structure and formalism of multilayer networks. We then discuss quantitative mechanisms of psychological phenomena that could not be observed in single-layer networks and were only unveiled by combining multiple layers of the lexicon: (i) multiplex viability highlights language kernels and facilitative effects of knowledge processing in healthy and clinical populations; (ii) multilayer community detection enables contextual meaning reconstruction depending on psycholinguistic features; (iii) layer analysis can mediate latent interactions of mediation, suppression, and facilitation for lexical access. By outlining novel quantitative perspectives where multilayer networks can shed light on cognitive knowledge representations, including in next-generation brain/mind models, we discuss key limitations and promising directions for cutting-edge future research.

Assessing cortical excitability with electroencephalography: A pilot study with EEG-iTBS.

BACKGROUND: Cortical excitability measures neural reactivity to stimuli, usually delivered via Transcranial Magnetic Stimulation (TMS). Excitation/inhibition balance (E/I) is the ongoing equilibrium between excitatory and inhibitory activity of neural circuits. According to some studies, E/I could be estimated in-vivo and non-invasively through the modeling of electroencephalography (EEG) signals and termed 'intrinsic excitability' measures. Several measures have been proposed (phase consistency in the gamma band, sample entropy, exponent of the power spectral density 1/f curve, E/I index extracted from detrend fluctuation analysis, and alpha power). Intermittent theta burst stimulation (iTBS) of the primary motor cortex (M1) is a non-invasive neuromodulation technique allowing controlled and focal enhancement of TMS cortical excitability and E/I of the stimulated hemisphere. OBJECTIVE: Investigating to what extent E/I estimates scale with TMS excitability and how they relate to each other. METHODS: M1 excitability (TMS) and several E/I estimates extracted from resting state EEG recordings were assessed before and after iTBS in a cohort of healthy subjects. RESULTS: Enhancement of TMS M1 excitability, as measured through motor-evoked potentials (MEPs), and phase consistency of the cortex in high gamma band correlated with each other. Other measures of E/I showed some expected results, but no correlation with TMS excitability measures or strong consistency with each other. CONCLUSIONS: EEG E/I estimates offer an intriguing opportunity to map cortical excitability non-invasively, with high spatio-temporal resolution and with a stimulus independent approach. While different EEG E/I estimates may reflect the activity of diverse excitatory-inhibitory circuits, spatial phase synchrony in the gamma band is the measure that best captures excitability changes in the primary motor cortex.

Investigating Dynamic High-Order Interactions in Physiological Networks through Predictive Information Decomposition.

We present an approach to assess redundant and synergistic interactions in network systems via the information-theoretic analysis of multivariate physiological processes. The approach sets up a strategy to decompose the information shared between the present states of a group of random processes and their own past states into unique contributions arising from the past of subgroups of processes and redundant and synergistic contributions arising from the dynamic interaction among the subgroups. The method is illustrated in a theoretical example of linearly interacting Gaussian processes, showing that redundancy and synergy are related mostly to unidirectional coupling and to bidirectional coupling with internal dynamics. It is then applied to the network of short-term heart period, arterial pressure and respiratory variability probed in healthy subjects, showing that redundancy and synergy prevail respectively in cardiorespiratory interactions and in cardiovascular interactions in the resting state, and that postural stress increases the predictive information and the redundancy of physiological interactions.

Auditory white noise exposure results in intrinsic cortical excitability changes.

Cortical excitability is commonly measured by applying magnetic stimulation in combination with measuring behavioral response. This measure has, however, some shortcomings including spatial limitation to the primary motor cortex and not accounting for intrinsic excitability fluctuations. Here, we use a measure for intrinsic excitability based on phase synchronization previously validated for epilepsy. We apply this measure in 30 healthy participants' magnetoencephalography (MEG) recordings during the exposure of auditory white noise, a stimulus that has been suggested to modify cortical excitability. Using cortical parcellation of the MEG source data, we could find a specific pattern of increased and decreased excitability while participants are exposed to white noise vs. silence. Specifically, excitability during white noise exposure decreases in the frontal lobe and increases in the temporal lobe. This study thus adds to the understanding of cortical excitability changes due to specific environmental stimuli as well as the spatial extent of these effects.

brainlife.io: A decentralized and open source cloud platform to support neuroscience research.

Neuroscience research has expanded dramatically over the past 30 years by advancing standardization and tool development to support rigor and transparency. Consequently, the complexity of the data pipeline has also increased, hindering access to FAIR data analysis to portions of the worldwide research community. brainlife.io was developed to reduce these burdens and democratize modern neuroscience research across institutions and career levels. Using community software and hardware infrastructure, the platform provides open-source data standardization, management, visualization, and processing and simplifies the data pipeline. brainlife.io automatically tracks the provenance history of thousands of data objects, supporting simplicity, efficiency, and transparency in neuroscience research. Here brainlife.io's technology and data services are described and evaluated for validity, reliability, reproducibility, replicability, and scientific utility. Using data from 4 modalities and 3,200 participants, we demonstrate that brainlife.io's services produce outputs that adhere to best practices in modern neuroscience research.

Reduced connectivity of primary auditory and motor cortices during exposure to auditory white noise.

Auditory white noise (WN) is widely used in daily life for inducing sleep, and in neuroscience to mask unwanted environmental noise and cues. However, WN was recently reported to influence corticospinal excitability and behavioral performance. Here, we expand previous preliminary findings on the influence of WN exposure on cortical functioning, and we hypothesize that it may modulate cortical connectivity. We tested our hypothesis by performing magnetoencephalography in 20 healthy subjects. WN reduces cortical connectivity of the primary auditory and motor regions with very distant cortical areas, showing a right lateralized connectivity reduction for primary motor cortex. The present results, together with previous finding concerning WN impact on corticospinal excitability and behavioral performance, further support the role of WN as a modulator of cortical function. This suggest avoiding its unrestricted use as a masking tool, while purposely designed and controlled WN application could be exploited to harness brain function and to treat neuropsychiatric conditions.

Task matters: Individual MEG signatures from naturalistic and neurophysiological brain states.

The discovery that human brain connectivity data can be used as a "fingerprint" to identify a given individual from a population, has become a burgeoning research area in the neuroscience field. Recent studies have identified the possibility to extract these brain signatures from the temporal rich dynamics of resting-state magneto encephalography (MEG) recordings. Nevertheless, it is still uncertain to what extent MEG signatures can serve as an indicator of human identifiability during task-related conduct. Here, using MEG data from naturalistic and neurophysiological tasks, we show that identification improves in tasks relative to resting-state, providing compelling evidence for a task dependent axis of MEG signatures. Notably, improvements in identifiability were more prominent in strictly controlled tasks. Lastly, the brain regions contributing most towards individual identification were also modified when engaged in task activities. We hope that this investigation advances our understanding of the driving factors behind brain identification from MEG signals.

Gradients of O-information highlight synergy and redundancy in physiological applications.

The study of high order dependencies in complex systems has recently led to the introduction of statistical synergy, a novel quantity corresponding to a form of emergence in which patterns at large scales are not traceable from lower scales. As a consequence, several works in the last years dealt with the synergy and its counterpart, the redundancy. In particular, the O-information is a signed metric that measures the balance between redundant and synergistic statistical dependencies. In spite of its growing use, this metric does not provide insight about the role played by low-order scales in the formation of high order effects. To fill this gap, the framework for the computation of the O-information has been recently expanded introducing the so-called gradients of this metric, which measure the irreducible contribution of a variable (or a group of variables) to the high order informational circuits of a system. Here, we review the theory behind the O-information and its gradients and present the potential of these concepts in the field of network physiology, showing two new applications relevant to brain functional connectivity probed via functional resonance imaging and physiological interactions among the variability of heart rate, arterial pressure, respiration and cerebral blood flow.

Dynamic causal modelling shows a prominent role of local inhibition in alpha power modulation in higher visual cortex.

During resting-state EEG recordings, alpha activity is more prominent over the posterior cortex in eyes-closed (EC) conditions compared to eyes-open (EO). In this study, we characterized the difference in spectra between EO and EC conditions using dynamic causal modelling. Specifically, we investigated the role of intrinsic and extrinsic connectivity-within the visual cortex-in generating EC-EO alpha power differences over posterior electrodes. The primary visual cortex (V1) and the bilateral middle temporal visual areas (V5) were equipped with bidirectional extrinsic connections using a canonical microcircuit. The states of four intrinsically coupled subpopulations-within each occipital source-were also modelled. Using Bayesian model selection, we tested whether modulations of the intrinsic connections in V1, V5 or extrinsic connections (or a combination thereof) provided the best evidence for the data. In addition, using parametric empirical Bayes (PEB), we estimated group averages under the winning model. Bayesian model selection showed that the winning model contained both extrinsic connectivity modulations, as well as intrinsic connectivity modulations in all sources. The PEB analysis revealed increased extrinsic connectivity during EC. Overall, we found a reduction in the inhibitory intrinsic connections during EC. The results suggest that the intrinsic modulations in V5 played the most important role in producing EC-EO alpha differences, suggesting an intrinsic disinhibition in higher order visual cortex, during EC resting state.

Pre- and post-surgery brain tumor multimodal magnetic resonance imaging data optimized for large scale computational modelling.

We present a dataset of magnetic resonance imaging (MRI) data (T1, diffusion, BOLD) acquired in 25 brain tumor patients before the tumor resection surgery, and six months after the surgery, together with the tumor masks, and in 11 controls (recruited among the patients' caregivers). The dataset also contains behavioral and emotional scores obtained with standardized questionnaires. To simulate personalized computational models of the brain, we also provide structural connectivity matrices, necessary to perform whole-brain modelling with tools such as The Virtual Brain. In addition, we provide blood-oxygen-level-dependent imaging time series averaged across regions of interest for comparison with simulation results. An average resting state hemodynamic response function for each region of interest, as well as shape maps for each voxel, are also contributed.

Investigation on how dynamic effective connectivity patterns encode the fluctuating pain intensity in chronic migraine.

Chronic migraine is characterised by persistent headaches for >15 days per month; the intensity of the pain is fluctuating over time. Here, we explored the dynamic interplay of connectivity patterns between regions known to be related to pain processing and their relation to the ongoing dynamic pain experience. We recorded EEG from 80 sessions (20 chronic migraine patients in 4 separate sessions of 25 min). The patients were asked to continuously rate the intensity of their endogenous headache. On different time-windows, a dynamic causal model (DCM) of cross spectral responses was inverted to estimate connectivity strengths. For each patient and session, the evolving dynamics of effective connectivity were related to pain intensities and to pain intensity changes by using a Bayesian linear model. Hierarchical Bayesian modelling was further used to examine which connectivity-pain relations are consistent across sessions and across patients. The results reflect the multi-facetted clinical picture of the disease. Across all sessions, each patient with chronic migraine exhibited a distinct pattern of pain intensity-related cortical connectivity. The diversity of the individual findings are accompanied by inconsistent relations between the connectivity parameters and pain intensity or pain intensity changes at group level. This suggests a rejection of the idea of a common neuronal core problem for chronic migraine.

Approaching or Decentering? Differential Neural Networks Underlying Experiential Emotion Regulation and Cognitive Defusion.

The current study investigated the bottom-up experiential emotion regulation in comparison to the cognitiveve top down-approach of cognitive defusion. Rooted in an experiential- and client-centered psychotherapeutic approach, experiential emotion regulation involves an active, non-intervening, accepting, open and welcoming approach towards the bodily felt affective experience in a welcoming, compassionate way, expressed in 'experiential awareness' in a first phase, and its verbalization or 'experiential expression' in a second phase. Defusion refers to the ability to observe one's thoughts and feelings in a detached manner. Nineteen healthy participants completed an emotion regulation task during fMRI scanning by processing highly arousing negative events by images. Both experiential emotion regulation and cognitive defusion resulted in higher negative emotion compared to a 'watch' control condition. On the neurophysiological level, experiential emotion regulation recruited brain areas that regulate attention towards affective- and somatosensorial experience such as the anterior cingulate cortex, the paracingulate gyrus, the inferior frontal gyrus, and the prefrontal pole, areas underlying multisensory information integration (e.g., angular gyrus), and linking body states to emotion recognition and awareness (e.g., postcentral gyrus). Experiential emotion regulation, relative to the control condition, also resulted in a higher interaction between the anterior insular cortex and left amygdala while participants experienced less negative emotion. Cognitive defusion decreased activation in the subcortical areas such as the brainstem, the thalamus, the amygdala, and the hippocampus. In contrast to cognitive defusion, experiential emotion regulation relative to demonstrated greater activation in the left angular gyrus, indicating more multisensory information integration. These findings provide insight into different and specific neural networks underlying psychotherapy-based experiential emotion regulation and cognitive defusion.

WHOCARES: WHOle-brain CArdiac signal REgression from highly accelerated simultaneous multi-Slice fMRI acquisitions.

Objective. To spatio-temporally resolve cardiac signals in functional magnetic resonance imaging (fMRI) time-series of the human brain using neither external physiological measurements nor ad hoc modelling assumptions.Approach. Cardiac pulsation is a physiological confound of fMRI time-series that introduces spurious signal fluctuations in proximity to blood vessels. fMRI alone is not sufficiently fast to resolve cardiac pulsation. Depending on the ratio between the instantaneous heart-rate and the acquisition sampling frequency (1/TR, with TR being the repetition time), the cardiac signal may alias into the frequency band of neural activation so that its removal through spectral filtering techniques is generally not possible. In this paper, we show that it is feasible to temporally and spatially resolve cardiac signals throughout the brain even when cardiac aliasing occurs by combining fMRI hyper-sampling with simultaneous multislice (SMS) imaging. The technique, which we name WHOle-brain CArdiac signal REgression from highly accelerated simultaneous multi-Slice fMRI acquisitions (WHOCARES), was developed on 695 healthy subjects selected from the Human Connectome Project and its performance validated against the RETROICOR, HAPPY and the pulse oxymeter signal regression methods.Main results.WHOCARES is capable of retrieving voxel-wise cardiac signal regressors. This is achieved without employing external physiological recordings nor through ad hoc modelling assumptions. The performance of WHOCARES was, on average, superior to RETROICOR, HAPPY and the pulse oxymeter regression methods.Significance.WHOCARES holds basis for the reliable mapping of cardiac activity in fMRI time-series. WHOCARES can be employed for the retrospective removal of cardiac noise in publicly available fMRI datasets where physiological recordings are not available. WHOCARES is freely available athttps://github.com/gferrazzi/WHOCARES.

Theta-phase connectivity between medial prefrontal and posterior areas underlies novel instructions implementation.

Implementing novel instructions is a complex and uniquely human cognitive ability, that requires the rapid and flexible conversion of symbolic content into a format that enables the execution of the instructed behavior. Preparing to implement novel instructions, as opposed to their mere maintenance, involves the activation of the instructed motor plans, and the binding of the action information to the specific context in which this should be executed. Recent evidence and prominent computational models suggest that this efficient configuration of the system might involve a central role of frontal theta oscillations in establishing top-down long-range synchronization between distant and task-relevant brain areas. In the present EEG study (human subjects, 30 females, 4 males), we demonstrate that proactively preparing for the implementation of novels instructions, as opposed to their maintenance, involves a strengthened degree of connectivity in the theta frequency range between medial prefrontal and motor/visual areas. Moreover, we replicated previous results showing oscillatory features associated specifically with implementation demands, and extended on them demonstrating the role of theta oscillations in mediating the effect of task demands on behavioral performance. Taken together, these findings support our hypothesis that the modulation of connectivity patterns between frontal and task-relevant posterior brain areas is a core factor in the emergence of a behavior-guiding format from novel instructions.Significance statementEveryday life requires the use and manipulation of currently available information to guide behavior and reach specific goals. In the present study we investigate how the same instructed content elicits different neural activity depending on the task being performed. Crucially, connectivity between medial prefrontal cortex and posterior brain areas is strengthened when novel instructions have to be implemented, rather than simply maintained. This finding suggests that theta oscillations play a role in setting up a dynamic and flexible network of task-relevant regions optimized for the execution of the instructed behavior.

Auditory driven gamma synchrony is associated with cortical thickness in widespread cortical areas.

OBJECTIVE: Gamma synchrony is a fundamental functional property of the cerebral cortex, impaired in multiple neuropsychiatric conditions (i.e. schizophrenia, Alzheimer's disease, stroke etc.). Auditory stimulation in the gamma range allows to drive gamma synchrony of the entire cortical mantle and to estimate the efficiency of the mechanisms sustaining it. As gamma synchrony depends strongly on the interplay between parvalbumin-positive interneurons and pyramidal neurons, we hypothesize an association between cortical thickness and gamma synchrony. To test this hypothesis, we employed a combined magnetoencephalography (MEG) - Magnetic Resonance Imaging (MRI) study. METHODS: Cortical thickness was estimated from anatomical MRI scans. MEG measurements related to exposure of 40 Hz amplitude modulated tones were projected onto the cortical surface. Two measures of cortical synchrony were considered: (a) inter-trial phase consistency at 40 Hz, providing a vertex-wise estimation of gamma synchronization, and (b) phase-locking values between primary auditory cortices and whole cortical mantle, providing a measure of long-range cortical synchrony. A correlation between cortical thickness and synchronization measures was then calculated for 72 MRI-MEG scans. RESULTS: Both inter-trial phase consistency and phase locking values showed a significant positive correlation with cortical thickness. For inter-trial phase consistency, clusters of strong associations were found in the temporal and frontal lobes, especially in the bilateral auditory and pre-motor cortices. Higher phase-locking values corresponded to higher cortical thickness in the frontal, temporal, occipital and parietal lobes. DISCUSSION AND CONCLUSIONS: In healthy subjects, a thicker cortex corresponds to higher gamma synchrony and connectivity in the primary auditory cortex and beyond, likely reflecting underlying cell density involved in gamma circuitries. This result hints towards an involvement of gamma synchrony together with underlying brain structure in brain areas for higher order cognitive functions. This study contributes to the understanding of inherent cortical functional and structural brain properties, which might in turn constitute the basis for the definition of useful biomarkers in patients showing aberrant gamma synchronization.

Individual differences in mental imagery modulate effective connectivity of scene-selective regions during resting state.

Successful navigation relies on the ability to identify, perceive, and correctly process the spatial structure of a scene. It is well known that visual mental imagery plays a crucial role in navigation. Indeed, cortical regions encoding navigationally relevant information are also active during mental imagery of navigational scenes. However, it remains unknown whether their intrinsic activity and connectivity reflect the individuals' ability to imagine a scene. Here, we primarily investigated the intrinsic causal interactions among scene-selective brain regions such as Parahipoccampal Place Area (PPA), Retrosplenial Complex, and Occipital Place Area (OPA) using Dynamic Causal Modelling for resting-state functional magnetic resonance data. Second, we tested whether resting-state effective connectivity parameters among scene-selective regions could reflect individual differences in mental imagery in our sample, as assessed by the self-reported Vividness of Visual Imagery Questionnaire. We found an inhibitory influence of occipito-medial on temporal regions, and an excitatory influence of more anterior on more medial and posterior brain regions. Moreover, we found that a key role in imagery is played by the connection strength from OPA to PPA, especially in the left hemisphere, since the influence of the signal between these scene-selective regions positively correlated with good mental imagery ability. Our investigation contributes to the understanding of the complexity of the causal interaction among brain regions involved in navigation and provides new insight in understanding how an essential ability, such as mental imagery, can be explained by the intrinsic fluctuation of brain signal.

Brain simulation as a cloud service: The Virtual Brain on EBRAINS.

The Virtual Brain (TVB) is now available as open-source services on the cloud research platform EBRAINS (ebrains.eu). It offers software for constructing, simulating and analysing brain network models including the TVB simulator; magnetic resonance imaging (MRI) processing pipelines to extract structural and functional brain networks; combined simulation of large-scale brain networks with small-scale spiking networks; automatic conversion of user-specified model equations into fast simulation code; simulation-ready brain models of patients and healthy volunteers; Bayesian parameter optimization in epilepsy patient models; data and software for mouse brain simulation; and extensive educational material. TVB cloud services facilitate reproducible online collaboration and discovery of data assets, models, and software embedded in scalable and secure workflows, a precondition for research on large cohort data sets, better generalizability, and clinical translation.