The effect of common parameters of bipolar stimulation on brain evoked potentials.

OBJECTIVE: To identify optimal bipolar stimulation parameters for robust generation of brain evoked potentials (BEPs), namely the interelectrode distance (IED) and the intensity of stimulation (IS), in cortical and axonal stimulation. METHODS: In 15 patients who underwent awake surgery for brain tumor removal, BEPs were elicited at different values of IED and IS, respectively: 5 mm-5 mA, 5 mm-10 mA, and 10 mm-10 mA. The number of BEPs elicited by stimulation, as well as the delays and amplitudes of the N1 waves were compared between the different groups of stimulation parameters and according to the stimulated brain structure (cortical vs. axonal). RESULTS: The amplitudes of N1 increased with the intensity of bipolar stimulation, either in cortical or axonal stimulation, while N1 peak delays were not affected by the stimulation parameters. Furthermore, axonal stimulation produced more N1s than cortical stimulation, with lower latencies. CONCLUSIONS: Understanding the relationship between stimulation parameters and BEP is of utmost importance to determine whether the generated N1 waves accurately reflect the underlying structural anatomy. Other factors, such as stimulation frequency or pulse width and shape, may also play a role and warrant further investigation. SIGNIFICANCE: This study represents the first step in describing the influence of common bipolar stimulation parameters on robustness of BEPs by examining the impact of IED and IS on the N1 wave.

Mapping functional traces of opioid memories in the rat brain.

Addiction to psychoactive substances is a maladaptive learned behaviour. Contexts surrounding drug use integrate this aberrant mnemonic process and hold strong relapse-triggering ability. Here, we asked where context and salience might be concurrently represented in the brain during retrieval of drug-context paired associations. For this, we developed a morphine-conditioned place preference protocol that allows contextual stimuli presentation inside a magnetic resonance imaging scanner and investigated differences in activity and connectivity at context recall. We found context-specific responses to stimulus onset in multiple brain regions, namely, limbic, sensory and striatal. Differences in functional interconnectivity were found among amygdala, lateral habenula, and lateral septum. We also investigated alterations to resting-state functional connectivity and found increased centrality of the lateral septum in a proposed limbic network, as well as increased functional connectivity of the lateral habenula and hippocampal 'cornu ammonis' 1 region, after a protocol of associative drug-context. Finally, we found that pre- conditioned place preference resting-state connectivity of the lateral habenula and amygdala was predictive of inter-individual conditioned place preference score differences. Overall, our findings show that drug and saline-paired contexts establish distinct memory traces in overlapping functional brain microcircuits and that intrinsic connectivity of the habenula, septum, and amygdala likely underlies the individual maladaptive contextual learning to opioid exposure. We have identified functional maps of acquisition and retrieval of drug-related memory that may support the relapse-triggering ability of opioid-associated sensory and contextual cues. These findings may clarify the inter-individual sensitivity and vulnerability seen in addiction to opioids found in humans.

Conditional Generative Models for Simulation of EMG During Naturalistic Movements.

Numerical models of electromyography (EMG) signals have provided a huge contribution to our fundamental understanding of human neurophysiology and remain a central pillar of motor neuroscience and the development of human-machine interfaces. However, while modern biophysical simulations based on finite element methods (FEMs) are highly accurate, they are extremely computationally expensive and thus are generally limited to modeling static systems such as isometrically contracting limbs. As a solution to this problem, we propose to use a conditional generative model to mimic the output of an advanced numerical model. To this end, we present BioMime, a conditional generative neural network trained adversarially to generate motor unit (MU) activation potential waveforms under a wide variety of volume conductor parameters. We demonstrate the ability of such a model to predictively interpolate between a much smaller number of numerical model's outputs with a high accuracy. Consequently, the computational load is dramatically reduced, which allows the rapid simulation of EMG signals during truly dynamic and naturalistic movements.

On null models for temporal small-worldness in brain dynamics.

Brain dynamics can be modeled as a temporal brain network starting from the activity of different brain regions in functional magnetic resonance imaging (fMRI) signals. When validating hypotheses about temporal networks, it is important to use an appropriate statistical null model that shares some features with the treated empirical data. The purpose of this work is to contribute to the theory of temporal null models for brain networks by introducing the random temporal hyperbolic (RTH) graph model, an extension of the random hyperbolic (RH) graph, known in the study of complex networks for its ability to reproduce crucial properties of real-world networks. We focus on temporal small-worldness which, in the static case, has been extensively studied in real-world complex networks and has been linked to the ability of brain networks to efficiently exchange information. We compare the RTH graph model with standard null models for temporal networks and show it is the null model that best reproduces the small-worldness of resting brain activity. This ability to reproduce fundamental features of real brain networks, while adding only a single parameter compared with classical models, suggests that the RTH graph model is a promising tool for validating hypotheses about temporal brain networks.

We show that the random temporal hyperbolic (RTH) graph is a suitable null model for testing hypotheses about brain dynamics, after comparing it with the current state of the art and two other geometric null models. The static version of this theoretical model captures properties of various real-world networks, and its temporal version exhibits the temporal small-world property, for which we propose a new proper temporal definition. In particular, we show that the model best reproduces the temporal small-worldness measured in the empirical temporal network extracted from fMRI signals.

NeuroMotion: Open-source platform with neuromechanical and deep network modules to generate surface EMG signals during voluntary movement.

Neuromechanical studies investigate how the nervous system interacts with the musculoskeletal (MSK) system to generate volitional movements. Such studies have been supported by simulation models that provide insights into variables that cannot be measured experimentally and allow a large number of conditions to be tested before the experimental analysis. However, current simulation models of electromyography (EMG), a core physiological signal in neuromechanical analyses, remain either limited in accuracy and conditions or are computationally heavy to apply. Here, we provide a computational platform to enable future work to overcome these limitations by presenting NeuroMotion, an open-source simulator that can modularly test a variety of approaches to the full-spectrum synthesis of EMG signals during voluntary movements. We demonstrate NeuroMotion using three sample modules. The first module is an upper-limb MSK model with OpenSim API to estimate the muscle fibre lengths and muscle activations during movements. The second module is BioMime, a deep neural network-based EMG generator that receives nonstationary physiological parameter inputs, like the afore-estimated muscle fibre lengths, and efficiently outputs motor unit action potentials (MUAPs). The third module is a motor unit pool model that transforms the muscle activations into discharge timings of motor units. The discharge timings are convolved with the output of BioMime to simulate EMG signals during the movement. We first show how MUAP waveforms change during different levels of physiological parameter variations and different movements. We then show that the synthetic EMG signals during two-degree-of-freedom hand and wrist movements can be used to augment experimental data for regressing joint angles. Ridge regressors trained on the synthetic dataset were directly used to predict joint angles from experimental data. In this way, NeuroMotion was able to generate full-spectrum EMG for the first use-case of human forearm electrophysiology during voluntary hand, wrist, and forearm movements. All intermediate variables are available, which allows the user to study cause-effect relationships in the complex neuromechanical system, fast iterate algorithms before collecting experimental data, and validate algorithms that estimate non-measurable parameters in experiments. We expect this modular platform will enable validation of generative EMG models, complement experimental approaches and empower neuromechanical research.

Graph alignment exploiting the spatial organization improves the similarity of brain networks.

Every brain is unique, having its structural and functional organization shaped by both genetic and environmental factors over the course of its development. Brain image studies tend to produce results by averaging across a group of subjects, under the common assumption that it is possible to subdivide the cortex into homogeneous areas while maintaining a correspondence across subjects. We investigate this assumption: can the structural properties of a specific region of an atlas be assumed to be the same across subjects? This question is addressed by looking at the network representation of the brain, with nodes corresponding to brain regions and edges to their structural relationships. Using an unsupervised graph matching strategy, we align the structural connectomes of a set of healthy subjects, considering parcellations of different granularity, to understand the connectivity misalignment between regions. First, we compare the obtained permutations with four different algorithm initializations: Spatial Adjacency, Identity, Barycenter, and Random. Our results suggest that applying an alignment strategy improves the similarity across subjects when the number of parcels is above 100 and when using Spatial Adjacency and Identity initialization (the most plausible priors). Second, we characterize the obtained permutations, revealing that the majority of permutations happens between neighbors parcels. Lastly, we study the spatial distribution of the permutations. By visualizing the results on the cortex, we observe no clear spatial patterns on the permutations and all the regions across the context are mostly permuted with first and second order neighbors.

Tractography passes the test: Results from the diffusion-simulated connectivity (disco) challenge.

Estimating structural connectivity from diffusion-weighted magnetic resonance imaging is a challenging task, partly due to the presence of false-positive connections and the misestimation of connection weights. Building on previous efforts, the MICCAI-CDMRI Diffusion-Simulated Connectivity (DiSCo) challenge was carried out to evaluate state-of-the-art connectivity methods using novel large-scale numerical phantoms. The diffusion signal for the phantoms was obtained from Monte Carlo simulations. The results of the challenge suggest that methods selected by the 14 teams participating in the challenge can provide high correlations between estimated and ground-truth connectivity weights, in complex numerical environments. Additionally, the methods used by the participating teams were able to accurately identify the binary connectivity of the numerical dataset. However, specific false positive and false negative connections were consistently estimated across all methods. Although the challenge dataset doesn't capture the complexity of a real brain, it provided unique data with known macrostructure and microstructure ground-truth properties to facilitate the development of connectivity estimation methods.

A myoelectric digital twin for fast and realistic modelling in deep learning.

Muscle electrophysiology has emerged as a powerful tool to drive human machine interfaces, with many new recent applications outside the traditional clinical domains, such as robotics and virtual reality. However, more sophisticated, functional, and robust decoding algorithms are required to meet the fine control requirements of these applications. Deep learning has shown high potential in meeting these demands, but requires a large amount of high-quality annotated data, which is expensive and time-consuming to acquire. Data augmentation using simulations, a strategy applied in other deep learning applications, has never been attempted in electromyography due to the absence of computationally efficient models. We introduce a concept of Myoelectric Digital Twin - highly realistic and fast computational model tailored for the training of deep learning algorithms. It enables simulation of arbitrary large and perfectly annotated datasets of realistic electromyography signals, allowing new approaches to muscular signal decoding, accelerating the development of human-machine interfaces.

DORIS: A diffusion MRI-based 10 tissue class deep learning segmentation algorithm tailored to improve anatomically-constrained tractography.

Modern tractography algorithms such as anatomically-constrained tractography (ACT) are based on segmentation maps of white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF). These maps are generally estimated from a T1-weighted (T1w) image and then registered in diffusion weighted images (DWI) space. Registration of T1w to diffusion space and partial volume estimation are challenging and rarely voxel-perfect. Diffusion-based segmentation would, thus, potentially allow not to have higher quality anatomical priors injected in the tractography process. On the other hand, even if FA-based tractography is possible without T1 registration, the literature shows that this technique suffers from multiple issues such as holes in the tracking mask and a high proportion of generated broken and anatomically implausible streamlines. Therefore, there is an important need for a tissue segmentation algorithm that works directly in the native diffusion space. We propose DORIS, a DWI-based deep learning segmentation algorithm. DORIS outputs 10 different tissue classes including WM, GM, CSF, ventricles, and 6 other subcortical structures (putamen, pallidum, hippocampus, caudate, amygdala, and thalamus). DORIS was trained and validated on a wide range of subjects, including 1,000 individuals from 22 to 90 years old from clinical and research DWI acquisitions, from 5 public databases. In the absence of a "true" ground truth in diffusion space, DORIS used a silver standard strategy from Freesurfer output registered onto the DWI. This strategy is extensively evaluated and discussed in the current study. Segmentation maps provided by DORIS are quantitatively compared to Freesurfer and FSL-fast and the impacts on tractography are evaluated. Overall, we show that DORIS is fast, accurate, and reproducible and that DORIS-based tractograms produce bundles with a longer mean length and fewer anatomically implausible streamlines.

A Riemannian Revisiting of Structure-Function Mapping Based on Eigenmodes.

Understanding the link between brain structure and function may not only improve our knowledge of brain organization, but also lead to better quantification of pathology. To quantify this link, recent studies have attempted to predict the brain's functional connectivity from its structural connectivity. However, functional connectivity matrices live in the Riemannian manifold of the symmetric positive definite space and a specific attention must be paid to operate on this appropriate space. In this work we investigated the implications of using a distance based on an affine invariant Riemannian metric in the context of structure-function mapping. Specifically, we revisit previously proposed structure-function mappings based on eigendecomposition and test them on 100 healthy subjects from the Human Connectome Project using this adapted notion of distance. First, we show that using this Riemannian distance significantly alters the notion of similarity between subjects from a functional point of view. We also show that using this distance improves the correlation between the structural and functional similarity of different subjects. Finally, by using a distance appropriate to this manifold, we demonstrate the importance of mapping function from structure under the Riemannian manifold and show in particular that it is possible to outperform the group average and the so-called glass ceiling on the performance of mappings based on eigenmodes.

An Anisotropic 4D Filtering Approach to Recover Brain Activation From Paradigm-Free Functional MRI Data.

Context: Functional Magnetic Resonance Imaging (fMRI) is a non-invasive imaging technique that provides an indirect view into brain activity via the blood oxygen level dependent (BOLD) response. In particular, resting-state fMRI poses challenges to the recovery of brain activity without prior knowledge on the experimental paradigm, as it is the case for task fMRI. Conventional methods to infer brain activity from the fMRI signals, for example, the general linear model (GLM), require the knowledge of the experimental paradigm to define regressors and estimate the contribution of each voxel's time course to the task. To overcome this limitation, approaches to deconvolve the BOLD response and recover the underlying neural activations without a priori information on the task have been proposed. State-of-the-art techniques, and in particular the total activation (TA), formulate the deconvolution as an optimization problem with decoupled spatial and temporal regularization and an optimization strategy that alternates between the constraints. Approach: In this work, we propose a paradigm-free regularization algorithm named Anisotropic 4D-fMRI (A4D-fMRI) that is applied on the 4D fMRI image, acting simultaneously in the 3D space and 1D time dimensions. Based on the idea that large image variations should be preserved as they occur during brain activations, whereas small variations considered as noise should be removed, the A4D-fMRI applies an anisotropic regularization, thus recovering the location and the duration of brain activations. Results: Using the experimental paradigm as ground truth, the A4D-fMRI is validated on synthetic and real task-fMRI data from 51 subjects, and its performance is compared to the TA. Results show higher correlations of the recovered time courses with the ground truth compared to the TA and lower computational times. In addition, we show that the A4D-fMRI recovers activity that agrees with the GLM, without requiring or using any knowledge of the experimental paradigm.

Network alignment and similarity reveal atlas-based topological differences in structural connectomes.

The interactions between different brain regions can be modeled as a graph, called connectome, whose nodes correspond to parcels from a predefined brain atlas. The edges of the graph encode the strength of the axonal connectivity between regions of the atlas that can be estimated via diffusion magnetic resonance imaging (MRI) tractography. Herein, we aim to provide a novel perspective on the problem of choosing a suitable atlas for structural connectivity studies by assessing how robustly an atlas captures the network topology across different subjects in a homogeneous cohort. We measure this robustness by assessing the alignability of the connectomes, namely the possibility to retrieve graph matchings that provide highly similar graphs. We introduce two novel concepts. First, the graph Jaccard index (GJI), a graph similarity measure based on the well-established Jaccard index between sets; the GJI exhibits natural mathematical properties that are not satisfied by previous approaches. Second, we devise WL-align, a new technique for aligning connectomes obtained by adapting the Weisfeiler-Leman (WL) graph-isomorphism test. We validated the GJI and WL-align on data from the Human Connectome Project database, inferring a strategy for choosing a suitable parcellation for structural connectivity studies. Code and data are publicly available.

On the generalizability of diffusion MRI signal representations across acquisition parameters, sequences and tissue types: Chronicles of the MEMENTO challenge.

Diffusion MRI (dMRI) has become an invaluable tool to assess the microstructural organization of brain tissue. Depending on the specific acquisition settings, the dMRI signal encodes specific properties of the underlying diffusion process. In the last two decades, several signal representations have been proposed to fit the dMRI signal and decode such properties. Most methods, however, are tested and developed on a limited amount of data, and their applicability to other acquisition schemes remains unknown. With this work, we aimed to shed light on the generalizability of existing dMRI signal representations to different diffusion encoding parameters and brain tissue types. To this end, we organized a community challenge - named MEMENTO, making available the same datasets for fair comparisons across algorithms and techniques. We considered two state-of-the-art diffusion datasets, including single-diffusion-encoding (SDE) spin-echo data from a human brain with over 3820 unique diffusion weightings (the MASSIVE dataset), and double (oscillating) diffusion encoding data (DDE/DODE) of a mouse brain including over 2520 unique data points. A subset of the data sampled in 5 different voxels was openly distributed, and the challenge participants were asked to predict the remaining part of the data. After one year, eight participant teams submitted a total of 80 signal fits. For each submission, we evaluated the mean squared error, the variance of the prediction error and the Bayesian information criteria. The received submissions predicted either multi-shell SDE data (37%) or DODE data (22%), followed by cartesian SDE data (19%) and DDE (18%). Most submissions predicted the signals measured with SDE remarkably well, with the exception of low and very strong diffusion weightings. The prediction of DDE and DODE data seemed more challenging, likely because none of the submissions explicitly accounted for diffusion time and frequency. Next to the choice of the model, decisions on fit procedure and hyperparameters play a major role in the prediction performance, highlighting the importance of optimizing and reporting such choices. This work is a community effort to highlight strength and limitations of the field at representing dMRI acquired with trending encoding schemes, gaining insights into how different models generalize to different tissue types and fiber configurations over a large range of diffusion encodings.

Diffusion MRI tractography filtering techniques change the topology of structural connectomes.

Objective.The use of non-invasive techniques for the estimation of structural brain networks (i.e. connectomes) opened the door to large-scale investigations on the functioning and the architecture of the brain, unveiling the link between neurological disorders and topological changes of the brain network. This study aims at assessing if and how the topology of structural connectomes estimated non-invasively with diffusion MRI is affected by the employment of tractography filtering techniques in structural connectomic pipelines. Additionally, this work investigates the robustness of topological descriptors of filtered connectomes to the common practice of density-based thresholding.Approach.We investigate the changes in global efficiency, characteristic path length, modularity and clustering coefficient on filtered connectomes obtained with the spherical deconvolution informed filtering of tractograms and using the convex optimization modelling for microstructure informed tractography. The analysis is performed on both healthy subjects and patients affected by traumatic brain injury and with an assessment of the robustness of the computed graph-theoretical measures with respect to density-based thresholding of the connectome.Main results.Our results demonstrate that tractography filtering techniques change the topology of brain networks, and thus alter network metrics both in the pathological and the healthy cases. Moreover, the measures are shown to be robust to density-based thresholding.Significance.The present work highlights how the inclusion of tractography filtering techniques in connectomic pipelines requires extra caution as they systematically change the network topology both in healthy subjects and patients affected by traumatic brain injury. Finally, the practice of low-to-moderate density-based thresholding of the connectomes is confirmed to have negligible effects on the topological analysis.

A unified framework for multimodal structure-function mapping based on eigenmodes.

Characterizing the connection between brain structure and brain function is essential for understanding how behaviour emerges from the underlying anatomy. A number of studies have shown that the network structure of the white matter shapes functional connectivity. Therefore, it should be possible to predict, at least partially, functional connectivity given the structural network. Many structure-function mappings have been proposed in the literature, including several direct mappings between the structural and functional connectivity matrices. However, the current literature is fragmented and does not provide a uniform treatment of current methods based on eigendecompositions. In particular, existing methods have never been compared to each other and their relationship explicitly derived in the context of brain structure-function mapping. In this work, we propose a unified computational framework that generalizes recently proposed structure-function mappings based on eigenmodes. Using this unified framework, we highlight the link between existing models and show how they can be obtained by specific choices of the parameters of our framework. By applying our framework to 50 subjects of the Human Connectome Project, we reproduce 6 recently published results, devise two new models and provide a direct comparison between all mappings. Finally, we show that a glass ceiling on the performance of mappings based on eigenmodes seems to be reached and conclude with possible approaches to break this performance limit.

Analytical and fast Fiber Orientation Distribution reconstruction in 3D-Polarized Light Imaging.

Three dimensional Polarized Light Imaging (3D-PLI) is an optical technique which allows mapping the spatial fiber architecture of fibrous postmortem tissues, at sub-millimeter resolutions. Here, we propose an analytical and fast approach to compute the fiber orientation distribution (FOD) from high-resolution vector data provided by 3D-PLI. The FOD is modeled as a sum of K orientations/Diracs on the unit sphere, described on a spherical harmonics basis and analytically computed using the spherical Fourier transform. Experiments are performed on rich synthetic data which simulate the geometry of the neuronal fibers and on human brain data. Results indicate the analytical FOD is computationally efficient and very fast, and has high angular precision and angular resolution. Furthermore, investigations on the right occipital lobe illustrate that our strategy of FOD computation enables the bridging of spatial scales from microscopic 3D-PLI information to macro- or mesoscopic dimensions of diffusion Magnetic Resonance Imaging (MRI), while being a means to evaluate prospective resolution limits for diffusion MRI to reconstruct region-specific white matter tracts. These results demonstrate the interest and great potential of our analytical approach.

Non-invasive inference of information flow using diffusion MRI, functional MRI, and MEG.

OBJECTIVE: To infer information flow in the white matter of the brain and recover cortical activity using functional MRI, diffusion MRI, and MEG without a manual selection of the white matter connections of interest. APPROACH: A Bayesian network which encodes the priors knowledge of possible brain states is built from imaging data. Diffusion MRI is used to enumerate all possible connections between cortical regions. Functional MRI is used to prune connections without manual intervention and increase the likelihood of specific regions being active. MEG data is used as evidence into this network to obtain a posterior distribution on cortical regions and connections. MAIN RESULTS: We show that our proposed method is able to identify connections associated with the a sensory-motor task. This allows us to build the Bayesian network with no manual selection of connections of interest. Using sensory-motor MEG evoked response as evidence into this network, our method identified areas known to be involved in a visuomotor task. In addition, information flow along white matter fiber bundles connecting those regions was also recovered. SIGNIFICANCE: Current methods to estimate white matter information flow are extremely invasive, therefore limiting our understanding of the interaction between cortical regions. The proposed method makes use of functional MRI, diffusion MRI, and M/EEG to infer communication between cortical regions, therefore opening the door to the non-invasive exploration of information flow in the white matter.

A computational Framework for generating rotation invariant features and its application in diffusion MRI.

In this work, we present a novel computational framework for analytically generating a complete set of algebraically independent Rotation Invariant Features (RIF) given the Laplace-series expansion of a spherical function. Our computational framework provides a closed-form solution for these new invariants, which are the natural expansion of the well known spherical mean, power-spectrum and bispectrum invariants. We highlight the maximal number of algebraically independent invariants which can be obtained from a truncated Spherical Harmonic (SH) representation of a spherical function and show that most of these new invariants can be linked to statistical and geometrical measures of spherical functions, such as the mean, the variance and the volume of the spherical signal. Moreover, we demonstrate their application to dMRI signal modeling including the Apparent Diffusion Coefficient (ADC), the diffusion signal and the fiber Orientation Distribution Function (fODF). In addition, using both synthetic and real data, we test the ability of our invariants to estimate brain tissue microstructure in healthy subjects and show that our framework provides more flexibility and open up new opportunities for innovative development in the domain of microstructure recovery from diffusion MRI.

Author Correction: The challenge of mapping the human connectome based on diffusion tractography.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.