Reconstructing EEG sources involves a complex pipeline, with the inverse problem being the most challenging. Multiple inversion algorithms are being continuously developed, aiming to tackle the non-uniqueness of this problem, which has been shown to be partially circumvented by including prior information in the inverse models. Despite a few efforts, there are still current and persistent controversies regarding the inversion algorithm of choice and the optimal set of spatial priors to be included in the inversion models. The use of simultaneous EEG-fMRI data is one approach to tackle this problem. The spatial resolution of fMRI makes fMRI derived spatial priors very convenient for EEG reconstruction, however, only task activation maps and resting-state networks (RSNs) have been explored so far, overlooking the recent, but already accepted, notion that brain networks exhibit dynamic functional connectivity fluctuations. The lack of a systematic comparison between different source reconstruction algorithms, considering potentially more brain-informative priors such as fMRI, motivates the search for better reconstruction models. Using simultaneous EEG-fMRI data, here we compared four different inversion algorithms (minimum norm, MN; low resolution electromagnetic tomography, LORETA; empirical Bayes beamformer, EBB; and multiple sparse priors, MSP) under a Bayesian framework (as implemented in SPM), each with three different sets of priors consisting of: (1) those specific to the algorithm; (2) those specific to the algorithm plus fMRI task activation maps and RSNs; and (3) those specific to the algorithm plus fMRI task activation maps and RSNs and network modules of task-related dFC states estimated from the dFC fluctuations. The quality of the reconstructed EEG sources was quantified in terms of model-based metrics, namely the expectation of the posterior probability P(model|data) and variance explained of the inversion models, and the overlap/proportion of brain regions known to be involved in the visual perception tasks that the participants were submitted to, and RSN templates, with/within EEG source components. Model-based metrics suggested that model parsimony is preferred, with the combination MSP and priors specific to this algorithm exhibiting the best performance. However, optimal overlap/proportion values were found using EBB and priors specific to this algorithm and fMRI task activation maps and RSNs or MSP and considering all the priors (algorithm priors, fMRI task activation maps and RSNs and dFC state modules), respectively, indicating that fMRI spatial priors, including dFC state modules, might contain useful information to recover EEG source components reflecting neuronal activity of interest. Our main results show that providing fMRI spatial derived priors that reflect the dynamics of the brain might be useful to map neuronal activity more accurately from EEG-fMRI. Furthermore, this work paves the way towards a more informative selection of the optimal EEG source reconstruction approach, which may be critical in future studies.

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Functional MRI (fMRI) is one of the most common brain imaging modalities used for understanding brain organization and connectivity abnormalities associated with multiple sclerosis (MS). The fMRI signal is highly perturbed by head motion, which degrades data quality and influences all image-derived metrics. Numerous correction approaches have been proposed over the years to overcome the problems induced by head motion, however, despite a few efforts, there are still current and persistent controversies regarding the best correction strategy. The lack of a systematic comparison between different correction approaches motivates the search for optimal correction models, particularly in studies with clinical populations prone to characterize by higher motion. Moreover, motion correction strategies gain more relevance in task-based designs, which are less explored compared to resting-state and may have a crucial role in describing the functioning of the brain and highlighting specific connectivity changes. We acquired fMRI data from a group of patients with early MS and matched healthy controls (HC) during performance of a visual task, characterized motion in both groups, and compared the most used motion correction methods. We compared task-activation metrics obtained from models without motion correction, models containing 6 or 24 motion parameters (MPs) as nuisance regressors, models containing 6 or 24 MPs and motion outliers detected with FD or DVARS as nuisance regressors (scrubbing) and models with 6 or 24 MPs where motion outliers were corrected through volume interpolation. To our knowledge, volume interpolation is a frequently used approach but was never compared with other existent methods. Our results showed that there were no differences in motion between groups, suggesting that recently diagnosed MS patients do not present problematic motion. In general, models with 6 MPs present higher Z-scores than models with 24 MPs, suggesting the 6 MPs as the best trade-off between motion correction and preservation of valuable information. However, correction approaches differ between groups, regarding the combination of MPs with correction of motion outliers. Models with 6 MPs and outliers volume interpolation or scrubbing with FD presented higher Z-scores in the MS group, while models with 6 MPs and scrubbing with DVARS or volume interpolation were the best combinations for the HC group. Differences between groups in motion correction strategies draw attention to the intrinsic impact of MS on fMRI analyses, which should be carefully addressed. This work paves the way towards finding an optimal motion correction strategy, which is required to improve the accuracy of fMRI analyses, crucially in clinical studies in MS and other patient populations.

IntroductionFunctional MRI (fMRI) is commonly used for understanding brain organization and connectivity abnormalities in neurological conditions, and in particular in multiple sclerosis (MS). However, head motion degrades fMRI data quality and influences all image-derived metrics. Persistent controversies regarding the best correction strategy motivates a systematic comparison, including methods such as scrubbing and volume interpolation, to find optimal correction models, particularly in studies with clinical populations prone to characterize by high motion. Moreover, strategies for correction of motion effects gain more relevance in task-based designs, which are less explored compared to resting-state, have usually lower sample sizes, and may have a crucial role in describing the functioning of the brain and highlighting specific connectivity changes.MethodsWe acquired fMRI data from 17 early MS patients and 14 matched healthy controls (HC) during performance of a visual task, characterized motion in both groups, and quantitatively compared the most used and easy to implement methods for correction of motion effects. We compared task-activation metrics obtained from: (i) models containing 6 or 24 motion parameters (MPs) as nuisance regressors; (ii) models containing nuisance regressors for 6 or 24 MPs and motion outliers (scrubbing) detected with Framewise Displacement or Derivative or root mean square VARiance over voxelS; and (iii) models with 6 or 24 MPs and motion outliers corrected through volume interpolation. To our knowledge, volume interpolation has not been systematically compared with scrubbing, nor investigated in task fMRI clinical studies in MS.ResultsNo differences in motion were found between groups, suggesting that recently diagnosed MS patients may not present problematic motion. In general, models with 6 MPs perform better than models with 24 MPs, suggesting the 6 MPs as the best trade-off between correction of motion effects and preservation of valuable information. Parsimonious models with 6 MPs and volume interpolation were the best combination for correcting motion in both groups, surpassing the scrubbing methods. A joint analysis regardless of the group further highlighted the value of volume interpolation.DiscussionVolume interpolation of motion outliers is an easy to implement technique, which may be an alternative to other methods and may improve the accuracy of fMRI analyses, crucially in clinical studies in MS and other neurological populations.

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Reconstructing EEG sources involves a complex pipeline, with the inverse problem being the most challenging. Multiple inversion algorithms are being continuously developed, aiming to tackle the non-uniqueness of this problem, which has been shown to be partially circumvented by also including fMRI-derived spatial priors in the inverse models. However, only task activation maps and resting-state networks (RSNs) have been explored so far, overlooking the recent, but already accepted, notion that brain networks exhibit dynamic functional connectivity (dFC) fluctuations. Moreover, there is no consensus regarding the inversion algorithm of choice, nor a systematic comparison between different sets of spatial priors. Using simultaneous EEG-fMRI data, here we compared four different inversion algorithms (MN, LORETA, EBB and MSP) under a Bayesian framework, each with three different sets of priors consisting of: 1) those specific to the algorithm (S1); 2) S1 plus fMRI task activation maps and RSNs (S2); and 3) S2 plus network modules of task-related dFC states estimated from the dFC fluctuations (S3). The quality of the reconstructed EEG sources was quantified in terms of model-based metrics, namely the free-energy and variance explained of the inversion models, and the overlap/proportion of brain regions known to be involved in the visual perception tasks that the participants were submitted to, and RSN templates, with/within EEG source components. Model-based metrics suggested that model parsimony is preferred, with the combination MSP+S1 exhibiting the best performance. However, optimal overlap/proportion values were found using EBB+S2 or MSP+S3, respectively, indicating that fMRI spatial priors, including dFC state modules, are crucial for the EEG source components to reflect neuronal activity of interest. Our results pave the way towards a more informative selection of the optimal EEG source reconstruction approach, which may be crucial in future studies.