Effect of scanning duration and sample size on reliability in resting state fMRI dynamic causal modeling analysis.

Despite its widespread use, resting-state functional magnetic resonance imaging (rsfMRI) has been criticized for low test-retest reliability. To improve reliability, researchers have recommended using extended scanning durations, increased sample size, and advanced brain connectivity techniques. However, longer scanning runs and larger sample sizes may come with practical challenges and burdens, especially in rare populations. Here we tested if an advanced brain connectivity technique, dynamic causal modeling (DCM), can improve reliability of fMRI effective connectivity (EC) metrics to acceptable levels without extremely long run durations or extremely large samples. Specifically, we employed DCM for EC analysis on rsfMRI data from the Human Connectome Project. To avoid bias, we assessed four distinct DCMs and gradually increased sample sizes in a randomized manner across ten permutations. We employed pseudo true positive and pseudo false positive rates to assess the efficacy of shorter run durations (3.6, 7.2, 10.8, 14.4 min) in replicating the outcomes of the longest scanning duration (28.8 min) when the sample size was fixed at the largest (n = 160 subjects). Similarly, we assessed the efficacy of smaller sample sizes (n = 10, 20, …, 150 subjects) in replicating the outcomes of the largest sample (n = 160 subjects) when the scanning duration was fixed at the longest (28.8 min). Our results revealed that the pseudo false positive rate was below 0.05 for all the analyses. After the scanning duration reached 10.8 min, which yielded a pseudo true positive rate of 92%, further extensions in run time showed no improvements in pseudo true positive rate. Expanding the sample size led to enhanced pseudo true positive rate outcomes, with a plateau at n = 70 subjects for the targeted top one-half of the largest ECs in the reference sample, regardless of whether the longest run duration (28.8 min) or the viable run duration (10.8 min) was employed. Encouragingly, smaller sample sizes exhibited pseudo true positive rates of approximately 80% for n = 20, and 90% for n = 40 subjects. These data suggest that advanced DCM analysis may be a viable option to attain reliable metrics of EC when larger sample sizes or run times are not feasible.

The effects of spatial leakage correction on the reliability of EEG-based functional connectivity networks.

Electroencephalography (EEG) functional connectivity (FC) estimates are confounded by the volume conduction problem. This effect can be greatly reduced by applying FC measures insensitive to instantaneous, zero-lag dependencies (corrected measures). However, numerous studies showed that FC measures sensitive to volume conduction (uncorrected measures) exhibit higher reliability and higher subject-level identifiability. We tested how source reconstruction contributed to the reliability difference of EEG FC measures on a large (n = 201) resting-state data set testing eight FC measures (including corrected and uncorrected measures). We showed that the high reliability of uncorrected FC measures in resting state partly stems from source reconstruction: idiosyncratic noise patterns define a baseline resting-state functional network that explains a significant portion of the reliability of uncorrected FC measures. This effect remained valid for template head model-based, as well as individual head model-based source reconstruction. Based on our findings we made suggestions how to best use spatial leakage corrected and uncorrected FC measures depending on the main goals of the study.

Reliability of variability and complexity measures for task and task-free BOLD fMRI.

Brain activity continuously fluctuates over time, even if the brain is in controlled (e.g., experimentally induced) states. Recent years have seen an increasing interest in understanding the complexity of these temporal variations, for example with respect to developmental changes in brain function or between-person differences in healthy and clinical populations. However, the psychometric reliability of brain signal variability and complexity measures-which is an important precondition for robust individual differences as well as longitudinal research-is not yet sufficiently studied. We examined reliability (split-half correlations) and test-retest correlations for task-free (resting-state) BOLD fMRI as well as split-half correlations for seven functional task data sets from the Human Connectome Project to evaluate their reliability. We observed good to excellent split-half reliability for temporal variability measures derived from rest and task fMRI activation time series (standard deviation, mean absolute successive difference, mean squared successive difference), and moderate test-retest correlations for the same variability measures under rest conditions. Brain signal complexity estimates (several entropy and dimensionality measures) showed moderate to good reliabilities under both, rest and task activation conditions. We calculated the same measures also for time-resolved (dynamic) functional connectivity time series and observed moderate to good reliabilities for variability measures, but poor reliabilities for complexity measures derived from functional connectivity time series. Global (i.e., mean across cortical regions) measures tended to show higher reliability than region-specific variability or complexity estimates. Larger subcortical regions showed similar reliability as cortical regions, but small regions showed lower reliability, especially for complexity measures. Lastly, we also show that reliability scores are only minorly dependent on differences in scan length and replicate our results across different parcellation and denoising strategies. These results suggest that the variability and complexity of BOLD activation time series are robust measures well-suited for individual differences research. Temporal variability of global functional connectivity over time provides an important novel approach to robustly quantifying the dynamics of brain function. PRACTITIONER POINTS: Variability and complexity measures of BOLD activation show good split-half reliability and moderate test-retest reliability. Measures of variability of global functional connectivity over time can robustly quantify neural dynamics. Length of fMRI data has only a minor effect on reliability.

Advancing motion denoising of multiband resting-state functional connectivity fMRI data.

Simultaneous multi-slice (multiband) accelerated functional magnetic resonance imaging (fMRI) provides dramatically improved temporal and spatial resolution for resting-state functional connectivity (RSFC) studies of the human brain in health and disease. However, multiband acceleration also poses unique challenges for denoising of subject motion induced data artifacts, the presence of which is a major confound in RSFC research that substantively diminishes reliability and reproducibility. We comprehensively evaluated existing and novel approaches to volume censoring-based motion denoising in the Human Connectome Project (HCP) dataset. We show that assumptions underlying common metrics for evaluating motion denoising pipelines, especially those based on quality control-functional connectivity (QC-FC) correlations and differences between high- and low-motion participants, are problematic, and appear to be inappropriate in their current widespread use as indicators of comparative pipeline performance and as targets for investigators to use when tuning pipelines for their own datasets. We further develop two new quantitative metrics that are instead agnostic to QC-FC correlations and other measures that rely upon the null assumption that no true relationships exist between trait measures of subject motion and functional connectivity, and demonstrate their use as benchmarks for comparing volume censoring methods. Finally, we develop and validate quantitative methods for determining dataset-specific optimal volume censoring parameters prior to the final analysis of a dataset, and provide straightforward recommendations and code for all investigators to apply this optimized approach to their own RSFC datasets.

Spatial Bayesian GLM on the cortical surface produces reliable task activations in individuals and groups.

The general linear model (GLM) is a widely popular and convenient tool for estimating the functional brain response and identifying areas of significant activation during a task or stimulus. However, the classical GLM is based on a massive univariate approach that does not explicitly leverage the similarity of activation patterns among neighboring brain locations. As a result, it tends to produce noisy estimates and be underpowered to detect significant activations, particularly in individual subjects and small groups. A recently proposed alternative, a cortical surface-based spatial Bayesian GLM, leverages spatial dependencies among neighboring cortical vertices to produce more accurate estimates and areas of functional activation. The spatial Bayesian GLM can be applied to individual and group-level analysis. In this study, we assess the reliability and power of individual and group-average measures of task activation produced via the surface-based spatial Bayesian GLM. We analyze motor task data from 45 subjects in the Human Connectome Project (HCP) and HCP Retest datasets. We also extend the model to multi-run analysis and employ subject-specific cortical surfaces rather than surfaces inflated to a sphere for more accurate distance-based modeling. Results show that the surface-based spatial Bayesian GLM produces highly reliable activations in individual subjects and is powerful enough to detect trait-like functional topologies. Additionally, spatial Bayesian modeling enhances reliability of group-level analysis even in moderately sized samples (n=45). Notably, the power of the spatial Bayesian GLM to detect activations above a scientifically meaningful effect size is nearly invariant to sample size, exhibiting high power even in small samples (n=10). The spatial Bayesian GLM is computationally efficient in individuals and groups and is convenient to implement with the open-source BayesfMRI R package.

Reproducibility of graph measures derived from resting-state MEG functional connectivity metrics in sensor and source spaces.

Prior studies have used graph analysis of resting-state magnetoencephalography (MEG) to characterize abnormal brain networks in neurological disorders. However, a present challenge for researchers is the lack of guidance on which network construction strategies to employ. The reproducibility of graph measures is important for their use as clinical biomarkers. Furthermore, global graph measures should ideally not depend on whether the analysis was performed in the sensor or source space. Therefore, MEG data of the 89 healthy subjects of the Human Connectome Project were used to investigate test-retest reliability and sensor versus source association of global graph measures. Atlas-based beamforming was used for source reconstruction, and functional connectivity (FC) was estimated for both sensor and source signals in six frequency bands using the debiased weighted phase lag index (dwPLI), amplitude envelope correlation (AEC), and leakage-corrected AEC. Reliability was examined over multiple network density levels achieved with proportional weight and orthogonal minimum spanning tree thresholding. At a 100% density, graph measures for most FC metrics and frequency bands had fair to excellent reliability and significant sensor versus source association. The greatest reliability and sensor versus source association was obtained when using amplitude metrics. Reliability was similar between sensor and source spaces when using amplitude metrics but greater for the source than the sensor space in higher frequency bands when using the dwPLI. These results suggest that graph measures are useful biomarkers, particularly for investigating functional networks based on amplitude synchrony.

The bright side and dark side of daydreaming predict creativity together through brain functional connectivity.

Daydreaming and creativity have similar cognitive processes and neural basis. However, few empirical studies have examined the relationship between daydreaming and creativity using cognitive neuroscience methods. The present study explored the relationship between different types of daydreaming and creativity and their common neural basis. The behavioral results revealed that positive constructive daydreaming is positively related to creativity, while poor attentional control is negatively related to it. Machine learning framework was adopted to examine the predictive effect of daydreaming-related brain functional connectivity (FC) on creativity. The results demonstrated that task FCs related to positive constructive daydreaming and task FCs related to poor attentional control both predicted an individual's creativity score successfully. In addition, task FCs combining the positive constructive daydreaming and poor attentional control also had significant predictive effect on creativity score. Furthermore, predictive analysis based on resting-state FCs showed similar patterns. Both of the subscale-related FCs and combined FCs had significant predictive effect on creativity score. Further analysis showed the task and the resting-state FCs both mainly located in the default mode network, central executive network, salience network, and attention network. These results showed that daydreaming was closely related to creativity, as they shared common FC basis.

Boost in Test-Retest Reliability in Resting State fMRI with Predictive Modeling.

Recent studies found low test-retest reliability in functional magnetic resonance imaging (fMRI), raising serious concerns among researchers, but these studies mostly focused on the reliability of individual fMRI features (e.g., individual connections in resting state connectivity maps). Meanwhile, neuroimaging researchers increasingly employ multivariate predictive models that aggregate information across a large number of features to predict outcomes of interest, but the test-retest reliability of predicted outcomes of these models has not previously been systematically studied. Here we apply 10 predictive modeling methods to resting state connectivity maps from the Human Connectome Project dataset to predict 61 outcome variables. Compared with mean reliability of individual resting state connections, we find mean reliability of the predicted outcomes of predictive models is substantially higher for all 10 modeling methods assessed. Moreover, improvement was consistently observed across all scanning and processing choices (i.e., scan lengths, censoring thresholds, volume- vs. surface-based processing). For the most reliable methods, the reliability of predicted outcomes was mostly, though not exclusively, in the "good" range (above 0.60). Finally, we identified three mechanisms that help to explain why predicted outcomes of predictive models have higher reliability than individual imaging features. We conclude that researchers can potentially achieve higher test-retest reliability by making greater use of predictive models.

Resample aggregating improves the generalizability of connectome predictive modeling.

It is a longstanding goal of neuroimaging to produce reliable, generalizable models of brain behavior relationships. More recently, data driven predictive models have become popular. However, overfitting is a common problem with statistical models, which impedes model generalization. Cross validation (CV) is often used to estimate expected model performance within sample. Yet, the best way to generate brain behavior models, and apply them out-of-sample, on an unseen dataset, is unclear. As a solution, this study proposes an ensemble learning method, in this case resample aggregating, encompassing both model parameter estimation and feature selection. Here we investigate the use of resampled aggregated models when used to estimate fluid intelligence (fIQ) from fMRI based functional connectivity (FC) data. We take advantage of two large openly available datasets, the Human Connectome Project (HCP), and the Philadelphia Neurodevelopmental Cohort (PNC). We generate aggregated and non-aggregated models of fIQ in the HCP, using the Connectome Prediction Modelling (CPM) framework. Over various test-train splits, these models are evaluated in sample, on left-out HCP data, and out-of-sample, on PNC data. We find that a resample aggregated model performs best both within- and out-of-sample. We also find that feature selection can vary substantially within-sample. More robust feature selection methods, as detailed here, are needed to improve cross sample performance of CPM based brain behavior models.

Degree of improving TMS focality through a geometrically stable solution of an inverse TMS problem.

The Transcranial Magnetic Stimulation (TMS) inverse problem (TMS-IP) investigated in this study aims to focus the TMS induced electric field close to a specified target point defined on the gray matter interface in the M1HAND area while otherwise minimizing it. The goal of the study is to numerically evaluate the degree of improvement of the TMS-IP solutions relative to the well-known sulcus-aligned mapping (a projection approach with the 90∘ local sulcal angle). In total, 1536 individual TMS-IP solutions have been analyzed for multiple target points and multiple subjects using the boundary element fast multipole method (BEM-FMM) as the forward solver. Our results show that the optimal TMS inverse-problem solutions improve the focality - reduce the size of the field "hot spot" and its deviation from the target - by approximately 21-33% on average for all considered subjects, all observation points, two distinct coil types, two segmentation types, two intracortical observation surfaces under study, and three tested values of the field threshold. The inverse-problem solutions with the maximized focality simultaneously improve the TMS mapping resolution (differentiation between neighbor targets separated by approximately 10 mm) although this improvement is quite modest. Coil position/orientation and conductivity uncertainties have been included into consideration as the corresponding de-focalization factors. The present results will change when the levels of uncertainties change. Our results also indicate that the accuracy of the head segmentation critically influences the expected TMS-IP performance.

The relationship between EEG and fMRI connectomes is reproducible across simultaneous EEG-fMRI studies from 1.5T to 7T.

Both electroencephalography (EEG) and functional Magnetic Resonance Imaging (fMRI) are non-invasive methods that show complementary aspects of human brain activity. Despite measuring different proxies of brain activity, both the measured blood-oxygenation (fMRI) and neurophysiological recordings (EEG) are indirectly coupled. The electrophysiological and BOLD signal can map the underlying functional connectivity structure at the whole brain scale at different timescales. Previous work demonstrated a moderate but significant correlation between resting-state functional connectivity of both modalities, however there is a wide range of technical setups to measure simultaneous EEG-fMRI and the reliability of those measures between different setups remains unknown. This is true notably with respect to different magnetic field strengths (low and high field) and different spatial sampling of EEG (medium to high-density electrode coverage). Here, we investigated the reproducibility of the bimodal EEG-fMRI functional connectome in the most comprehensive resting-state simultaneous EEG-fMRI dataset compiled to date including a total of 72 subjects from four different imaging centers. Data was acquired from 1.5T, 3T and 7T scanners with simultaneously recorded EEG using 64 or 256 electrodes. We demonstrate that the whole-brain monomodal connectivity reproducibly correlates across different datasets and that a moderate crossmodal correlation between EEG and fMRI connectivity of r ≈ 0.3 can be reproducibly extracted in low- and high-field scanners. The crossmodal correlation was strongest in the EEG-ß frequency band but exists across all frequency bands. Both homotopic and within intrinsic connectivity network (ICN) connections contributed the most to the crossmodal relationship. This study confirms, using a considerably diverse range of recording setups, that simultaneous EEG-fMRI offers a consistent estimate of multimodal functional connectomes in healthy subjects that are dominantly linked through a functional core of ICNs across spanning across the different timescales measured by EEG and fMRI. This opens new avenues for estimating the dynamics of brain function and provides a better understanding of interactions between EEG and fMRI measures. This observed level of reproducibility also defines a baseline for the study of alterations of this coupling in pathological conditions and their role as potential clinical markers.

Reliability modelling of resting-state functional connectivity.

Resting-state functional magnetic resonance imaging (rs-fMRI) has an inherently low signal-to-noise ratio largely due to thermal and physiological noise that attenuates the functional connectivity (FC) estimates. Such attenuation limits the reliability of FC and may bias its association with other traits. Low reliability also limits heritability estimates. Classical test theory can be used to obtain a true correlation estimate free of random measurement error from parallel tests, such as split-half sessions of a rs-fMRI scan. We applied a measurement model to split-half FC estimates from the resting-state fMRI data of 1003 participants from the Human Connectome Project (HCP) to examine the benefit of reliability modelling of FC in association with traits from various domains. We evaluated the efficiency of the measurement model on extracting a stable and reliable component of FC and its association with several traits for various sample sizes and scan durations. In addition, we aimed to replicate our previous findings of increased heritability estimates when using a measurement model in a longitudinal adolescent twin cohort. The split-half measurement model improved test-retest reliability of FC on average with +0.33 points (from +0.49 to +0.82), improved strength of associations between FC and various traits on average 1.2-fold (range 1.09-1.35), and increased heritability estimates on average with +20% points (from 39% to 59%) for the full HCP dataset. On average, about half of the variance in split-session FC estimates was attributed to the stable and reliable component of FC. Shorter scan durations showed greater benefit of reliability modelling (up to 1.6-fold improvement), with an additional gain for smaller sample sizes (up to 1.8-fold improvement). Reliability modelling of FC based on a split-half using a measurement model can benefit genetic and behavioral studies by extracting a stable and reliable component of FC that is free from random measurement error and improves genetic and behavioral associations.

Exploring MEG brain fingerprints: Evaluation, pitfalls, and interpretations.

Individual characterization of subjects based on their functional connectome (FC), termed "FC fingerprinting", has become a highly sought-after goal in contemporary neuroscience research. Recent functional magnetic resonance imaging (fMRI) studies have demonstrated unique characterization and accurate identification of individuals as an accomplished task. However, FC fingerprinting in magnetoencephalography (MEG) data is still widely unexplored. Here, we study resting-state MEG data from the Human Connectome Project to assess the MEG FC fingerprinting and its relationship with several factors including amplitude- and phase-coupling functional connectivity measures, spatial leakage correction, frequency bands, and behavioral significance. To this end, we first employ two identification scoring methods, differential identifiability and success rate, to provide quantitative fingerprint scores for each FC measurement. Secondly, we explore the edgewise and nodal MEG fingerprinting patterns across the different frequency bands (delta, theta, alpha, beta, and gamma). Finally, we investigate the cross-modality fingerprinting patterns obtained from MEG and fMRI recordings from the same subjects. We assess the behavioral significance of FC across connectivity measures and imaging modalities using partial least square correlation analyses. Our results suggest that fingerprinting performance is heavily dependent on the functional connectivity measure, frequency band, identification scoring method, and spatial leakage correction. We report higher MEG fingerprinting performances in phase-coupling methods, central frequency bands (alpha and beta), and in the visual, frontoparietal, dorsal-attention, and default-mode networks. Furthermore, cross-modality comparisons reveal a certain degree of spatial concordance in fingerprinting patterns between the MEG and fMRI data, especially in the visual system. Finally, the multivariate correlation analyses show that MEG connectomes have strong behavioral significance, which however depends on the considered connectivity measure and temporal scale. This comprehensive, albeit preliminary investigation of MEG connectome test-retest identifiability offers a first characterization of MEG fingerprinting in relation to different methodological and electrophysiological factors and contributes to the understanding of fingerprinting cross-modal relationships. We hope that this first investigation will contribute to setting the grounds for MEG connectome identification.

Temporal complexity of fMRI is reproducible and correlates with higher order cognition.

It has been hypothesized that resting state networks (RSNs), extracted from resting state functional magnetic resonance imaging (rsfMRI), likely display unique temporal complexity fingerprints, quantified by their multiscale entropy patterns (McDonough and Nashiro, 2014). This is a hypothesis with a potential capacity for developing digital biomarkers of normal brain function, as well as pathological brain dysfunction. Nevertheless, a limitation of McDonough and Nashiro (2014) was that rsfMRI data from only 20 healthy individuals was used for the analysis. To validate this hypothesis in a larger cohort, we used rsfMRI datasets of 987 healthy young adults from the Human Connectome Project (HCP), aged 22-35, each with four 14.4-min rsfMRI recordings and parcellated into 379 brain regions. We quantified multiscale entropy of rsfMRI time series averaged at different cortical and sub-cortical regions. We performed effect-size analysis on the data in 8 RSNs. Given that the morphology of multiscale entropy is affected by the choice of its tolerance parameter (r) and embedding dimension (m), we repeated the analyses at multiple values of r and m including the values used in McDonough and Nashiro (2014). Our results reinforced high temporal complexity in the default mode and frontoparietal networks. Lowest temporal complexity was observed in the subcortical areas and limbic system. We investigated the effect of temporal resolution (determined by the repetition time TR) after downsampling of rsfMRI time series at two rates. At a low temporal resolution, we observed increased entropy and variance across datasets. Test-retest analysis showed that findings were likely reproducible across individuals over four rsfMRI runs, especially when the tolerance parameter r is equal to 0.5. The results confirmed that the relationship between functional brain connectivity strengths and rsfMRI temporal complexity changes over time scales. Finally, a non-random correlation was observed between temporal complexity of RSNs and fluid intelligence suggesting that complex dynamics of the human brain is an important attribute of high-level brain function.

Reproducible coactivation patterns of functional brain networks reveal the aberrant dynamic state transition in schizophrenia.

It is well documented that massive dynamic information is contained in the resting-state fMRI. Recent studies have identified recurring states dominated by similar coactivation patterns (CAPs) and revealed their temporal dynamics. However, the reproducibility and generalizability of the CAP analysis are unclear. To address this question, the effects of methodological pipelines on CAP are comprehensively evaluated in this study, including the preprocessing, network construction, cluster number and three independent cohorts. The CAP state dynamics are characterized by the fraction of time, persistence, counts, and transition probability. Results demonstrate six reliable CAP states and their dynamic characteristics are also reproducible. The state transition probability is found to be positively associated with the spatial similarity. Furthermore, the aberrant CAP states in schizophrenia have been investigated by using the reproducible method on three cohorts. Schizophrenia patients spend less time in CAP states that involve the fronto-parietal network, but more time in CAP states that involve the default mode and salience network. The aberrant dynamic characteristics of CAP states are correlated with the symptom severity. These results reveal the reproducibility and generalizability of the CAP analysis, which can provide novel insights into the neuropathological mechanism associated with aberrant brain network dynamics of schizophrenia.

The coupling of BOLD signal variability and degree centrality underlies cognitive functions and psychiatric diseases.

Brain signal variability has been consistently linked to functional integration; however, whether this coupling is associated with cognitive functions and/or psychiatric diseases has not been clarified. Using multiple multimodality datasets, including resting-state functional magnetic resonance imaging (rsfMRI) data from the Human Connectome Project (HCP: N = 927) and a Beijing sample (N = 416) and cerebral blood flow (CBF) and rsfMRI data from a Hangzhou sample (N = 29), we found that, compared with the existing variability measure (i.e., SDBOLD), the mean-scaled (standardized) fractional standard deviation of the BOLD signal (mfSDBOLD) maintained very high test-retest reliability, showed greater cross-site reliability and was less affected by head motion. We also found strong reproducible couplings between the mfSDBOLD and functional integration measured by the degree centrality (DC), both cross-voxel and cross-subject, which were robust to scanning and preprocessing parameters. Moreover, both mfSDBOLD and DC were correlated with CBF, suggesting a common physiological basis for both measures. Critically, the degree of coupling between mfSDBOLD and long-range DC was positively correlated with individuals' cognitive total composite scores. Brain regions with greater mismatches between mfSDBOLD and long-range DC were more vulnerable to brain diseases. Our results suggest that BOLD signal variability could serve as a meaningful index of local function that underlies functional integration in the human brain and that a strong coupling between BOLD signal variability and functional integration may serve as a hallmark of balanced brain networks that are associated with optimal brain functions.

A systematic evaluation of source reconstruction of resting MEG of the human brain with a new high-resolution atlas: Performance, precision, and parcellation.

Noninvasive functional neuroimaging of the human brain can give crucial insight into the mechanisms that underpin healthy cognition and neurological disorders. Magnetoencephalography (MEG) measures extracranial magnetic fields originating from neuronal activity with high temporal resolution, but requires source reconstruction to make neuroanatomical inferences from these signals. Many source reconstruction algorithms are available, and have been widely evaluated in the context of localizing task-evoked activities. However, no consensus yet exists on the optimum algorithm for resting-state data. Here, we evaluated the performance of six commonly-used source reconstruction algorithms based on minimum-norm and beamforming estimates. Using human resting-state MEG, we compared the algorithms using quantitative metrics, including resolution properties of inverse solutions and explained variance in sensor-level data. Next, we proposed a data-driven approach to reduce the atlas from the Human Connectome Project's multi-modal parcellation of the human cortex based on metrics such as MEG signal-to-noise-ratio and resting-state functional connectivity gradients. This procedure produced a reduced cortical atlas with 230 regions, optimized to match the spatial resolution and the rank of MEG data from the current generation of MEG scanners. Our results show that there is no "one size fits all" algorithm, and make recommendations on the appropriate algorithms depending on the data and aimed analyses. Our comprehensive comparisons and recommendations can serve as a guide for choosing appropriate methodologies in future studies of resting-state MEG.

Diagnostic power of resting-state fMRI for detection of network connectivity in Alzheimer's disease and mild cognitive impairment: A systematic review.

Resting-state fMRI (rs-fMRI) detects functional connectivity (FC) abnormalities that occur in the brains of patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). FC of the default mode network (DMN) is commonly impaired in AD and MCI. We conducted a systematic review aimed at determining the diagnostic power of rs-fMRI to identify FC abnormalities in the DMN of patients with AD or MCI compared with healthy controls (HCs) using machine learning (ML) methods. Multimodal support vector machine (SVM) algorithm was the commonest form of ML method utilized. Multiple kernel approach can be utilized to aid in the classification by incorporating various discriminating features, such as FC graphs based on "nodes" and "edges" together with structural MRI-based regional cortical thickness and gray matter volume. Other multimodal features include neuropsychiatric testing scores, DTI features, and regional cerebral blood flow. Among AD patients, the posterior cingulate cortex (PCC)/Precuneus was noted to be a highly affected hub of the DMN that demonstrated overall reduced FC. Whereas reduced DMN FC between the PCC and anterior cingulate cortex (ACC) was observed in MCI patients. Evidence indicates that the nodes of the DMN can offer moderate to high diagnostic power to distinguish AD and MCI patients. Nevertheless, various concerns over the homogeneity of data based on patient selection, scanner effects, and the variable usage of classifiers and algorithms pose a challenge for ML-based image interpretation of rs-fMRI datasets to become a mainstream option for diagnosing AD and predicting the conversion of HC/MCI to AD.

Validating dynamicity in resting state fMRI with activation-informed temporal segmentation.

Confirming the presence (or absence) of dynamic functional connectivity (dFC) states during rest is an important open question in the field of cognitive neuroscience. The prevailing dFC framework aims to identify dynamics directly from connectivity estimates with a sliding window approach, however this method suffers from several drawbacks including sensitivity to window size and poor test-retest reliability. We hypothesize that time-varying changes in functional connectivity are mirrored by significant temporal changes in functional activation, and that this coupling can be leveraged to study dFC without the need for a predefined sliding window. Here, we introduce a data-driven dFC framework, which involves informed segmentation of fMRI time series at candidate FC state transition points estimated from changes in whole-brain functional activation, rather than a fixed-length sliding window. We show our approach reliably identifies true cognitive state change points when applied on block-design working memory task data and outperforms the standard sliding window approach in both accuracy and computational efficiency in this context. When applied to data from four resting state fMRI scanning sessions, our method consistently recovers five reliable FC states, and subject-specific features derived from these states show significant correlation with behavioral phenotypes of interest (cognitive ability, personality). Overall, these results suggest abrupt whole-brain changes in activation can be used as a marker for changes in connectivity states and provides new evidence for the existence of time-varying FC in rest.

Bayesian estimation of maximum entropy model for individualized energy landscape analysis of brain state dynamics.

The pairwise maximum entropy model (MEM) for resting state functional MRI (rsfMRI) has been used to generate energy landscape of brain states and to explore nonlinear brain state dynamics. Researches using MEM, however, has mostly been restricted to fixed-effect group-level analyses, using concatenated time series across individuals, due to the need for large samples in the parameter estimation of MEM. To mitigate the small sample problem in analyzing energy landscapes for individuals, we propose a Bayesian estimation of individual MEM using variational Bayes approximation (BMEM). We evaluated the performances of BMEM with respect to sample sizes and prior information using simulation. BMEM showed advantages over conventional maximum likelihood estimation in reliably estimating model parameters for individuals with small sample data, particularly utilizing the empirical priors derived from group data. We then analyzed individual rsfMRI of the Human Connectome Project to show the usefulness of MEM in differentiating individuals and in exploring neural correlates for human behavior. MEM and its energy landscape properties showed high subject specificity comparable to that of functional connectivity. Canonical correlation analysis identified canonical variables for MEM highly associated with cognitive scores. Inter-individual variations of cognitive scores were also reflected in energy landscape properties such as energies, occupation times, and basin sizes at local minima. We conclude that BMEM provides an efficient method to characterize dynamic properties of individuals using energy landscape analysis of individual brain states.