Individual characteristics outperform resting-state fMRI for the prediction of behavioral phenotypes.

In this study, we aimed to compare imaging-based features of brain function, measured by resting-state fMRI (rsfMRI), with individual characteristics such as age, gender, and total intracranial volume to predict behavioral measures. We developed a machine learning framework based on rsfMRI features in a dataset of 20,000 healthy individuals from the UK Biobank, focusing on temporal complexity and functional connectivity measures. Our analysis across four behavioral phenotypes revealed that both temporal complexity and functional connectivity measures provide comparable predictive performance. However, individual characteristics consistently outperformed rsfMRI features in predictive accuracy, particularly in analyses involving smaller sample sizes. Integrating rsfMRI features with demographic data sometimes enhanced predictive outcomes. The efficacy of different predictive modeling techniques and the choice of brain parcellation atlas were also examined, showing no significant influence on the results. To summarize, while individual characteristics are superior to rsfMRI in predicting behavioral phenotypes, rsfMRI still conveys additional predictive value in the context of machine learning, such as investigating the role of specific brain regions in behavioral phenotypes.

Mapping the interplay of atrial fibrillation, brain structure, and cognitive dysfunction.

INTRODUCTION: Atrial fibrillation (AF) is associated with an elevated risk of cognitive impairment and dementia. Understanding the cognitive sequelae and brain structural changes associated with AF is vital for addressing ensuing health care needs. METHODS AND RESULTS: We examined 1335 stroke-free individuals with AF and 2683 matched controls using neuropsychological assessments and multimodal neuroimaging. The analysis revealed that individuals with AF exhibited deficits in executive function, processing speed, and reasoning, accompanied by reduced cortical thickness, elevated extracellular free-water content, and widespread white matter abnormalities, indicative of small vessel pathology. Notably, brain structural differences statistically mediated the relationship between AF and cognitive performance. DISCUSSION: Integrating a comprehensive analysis approach with extensive clinical and magnetic resonance imaging data, our study highlights small vessel pathology as a possible unifying link among AF, cognitive decline, and abnormal brain structure. These insights can inform diagnostic approaches and motivate the ongoing implementation of effective therapeutic strategies. Highlights We investigated neuropsychological and multimodal neuroimaging data of 1335 individuals with atrial fibrillation (AF) and 2683 matched controls. Our analysis revealed AF-associated deficits in cognitive domains of attention, executive function, processing speed, and reasoning. Cognitive deficits in the AF group were accompanied by structural brain alterations including reduced cortical thickness and gray matter volume, alongside increased extracellular free-water content as well as widespread differences of white matter integrity. Structural brain changes statistically mediated the link between AF and cognitive performance, emphasizing the potential of structural imaging markers as a diagnostic tool in AF-related cognitive decline.

A latent clinical-anatomical dimension relating metabolic syndrome to brain structure and cognition.

The link between metabolic syndrome (MetS) and neurodegenerative as well as cerebrovascular conditions holds substantial implications for brain health in at-risk populations. This study elucidates the complex relationship between MetS and brain health by conducting a comprehensive examination of cardiometabolic risk factors, brain morphology, and cognitive function in 40,087 individuals. Multivariate, data-driven statistics identified a latent dimension linking more severe MetS to widespread brain morphological abnormalities, accounting for up to 71% of shared variance in the data. This dimension was replicable across sub-samples. In a mediation analysis, we could demonstrate that MetS-related brain morphological abnormalities mediated the link between MetS severity and cognitive performance in multiple domains. Employing imaging transcriptomics and connectomics, our results also suggest that MetS-related morphological abnormalities are linked to the regional cellular composition and macroscopic brain network organization. By leveraging extensive, multi-domain data combined with a dimensional stratification approach, our analysis provides profound insights into the association of MetS and brain health. These findings can inform effective therapeutic and risk mitigation strategies aimed at maintaining brain integrity.

Intermediately synchronised brain states optimise trade-off between subject specificity and predictive capacity.

Functional connectivity (FC) refers to the statistical dependencies between activity of distinct brain areas. To study temporal fluctuations in FC within the duration of a functional magnetic resonance imaging (fMRI) scanning session, researchers have proposed the computation of an edge time series (ETS) and their derivatives. Evidence suggests that FC is driven by a few time points of high-amplitude co-fluctuation (HACF) in the ETS, which may also contribute disproportionately to interindividual differences. However, it remains unclear to what degree different time points actually contribute to brain-behaviour associations. Here, we systematically evaluate this question by assessing the predictive utility of FC estimates at different levels of co-fluctuation using machine learning (ML) approaches. We demonstrate that time points of lower and intermediate co-fluctuation levels provide overall highest subject specificity as well as highest predictive capacity of individual-level phenotypes.

A latent clinical-anatomical dimension relating metabolic syndrome to brain structure and cognition.

The link between metabolic syndrome (MetS) and neurodegenerative as well cerebrovascular conditions holds substantial implications for brain health in at-risk populations. This study elucidates the complex relationship between MetS and brain health by conducting a comprehensive examination of cardiometabolic risk factors, cortical morphology, and cognitive function in 40,087 individuals. Multivariate, data-driven statistics identified a latent dimension linking more severe MetS to widespread brain morphological abnormalities, accounting for up to 71% of shared variance in the data. This dimension was replicable across sub-samples. In a mediation analysis we could demonstrate that MetS-related brain morphological abnormalities mediated the link between MetS severity and cognitive performance in multiple domains. Employing imaging transcriptomics and connectomics, our results also suggest that MetS-related morphological abnormalities are linked to the regional cellular composition and macroscopic brain network organization. By leveraging extensive, multi-domain data combined with a dimensional stratification approach, our analysis provides profound insights into the association of MetS and brain health. These findings can inform effective therapeutic and risk mitigation strategies aimed at maintaining brain integrity.

Temporal complexity of EEG encodes human alertness.

Objective. Automatic human alertness monitoring has recently become an important research topic with important applications in many areas such as the detection of drivers' fatigue, monitoring of monotonous tasks that require a high level of alertness such as traffic control and nuclear power plant monitoring, and sleep staging. In this study, we propose that balanced dynamics of Electroencephalography (EEG) (so called EEG temporal complexity) is a potentially useful feature for identifying human alertness states. Recently, a new signal entropy measure, called range entropy (RangeEn), was proposed to overcome some limitations of two of the most widely used entropy measures, namely approximate entropy (ApEn) and Sample Entropy (SampEn), and showed its relevance for the study of time domain EEG complexity. In this paper, we investigated whether the RangeEn holds discriminating information associated with human alertness states, namely awake, drowsy, and sleep and compare its performance against those of SampEn and ApEn.Approach. We used EEG data from 60 healthy subjects of both sexes and different ages acquired during whole night sleeps. Using a 30 s sliding window, we computed the three entropy measures of EEG and performed statistical analyses to evaluate the ability of these entropy measures to discriminate among the different human alertness states.Main results. Although the three entropy measures contained useful information about human alertness, RangeEn showed a higher discriminative capability compared to ApEn and SampEn especially when using EEG within the beta frequency band.Significance. Our findings highlight the EEG temporal complexity evolution through the human alertness states. This relationship can potentially be exploited for the development of automatic human alertness monitoring systems and diagnostic tools for different neurological and sleep disorders, including insomnia.

On the Spatial Distribution of Temporal Complexity in Resting State and Task Functional MRI.

Measuring the temporal complexity of functional MRI (fMRI) time series is one approach to assess how brain activity changes over time. In fact, hemodynamic response of the brain is known to exhibit critical behaviour at the edge between order and disorder. In this study, we aimed to revisit the spatial distribution of temporal complexity in resting state and task fMRI of 100 unrelated subjects from the Human Connectome Project (HCP). First, we compared two common choices of complexity measures, i.e., Hurst exponent and multiscale entropy, and observed a high spatial similarity between them. Second, we considered four tasks in the HCP dataset (Language, Motor, Social, and Working Memory) and found high task-specific complexity, even when the task design was regressed out. For the significance thresholding of brain complexity maps, we used a statistical framework based on graph signal processing that incorporates the structural connectome to develop the null distributions of fMRI complexity. The results suggest that the frontoparietal, dorsal attention, visual, and default mode networks represent stronger complex behaviour than the rest of the brain, irrespective of the task engagement. In sum, the findings support the hypothesis of fMRI temporal complexity as a marker of cognition.

Effective connectivity in brain networks estimated using EEG signals is altered in children with ADHD.

This study presents a methodology developed for estimating effective connectivity in brain networks (BNs) using multichannel scalp EEG recordings. The methodology uses transfer entropy as an information transfer measure to detect pair-wise directed information transfer between EEG signals within δ, θ, α, ß and γ-bands. The developed methodology is then used to study the properties of directed BNs in children with attention-deficit hyperactivity disorder (ADHD) and compare them with that of the healthy controls using both statistical and receiver operating characteristic (ROC) analyses. The results indicate that directed information transfer between scalp EEG electrodes in the ADHD subjects differs significantly compared to the healthy ones. The results of the statistical and ROC analyses of frequency-specific graph measures demonstrate their highly discriminative ability between the two groups. Specifically, the graph measures extracted from the estimated directed BNs in the ß-band show the highest discrimination between the ADHD and control groups. These findings are in line with the fact that ß-band reflects active concentration, motor activity, and anxious mental states. The reported results show that the developed methodology has the capacity to be used for investigating patterns of directed BNs in neuropsychiatric disorders.

Automatic detection of generalized paroxysmal fast activity in interictal EEG using time-frequency analysis.

OBJECTIVE: Markup of generalized interictal epileptiform discharges (IEDs) on EEG is an important step in the diagnosis and characterization of epilepsy. However, manual EEG markup is a time-consuming, subjective, and the specialized task where the human reviewer needs to visually inspect a large amount of data to facilitate accurate clinical decisions. In this study, we aimed to develop a framework for automated detection of generalized paroxysmal fast activity (GPFA), a generalized IED seen in scalp EEG recordings of patients with the severe epilepsy of Lennox-Gastaut syndrome (LGS). METHODS: We studied 13 children with LGS who had GPFA events in their interictal EEG recordings. Time-frequency information derived from manually marked IEDs across multiple EEG channels was used to automatically detect similar events in each patient's interictal EEG. We validated true positives and false positives of the proposed spike detection approach using both standalone scalp EEG and simultaneous EEG-functional MRI (EEG-fMRI) recordings. RESULTS: GPFA events displayed a consistent low-high frequency arrangement in the time-frequency domain. This 'bimodal' spectral feature was most prominent over frontal EEG channels. Our automatic detection approach using this feature identified EEG events with similar time-frequency properties to the manually marked GPFAs. Brain maps of EEG-fMRI signal change during these automatically detected IEDs were comparable to the EEG-fMRI brain maps derived from manual IED markup. CONCLUSION: GPFA events have a characteristic bimodal time-frequency feature that can be automatically detected from scalp EEG recordings in patients with LGS. The validity of this time-frequency feature is demonstrated by EEG-fMRI analysis of automatically detected events, which recapitulates the brain maps we have previously shown to underlie generalized IEDs in LGS. SIGNIFICANCE: This study provides a novel methodology that enables a fast, automated, and objective inspection of generalized IEDs in LGS. The proposed framework may be extendable to a wider range of epilepsy syndromes in which monitoring the burden of epileptic activity can aid clinical decision-making and faster assessment of treatment response and estimation of future seizure risk.

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.

Dynamic analysis of fMRI activation during epileptic spikes can help identify the seizure origin.

OBJECTIVE: We use the dynamic electroencephalography-functional magnetic resonance imaging (EEG-fMRI) method to incorporate variability in the amplitude and field of the interictal epileptic discharges (IEDs) into the fMRI analysis. We ask whether IED variability analysis can (a) identify additional activated brain regions during the course of IEDs, not seen in standard analysis; and (b) demonstrate the origin and spread of epileptic activity. We explore whether these functional changes recapitulate the structural connections and propagation of epileptic activity during seizures. METHODS: Seventeen patients with focal epilepsy and at least 30 IEDs of a single type during simultaneous EEG-fMRI were studied. IED variability and EEG source imaging (ESI) analysis extracted time-varying dynamic changes. General linear modeling (GLM) generated static functional maps. Dynamic maps were compared to static functional maps. The dynamic sequence from IED variability was compared to the ESI results. In a subset of patients, we investigated structural connections between active brain regions using diffusion-based fiber tractography. RESULTS: IED variability distinguished the origin of epileptic activity from its propagation in 15 of 17 (88%) patients. This included two cases where no result was obtained from the standard GLM analysis. In both of these cases, IED variability revealed activation in line with the presumed epileptic focus. Two cases showed no result from either method. Both had very high spike rates associated with dysplasia in the postcentral gyrus. In all 15 cases with dynamic activation, the observed dynamics were concordant with ESI. Fiber tractography identified specific white matter pathways between brain regions that were active at IED onset and propagation. SIGNIFICANCE: Dynamic techniques involving IED variability can provide additional power for EEG-fMRI analysis, compared to standard analysis, revealing additional biologically plausible information in cases with no result from the standard analysis and gives insight into the origin and spread of IEDs.

Reducing the influence of intramodular connectivity in participation coefficient.

Both natural and engineered networks are often modular. Whether a network node interacts with only nodes from its own module or nodes from multiple modules provides insight into its functional role. The participation coefficient (PC) is typically used to measure this attribute, although its value also depends on the size and connectedness of the module it belongs to and may lead to nonintuitive identification of highly connected nodes. Here, we develop a normalized PC that reduces the influence of intramodular connectivity compared with the conventional PC. Using brain, C. elegans, airport, and simulated networks, we show that our measure of participation is not influenced by the size or connectedness of modules, while preserving conceptual and mathematical properties, of the classic formulation of PC. Unlike the conventional PC, we identify London and New York as high participators in the air traffic network and demonstrate stronger associations with working memory in human brain networks, yielding new insights into nodal participation across network modules.

Clinical benefit of presurgical EEG-fMRI in difficult-to-localize focal epilepsy: A single-institution retrospective review.

OBJECTIVE: The aim of this report is to present our clinical experience of electroencephalography-functional magnetic resonance imaging (EEG-fMRI) in localizing the epileptogenic focus, and to evaluate the clinical impact and challenges associated with the use of EEG-fMRI in pharmacoresistant focal epilepsy. METHODS: We identified EEG-fMRI studies (n = 118) in people with focal epilepsy performed at our center from 2003 to 2018. Participants were referred from our Comprehensive Epilepsy Program in an exploratory research effort to address often difficult clinical questions, due to complex and difficult-to-localize epilepsy. We assessed the success of each study, the clinical utility of the result, and when surgery was performed, the postoperative outcome. RESULTS: Overall, 50% of EEG-fMRI studies were successful, meaning that data were of good quality and interictal epileptiform discharges were recorded. With an altered recruitment strategy since 2012 with increased inclusion of patients who were inpatients for video-EEG monitoring, we found that this patients in this selected group were more likely to have epileptic discharges detected during EEG-fMRI (96% of inpatients vs 29% of outpatients, P<.0001). To date, 48% (57 of 118) of patients have undergone epilepsy surgery. In 10 cases (17% of the 59 successful studies) the EEG-fMRI result had a "critical impact" on the surgical decision. These patients were difficult to localize because of subtle abnormalities, apparently normal MRI, or extensive structural abnormalities. All 10 had a good seizure outcome at 1 year after surgery (mean follow-up 6.5 years). SIGNIFICANCE: EEG-fMRI results can assist identification of the epileptogenic focus in otherwise difficult-to-localize cases of pharmacoresistant focal epilepsy. Surgery determined largely by localization from the EEG-fMRI result can lead to good seizure outcomes. A limitation of this study is its retrospective design with nonconsecutive recruitment. Prospective clinical trials with well-defined inclusion criteria are needed to determine the overall benefit of EEG-fMRI for preoperative localization and postoperative outcome in focal epilepsy.

Human GABRG2 generalized epilepsy: Increased somatosensory and striatothalamic connectivity.

OBJECTIVE: To map functional MRI (fMRI) connectivity within and between the somatosensory cortex, putamen, and ventral thalamus in individuals from a family with a GABAergic deficit segregating with febrile seizures and genetic generalized epilepsy. METHODS: We studied 5 adults from a family with early-onset absence epilepsy and/or febrile seizures and a GABAA receptor subunit gamma2 pathogenic variant (GABRG2[R43Q]) vs 5 age-matched controls. We infer differences between participants with the GABRG2 pathogenic variant and controls in resting-state fMRI connectivity within and between the somatosensory cortex, putamen, and ventral thalamus. RESULTS: We observed increased fMRI connectivity within the somatosensory cortex and between the putamen and ventral thalamus in all individuals with the GABRG2 pathogenic variant compared with controls. Post hoc analysis showed less pronounced changes in fMRI connectivity within and between the primary visual cortex and precuneus. CONCLUSIONS: Although our sample size was small, this preliminary study suggests that individuals with a GABRG2 pathogenic variant, raising risk of febrile seizures and generalized epilepsy, display underlying increased functional connectivity both within the somatosensory cortex and in striatothalamic networks. This human network model aligns with rodent research and should be further validated in larger cohorts, including other individuals with generalized epilepsy with and without known GABA pathogenic variants.

Towards fast and reliable simultaneous EEG-fMRI analysis of epilepsy with automatic spike detection.

OBJECTIVE: The process of manually marking up epileptic spikes for simultaneous electroencephalogram (EEG) and resting state functional MRI (rsfMRI) analysis in epilepsy studies is a tedious and subjective task for a human expert. The aim of this study was to evaluate whether automatic EEG spike detection can facilitate EEG-rsfMRI analysis, and to assess its potential as a clinical tool in epilepsy. METHODS: We implemented a fast algorithm for detection of uniform interictal epileptiform discharges (IEDs) in one-hour scalp EEG recordings of 19 refractory focal epilepsy datasets (from 16 patients) who underwent a simultaneous EEG-rsfMRI recording. Our method was based on matched filtering of an IED template (derived from human markup) used to automatically detect other 'similar' EEG events. We compared simultaneous EEG-rsfMRI results between automatic IED detection and standard analysis with human EEG markup only. RESULTS: In contrast to human markup, automatic IED detection takes a much shorter time to detect IEDs and export an output text file containing spike timings. In 13/19 focal epilepsy datasets, statistical EEG-rsfMRI maps based on automatic spike detection method were comparable with human markup, and in 6/19 focal epilepsy cases automatic spike detection revealed additional brain regions not seen with human EEG markup. Additional events detected by our automated method independently revealed similar patterns of activation to a human markup. Overall, automatic IED detection provides greater statistical power in EEG-rsfMRI analysis compared to human markup in a short timeframe. CONCLUSIONS: Automatic spike detection is a simple and fast method that can reproduce comparable and, in some cases, even superior results compared to the common practice of manual EEG markup in EEG-rsfMRI analysis of epilepsy. SIGNIFICANCE: Our study shows that IED detection algorithms can be effectively used in epilepsy clinical settings. This work further helps in translating EEG-rsfMRI research into a fast, reliable and easy-to-use clinical tool for epileptologists.

Multilayer network switching rate predicts brain performance.

Large-scale brain dynamics are characterized by repeating spatiotemporal connectivity patterns that reflect a range of putative different brain states that underlie the dynamic repertoire of brain functions. The role of transition between brain networks is poorly understood, and whether switching between these states is important for behavior has been little studied. Our aim was to model switching between functional brain networks using multilayer network methods and test for associations between model parameters and behavioral measures. We calculated time-resolved fMRI connectivity in 1,003 healthy human adults from the Human Connectome Project. The time-resolved fMRI connectivity data were used to generate a spatiotemporal multilayer modularity model enabling us to quantify network switching, which we define as the rate at which each brain region transits between different networks. We found (i) an inverse relationship between network switching and connectivity dynamics, where the latter was defined in terms of time-resolved fMRI connections with variance in time that significantly exceeded phase-randomized surrogate data; (ii) brain connectivity was lower during intervals of network switching; (iii) brain areas with frequent network switching had greater temporal complexity; (iv) brain areas with high network switching were located in association cortices; and (v) using cross-validated elastic net regression, network switching predicted intersubject variation in working memory performance, planning/reasoning, and amount of sleep. Our findings shed light on the importance of brain dynamics predicting task performance and amount of sleep. The ability to switch between network configurations thus appears to be a fundamental feature of optimal brain function.

On the relationship between instantaneous phase synchrony and correlation-based sliding windows for time-resolved fMRI connectivity analysis.

Correlation-based sliding window analysis (CSWA) is the most commonly used method to estimate time-resolved functional MRI (fMRI) connectivity. However, instantaneous phase synchrony analysis (IPSA) is gaining popularity mainly because it offers single time-point resolution of time-resolved fMRI connectivity. We aim to provide a systematic comparison between these two approaches, on temporal, topological and anatomical levels. For this purpose, we used resting-state fMRI data from two separate cohorts with different temporal resolutions (45 healthy subjects from Human Connectome Project fMRI data with repetition time of 0.72 s and 25 healthy subjects from a separate validation fMRI dataset with a repetition time of 3 s). For time-resolved functional connectivity analysis, we calculated tapered CSWA over a wide range of different window lengths that were compared to IPSA. We found a strong association in connectivity dynamics between IPSA and CSWA when considering the absolute values of CSWA. The association between CSWA and IPSA was stronger for a window length of ∼20 s (shorter than filtered fMRI wavelength) than ∼100 s (longer than filtered fMRI wavelength), irrespective of the sampling rate of the underlying fMRI data. Narrow-band filtering of fMRI data (0.03-0.07 Hz) yielded a stronger relationship between IPSA and CSWA than wider-band (0.01-0.1 Hz). On a topological level, time-averaged IPSA and CSWA nodes were non-linearly correlated for both short (∼20 s) and long (∼100 s) windows, mainly because nodes with strong negative correlations (CSWA) displayed high phase synchrony (IPSA). IPSA and CSWA were anatomically similar in the default mode network, sensory cortex, insula and cerebellum. Our results suggest that IPSA and CSWA provide comparable characterizations of time-resolved fMRI connectivity for appropriately chosen window lengths. Although IPSA requires narrow-band fMRI filtering, it does not mandate a (semi-)arbitrary choice of window length and window overlap. A code for calculating IPSA is provided.

Range Entropy: A Bridge between Signal Complexity and Self-Similarity.

Approximate entropy (ApEn) and sample entropy (SampEn) are widely used for temporal complexity analysis of real-world phenomena. However, their relationship with the Hurst exponent as a measure of self-similarity is not widely studied. Additionally, ApEn and SampEn are susceptible to signal amplitude changes. A common practice for addressing this issue is to correct their input signal amplitude by its standard deviation. In this study, we first show, using simulations, that ApEn and SampEn are related to the Hurst exponent in their tolerance r and embedding dimension m parameters. We then propose a modification to ApEn and SampEn called range entropy or RangeEn. We show that RangeEn is more robust to nonstationary signal changes, and it has a more linear relationship with the Hurst exponent, compared to ApEn and SampEn. RangeEn is bounded in the tolerance r-plane between 0 (maximum entropy) and 1 (minimum entropy) and it has no need for signal amplitude correction. Finally, we demonstrate the clinical usefulness of signal entropy measures for characterisation of epileptic EEG data as a real-world example.

Dynamic coupling between fMRI local connectivity and interictal EEG in focal epilepsy: A wavelet analysis approach.

Simultaneous scalp EEG-fMRI recording is a noninvasive neuroimaging technique for combining electrophysiological and hemodynamic aspects of brain function. Despite the time-varying nature of both measurements, their relationship is usually considered as time-invariant. The aim of this study was to detect direct associations between scalp-recorded EEG and regional changes of hemodynamic brain connectivity in focal epilepsy through a time-frequency paradigm. To do so, we developed a voxel-wise framework that analyses wavelet coherence between dynamic regional phase synchrony (DRePS, calculated from fMRI) and band amplitude fluctuation (BAF) of a target EEG electrode with dominant interictal epileptiform discharges (IEDs). As a proof of concept, we applied this framework to seven patients with focal epilepsy. The analysis produced patient-specific spatial maps of DRePS-BAF coupling, which highlight regions with a strong link between EEG power and local fMRI connectivity. Although we observed DRePS-BAF coupling proximate to the suspected seizure onset zone in some patients, our results suggest that DRePS-BAF is more likely to identify wider 'epileptic networks'. We also compared DRePS-BAF with standard EEG-fMRI analysis based on general linear modelling (GLM). There was, in general, little overlap between the DRePS-BAF maps and GLM maps. However, in some subjects the spatial clusters revealed by these two analyses appeared to be adjacent, particularly in medial posterior cortices. Our findings suggest that (1) there is a strong time-varying relationship between local fMRI connectivity and interictal EEG power in focal epilepsy, and (2) that DRePS-BAF reflect different aspects of epileptic network activity than standard EEG-fMRI analysis. These two techniques, therefore, appear to be complementary. Hum Brain Mapp 38:5356-5374, 2017. © 2017 Wiley Periodicals, Inc.