Network perspectives on epilepsy using EEG/MEG source connectivity

The evolution of EEG/MEG source connectivity is both, a promising, and controversial advance in the characterization of epileptic brain activity. In this narrative review we elucidate the potential of this technology to provide an intuitive view of the epileptic network at its origin, the different brain regions involved in the epilepsy, without the limitation of electrodes at the scalp level. Several studies have confirmed the added value of using source connectivity to localize the seizure onset zone and irritative zone or to quantify the propagation of epileptic activity over time. It has been shown in pilot studies that source connectivity has the potential to obtain prognostic correlates, to assist in the diagnosis of the epilepsy type even in the absence of visually noticeable epileptic activity in the EEG/MEG, and to predict treatment outcome. Nevertheless, prospective validation studies in large and heterogeneous patient cohorts are still lacking and are needed to bring these techniques into clinical use. Moreover, the methodological approach is challenging, with several poorly examined parameters that most likely impact the resulting network patterns. These fundamental challenges affect all potential applications of EEG/MEG source connectivity analysis, be it in a resting, spiking, or ictal state, and also its application to cognitive activation of the eloquent area in presurgical evaluation. However, such method can allow unique insights into physiological and pathological brain functions and have great potential in (clinical) neuroscience

Predictive decoding of neural data

In the last five decades the number of techniques available for non-invasive functional imaging has increased dramatically. Researchers today can choose from a variety of imaging modalities that include EEG, MEG, PET, SPECT, MRI, and fMRI. This doctoral dissertation offers a methodology for the reliable analysis of neural data at different levels of investigation. By using statistical learning algorithms the proposed approach allows single-trial analysis of various neural data by decoding them into variables of interest. Unbiased testing of the decoder on new samples of the data provides a generalization assessment of decoding performance reliability. Through consecutive analysis of the constructed decoder\u27s sensitivity it is possible to identify neural signal components relevant to the task of interest. The proposed methodology accounts for covariance and causality structures present in the signal. This feature makes it more powerful than conventional univariate methods which currently dominate the neuroscience field. Chapter 2 describes the generic approach toward the analysis of neural data using statistical learning algorithms. Chapter 3 presents an analysis of results from four neural data modalities: extracellular recordings, EEG, MEG, and fMRI. These examples demonstrate the ability of the approach to reveal neural data components which cannot be uncovered with conventional methods. A further extension of the methodology, Chapter 4 is used to analyze data from multiple neural data modalities: EEG and fMRI. The reliable mapping of data from one modality into the other provides a better understanding of the underlying neural processes. By allowing the spatial-temporal exploration of neural signals under loose modeling assumptions, it removes potential bias in the analysis of neural data due to otherwise possible forward model misspecification. The proposed methodology has been formalized into a free and open source Python framework for statistical learning based data analysis. This framework, PyMVPA, is described in Chapter 5

Traveling EEG slow oscillation along the dorsal attention network initiates spontaneous perceptual switching

An ambiguous figure such as the Necker cube causes spontaneous perceptual switching (SPS). The mechanism of SPS in multistable perception has not yet been determined. Although early psychological studies suggested that SPS may be caused by fatigue or satiation of orientation, the neural mechanism of SPS is still unknown. Functional magnetic resonance imaging (fMRI) has shown that the dorsal attention network (DAN), which mainly controls voluntary attention, is involved in bistable perception of the Necker cube. To determine whether neural dynamics along the DAN cause SPS, we performed simultaneous electroencephalography (EEG) and fMRI during an SPS task with the Necker cube, with every SPS reported by pressing a button. This EEG–fMRI integrated analysis showed that (a) 3–4 Hz spectral EEG power modulation at fronto-central, parietal, and centro-parietal electrode sites sequentially appeared from 750 to 350 ms prior to the button press; and (b) activations correlating with the EEG modulation traveled along the DAN from the frontal to the parietal regions. These findings suggest that slow oscillation initiates SPS through global dynamics along the attentional system such as the DAN

Brain activation time-locked to sleep spindles associated with human cognitive abilities

Copyright © 2019 Fang, Ray, Owen and Fogel. Simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI) studies have revealed brain activations time-locked to spindles. Yet, the functional significance of these spindle-related brain activations is not understood. EEG studies have shown that inter-individual differences in the electrophysiological characteristics of spindles (e.g., density, amplitude, duration) are highly correlated with Reasoning abilities (i.e., fluid intelligence ; problem solving skills, the ability to employ logic, identify complex patterns), but not short-term memory (STM) or verbal abilities. Spindle-dependent reactivation of brain areas recruited during new learning suggests night-to-night variations reflect offline memory processing. However, the functional significance of stable, trait-like inter-individual differences in brain activations recruited during spindle events is unknown. Using EEG-fMRI sleep recordings, we found that a subset of brain activations time-locked to spindles were specifically related to Reasoning abilities but were unrelated to STM or verbal abilities. Thus, suggesting that individuals with higher fluid intelligence have greater activation of brain regions recruited during spontaneous spindle events. This may serve as a first step to further understand the function of sleep spindles and the brain activity which supports the capacity for Reasoning

Memory Function and Brain Functional Connectivity Adaptations Following Multiple-Modality Exercise and Mind–Motor Training in Older Adults at Risk of Dementia: An Exploratory Sub-Study

© Copyright © 2020 Boa Sorte Silva, Nagamatsu, Gill, Owen and Petrella. Background: Multiple-modality exercise improves brain function. However, whether task-based brain functional connectivity (FC) following exercise suggests adaptations in preferential brain regions is unclear. The objective of this study was to explore memory function and task-related FC changes following multiple-modality exercise and mind–motor training in older adults with subjective cognitive complaints. Methods: We performed secondary analysis of memory function data in older adults [n = 127, mean age 67.5 (7.3) years, 71% women] randomized to an exercise intervention comprised of 45 min of multiple-modality exercise with additional 15 min of mind-motor training (M4 group, n = 63) or an active control group (M2 group, n = 64). In total, both groups exercised for 60 min/day, 3 days/week, for 24 weeks. We then conducted exploratory analyses of functional magnetic resonance imaging (fMRI) data collected from a sample of participants from the M4 group [n = 9, mean age 67.8 (8.8) years, 8 women] who completed baseline and follow-up task-based fMRI assessment. Four computer-based memory tasks from the Cambridge Brain Sciences cognitive battery (i.e. Monkey Ladder, Spatial Span, Digit Span, Paired Associates) were employed, and participants underwent 5 min of continuous fMRI data collection while completing the tasks. Behavioral data were analyzed using linear mixed models for repeated measures and paired-samples t-test. All fMRI data were analyzed using group-level independent component analysis and dual regression procedures, correcting for voxel-wise comparisons. Results: Our findings indicated that the M4 group showed greater improvements in the Paired Associates tasks compared to the M2 group at 24 weeks [mean difference: 0.47, 95% confidence interval (CI): 0.08 to 0.86, p = 0.019]. For our fMRI analysis, dual regression revealed significant decrease in FC co-activation in the right precentral/postcentral gyri after the exercise program during the Spatial Span task (corrected p = 0.008), although there was no change in the behavioral task performance. Only trends for changes in FC were found for the other tasks (all corrected p \u3c 0.09). In addition, for the Paired Associates task, there was a trend for increased co-activation in the right temporal lobe (Brodmann Area = 38, corrected p = 0.07), and left middle frontal temporal gyrus (corrected p = 0.06). Post hoc analysis exploring voxel FC within each group spatial map confirmed FC activation trends observed from dual regression. Conclusion: Our findings suggest that multiple modality exercise with mind–motor training resulted in greater improvements in memory compared to an active control group. There were divergent FC adaptations including significant decreased co-activation in the precentral/postcentral gyri during the Spatial Span task. Borderline significant changes during the Paired Associates tasks in FC provided insight into the potential of our intervention to promote improvements in visuospatial memory and impart FC adaptations in brain regions relevant to Alzheimer’s disease risk. Clinical Trial Registration: The trial was registered in ClinicalTrials.gov in April 2014, Identifier: NCT02136368

Brain Activation Time-Locked to Sleep Spindles Associated With Human Cognitive Abilities

Simultaneous electroencephalography and functional magnetic resonance imaging (EEG–fMRI) studies have revealed brain activations time-locked to spindles. Yet, the functional significance of these spindle-related brain activations is not understood. EEG studies have shown that inter-individual differences in the electrophysiological characteristics of spindles (e.g., density, amplitude, duration) are highly correlated with “Reasoning” abilities (i.e., “fluid intelligence”; problem solving skills, the ability to employ logic, identify complex patterns), but not short-term memory (STM) or verbal abilities. Spindle-dependent reactivation of brain areas recruited during new learning suggests night-to-night variations reflect offline memory processing. However, the functional significance of stable, trait-like inter-individual differences in brain activations recruited during spindle events is unknown. Using EEG–fMRI sleep recordings, we found that a subset of brain activations time-locked to spindles were specifically related to Reasoning abilities but were unrelated to STM or verbal abilities. Thus, suggesting that individuals with higher fluid intelligence have greater activation of brain regions recruited during spontaneous spindle events. This may serve as a first step to further understand the function of sleep spindles and the brain activity which supports the capacity for Reasoning

Simultaneous EEG-fMRI : novel methods for EEG artefacts reduction at source

This thesis describes the development and application of novel techniques to reduce the EEG artefacts at source during the simultaneous acquisition of EEG and fMRI data. The work described in this thesis was carried out by the author in the Sir Peter Mansfield Magnetic Resonance Centre, School of Physics & Astronomy at the University of Nottingham, between October 2010 and January 2013. Large artefacts compromise EEG data quality during simultaneous fMRI. These artefact voltages pose heavy demands on the bandwidth and dynamic range of EEG amplifiers and mean that even small fractional variations in the artefact voltages give rise to significant residual artefacts after correction, which can easily swamp signals from brain activity. Therefore any intrinsic reduction in the magnitude of the artefacts would be highly advantageous, allowing data with a higher bandwidth to be acquired without amplifier saturation, and facilitating improved detection of brain activity. This thesis firstly explores a new method for reducing the gradient artefact (GA), which is induced in EEG data recorded during concurrent MRI, by investigating the effects of the cable configuration on the characteristics of the GA. This work showed that the GA amplitude and its sensitivity to movement of the cabling is reduced by minimising wire loop areas in the cabling between the EEG cap and amplifier. Another novel approach for reducing the magnitude and variability of the artefacts is the use of an EEG cap that incorporates electrodes embedded in a reference layer, which has a similar conductivity to tissue and is electrically isolated from the scalp. With this arrangement, the artefact voltages produced on the reference layer leads are theoretically similar to those induced in the scalp leads, but neuronal signals are not detected in the reference layer. Therefore taking the difference of the voltages in the reference and scalp channels should reduce the artefacts, without affecting sensitivity to neuronal signals. The theoretical efficacy of artefact correction that can be achieved by using this new reference layer artefact subtraction (RLAS) method was investigated. This was done through separate electromagnetic simulations of the artefacts induced in a hemispherical reference layer and a spherical volume conductor in a time-varying magnetic field and the results showed that similar artefacts are induced on the surface of both conductors. Simulations are also performed to find the optimal design for an RLAS system, by varying the geometry of the system. A simple experimental realisation of the RLAS system was implemented to investigate the degree of artefact attenuation that can be achieved via RLAS. Through a series of experiments on phantoms and human subjects, it is shown here that RLAS significantly reduces the GA, pulse (PA) and motion (MA) artefacts, while allowing accurate recording of neuronal signals. The results indicate that RLAS generally outperforms the standard artefact correction method, average artefact subtraction (AAS), in the removal of the GA and PA when motion is present, while the combination of RLAS and AAS always produces higher artefact attenuation than AAS alone. Additionally, this work demonstrates that RLAS greatly attenuates the unpredictable and highly variable MA that are very hard to remove using post-processing methods

Simultaneous EEG-fMRI : novel methods for EEG artefacts reduction at source

This thesis describes the development and application of novel techniques to reduce the EEG artefacts at source during the simultaneous acquisition of EEG and fMRI data. The work described in this thesis was carried out by the author in the Sir Peter Mansfield Magnetic Resonance Centre, School of Physics & Astronomy at the University of Nottingham, between October 2010 and January 2013. Large artefacts compromise EEG data quality during simultaneous fMRI. These artefact voltages pose heavy demands on the bandwidth and dynamic range of EEG amplifiers and mean that even small fractional variations in the artefact voltages give rise to significant residual artefacts after correction, which can easily swamp signals from brain activity. Therefore any intrinsic reduction in the magnitude of the artefacts would be highly advantageous, allowing data with a higher bandwidth to be acquired without amplifier saturation, and facilitating improved detection of brain activity. This thesis firstly explores a new method for reducing the gradient artefact (GA), which is induced in EEG data recorded during concurrent MRI, by investigating the effects of the cable configuration on the characteristics of the GA. This work showed that the GA amplitude and its sensitivity to movement of the cabling is reduced by minimising wire loop areas in the cabling between the EEG cap and amplifier. Another novel approach for reducing the magnitude and variability of the artefacts is the use of an EEG cap that incorporates electrodes embedded in a reference layer, which has a similar conductivity to tissue and is electrically isolated from the scalp. With this arrangement, the artefact voltages produced on the reference layer leads are theoretically similar to those induced in the scalp leads, but neuronal signals are not detected in the reference layer. Therefore taking the difference of the voltages in the reference and scalp channels should reduce the artefacts, without affecting sensitivity to neuronal signals. The theoretical efficacy of artefact correction that can be achieved by using this new reference layer artefact subtraction (RLAS) method was investigated. This was done through separate electromagnetic simulations of the artefacts induced in a hemispherical reference layer and a spherical volume conductor in a time-varying magnetic field and the results showed that similar artefacts are induced on the surface of both conductors. Simulations are also performed to find the optimal design for an RLAS system, by varying the geometry of the system. A simple experimental realisation of the RLAS system was implemented to investigate the degree of artefact attenuation that can be achieved via RLAS. Through a series of experiments on phantoms and human subjects, it is shown here that RLAS significantly reduces the GA, pulse (PA) and motion (MA) artefacts, while allowing accurate recording of neuronal signals. The results indicate that RLAS generally outperforms the standard artefact correction method, average artefact subtraction (AAS), in the removal of the GA and PA when motion is present, while the combination of RLAS and AAS always produces higher artefact attenuation than AAS alone. Additionally, this work demonstrates that RLAS greatly attenuates the unpredictable and highly variable MA that are very hard to remove using post-processing methods

Simultaneous EEG-fMRI at ultra-high field for the study of human brain function

Scalp electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) have highly complementary domains, and their combination has been actively sought within neuroscience research. The important gains in fMRI sensitivity achieved with higher field strengths open exciting perspectives for combined EEG-fMRI; however, simultaneous acquisitions are subject to highly undesirable interactions between the two modalities, which can strongly compromise data quality and subject safety, and most of these interactions are increased at higher fields. The work described in this thesis was centered on the development of simultaneous EEG-fMRI in humans at 7T, covering aspects of subject safety, signal quality assessment, and quality improvement. Additionally, given the potential value of high-field EEG-fMRI to study the neuronal correlates of so-called negative BOLD responses, an initial fMRI study was dedicated to these phenomena. The initial fMRI study aimed to characterize positive (PBR) and negative BOLD responses (NBR) to visual checkerboard stimulation of varying contrast and duration, focusing on NBRs occurring in visual and in auditory cortical regions. Results showed that visual PBRs and both visual and auditory NBRs significantly depend on stimulus contrast and duration, suggesting a dynamic system of visual-auditory interactions, sensitive to stimulus contrast and duration. The neuronal correlates of these interactions could not be addressed in higher detail with fMRI alone, yet could potentially be clarified in future work with combined EEG-fMRI. Moving on to simultaneous EEG-fMRI implementation, the first stage comprised an assessment of potential safety concerns at 7T. The safety tests comprised numerical simulations of RF power distribution and real temperature measurements on a phantom during acquisition. Overall, no significant safety concerns were found for the setup tested. A characterization of artifacts induced on MRI data due to the presence of EEG components was then performed. With the introduction of the EEG system, functional and anatomical images exhibited general losses in spatial SNR, with a smaller loss in temporal SNR in fMRI data. B0 and B1 field mapping pointed towards RF pulse disruption as the major degradation mechanism affecting MRI data. The main part of this work focused on EEG artifacts induced by MRI. The first step focused on optimizing signal transmission between the EEG cap and amplifiers, to minimize artifact contamination at this important stage. Along this line, adequate cable shortening and bundling effectively reduced environment noise in EEG recordings. Simultaneous acquisitions were then performed on humans using the optimized setup. On average, EEG data exhibited clear alpha modulation and average visual evoked potentials (VEP), with concomitant BOLD signal changes. In the second step, a novel approach for head motion artifact detection was developed, based on a simple modification of the EEG cap, and simultaneous acquisitions were performed in volunteers undergoing visual checkerboard stimulation. After gradient artifact correction, EEG signal variance was found to be largely dominated by pulse artifacts, but contributions from spontaneous motion were still comparable to those of neuronal activity. Using a combination of pulse artifact correction, motion artifact correction and ICA denoising, strong improvements in data quality could be obtained, especially at a single-trial level