Integration of Simultaneous Resting-State EEG, fMRI, and Eye Tracker Methods to Determine and Verify EEG Vigilance Measure

Resting-state functional magnetic resonance imaging (rsfMRI) has been widely used for studying the (presumably) awake and alert human brain. Although rsfMRI scans are typically collected while individuals are instructed to focus their eyes on a fixation cross, objective and verified experimental measures to quantify degree of alertness (e.g., vigilance) are not readily available. Concurrent electroencephalography and fMRI (EEG-fMRI) measurements are also widely used to study human brain with high spatial/temporal resolution. EEG is the modality extensively used for estimating vigilance during eyes-closed resting state. On the other hand, pupil size measured using an eye-tracker device could provide an indirect index of vigilance. In this study, we investigated whether simultaneous multimodal EEG-fMRI combined with eye-tracker measurements can be used to determine EEG signal feature associated with pupil size changes (e.g., vigilance measure) in healthy human subjects (n=10) during brain rest with eyes open. We found that EEG frontal and occipital beta power (FOBP) correlates with pupil size changes, an indirect index for locus coeruleus activity implicated in vigilance regulation (r=0.306, p<0.001). Moreover, FOBP also correlated with heart rate (r=0.255, p<0.001), as well as several brain regions in the anti-correlated network, including the bilateral insula and inferior parietal lobule. These results support the conclusion that FOBP is an objective measure of vigilance in healthy human subjects

Intra- and Inter-Scanner Reliability of Voxel-Wise Whole-Brain Analytic Metrics for Resting State fMRI

As the multi-center studies with resting-state functional magnetic resonance imaging (RS-fMRI) have been more and more applied to neuropsychiatric studies, both intra- and inter-scanner reliability of RS-fMRI are becoming increasingly important. The amplitude of low frequency fluctuation (ALFF), regional homogeneity (ReHo), and degree centrality (DC) are 3 main RS-fMRI metrics in a way of voxel-wise whole-brain (VWWB) analysis. Although the intra-scanner reliability (i.e., test-retest reliability) of these metrics has been widely investigated, few studies has investigated their inter-scanner reliability. In the current study, 21 healthy young subjects were enrolled and scanned with blood oxygenation level dependent (BOLD) RS-fMRI in 3 visits (V1 – V3), with V1 and V2 scanned on a GE MR750 scanner and V3 on a Siemens Prisma. RS-fMRI data were collected under two conditions, eyes open (EO) and eyes closed (EC), each lasting 8 minutes. We firstly evaluated the intra- and inter-scanner reliability of ALFF, ReHo, and DC. Secondly, we measured systematic difference between two scanning visits of the same scanner as well as between two scanners. Thirdly, to account for the potential difference of intra- and inter-scanner local magnetic field inhomogeneity, we measured the difference of relative BOLD signal intensity to the mean BOLD signal intensity of the whole brain between each pair of visits. Last, we used percent amplitude of fluctuation (PerAF) to correct the difference induced by relative BOLD signal intensity. The inter-scanner reliability was much worse than intra-scanner reliability; Among the VWWB metrics, DC showed the worst (both for intra-scanner and inter-scanner comparisons). PerAF showed similar intra-scanner reliability with ALFF and the best reliability among all the 4 metrics. PerAF reduced the influence of BOLD signal intensity and hence increase the inter-scanner reliability of ALFF. For multi-center studies, inter-scanner reliability should be taken into account

Statistical approaches for resting state fMRI data analysis

This doctoral dissertation investigates the methodology to explore brain dynamics from resting state fMRI data. A standard resting state fMRI study gives rise to massive amounts of noisy data with a complicated spatio-temporal correlation structure. There are two main objectives in the analysis of these noisy data: establishing the link between neural activity and the measured signal, and determining distributed brain networks that correspond to brain function. These measures can then be used as indicators of psychological, cognitive or pathological states. Two main issues will be addressed: retrieving and interpreting the hemodynamic response function (HRF) at rest, and dealing with the redundancy inherent to fMRI data. Novel approaches are introduced, discussed and validated on simulated data and on real datasets, in health and disease, in order to track modulation of brain dynamics and HRF across different pathophysiological conditions

Functional Organization of the Brain at Rest and During Complex Tasks Using fMRI

How and why functional connectivity (FC), which captures the correlations among brain regions and/or networks, differs in various brain states has been incompletely understood. I review high-level background on this problem and how it relates to 1) the contributions of task-evoked activity, 2) white-matter fMRI, and 3) disease states in Chapter 1. In Chapter 2, based on the notion that brain activity during a task reflects an unknown mixture of spontaneous activity and task-evoked responses, we uncovered that the difference in FC between a task state (a naturalistic movie) and resting state only marginally (3-15%) reflects task-evoked connectivity. Instead, these changes may reflect changes in spontaneously emerging networks. In Chapter 3, we were able to show subtle task-related differences in the white matter using fMRI, which has only rarely been used to study functions in this tissue type. In doing so, we also demonstrated that white matter independent components were also hierarchically organized into axonal fiber bundles, challenging the conventional practice of taking white-matter signals as noise or artifacts. Finally, in Chapter 4, we examined the utility of combining FC with task-activation studies in uncovering changes in brain activity during preclinical Alzheimer\u27s Disease (mild cognitive impairment (MCI) and subjective cognitive decline (SCD) populations), based on data collected at the Indiana University School of Medicine. We found a reduction in neural task-based activations and resting-state FC that appeared to be directly related to diagnostic severity. Taken together, the work presented in this dissertation paves the way for a novel framework for understanding neural dynamics in health and disease

Biomedical Signal Analysis of the Brain and Systemic Physiology

Near-infrared spectroscopy (NIRS) is a non-invasive and easy-to-use diagnostic technique that enables real-time tissue oxygenation measurements applied in various contexts and for different purposes. Continuous monitoring with NIRS of brain oxygenation, for example, in neonatal intensive care units (NICUs), is essential to prevent lifelong disabilities in newborns. Moreover, NIRS can be applied to observe brain activity associated with hemodynamic changes in blood flow due to neurovascular coupling. In the latter case, NIRS contributes to studying cognitive processes allowing to conduct experiments in natural and socially interactive contexts of everyday life. However, it is essential to measure systemic physiology and NIRS signals concurrently. The combination of brain and body signals enables to build sophisticated systems that, for example, reduce the false alarms that occur in NICUs. Furthermore, since fNIRS signals are influenced by systemic physiology, it is essential to understand how the latter impacts brain signals in functional studies. There is an interesting brain body coupling that has rarely been investigated yet. To take full advantage of these brain and body data, the aim of this thesis was to develop novel approaches to analyze these biosignals to extract the information and identify new patterns, to solve different research or clinical questions. For this the development of new methodological approaches and sophisticated data analysis is necessary, because often the identification of these patterns is challenging or not possible with traditional methods. In such cases, automatic machine learning (ML) techniques are beneficial. The first contribution of this work was to assess the known systemic physiology augmented (f)NIRS approach for clinical use and in everyday life. Based on physiological and NIRS signals of preterm infants, an ML-based classification system has been realized, able to reduce the false alarms in NICUs by providing a high sensitivity rate. In addition, the SPA-fNIRS approach was further applied in adults during a breathing task. The second contribution of this work was the advancement of the classical fNIRS hyperscanning method by adding systemic physiology measures. For this, new biosignal analyses in the time-frequency domain have been developed and tested in a simple nonverbal synchrony task between pairs of subjects. Furthermore, based on SPA-fNIRS hyperscanning data, another ML-based system was created, which is able distinguish familiar and unfamiliar pairs with high accuracy. This approach enables to determine the strength of social bonds in a wide range of social interaction contexts. In conclusion, we were the first group to perform a SPA-fNIRS hyperscanning study capturing changes in cerebral oxygenation and hemodynamics as well as systemic physiology in two subjects simultaneously. We applied new biosignals analysis methods enabling new insights into the study of social interactions. This work opens the door to many future inter-subjects fNIRS studies with the benefit of assessing the brain-to-brain, the brain-to-body, and body-to-body coupling between pairs of subjects

Functional Magnetic Resonance Imaging

"Functional Magnetic Resonance Imaging - Advanced Neuroimaging Applications" is a concise book on applied methods of fMRI used in assessment of cognitive functions in brain and neuropsychological evaluation using motor-sensory activities, language, orthographic disabilities in children. The book will serve the purpose of applied neuropsychological evaluation methods in neuropsychological research projects, as well as relatively experienced psychologists and neuroscientists. Chapters are arranged in the order of basic concepts of fMRI and physiological basis of fMRI after event-related stimulus in first two chapters followed by new concepts of fMRI applied in constraint-induced movement therapy; reliability analysis; refractory SMA epilepsy; consciousness states; rule-guided behavioral analysis; orthographic frequency neighbor analysis for phonological activation; and quantitative multimodal spectroscopic fMRI to evaluate different neuropsychological states

Test-retest Reliability Of Cerebral Blood Flow In Healthy Individuals Using Arterial Spin Labeling: Findings From The Embarc Study

Introduction—Previous investigations of test-retest reliability of cerebral blood flow (CBF) at rest measured with pseudo-continuous Arterial Spin Labeling (pCASL) demonstrated good reliability, but are limited by the use of similar scanner platforms. In the present study we examined test-retest reliability of CBF in regions implicated in emotion and the default mode network