Complex-valued Time Series Modeling for Improved Activation Detection in fMRI Studies

A complex-valued data-based model with th order autoregressive errors and general real/imaginary error covariance structure is proposed as an alternative to the commonly used magnitude-only data-based autoregressive model for fMRI time series. Likelihood-ratio-test-based activation statistics are derived for both models and compared for experimental and simulated data. For a dataset from a right-hand finger-tapping experiment, the activation map obtained using complex-valued modeling more clearly identifies the primary activation region (left functional central sulcus) than the magnitude-only model. Such improved accuracy in mapping the left functional central sulcus has important implications in neurosurgical planning for tumor and epilepsy patients. Additionally, we develop magnitude and phase detrending procedures for complex-valued time series and examine the effect of spatial smoothing. These methods improve the power of complex-valued data-based activation statistics. Our results advocate for the use of the complex-valued data and the modeling of its dependence structures as a more efficient and reliable tool in fMRI experiments over the current practice of using only magnitude-valued datasets

ICA of Functional MRI Data: An Overview

Independent component analysis (ICA) has found a fruitful application in the analysis of functional magnetic resonance imaging (fMRI) data. A principal advantage of this approach is its applicability to cognitive paradigms for which detailed a priori models of brain activity are not available. ICA has been successfully utilized in a number of exciting fMRI applications including the identification of various signal-types (e.g. task and transiently task-related, and physiology-related signals) in the spatial or temporal domain, the analysis of multi-subject fMRI data, the incorporation of a priori information, and for the analysis of complex-valued fMRI data (which has proved challenging for standard approaches). In this paper, we 1) introduce fMRI data and its properties, 2) review the basic motivation for using ICA on fMRI data, and 3) review the current work on ICA of fMRI with some specific examples from our own work. The purpose of this paper is to motivate ICA research to focus upon this exciting application

Exploring the Neural Mechanisms of Physics Learning

This dissertation presents a series of neuroimaging investigations and achievements that strive to deepen and broaden our understanding of human problem solving and physics learning. Neuroscience conceives of dynamic relationships between behavior, experience, and brain structure and function, but how neural changes enable human learning across classroom instruction remains an open question. At the same time, physics is a challenging area of study in which introductory students regularly struggle to achieve success across university instruction. Research and initiatives in neuroeducation promise a new understanding into the interactions between biology and education, including the neural mechanisms of learning and development. These insights may be particularly useful in understanding how students learn, which is crucial for helping them succeed. Towards this end, we utilize methods in functional magnetic resonance imaging (fMRI), as informed by education theory, research, and practice, to investigate the neural mechanisms of problem solving and learning in students across semester-long University-level introductory physics learning environments. In the first study, we review and synthesize the neuroimaging problem solving literature and perform quantitative coordinate-based meta-analysis on 280 problem solving experiments to characterize the common and dissociable brain networks that underlie human problem solving across different representational contexts. Then, we describe the Understanding the Neural Mechanisms of Physics Learning project, which was designed to study functional brain changes associated with learning and problem solving in undergraduate physics students before and after a semester of introductory physics instruction. We present the development, facilitation, and data acquisition for this longitudinal data collection project. We then perform a sequence of fMRI analyses of these data and characterize the first-time observations of brain networks underlying physics problem solving in students after university physics instruction. We measure sustained and sequential brain activity and functional connectivity during physics problem solving, test brain-behavior relationships between accuracy, difficulty, strategy, and conceptualization of physics ideas, and describe differences in student physics-related brain function linked with dissociations in conceptual approach. The implications of these results to inform effective instructional practices are discussed. Then, we consider how classroom learning impacts the development of student brain function by examining changes in physics problem solving-related brain activity in students before and after they completed a semester-long Modeling Instruction physics course. Our results provide the first neurobiological evidence that physics learning environments drive the functional reorganization of large-scale brain networks in physics students. Through this collection of work, we demonstrate how neuroscience studies of learning can be grounded in educational theory and pedagogy, and provide deep insights into the neural mechanisms by which students learn physics

Functional quantitative susceptibility mapping (fQSM)

Blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) is a powerful technique, typically based on the statistical analysis of the magnitude component of the complex time-series. Here, we additionally interrogated the phase data of the fMRI time-series and used quantitative susceptibility mapping (QSM) in order to investigate the potential of functional QSM (fQSM) relative to standard magnitude BOLD fMRI. High spatial resolution data (1 mm isotropic) were acquired every 3 seconds using zoomed multi-slice gradient-echo EPI collected at 7 T in single orientation (SO) and multiple orientation (MO) experiments, the latter involving 4 repetitions with the subject's head rotated relative to B0. Statistical parametric maps (SPM) were reconstructed for magnitude, phase and QSM time-series and each was subjected to detailed analysis. Several fQSM pipelines were evaluated and compared based on the relative number of voxels that were coincidentally found to be significant in QSM and magnitude SPMs (common voxels). We found that sensitivity and spatial reliability of fQSM relative to the magnitude data depended strongly on the arbitrary significance threshold defining “activated” voxels in SPMs, and on the efficiency of spatio-temporal filtering of the phase time-series. Sensitivity and spatial reliability depended slightly on whether MO or SO fQSM was performed and on the QSM calculation approach used for SO data. Our results present the potential of fQSM as a quantitative method of mapping BOLD changes. We also critically discuss the technical challenges and issues linked to this intriguing new technique

Temporal and Spatial Independent Component Analysis for fMRI Data Sets Embedded in the AnalyzeFMRI R Package

For statistical analysis of functional magnetic resonance imaging (fMRI) data sets, we propose a data-driven approach based on independent component analysis (ICA) implemented in a new version of the AnalyzeFMRI R package. For fMRI data sets, spatial dimension being much greater than temporal dimension, spatial ICA is the computationally tractable approach generally proposed. However, for some neuroscientific applications, temporal independence of source signals can be assumed and temporal ICA becomes then an attractive exploratory technique. In this work, we use a classical linear algebra result ensuring the tractability of temporal ICA. We report several experiments on synthetic data and real MRI data sets that demonstrate the potential interest of our R package

Principles of sensorimotor control and learning in complex motor tasks

The brain coordinates a continuous coupling between perception and action in the presence of uncertainty and incomplete knowledge about the world. This mapping is enabled by control policies and motor learning can be perceived as the update of such policies on the basis of improving performance given some task objectives. Despite substantial progress in computational sensorimotor control and empirical approaches to motor adaptation, to date it remains unclear how the brain learns motor control policies while updating its internal model of the world. In light of this challenge, we propose here a computational framework, which employs error-based learning and exploits the brain’s inherent link between forward models and feedback control to compute dynamically updated policies. The framework merges optimal feedback control (OFC) policy learning with a steady system identification of task dynamics so as to explain behavior in complex object manipulation tasks. Its formalization encompasses our empirical findings that action is learned and generalised both with regard to a body-based and an object-based frame of reference. Importantly, our approach predicts successfully how the brain makes continuous decisions for the generation of complex trajectories in an experimental paradigm of unfamiliar task conditions. A complementary method proposes an expansion of the motor learning perspective at the level of policy optimisation to the level of policy exploration. It employs computational analysis to reverse engineer and subsequently assess the control process in a whole body manipulation paradigm. Another contribution of this thesis is to associate motor psychophysics and computational motor control to their underlying neural foundation; a link which calls for further advancement in motor neuroscience and can inform our theoretical insight to sensorimotor processes in a context of physiological constraints. To this end, we design, build and test an fMRI-compatible haptic object manipulation system to relate closed-loop motor control studies to neurophysiology. The system is clinically adjusted and employed to host a naturalistic object manipulation paradigm on healthy human subjects and Friedreich’s ataxia patients. We present methodology that elicits neuroimaging correlates of sensorimotor control and learning and extracts longitudinal neurobehavioral markers of disease progression (i.e. neurodegeneration). Our findings enhance the understanding of sensorimotor control and learning mechanisms that underlie complex motor tasks. They furthermore provide a unified methodological platform to bridge the divide between behavior, computation and neural implementation with promising clinical and technological implications (e.g. diagnostics, robotics, BMI).Open Acces

Dimensionpudotusmenetelmiä fMRI-analyysissä ja visualisoinnissa

The need to model and understand high-dimensional, noisy data sets is common in many domains these day, among them neuroimaging and fMRI analysis. Dimensionality reduction and variable selection are two common strategies for dealing with high-dimensional data, either as a pre-processing step prior to further analysis, or as an analysis step itself. This thesis discusses both dimensionality reduction and variable selection, with a focus on fMRI analysis, visualization, and applications of visualization in fMRI analysis. Three new algorithms are introduced. The first algorithm uses a sparse Canonical Correlation Analysis model and a high-dimensional stimulus representation to find relevant voxels (variables) in fMRI experiments with complex natural stimuli. Experiments on a data set involving music show that the algorithm successfully retrieves voxels relevant to the experimental condition. The second algorithm, NeRV, is a dimensionality reduction method for visualization high-dimensional data using scatterplots. A simple abstract model of the way a human studies a scatterplot is formulated, and NeRV is derived as an algorithm for producing optimal visualizations in terms of this model. Experiments show that NeRV is superior to conventional dimensionality reduction methods in terms of this model. NeRV is also used to perform a novel form of exploratory data analysis on the fMRI voxels selected by the first algorithm; the analysis simultaneously demonstrates the usefulness of NeRV in practice and offers further insights into the performance of the voxel selection algorithm. The third algorithm, LDA-NeRV, combines a Bayesian latent-variable model for graphs with NeRV to produce one of the first principled graph drawing methods. Experiments show that LDA-NeRV is capable of visualizing structure that conventional graph drawing methods fail to reveal.Monilla aloilla esiintyy tarve korkeaulotteisen, kohinaisen datan analysoimiseen. Algorithminen dimensionpudotus tai muuttujanvalinta ovat usein sovellettavia lähestymistapoja, joko muuta analyysiä edeltävänä esikäsittelynä tai itsenäisenä analyysinä. Tässä työssä käsitellään sekä dimensionpudotusta että muuttujanvalintaa, keskittyen erityisesti fMRI-dataaan ja visualisointiin. Työssä esitellään kolme uutta algoritmia. Ensimmäinen algoritmi käyttää harvaa kanonista korrelaaioanalyysi-mallia (CCA) ja koeärsykkeen korkeaulotteista piirre-esitystä olennaisten vokseleiden (muuttujien) valitsemiseen fMRI-kokeissa, joissa koehenkilöt altistetaan monimutkaiselle luonnolliselle ärsykkeelle, kuten esimerkiksi musiikille. Kokeet musiikkia ärsykkeenä käyttävän fMRI-kokeen kanssa osoittavat algoritmin löytävän tärkeitä vokseleita. Toinen algoritmi, NeRV, on dimensionpudotusmenetelmä korkeaulotteisen datan visualisoimiseen hajontakuvion avulla. NeRV pohjautuu yksinkertaiseen abstraktiin malliin ihmisen tavalle tulkita hajontakuviota. Kokeet osoittavat NeRVin olevan perinteisiä menetelmiä parempi tämän visualisointimallin mielessä. Lisäksi NeRViä sovelletaan ensimmäisen algoritmin valitsemien fMRI-vokseleiden visuaaliseen analyysiin; analyysi sekä osoittaa NeRVin hyödyllisyyden käytännössä että tarjoaa uusia näkökulmia vokselinvalintatulosten ymmärtämiseen. Kolmas algoritmi, LDA-NeRV, on NeRViä ja bayesiläistä latenttimuuttujamallia soveltava visualisointimenetelmä graafeille. Kokeet osoittavat LDA-NeRVin kykenevän visualisoimaan rakennetta, jota perinteiset visualisointimenetelmät eivät tuo esiin

Advances in image acquisition and filtering for MRI neuroimaging at 7 tesla

Performing magnetic resonance imaging at high magnetic field strength promises many improvements over low fields that are of direct benefit in functional neuroimaging. This includes the possibility of improved signal-to-noise levels, and increased BOLD functional contrast and spatial specificity. However, human MRI at 7T and above suffers from unique engineering challenges that limit the achievable gains. In this thesis, three technological developments are introduced, all of which address separate issues associated with functional magnetic resonance neuroimaging at very high magnetic field strengths. First, the image homogeneity problem is addressed by investigating methods of RF shimming — modifying the excitation portion of the MRI experiment for use with multi-channel RF coils. It is demonstrated that in 2D MRI experiments, shimming on a slice-by slice basis allows utilization of an extra degree of freedom available from the slice dimension, resulting in significant gains in image homogeneity and reduced RF power requirements. After acceptable images are available, we move to address complications of high field imaging that manifest in the fMRI time series. In the second paper, the increased physiological noise present in BOLD time series at high field is addressed with a unique data-driven noise regressor scheme based upon information in the phase component of the MRI signal. It is demonstrated that this method identifies and removes a significant portion of physiological signals, and performs as good or better than other popular data driven methods that use only the magnitude signal information. Lastly, the BOLD phase signal is again leveraged to address the confounding role of veins in resting state BOLD fMRI experiments. The phase regressor technique (previously developed by Dr. Menon) is modified and applied to resting state fMRI to remove macro vascular contributions in the datasets, leading to changes in spatial extent and connectivity of common resting state networks on single subjects and at the group level

Exploration of material dependent memory lateralization of the hippocampus and adjourning anatomical regions by fMRI

The concept of functional asymmetry is a basic principle of organization of human brain function. This basic concept also applies to the encoding of memory data. A number of studies have been conducted to explore the asymmetry of memory encoding using functional magnetic resonance imaging (fMRI), a technique which utilizes the high oxygen levels in activated brain areas to indirectly detect brain activation. The lateralization of encoding processes is determined, among other things, by the verbalizability of the memorized material (Golby, Poldrack et al. 2001; Golby, Poldrack et al. 2002; Powell, Koepp et al. 2005). Encoding of verbal stimuli preferentially relies on left-hemispheric brain regions, while encoding of visual (non-verbal) material relies on right-hemispheric areas. The study of Jansen et al. (Jansen, Sehlmeyer et al. 2009) was used as prototype study for this project, though only containing two stimulus classes and not addressing the issue of reliability. Reliability has only been addressed by a few studies (Bennett and Miller 2010), why we enclosed it into my study. The four objectives of this study are: 1. Implementations of the task at the new 3 tesla Siemens MRI scanner. 2. Expansion of the paradigm by two newly implemented stimulus classes 3. Development of stimuli with less verbalizeable patterns 4. Testing the reliability of the results by comparing it to a second run of the study The establishment of the paradigm at the new scanner was successful. Through the inclusion of two additional stimulus classes (Scenes and Faces), to the existing classes (words and shapes), two additional steps between the existing very well verbalizeable and almost not verbalizeable, were established. The newly introduced almost not verbalizeable patterns showed, as expected, right lateralized activations. Overall similar results to those already published by Golby et al. and Jansen et al could be achieved. The reliability of the results was not entirely homogenous, since the two implemented techniques, the intra-class-correlations (ICC) and the lateralization indices (LI), showed deviating results. LIs resulted in a quite good reliability, but ICCs showed good reliability only for a few select activation clusters. This indicates that in the planning of future fMRI studies, reliability should be a key issue