Multiscale adaptive smoothing models for the hemodynamic response function in fMRI

In the event-related functional magnetic resonance imaging (fMRI) data analysis, there is an extensive interest in accurately and robustly estimating the hemodynamic response function (HRF) and its associated statistics (e.g., the magnitude and duration of the activation). Most methods to date are developed in the time domain and they have utilized almost exclusively the temporal information of fMRI data without accounting for the spatial information. The aim of this paper is to develop a multiscale adaptive smoothing model (MASM) in the frequency domain by integrating the spatial and frequency information to adaptively and accurately estimate HRFs pertaining to each stimulus sequence across all voxels in a three-dimensional (3D) volume. We use two sets of simulation studies and a real data set to examine the finite sample performance of MASM in estimating HRFs. Our real and simulated data analyses confirm that MASM outperforms several other state-of-the-art methods, such as the smooth finite impulse response (sFIR) model.Comment: Published in at http://dx.doi.org/10.1214/12-AOAS609 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Investigation of the neurovascular coupling in positive and negative BOLD responses in human brain at 7T

Decreases in stimulus-dependent blood oxygenation level dependent (BOLD) signal and their underlying neurovascular origins have recently gained considerable interest. In this study a multi-echo, BOLD-corrected vascular space occupancy (VASO) functional magnetic resonance imaging (fMRI) technique was used to investigate neurovascular responses during stimuli that elicit positive and negative BOLD responses in human brain at 7 T. Stimulus-induced BOLD, cerebral blood volume (CBV), and cerebral blood flow (CBF) changes were measured and analyzed in ‘arterial’ and ‘venous’ blood compartments in macro- and microvasculature. We found that the overall interplay of mean CBV, CBF and BOLD responses is similar for tasks inducing positive and negative BOLD responses. Some aspects of the neurovascular coupling however, such as the temporal response, cortical depth dependence, and the weighting between ‘arterial’ and ‘venous’ contributions, are significantly different for the different task conditions. Namely, while for excitatory tasks the BOLD response peaks at the cortical surface, and the CBV change is similar in cortex and pial vasculature, inhibitory tasks are associated with a maximum negative BOLD response in deeper layers, with CBV showing strong constriction of surface arteries and a faster return to baseline. The different interplays of CBV, CBF and BOLD during excitatory and inhibitory responses suggests different underlying hemodynamic mechanisms

Statistical Analysis of fMRI Time-Series: A Critical Review of the GLM Approach.

Functional magnetic resonance imaging (fMRI) is one of the most widely used tools to study the neural underpinnings of human cognition. Standard analysis of fMRI data relies on a general linear model (GLM) approach to separate stimulus induced signals from noise. Crucially, this approach relies on a number of assumptions about the data which, for inferences to be valid, must be met. The current paper reviews the GLM approach to analysis of fMRI time-series, focusing in particular on the degree to which such data abides by the assumptions of the GLM framework, and on the methods that have been developed to correct for any violation of those assumptions. Rather than biasing estimates of effect size, the major consequence of non-conformity to the assumptions is to introduce bias into estimates of the variance, thus affecting test statistics, power, and false positive rates. Furthermore, this bias can have pervasive effects on both individual subject and group-level statistics, potentially yielding qualitatively different results across replications, especially after the thresholding procedures commonly used for inference-making

A novel method of combining blood oxygenation and blood flow sensitive magnetic resonance imaging techniques to measure the cerebral blood flow and oxygen metabolism responses to an unknown neural stimulus.

Simultaneous implementation of magnetic resonance imaging methods for Arterial Spin Labeling (ASL) and Blood Oxygenation Level Dependent (BOLD) imaging makes it possible to quantitatively measure the changes in cerebral blood flow (CBF) and cerebral oxygen metabolism (CMRO(2)) that occur in response to neural stimuli. To date, however, the range of neural stimuli amenable to quantitative analysis is limited to those that may be presented in a simple block or event related design such that measurements may be repeated and averaged to improve precision. Here we examined the feasibility of using the relationship between cerebral blood flow and the BOLD signal to improve dynamic estimates of blood flow fluctuations as well as to estimate metabolic-hemodynamic coupling under conditions where a stimulus pattern is unknown. We found that by combining the information contained in simultaneously acquired BOLD and ASL signals through a method we term BOLD Constrained Perfusion (BCP) estimation, we could significantly improve the precision of our estimates of the hemodynamic response to a visual stimulus and, under the conditions of a calibrated BOLD experiment, accurately determine the ratio of the oxygen metabolic response to the hemodynamic response. Importantly we were able to accomplish this without utilizing a priori knowledge of the temporal nature of the neural stimulus, suggesting that BOLD Constrained Perfusion estimation may make it feasible to quantitatively study the cerebral metabolic and hemodynamic responses to more natural stimuli that cannot be easily repeated or averaged

Detecting language activations with functional magnetic resonance imaging

This thesis investigates a number of factors that affect sensitivity to language activations in functional Magnetic Resonance Imaging (fMRI). In the first part, I investigate the impact of experimental design parameters on the ability to detect language activations. These parameters include stimulus rate, stimulus duration, stimulus amplitude, epoch length and stimulus ordering. Crucially, they may affect sensitivity in multiple ways that include neurophysiological, efficiency-mediated and BOLD saturation effects. I illustrate and discuss these effects by presenting biophysical simulations and fMRI studies of single word and pseudoword reading. In addition, I focus on the differential effects of the above parameters in Positron Emission Tomography and fMRI studies. In the second part, I investigate the impact of the analysis used to estimate effects of interest from the data. I compare event-related and epoch analyses and show that, even in the context of blocked design fMRI, an event-related model may provide greater sensitivity than an epoch model. I then address the notion that experimentally-induced effects may be detected not only as task-dependent changes in regional responses but also as changes in connectivity amongst functionally connected regions. These two complementary approaches are motivated by two fundamental principles of brain organisation: functional specialisation and functional integration. I present two fMRI studies investigating the neural correlates of reading words and pseudowords in terms of functional specialisation and functional integration. Furthermore, in both studies I address the issue of inter-subject variability, which may be a critical determinant of sensitivity. Men

Visual control of flight speed in Drosophila melanogaster

Flight control in insects depends on self-induced image motion (optic flow), which the visual system must process to generate appropriate corrective steering maneuvers. Classic experiments in tethered insects applied rigorous system identification techniques for the analysis of turning reactions in the presence of rotating pattern stimuli delivered in open-loop. However, the functional relevance of these measurements for visual free-flight control remains equivocal due to the largely unknown effects of the highly constrained experimental conditions. To perform a systems analysis of the visual flight speed response under free-flight conditions, we implemented a `one-parameter open-loop' paradigm using `TrackFly' in a wind tunnel equipped with real-time tracking and virtual reality display technology. Upwind flying flies were stimulated with sine gratings of varying temporal and spatial frequencies, and the resulting speed responses were measured from the resulting flight speed reactions. To control flight speed, the visual system of the fruit fly extracts linear pattern velocity robustly over a broad range of spatio–temporal frequencies. The speed signal is used for a proportional control of flight speed within locomotor limits. The extraction of pattern velocity over a broad spatio–temporal frequency range may require more sophisticated motion processing mechanisms than those identified in flies so far. In Drosophila, the neuromotor pathways underlying flight speed control may be suitably explored by applying advanced genetic techniques, for which our data can serve as a baseline. Finally, the high-level control principles identified in the fly can be meaningfully transferred into a robotic context, such as for the robust and efficient control of autonomous flying micro air vehicles