Nonparametric Estimation of Hemodynamic Response Function: A Frequency Domain Approach

The impact of temporal regularization on estimates of the BOLD hemodynamic response function: A comparative analysis

Non-parametric hemodynamic response function (HRF) estimation in noisy functional Magnetic Resonance Imaging (fMRI) plays an important role when investigating the temporal dynamic of a brain region response during activations. Assuming the drift Lipschitz continuous; a new algorithm for non-parametric HRF estimation is derived in this paper. The proposed algorithm estimates the HRF by applying a first order differencing to the fMRI time series samples. It is shown that the proposed HRF estimator is √(N) consistent. Its performance is assessed using both simulated and a real fMRI data sets obtained from an event-related fMRI experiment. The application results reveal that the proposed HRF estimation method is efficient both computationally and in term of accuracy.

Non-parametric hemodynamic response function (HRF) estimation in noisy functional near-infrared spectroscopy (fNIRS) plays an important role when investigating the temporal dynamics of a brain region response during activations. Assuming the drift Lipschitz continuous; a new algorithm for non-parametric HRF estimation from the oxygenated (HbO) and deoxygenated (HbR) fNIRS time-series is derived in this paper. The proposed algorithm estimates the HRF by applying a first order differencing to the fNIRS time series samples. It is shown that the proposed HRF estimator is √N consistent. Its performance is assessed using both simulated and a real fNIRS data set obtained from a motor activity experiment. The application results reveal that the proposed HRF estimation method is efficient both computationally and in terms of accuracy.

In functional magnetic resonance imaging (fMRI), the hemodynamic response function (HRF) represents the impulse response of the neurovascular system. Its identification is essential for a deeper understanding of the dynamics of cerebral activity. In previous papers, we developed a voxelwise approach, i.e. based on a single time-course. In this paper, we propose an extension to cope with region-based HRF estimation. We introduce a spatial homogeneous model that assumes the same HRF shape for a majority of voxels within a given region-of-interest (ROI). A least trimmed squares estimator is employed to select those voxels. A Bayesian HRF estimation is then performed with the corresponding time courses. Our approach is tested on real fMRI data to illustrate the gain in robustness achieved with the region-based estimate.

In an event-related functional MRI data analysis, an accurate and robust extraction of the hemodynamic response function (HRF) and its associated statistics (e.g., magnitude, width, and time to peak) is critical to infer quantitative information about the relative timing of the neuronal events in different brain regions. The aim of this paper is to develop a multiscale adaptive smoothing model (MASM) to accurately estimate HRFs pertaining to each stimulus sequence across all voxels. MASM explicitly accounts for both spatial and temporal smoothness information, while incorporating such information to adaptively estimate HRFs in the frequency domain. One simulation study and a real data set are used to demonstrate the methodology and examine its finite sample performance in HRF estimation, which confirms that MASM significantly outperforms the existing methods including the smooth finite impulse response model, the inverse logit model and the canonical HRF.

Using patient-specific hemodynamic response functions in combined EEG-fMRI studies in epilepsy

The hemodynamic response function (HRF), reflecting cerebral blood flow in response to neural activity, plays a crucial role in the analysis of the brain data obtained by functional magnetic resonance imaging (fMRI). In this s tudy, a comparison of two s tatis tical models was performed to evaluate HRF for block design. Materials and Methods: fMRI data from 3 patients with brain tumor were taken using a 3 Tesla scanner. Analysis of fMRI data was performed by the SPM12 toolbox in MATLAB software. The AIC, SBC and MSE indices were used to select the mos t convenient HRF mode. Results: Based on the simulation data, HRF es timated by canonical HRF model plus time derivations (TD) model was more consis tent with simulated HRF. These models were evaluated on real data. The MSE, AIC and SBC indices were obtained for TD-logis tic model (IL) models (for TD and logis tic IL models; 0.052, 1235.1, 1223.9 and 0.068, -1091.5, 1049.2, respectively). Based on the average values of T, W, H and model selection indicators, IL model for es timating HRF in healthy regions of the brain and brain tumor is a more appropriate approach. Conclusion:

In the rodent brain the hemodynamic response to a brief external stimulus changes significantly during development. Analogous changes in human infants would complicate the determination and use of the hemodynamic response function (HRF) for functional magnetic resonance imaging (fMRI) in developing populations. We aimed to characterize HRF in human infants before and after the normal time of birth using rapid sampling of the Blood Oxygen Level Dependent (BOLD) signal. A somatosensory stimulus and an event related experimental design were used to collect data from 10 healthy adults, 15 sedated infants at term corrected post menstrual age (PMA) (median 41 + 1 weeks), and 10 preterm infants (median PMA 34 + 4 weeks). A positive amplitude HRF waveform was identified across all subject groups, with a systematic maturational trend in terms of decreasing time-to-peak and increasing positive peak amplitude associated with increasing age. Application of the age-appropriate HRF models to fMRI data significantly improved the precision of the fMRI analysis. These findings support the notion of a structured development in the brain's response to stimuli across the last trimester of gestation and beyond.

Detecting white matter activity using conventional 3 Tesla fMRI: An evaluation of standard field strength and hemodynamic response function

In BOLD fMRI data analysis, robust and accurate estimation of the Hemodynamic Response Function (HRF) is still under investigation. Parametric methods assume the shape of the HRF to be known and constant throughout the brain, whereas non-parametric methods mostly rely on artificially increasing the signal-to-noise ratio. We extend and develop a previously proposed method that makes use of basic yet relevant temporal information about the underlying physiological process of the brain BOLD response in order to infer the HRF in a Bayesian framework. A general hypothesis test is also proposed, allowing to take advantage of the knowledge gained regarding the HRF to perform activation detection. The performances of the method are then evaluated by simulation. Great improvement is shown compared to the Maximum-Likelihood estimate in terms of estimation error, variance, and bias. Robustness of the estimators with regard to the actual noise structure or level, as well as the stimulus sequence, is also proven. Lastly, fMRI data with an event-related paradigm are analyzed. As suspected, the regions selected from highly discriminating activation maps resulting from the method exhibit a certain inter-regional homogeneity in term of HRF shape, as well as noticeable inter-regional differences.

BOLD fMRI has become a prevalent method to study cerebral sensory processing in rodent disease models, including pain and mechanical hypersensitivity. fMRI data analysis is frequently combined with a general-linear-model (GLM) -based analysis, which uses the convolution of a hemodynamic response function (HRF) with the stimulus paradigm. However, several studies indicated that the HRF differs across species, sexes, brain structures, and experimental factors, including stimulation modalities or anesthesia, and hence might strongly affect the outcome of BOLD analyzes. While considerable work has been done in humans and rats to understand the HRF, much less is known in mice. As a prerequisite to investigate mechano-sensory processing and BOLD fMRI data in male and female mice, we (1) designed a rotating stimulator that allows application of two different mechanical modalities, including innocuous von Frey and noxious pinprick stimuli and (2) determined and statistically compared HRFs across 30 brain structures and experimental conditions, including sex and, stimulus modalities. We found that mechanical stimulation lead to brain-wide BOLD signal changes thereby allowing extraction of HRFs from multiple brain structures. However, we did not find differences in HRFs across all brain structures and experimental conditions. Hence, we computed a whole-brain mouse HRF, which is based on 88 functional scans from 30 mice. A comparison of this mouse-specific HRF with our previously reported rat-derived HRF showed significantly slower kinetics in mice. Finally, we detected pronounced differences in cerebral BOLD activation between male and female mice with mechanical stimulation, thereby exposing divergent processing of noxious and innocuous stimuli in both sexes.

Functional magnetic resonance imaging (fMRI) has, since its de scription fifteen years ago, become the most common in-vivo neuroimaging technique. FMRI allows the identification of brain areas which are related to specific tasks, by statistical analysis of the BOLD (blood oxigenation level dependent) signal. Classically, the observed BOLD signal is compared to an expected haemodynamic response function (HRF) using a general linear model (GLM). However, the results of GLM rely on the HRF specification, which is usually determined in an ad hoc fashion. For periodic experimental designs, we propose a multisubject frequency domain brain mapping, which requires only the stimulation frequency, and consequently avoids subjective choices of HRF. We present some computational simulations, which demon strate a good performance of the proposed approach in short length time series. In addition, an application to real fMRI datasets is also presented.

The hemodynamic response function (HRF) describes the dynamic process of the blood oxygen level dependent (BOLD) signal evoked by a very short stimulus of unit intensity. Understanding HRF is a key issue for exploring the underlying dynamics of nervous system activation. Some researches suggested that the shape of HRF varied with different brain regions and different subjects, even at different time point in the same brain region of a subject. In this work, epilepsy discharges were adopted as markers of short stimuli, and then we use EEG-fMRI method to investigate HRF in temporal lobe epilepsy with interictal regional slow wave. Five patients with idiopathic temporal lobe epilepsy were enrolled in this study, the peak delay and amplitude of the estimated HRF was compared with Gamma, Glover and the SPM canonical HRF, and the results show that the delay of the estimated HRF is different from either one of the three theoretical model, thus further study on both theoretical model and real data estimation is needed.

The hemodynamic response function (HRF) links neuronal activity to functional magnetic resonance imaging (fMRI) signals. While most fMRI studies use a canonical HRF, increasing evidence from studies of healthy subjects suggests that the HRF depends on anatomical location and disease states. Here, we investigate how HRF variability relates to anatomical location and pathology in the epileptic brain, using a large simultaneous electroencephalogram and fMRI dataset. Applying HRF deconvolution and temporal decomposition, we built the first whole-brain HRF library specific to epilepsy, identifying four distinct shape groups. We mapped HRF features across parcellations of two atlases using novel Bayesian hierarchical models. In non-epileptogenic regions, HRF shape and spatial distributions align with findings from healthy subjects. Within pathological regions, they vary significantly according to pathology. Our results indicate that HRF variability is associated with pathology, in addition to its dependence on anatomical location, motivating region- and pathology-based HRF modulation in epilepsy studies.

.SignificanceDeaf and hard-of-hearing infants’ hemodynamic response function (HRF) has not yet been characterized. However, without an appropriate estimate of their HRF, neuroimaging modalities relying on hemodynamic responses, e.g., functional magnetic resonance imaging (fMRI) or functional near-infrared spectroscopy (fNIRS), cannot be used reliably in this population, e.g., prior to and following cochlear implantation. We contribute to better theoretical models of and more suitable therapeutic interventions for the neural changes induced by auditory and language deprivation in deaf infants.AimWe aim to characterize the parameters of the HRF of deaf and hard-of-hearing infants in response to Italian.ApproachWe measured 2- to 20-month-old Italian-exposed infants’ HRF to Italian using fNIRS in the bilateral temporal, i.e., auditory, cortices. We characterized the HRF for all infants and for three clinically relevant subsets: (i) monolingual Italian infants, (ii) genetically deaf infants, and (iii) infants aged 5 to 12 months. We computed the following parameters: peak amplitude, time-to-peak, full width at half maximum, and where present, the amplitude and latency of the initial dip and/or the final undershoot, using a model-based parameter fitting approach. We statistically compared these HRF parameters to those of typically hearing infants.ResultsDeaf and typically hearing infants showed largely similar HRFs, with both groups reaching comparable main peak amplitudes. Minor differences have been found in the latencies of some response components.ConclusionsOur results provide the first detailed characterization of the hemodynamic response to native-language speech in deaf and hard-of-hearing infants, improving clinical and therapeutic approaches through more accurate analysis of fMRI and fNIRS data.