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V D Calhoun

Publications and source records attributed to V D Calhoun.

12 recordsLinked to original sources

Method for multimodal analysis of independent source differences in schizophrenia: combining gray matter structural and auditory oddball functional data.

The acquisition of both structural MRI (sMRI) and functional MRI (fMRI) data for a given study is a very common practice. However, these data are typically examined in separate analyses, rather than in a combined model. We propose a novel methodology to perform independent component analysis across image modalities, specifically, gray matter images and fMRI activation images as well as a joint histogram visualization technique. Joint independent component analysis (jICA) is used to decompose a matrix with a given row consisting of an fMRI activation image resulting from auditory oddball target stimuli and an sMRI gray matter segmentation image, collected from the same individual. We analyzed data collected on a group of schizophrenia patients and healthy controls using the jICA approach. Spatially independent joint-components are estimated and resulting components were further analyzed only if they showed a significant difference between patients and controls. The main finding was that group differences in bilateral parietal and frontal as well as posterior temporal regions in gray matter were associated with bilateral temporal regions activated by the auditory oddball target stimuli. A finding of less patient gray matter and less hemodynamic activity for target detection in these bilateral anterior temporal lobe regions was consistent with previous work. An unexpected corollary to this finding was that, in the regions showing the largest group differences, gray matter concentrations were larger in patients vs. controls, suggesting that more gray matter may be related to less functional connectivity in the auditory oddball fMRI task.

Acoustic Stimulation↗

Neuronal chronometry of target detection: fusion of hemodynamic and event-related potential data.

Event-related potential (ERP) studies of the brain's response to infrequent, target (oddball) stimuli elicit a sequence of physiological events, the most prominent and well studied being a complex, the P300 (or P3) peaking approximately 300 ms post-stimulus for simple stimuli and slightly later for more complex stimuli. Localization of the neural generators of the human oddball response remains challenging due to the lack of a single imaging technique with good spatial and temporal resolution. Here, we use independent component analyses to fuse ERP and fMRI modalities in order to examine the dynamics of the auditory oddball response with high spatiotemporal resolution across the entire brain. Initial activations in auditory and motor planning regions are followed by auditory association cortex and motor execution regions. The P3 response is associated with brainstem, temporal lobe, and medial frontal activity and finally a late temporal lobe "evaluative" response. We show that fusing imaging modalities with different advantages can provide new information about the brain.

Adult↗

Semi-blind ICA of fMRI: A method for utilizing hypothesis-derived time courses in a spatial ICA analysis.

Independent component analysis (ICA) is a data-driven approach utilizing high-order statistical moments to find maximally independent sources that has found fruitful application in functional magnetic resonance imaging (fMRI). Being a blind source separation technique, ICA does not require any explicit constraints upon the fMRI time courses. However, for some fMRI data analysis applications, such as for the analysis of an event-related paradigm, it would be useful to flexibly incorporate paradigm information into the ICA analysis. In this paper, we present an approach for constrained or semi-blind ICA (sbICA) analysis of event-related fMRI data by imposing regularization on certain estimated time courses using the paradigm information. We demonstrate the performance of our approach using both simulations and fMRI data from a three-stimulus auditory oddball paradigm. Simulation results suggest that (1) a regression approach slightly outperforms ICA when prior information is accurate and ICA outperforms the general linear model (GLM)-based approach when prior information is not completely accurate, (2) prior information improves the robustness of ICA in the presence of noise, and (3) ICA analysis using prior information with temporal constraints can outperform a regression approach when the prior information is not completely accurate. Using fMRI data, we compare a regression-based conjunction analysis of target and novel stimuli, both of which elicit an orienting response, to an sbICA approach utilizing both the target and novel stimuli to constrain the ICA time courses. Results show similar positive associations for both GLM and sbICA, but sbICA detects additional negative associates consistent with regions implicated in a default mode of brain activity. This suggests that task-related default mode decreases have a more "complex" signal that benefits from a flexible modeling approach. Compared with a traditional GLM approach, the sbICA approach provides a flexible way to analyze fMRI data that reduces the assumptions placed upon the hemodynamic response of the brain. The advantages and limitations of our technique are discussed in detail in the manuscript to provide guidelines to the reader for developing useful applications. The use of prior time course information in a spatial ICA analysis, which combines elements of both a regression approach and a blind ICA approach, may prove to be a useful tool for fMRI analysis.

Auditory Perception↗

Using virtual reality to study alcohol intoxication effects on the neural correlates of simulated driving.

The use of virtual reality in the form of simulated tasks can provide a realistic environment in which to study complex naturalistic behaviors. Many of the behavioral effects of alcohol intoxication are well known, but there is relatively little imaging evidence examining how alcohol exposure might transiently modulate brain function, especially in the context of task performance. In this review, we provide a brief synopsis of previous work using functional magnetic resonance imaging (fMRI) to study the neural correlates of alcohol intoxication. We describe in detail two studies from our published work, the first involving a visual perception paradigm, and the second involving virtual reality through a naturalistic behavior; simulated driving. Participants received single-blind individualized doses of beverage alcohol designed to produce blood alcohol content (BAC) of 0.04 and 0.08 or placebo. Subjects were fMRI scanned after training to asymptote performance. In both studies we found specific circuits that were differentially modulated by alcohol, we revealed both global and local effects of alcohol, and we examined relationships between behavior, brain function, and alcohol blood levels.

Adolescent↗

fMRI analysis with the general linear model: removal of latency-induced amplitude bias by incorporation of hemodynamic derivative terms.

Functional magnetic resonance imaging (fMRI) data are often analyzed using the general linear model employing a hypothesized neural model convolved with a hemodynamic response function. Mismatches between this hemodynamic model and the data can be induced by spatially varying delays or slice-timing differences. It is common practice to desensitize the analysis to such delays by incorporation of the hemodynamic model plus its temporal derivative. The rationale often used is that additional variance will be captured and regressed out from the data. Though this is true, it ignores the potential for amplitude bias induced by small model mismatches due to, for example, variable hemodynamic delays and is not helpful for "random effects" analyses which typically do not account for the first level variance at all. Amplitude bias is due to the use of only the nonderivative portion of the model in the final test for significant amplitudes. We propose instead testing an amplitude value that is a function of both the nonderivative and the derivative terms of the model. Using simulations, we show that the proposed amplitude test does not suffer from delay-induced bias and that a model incorporating temporal derivatives is a more natural test for amplitude differences. The proposed test is applied in a random-effects analysis of 100 subjects. It reveals increased amplitudes in areas consistent with the task, with the largest increases in regions with greater hemodynamic delays.

Acoustic Stimulation↗

Latency (in)sensitive ICA. Group independent component analysis of fMRI data in the temporal frequency domain.

Independent component analysis (ICA), a data-driven approach utilizing high-order statistical moments to find maximally independent sources, has found fruitful application in functional magnetic resonance imaging (fMRI). A limitation of the standard fMRI ICA model is that a given component's time course is required to have the same delay at every voxel. As spatially varying delays (SVDs) may be found in fMRI data, using an ICA model with a fixed temporal delay for each source will have two implications. Larger SVDs can result in the splitting of regions with different delays into different components. Second, smaller SVDs can result in a biased ICA amplitude estimate due to only a slight delay difference. We propose a straightforward approach for incorporating this prior temporal information and removing the limitation of a fixed source delay by performing ICA on the amplitude spectrum of the original fMRI data (thus removing latency information). A latency map is then estimated for each component using the resulting component images and the raw data. We show that voxels with similar time courses, but different delays, are grouped into the same component. Additionally, when using traditional ICA, the amplitudes of motor areas are diminished due to systematic delay differences between visual and motor areas. The amplitudes are more accurately estimated when using a latency-insensitive ICA approach. The resulting time courses, the component maps, and the latency maps may prove useful as an addition to the collection of methods for fMRI data analysis.

Adult↗

Independent component analysis of fMRI data in the complex domain.

In BOLD fMRI a series of MR images is acquired and examined for task-related amplitude changes. These functional changes are small, so it is important to maximize detection efficiency. Virtually all fMRI processing strategies utilize magnitude information and ignore the phase, resulting in an unnecessary loss of efficiency. As the optimum way to model the phase information is not clear, a flexible modeling technique is useful. To analyze complex data sets, independent component analysis (ICA), a data-driven approach, is proposed. In ICA, the data are modeled as spatially independent components multiplied by their respective time-courses. There are thus three possible approaches: 1) the time-courses can be complex-valued, 2) the images can be complex-valued, or 3) both the time-courses and the images can be complex-valued. These analytic approaches are applied to data from a visual stimulation paradigm, and results from three complex analysis models are presented and compared with magnitude-only results. Using the criterion of the number of contiguous activated voxels at a given threshold, an average of 12-23% more voxels are detected by complex-valued ICA estimation at a threshold of /Z/ > 2.5. Additionally, preliminary results from the complex models reveal a phase modulation similar to the magnitude time-course in some voxels, and oppositely modulated in other voxels.

Brain↗

Rapid method for correction of CSF partial volume in quantitative proton MR spectroscopic imaging.

Partial volume effects with cerebrospinal fluid (CSF), if uncorrected, can lead to underestimation of metabolite concentrations in quantitative proton magnetic resonance spectroscopic imaging (MRSI) of the brain. A rapid method for the correction of CSF partial volume effects is described based on selective CSF imaging using long echo time (TE) fast spin echo (FSE) magnetic resonance imaging (MRI). In order to achieve maximum suppression of signal from brain parenchyma, the FSE sequence is coupled with an inversion recovery (IR) pulse. Scan time is minimized using single shot (SS) IR-FSE. The method is validated against a current "gold standard" for the determination of CSF volumes, namely, segmented 3D spoiled gradient-echo (SPGR) scans. Excellent agreement in CSF percentage determined by the two methods was found (linear regression analysis: slope = 0.99 +/- 0.02, intercept = 2.08 +/- 0.45; mean +/- standard errors, R = 0.93) in pooled data from four healthy subjects. An example of the use of SS-IR-FSE for partial volume correction in a leukodystrophy patient with T(2) hyperintense lesions is demonstrated. SS-IR-FSE is a simple and rapid method for applying partial volume corrections in quantitative proton MRSI, which may be of particular value in the clinical environment when time constraints do not allow longer, perhaps more accurate segmentation methods to be used.

Adult↗

Spatial and temporal independent component analysis of functional MRI data containing a pair of task-related waveforms.

Independent component analysis (ICA) is a technique that attempts to separate data into maximally independent groups. Achieving maximal independence in space or time yields two varieties of ICA meaningful for functional MRI (fMRI) applications: spatial ICA (SICA) and temporal ICA (TICA). SICA has so far dominated the application of ICA to fMRI. The objective of these experiments was to study ICA with two predictable components present and evaluate the importance of the underlying independence assumption in the application of ICA. Four novel visual activation paradigms were designed, each consisting of two spatiotemporal components that were either spatially dependent, temporally dependent, both spatially and temporally dependent, or spatially and temporally uncorrelated, respectively. Simulated data were generated and fMRI data from six subjects were acquired using these paradigms. Data from each paradigm were analyzed with regression analysis in order to determine if the signal was occurring as expected. Spatial and temporal ICA were then applied to these data, with the general result that ICA found components only where expected, e.g., S(T)ICA "failed" (i.e., yielded independent components unrelated to the "self-evident" components) for paradigms that were spatially (temporally) dependent, and "worked" otherwise. Regression analysis proved a useful "check" for these data, however strong hypotheses will not always be available, and a strength of ICA is that it can characterize data without making specific modeling assumptions. We report a careful examination of some of the assumptions behind ICA methodologies, provide examples of when applying ICA would provide difficult-to-interpret results, and offer suggestions for applying ICA to fMRI data especially when more than one task-related component is present in the data.

Algorithms↗

A method for making group inferences from functional MRI data using independent component analysis.

Independent component analysis (ICA) is a promising analysis method that is being increasingly applied to fMRI data. A principal advantage of this approach is its applicability to cognitive paradigms for which detailed models of brain activity are not available. Independent component analysis has been successfully utilized to analyze single-subject fMRI data sets, and an extension of this work would be to provide for group inferences. However, unlike univariate methods (e.g., regression analysis, Kolmogorov-Smirnov statistics), ICA does not naturally generalize to a method suitable for drawing inferences about groups of subjects. We introduce a novel approach for drawing group inferences using ICA of fMRI data, and present its application to a simple visual paradigm that alternately stimulates the left or right visual field. Our group ICA analysis revealed task-related components in left and right visual cortex, a transiently task-related component in bilateral occipital/parietal cortex, and a non-task-related component in bilateral visual association cortex. We address issues involved in the use of ICA as an fMRI analysis method such as: (1) How many components should be calculated? (2) How are these components to be combined across subjects? (3) How should the final results be thresholded and/or presented? We show that the methodology we present provides answers to these questions and lay out a process for making group inferences from fMRI data using independent component analysis.

Algorithms↗

fMRI activation in a visual-perception task: network of areas detected using the general linear model and independent components analysis.

The Motor-Free Visual Perception Test, revised (MVPT-R), provides a measure of visual perceptual processing. It involves different cognitive elements including visual discrimination, spatial relationships, and mental rotation. We adapted the MVPT-R to an event-related functional MRI (fMRI) environment to investigate the brain regions involved in the interrelation of these cognitive elements. Two complementary analysis methods were employed to characterize the fMRI data: (a) a general linear model SPM approach based upon a model of the time course and a hemodynamic response estimate and (b) independent component analysis (ICA), which does not constrain the specific shape of the time course per se, although we did require it to be at least transiently task-related. Additionally, we implemented ICA in a novel way to create a group average that was compared with the SPM group results. Both methods yielded similar, but not identical, results and detected a network of robustly activated visual, inferior parietal, and frontal eye-field areas as well as thalamus and cerebellum. SPM appeared to be the more sensitive method and has a well-developed theoretical approach to thresholding. The ICA method segregated functional elements into separate maps and identified additional regions with extended activation in response to presented events. The results demonstrate the utility of complementary analyses for fMRI data and suggest that the cerebellum may play a significant role in visual perceptual processing. Additionally, results illustrate functional connectivity between frontal eye fields and prefrontal and parietal regions.

Attention↗

A finite element model for predicting the distribution of drugs delivered intracranially to the brain.

Drug therapy to the central nervous system is complicated by the presence of the blood-brain barrier. The development of new drug delivery techniques to overcome this obstacle will be aided by a clear understanding of the transport processes in the brain. A rigorous theoretical framework of the transport of drugs delivered locally to the parenchyma has been developed using the finite element method. Magnetic resonance imaging has been used to track the transport of paramagnetic contrast markers in the brain. The information obtained by postprocessing spin-echo, T1-weighted, and proton density images has been used to refine the mathematical model that includes realistic brain geometry and salient anatomic features and allows for two-dimensional transport of chemical species, including both diffusive and convective contributions. In addition, the effects of regional differences in tissue properties, ventricular boundary, and edema on the transport have been considered. The model has been used to predict transport of interleukin-2 in the brain and study the major determinants of transport, at both early and late times after drug delivery.

Animals↗