R.T. Constable

An Event-related Neuroimaging Study Distinguishing Form and Content in Sentence Processing

Two coordinated experiments using functional Magnetic Resonance Imaging (fMRI) investigated whether the brain represents language form (grammatical structure) separately from its meaning content (semantics). While in the scanner, 14 young, unimpaired adults listened to simple sentences that were either nonanomalous or contained a grammatical error (for example, Trees can grew.), or a semantic anomaly (for example, Trees can eat.). A same/different tone pitch judgment task provided a baseline that isolated brain activity associated with linguistic processing from background activity generated by attention to the task and analysis of the auditory input. Sites selectively activated by sentence processing were found in both hemispheres in inferior frontal, middle, and superior frontal, superior temporal, and temporo-parietal regions. Effects of syntactic and semantic anomalies were differentiated by some nonoverlapping areas of activation: Syntactic anomaly triggered significantly increased activity in and around Brocas area, whereas semantic anomaly activated several other sites anteriorly and posteriorly, among them Wernickes area. These dissociations occurred when listeners were not required to attend to the anomaly. The results confirm that linguistic operations in sentence processing can be isolated from nonlinguistic operations and support the hypothesis of a specialization for syntactic processing.

Estimation of 3-D left ventricular deformation from medical images using biomechanical models

The quantitative estimation of regional cardiac deformation from three-dimensional (3-D) image sequences has important clinical implications for the assessment of viability in the heart wall. We present here a generic methodology for estimating soft tissue deformation which integrates image-derived information with biomechanical models, and apply it to the problem of cardiac deformation estimation. The method is image modality independent. The images are segmented interactively and then initial correspondence is established using a shape-tracking approach. A dense motion field is then estimated using a transversely isotropic, linear-elastic model, which accounts for the muscle fiber directions in the left ventricle. The dense motion field is in turn used to calculate the deformation of the heart wall in terms of strain in cardiac specific directions. The strains obtained using this approach in open-chest dogs before and after coronary occlusion, exhibit a high correlation with strains produced in the same animals using implanted markers. Further, they show good agreement with previously published results in the literature. This proposed method provides quantitative regional 3-D estimates of heart deformation.

Dynamic Time Course of Typical Childhood Absence Seizures: EEG, Behavior, and Functional Magnetic Resonance Imaging

Absence seizures are 5–10 s episodes of impaired consciousness accompanied by 3–4 Hz generalized spike-and-wave discharge on electroencephalography (EEG). The time course of functional magnetic resonance imaging (fMRI) changes in absence seizures in relation to EEG and behavior is not known. We acquired simultaneous EEG–fMRI in 88 typical childhood absence seizures from nine pediatric patients. We investigated behavior concurrently using a continuous performance task or simpler repetitive tapping task. EEG time–frequency analysis revealed abrupt onset and end of 3–4 Hz spike-wave discharges with a mean duration of 6.6 s. Behavioral analysis also showed rapid onset and end of deficits associated with electrographic seizure start and end. In contrast, we observed small early fMRI increases in the orbital/medial frontal and medial/lateral parietal cortex >5 s before seizure onset, followed by profound fMRI decreases continuing >20 s after seizure end. This time course differed markedly from the hemodynamic response function (HRF) model used in conventional fMRI analysis, consisting of large increases beginning after electrical event onset, followed by small fMRI decreases. Other regions, such as the lateral frontal cortex, showed more balanced fMRI increases followed by approximately equal decreases. The thalamus showed delayed increases after seizure onset followed by small decreases, most closely resembling the HRF model. These findings reveal a complex and long-lasting sequence of fMRI changes in absence seizures, which are not detectable by conventional HRF modeling in many regions. These results may be important mechanistically for seizure initiation and termination and may also contribute to changes in EEG and behavior.Absence seizures are 5–10 second episodes of impaired consciousness accompanied by 3–4Hz generalized spike-and-wave discharge on electroencephalography (EEG). The timecourse of functional magnetic resonance imaging (fMRI) changes in absence seizures in relation to EEG and behavior is not known. We acquired simultaneous EEG-fMRI in 88 typical childhood absence seizures from 9 pediatric patients. We investigated behavior concurrently using a continuous performance task (CPT) or simpler repetitive tapping task (RTT). EEG time-frequency analysis revealed abrupt onset and end of 3–4 Hz spike-wave discharges with a mean duration of 6.6 s. Behavioral analysis also showed rapid onset and end of deficits associated with electrographic seizure start and end. In contrast, we observed small early fMRI increases in the orbital/medial frontal and medial/lateral parietal cortex >5s before seizure onset, followed by profound fMRI decreases continuing >20s after seizure end. This timecourse differed markedly from the hemodynamic response function (HRF) model used in conventional fMRI analysis, consisting of large increases beginning after electrical event onset, followed by small fMRI decreases. Other regions, such as the lateral frontal cortex, showed more balanced fMRI increases followed by approximately equal decreases. The thalamus showed delayed increases after seizure onset followed by small decreases, most closely resembling the HRF model. These findings reveal a complex and long lasting sequence of fMRI changes in absence seizures, which are not detectible by conventional HRF modeling in many regions. These results may be important mechanistically for seizure initiation and termination and may also contribute to changes in EEG and behavior.

Groupwise whole-brain parcellation from resting-state fMRI data for network node identification.

In this paper, we present a groupwise graph-theory-based parcellation approach to define nodes for network analysis. The application of network-theory-based analysis to extend the utility of functional MRI has recently received increased attention. Such analyses require first and foremost a reasonable definition of a set of nodes as input to the network analysis. To date many applications have used existing atlases based on cytoarchitecture, task-based fMRI activations, or anatomic delineations. A potential pitfall in using such atlases is that the mean timecourse of a node may not represent any of the constituent timecourses if different functional areas are included within a single node. The proposed approach involves a groupwise optimization that ensures functional homogeneity within each subunit and that these definitions are consistent at the group level. Parcellation reproducibility of each subunit is computed across multiple groups of healthy volunteers and is demonstrated to be high. Issues related to the selection of appropriate number of nodes in the brain are considered. Within typical parameters of fMRI resolution, parcellation results are shown for a total of 100, 200, and 300 subunits. Such parcellations may ultimately serve as a functional atlas for fMRI and as such three atlases at the 100-, 200- and 300-parcellation levels derived from 79 healthy normal volunteers are made freely available online along with tools to interface this atlas with SPM, BioImage Suite and other analysis packages.

Neural correlates of post-error slowing during a stop signal task: A functional magnetic resonance imaging study

The ability to detect errors and adjust behavior accordingly is essential for maneuvering in an uncertain environment. Errors are particularly prone to occur when multiple, conflicting responses are registered in a situation that requires flexible behavioral outputs; for instance, when a go signal requires a response and a stop signal requires inhibition of the response during a stop signal task (SST). Previous studies employing the SST have provided ample evidence indicating the importance of the medial cortical brain regions in conflict/error processing. Other studies have also related these regional activations to postconflict/error behavioral adjustment. However, very few studies have directly explored the neural correlates of postconflict/error behavioral adjustment. Here we employed an SST to elicit errors in approximately half of the stop trials despite constant behavioral adjustment of the observers. Using functional magnetic resonance imaging, we showed that prefrontal loci including the ventrolateral prefrontal cortex are involved in post-error slowing in reaction time. These results delineate the neural circuitry specifically involved in error-associated behavioral modifications.

Prenatal and Adolescent Exposure to Tobacco Smoke Modulates the Development of White Matter Microstructure

Prenatal exposure to maternal smoking has been linked to cognitive and auditory processing deficits in offspring. Preclinical studies have demonstrated that exposure to nicotine disrupts neurodevelopment during gestation and adolescence, possibly by disrupting the trophic effects of acetylcholine. Given recent clinical and preclinical work suggesting that neurocircuits that support auditory processing may be particularly vulnerable to developmental disruption by nicotine, we examined white matter microstructure in 67 adolescent smokers and nonsmokers with and without prenatal exposure to maternal smoking. The groups did not differ in age, educational attainment, IQ, years of parent education, or symptoms of inattention. Diffusion tensor anisotropy and anatomical magnetic resonance images were acquired, and auditory attention was assessed, in all subjects. Both prenatal exposure and adolescent exposure to tobacco smoke was associated with increased fractional anisotropy (FA) in anterior cortical white matter. Adolescent smoking was also associated with increased FA of regions of the internal capsule that contain auditory thalamocortical and corticofugal fibers. FA of the posterior limb of the left internal capsule was positively correlated with reaction time during performance of an auditory attention task in smokers but not in nonsmokers. Development of anterior cortical and internal capsule fibers may be particularly vulnerable to disruption in cholinergic signaling induced by nicotine in tobacco smoke. Nicotine-induced disruption of the development of auditory corticofugal fibers may interfere with the ability of these fibers to modulate ascending auditory signals, leading to greater noise and reduced efficiency of neurocircuitry that supports auditory processing.

Predicting reading performance from neuroimaging profiles : The cerebral basis of phonological effects in printed word identification

This study linked 2 experimental paradigms for the analytic study of reading that heretofore have been used separately. Measures on a lexical decision task designed to isolate phonological effects in the identification of printed words were examined in young adults. The results were related to previously obtained measures of brain activation patterns for these participants derived from functional magnetic resonance imaging (fMRI). The fMRI measures were taken as the participants performed tasks that were designed to isolate orthographic, phonological, and lexical-semantic processes in reading. Individual differences in the magnitude of phonological effects in word recognition, as indicated by spelling-to-sound regularity effects on lexical decision latencies and by sensitivity to stimulus length effects, were strongly related to differences in the degree of hemispheric lateralization in 2 cortical regions.

Composite image formation in z-shimmed functional MR imaging

A challenge in functional magnetic resonance imaging (fMRI) is to develop imaging methods that are highly sensitive to microscopic field inhomogeneities [the blood oxygenation level‐dependent (BOLD) effect] and minimally sensitivity to macroscopic fields. z‐Shimming compensates for the through‐plane dephasing that arises in gradient‐echo images due to magnetic field inhomogeneities. To date, an analysis of the formation of composite images from multiple z‐shim acquisitions has not been presented. This work compares three strategies for forming composite images, one of which is introduced for the first time, against the nominal image acquisition. True‐versus false‐positive rates of activation detection are considered, in addition to the time efficiency of the methods. It is shown that z‐shimming can provide uniform spatial sensitivity, resulting in increased activation detectability, in many cases outperforming the nominal imaging approach. Time efficiency is shown to be dependent on field uniformity. Theory, computer simulations, and results from fMRI studies are used to demonstrate the performance of these methods. Magn Reson Med 42:110–117, 1999.

Simultaneous EEG, fMRI, and behavior in typical childhood absence seizures

Purpose:  Absence seizures cause transient impairment of consciousness. Typical absence seizures occur in children, and are accompanied by 3–4‐Hz spike–wave discharges (SWDs) on electroencephalography (EEG). Prior EEG–functional magnetic resonance imaging (fMRI) studies of SWDs have shown a network of cortical and subcortical changes during these electrical events. However, fMRI during typical childhood absence seizures with confirmed impaired consciousness has not been previously investigated.

Signal-to-noise and contrast in fast spin echo (FSE) and inversion recovery FSE imaging

Fast spin echo (FSE) imaging has recently experienced a renewed enthusiasm in the clinical setting for its ability to provide high contrast T2-weighted images in short imaging times. This article evaluates the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) properties of the FSE sequence, inversion recovery (IR) FSE sequence, and conventional SE imaging. The results indicate that FSE imaging displays similar contrast properties to SE imaging, but that the SNR and CNR are improved secondary to the longer TRs and longer effective TEs that may be used. The SNR per unit time of the FSE sequence, and hence its efficiency, is at least a factor of 8 better than the SE sequence when 16 echoes are acquired for each excitation. The addition of a slice selective inversion pulse in IR-FSE allows rapid generation of IR images with image contrast similar to that of conventional IR sequences. When used with a multicoil array for abdominal, pelvic, and spine imaging, the IR-FSE sequence produces images that are virtually free of motion artifact from the subcutaneous fat immediately adjacent to the coils. Both FSE and IR-FSE, when compared with SE imaging, provide superior image contrast and SNR in reduced imaging time.