Biomedical subjects

R T Constable

Publications and source records attributed to R T Constable.

At least 19 recordsLinked to original sources

PubMed2005

Spatial resolution, signal-to-noise ratio, and smoothing in multi-subject functional MRI studies.

Functional MRI is aimed at localizing cortical activity to understand the role of specific cortical regions, providing insight into the neurophysiological underpinnings of brain function. Scientists developing fMRI methodology seek to improve detection of subtle activations and to spatially localize these activations more precisely. Except for applications in the clinical environment, such as functional mapping in patients prior to neurosurgical intervention, most basic neuroscience studies involve group level random-effects analyses. Prior to grouping data, the data from each individual are typically smoothed. A wide range of motivations for smoothing have been given including to match the spatial scale of hemodynamic responses, to normalize the error distribution (by the Central Limit Theorem) to improve the validity of inferences based on parametric tests, and, in the context of inter-subject averaging smoothing has been shown necessary to project the data down to a scale where homologies in functional anatomy are expressed across subjects. This work demonstrates that, for single-subject studies, if smoothing is to be employed, the data should be acquired at lower resolutions to maximize SNR. The benefits of a low-resolution acquisition are limited by partial volume effects and by the weak impact of resolution-dependent noise on the overall group level statistics. Given that inter-subject noise dominates across a range of tasks, improvements in within-subject noise, through changes in acquisition strategy or even moving to higher field strength, may do little to improve group statistics. Such improvements however may greatly impact single-subject studies such as those used in neurosurgical planning.

Artifacts↗

PubMed2005

Neural correlates of temporal-order judgments versus those of spatial-location: deactivation of hippocampus may facilitate spatial performance.

The retrieval of temporal-order versus spatial-location information was investigated using fMRI. The primary finding in the hippocampus proper, seen in region of interest analyses, was an increase in BOLD signal intensity for temporal retrieval, and a decrease in signal intensity for spatial retrieval, relative to baseline. The negative BOLD signal change with spatial memory processing, while unexpected, is consistent with the recent fMRI literature indicating decreased BOLD can be associated with neuronal activation, and it is argued that the deactivation observed here may facilitate spatial performance. Spatial-location judgments also yielded a stronger (positive) response in the right midfrontal gyrus, while temporal-order judgments (autobiographic condition only) showed greater activity in the left superior temporal gyrus, suggesting greater working memory demands and greater semantization for each judgment type, respectively. Finally, all conditions activated the left midfrontal gyrus, although autobiographic memories showed additional activity in the medial frontal gyrus.

Adult↗

PubMed2005

Amygdala responsiveness is modulated by tryptophan hydroxylase-2 gene variation.

The tryptophan hydroxylase-2 gene (TPH2) codes for the enzyme of serotonin (5-HT) synthesis in the brain and variation of TPH2 has been implicated in disorders of emotion regulation. Here, we used functional magnetic resonance imaging (fMRI) to demonstrate that a potentially functional variant of TPH2 modulates amygdala responsiveness to emotional stimuli of both negative and positive valence.

Adolescent↗

PubMed2001

Repetition time in echo planar functional MRI.

To date, surprisingly little attention has been directed toward determining the optimum TR in a functional imaging experiment. A survey of the literature reveals a wide range of TRs, but little justification for a specific TR. Long-TR functional imaging experiments provide maximum signal-to-noise ratio (SNR) in the raw images; allow for the collection of a large number of slice locations; and decrease the size of the data set acquired, simplifying storage and handling. This work, however, demonstrates that long-TR imaging sacrifices statistical power when the paradigm timing is held fixed. That is, for a fixed-run duration consisting of multiple activation/control blocks, shorter TR acquisitions (on the order of 1000 ms) provide better discrimination between the activated and nonactivated brain tissue regions than do long-TR acquisitions (on the order of 4000 ms). Results are shown for modeling the functional imaging experiment and for three different paradigms performed on normal subjects.

Adult↗

PubMed2001

The functional neural architecture of components of attention in language-processing tasks.

Using functional magnetic resonance imaging we examined three important dimensions of attentional control (selective attention, divided attention, and executive function) in 25 neurologically normal, right-handed men and women, using tasks involving the perception and processing of printed words, spoken words, or both. In the context of language-processing manipulations: selective attention resulted in increased activation at left hemisphere parietal sites as well as at inferior frontal sites, divided attention resulted in additional increases in activation at these same left hemisphere sites and was also uniquely associated with increased activation of homologous sites in the right hemisphere, and executive function (measured during a complex task requiring sequential decision-making) resulted in increased activation at frontal sites relative to all other conditions. Our findings provide support for the belief that specific functional aspects of attentional control in language processing involve widely distributed but distinctive cortical systems, with mechanisms associated with the control of perceptual selectivity involving primarily parietal and inferior frontal sites and executive function engaging specific sites in frontal cortex.

Adult↗

PubMed2001

Functional MRI of language processing: dependence on input modality and temporal lobe epilepsy.

PURPOSE: Functional magnetic resonance imaging (MRI) using two language-comprehension tasks was evaluated to determine its ability to lateralize language processing and identify regions that must be spared in surgery. METHODS: Two parallel cognitive language tasks, one using auditory input and the other visual input, were tested in a group of control subjects and in temporal lobe epilepsy patients who were candidates for surgical intervention. The patient studies provide an opportunity to compare functional MRI language localization with that obtained using Wada testing and electrocorticography. All of the patients in this study underwent all three procedures and a battery of neuropsychological testing. Such studies provide an opportunity not only to validate the fMRI findings but also, by comparing the patient results with those obtained in control subjects, to provide insight into the impact of a pathology such as epilepsy on cortical organization or functional patterns of activation. RESULTS: The results reveal both modality-dependent and modality-independent language-processing patterns for visual versus auditory task presentation. The visual language task activated distinct sites in Broca's area, BA (Brodmann area) 44 that were not activated in the auditory language task. The auditory language task strongly activated contralateral right BA22-21 area (homologous to Wernicke's area on the left). Language lateralization scores were significantly stronger for visual than for auditory task presentation. The conjunction of activation from the two different input modalities (modality-independent areas) likely highlights regions that perform more abstract computations (e.g., syntactic or pragmatic processing) in language processing. Modality-specific areas (e.g., right Wernicke, left fusiform gyrus, Broca BA44, supramarginal gyrus), appear to cope with the computations relevant to making contact with these more abstract dimensions. Patients showed recruitment of contralateral homologous language areas (p < 0.005) that was significantly above that found in a normal control group. Extra- and intraoperative cortical stimulations were concordant with the fMRI data in eight of 10 cases. The fMRI lateralization scores were also consistent with the Wada testing in 8/10 patients. CONCLUSIONS: The fMRI results demonstrate that the epileptic brain may be a progressive model for cortical plasticity.

Adult↗

PubMed2001

Quantification of 3-D regional myocardial deformation: shape-based analysis of magnetic resonance images.

A comprehensive three-dimensional (3-D) shape-based approach for quantification of regional myocardial deformations was evaluated in a canine model (n = 8 dogs) with the use of cine magnetic resonance imaging. The shape of the endocardial and epicardial surfaces was used to track the 3-D trajectories of a dense field of points over the cardiac cycle. The shape-based surface displacements are integrated with a continuum biomechanics model incorporating myofiber architecture to estimate both cardiac- and fiber-specific endocardial and epicardial strains and shears for 24 left ventricular regions. Whereas radial and circumferential end-systolic strains were fairly uniform, there was a significant apex-to-base gradient in longitudinal strain and radial-longitudinal shear. We also observed transmural epicardial-to-endocardial gradients in both cardiac- and fiber-specific strains. The increase in endocardial strain was accompanied by increases in radial-longitudinal shear and radial-fiber shears in the endocardium, supporting previous theories of regional myocardial deformation that predict considerable sliding between myocardial fibers.

Animals↗

PubMed2001

Patterns of functional magnetic resonance imaging activation in association with structural lesions in the rolandic region: a classification system.

OBJECT: Functional magnetic resonance (fMR) imaging of the motor cortex is a potentially powerful tool in the preoperative planning of surgical procedures in and around the rolandic region. Little is known about the patterns of fMR imaging activation associated with various pathological lesions in that region or their relation to motor skills before surgical intervention. METHODS: Twenty-two control volunteers and 44 patients whose pathologies included arteriovenous malformations (AVMs; 16 patients), congenital cortical abnormalities (11 patients), and tumors (17 patients) were studied using fMR imaging and a hand motor task paradigm. Activation maps were constructed for each participant, and changes in position or amplitude of the motor activation on the lesion side were compared with the activation pattern obtained in the contralateral hemisphere. A classification scheme of plasticity (Grades 1-6) based on interhemispheric pixel asymmetry and displacement of activation was used to compare maps between patients, and relative to hand motor dexterity and/or weakness. There was 89.4% interobserver agreement on classification of patterns of fMR imaging activation. Displacement of activation by mass effect was more likely with tumors. Cortical malformations offer a much higher functional reorganization than AVMs or tumors. High-grade plasticity is recruited to compensate for severe motor impairment. CONCLUSIONS: Pattern modification of fMR imaging activation can be systematized in a classification of motor cortex plasticity. This classification has shown good correlation among grading, brain lesions, and motor skills. This proposal of a classification scheme, in addition to facilitating data collection and processing from different institutions, is well suited for comparing risks associated with surgical intervention and patterns of functional recovery in relation to preoperative fMR imaging categorization. Such studies are underway at the authors' institution.

Adolescent↗

PubMed2001

A new method for quantification of spatial and temporal parameters of endocardial motion: evaluation of experimental infarction using magnetic resonance imaging.

BACKGROUND: With the development of high-resolution myocardial imaging there has evolved a need for automated techniques that can accurately quantify regional function. OBJECTIVE: To develop a new method for quantification of spatial and temporal parameters of endocardial motion. DESIGN: Magnetic resonance images were analyzed using a unique, shape-based approach that tracks endocardial surface motion at defined points through the cardiac cycle by minimizing the bending energy. SETTING: Animal instrumentation was performed in the Nuclear Cardiology Experimental Research Laboratory at Yale University, New Haven, Connecticut. Magnetic resonance imaging was performed at the Yale New Haven Hospital Center. ANIMALS: Eight mongrel canines were used. INTERVENTIONS: Electrocardiograph-gated gradient-echo magnetic resonance images were obtained before and after occlusion of the left anterior descending coronary. Thirty-two points along automatically defined endocardial contours were tracked. Average displacements and cumulative path lengths were computed from end-diastole for each point over the entire cardiac cycle. The average cumulative path length was computed for each of four quarters of systole for the normal, border and infarct zones. Shape-based parameters of systolic motion were compared with the centreline approach. Infarct zone was defined by postmortem histochemical staining. MAIN RESULTS: Displacement and cumulative path length over the cardiac cycle decreased significantly in the infarct and border zones (P<0.05), but did not change in the normal zone (P was not significant). Temporal changes in motion were observed in all zones. Displacement measured using the shape-based algorithm was more consistent than cumulative path length when compared with systolic motion measured using the centreline method. CONCLUSIONS: An automated, shape-based approach permits quantitative evaluation of both spatial and temporal parameters of regional endocardial motion from high-resolution electrocardiograph-gated images. Analysis of endocardial motion and cumulative motion over the entire cardiac cycle discriminated infarcted from normal and border regions.

Animals↗

PubMed2000

Network analysis of brain activations in working memory: behavior and age relationships.

Forty-six middle-aged female subjects were scanned using functional Magnetic Resonance Imaging (fMRI) during performance of three distinct stages of a working memory task-encoding, rehearsal, and recognition-for both printed pseudowords and visual forms. An expanse of areas, involving the inferior frontal, parietal, and extrastriate cortex, was active in response to stimuli during both the encoding and recognition periods. Additional increases during memory recognition were seen in right prefrontal regions, replicating a now-common finding [for reviews, see Fletcher et al. (1997) Trends Neurosci 20:213-218; MacLeod et al. (1998) NeuroImage 7:41-48], and broadly supporting the Hemispheric Encoding/Retrieval Asymmetry hypothesis [Tulving et al. (1994) Proc Natl Acad Sci USA 91:2016-2020]. Notably, this asymmetry was not qualified by the type of material being processed. A few sites demonstrated higher activity levels during the rehearsal period, in the absence of any new stimuli, including the medial extrastriate, precuneus, and the medial temporal lobe. Further analyses examined relationships among subjects' brain activations, age, and behavioral scores on working memory tests, acquired outside the scanner. Correlations between brain scores and behavior scores indicated that activations in a number of areas, mainly frontal, were associated with performance. A multivariate analysis, Partial Least Squares [McIntosh et al. (1996) NeuroImage 3:143-157, (1997) Hum Brain Map 5:323-327], was then used to extract component effects from this large set of univariate correlations. Results indicated that better memory performance outside the scanner was associated with higher activity at specific sites within the frontal and, additionally, the medial temporal lobes. Analysis of age effects revealed that younger subjects tended to activate more than older subjects in areas of extrastriate cortex, medial frontal cortex, and the right medial temporal lobe; older subjects tended to activate more than younger subjects in the insular cortex, right inferior temporal lobe, and right inferior frontal gyrus. These results extend recent reports indicating that these regions are specifically involved in the memory impairments seen with aging.

Adult↗

PubMed2000

Functional neuroanatomy of executive processes involved in dual-task performance.

The subjective experience of allocating one's attentional resources among competing tasks is nearly universal, and most current models of cognition include a mechanism that performs this allocation; examples include the central executive system and the supervisory attentional system. Yet, the exact form that an executive system might take and even its necessity for cognition are controversial. Dual-task paradigms have commonly been used to investigate executive function. The few neuroimaging studies of these paradigms have yielded contradictory findings. Using functional MRI, we imaged brain function during two dual-task paradigms, each with a common auditory component task (NOUN task) but varying with respect to a visual component task (SPACE or FACE tasks). In each of the two dual-task paradigms, the results showed that the activated areas varied with the component tasks, that all of the areas activated during dual task performance were also activated during the component tasks, and that surplus activation within activated areas during DUAL conditions was parsimoniously accounted for by the addition of the second task. These findings suggest that executive processes may be mediated by interactions between anatomically and functionally distinct systems engaged in performance of component tasks, as opposed to an area or areas dedicated to a generic executive system.

Brain↗

PubMed2000

Investigation of the human hippocampal formation using a randomized event-related paradigm and Z-shimmed functional MRI.

Functional neuroimaging of the hippocampal formation has presented a challenge to neuroscientists because of the small size of the hippocampus proper and its location at the basal level of the brain. Choosing the appropriate control condition for subtraction-based studies has also proved difficult. Event-related experimental designs are a powerful tool in behavioral and electrophysiological studies. Recently, such experimental designs have been applied to functional MR imaging studies but these studies used large intertrial intervals in order to separate the slow blood flow response from temporally adjacent events, severely limiting the number of events that can be presented in a single run. This leads to poor statistical power and restrictions on the design of the experimental paradigm. We present data obtained using a rapidly presented, randomized event-related paradigm, combined with a novel fMRI imaging method designed to improve imaging in basal brain regions. The results demonstrate bilateral activation in the hippocampal formation in identification of novel complex scenes distinct from a learned basis set of complex scenes. Differential activation is obtained in the counter task of identifying a learned target complex scene against a background of novel scenes. The results are also compared with the more conventional block design complex scene paradigms previously reported by others. The block design provides strong posterior activation, likely related more to visual scene processing, whereas the event-related design provides more anterior hippocampal activation with the encoding of novel scenes.

Adult↗

PubMed2000

Point-tracked quantitative analysis of left ventricular surface motion from 3-D image sequences.

We propose and validate the hypothesis that we can use differential shape properties of the myocardial surfaces to recover dense field motion from standard three-dimensional (3-D) image sequences (MRI and CT). Quantitative measures of left ventricular regional function can be further inferred from the point correspondence maps. The noninvasive, algorithm-derived results are validated on two levels. First, the motion trajectories are compared to those of implanted imaging-opaque markers of a canine model in two imaging modalities, where subpixel accuracy is achieved. Second, the validity of using motion parameters (path length and thickness changes) for detecting myocardial injury area is tested by comparing algorithms derived results to postmortem analysis TTC staining of myocardial tissue, where the achieved Pearson product-moment correlation value is 0.968.

Algorithms↗

PubMed2000

Accurate alignment of functional EPI data to anatomical MRI using a physics-based distortion model.

Mapping of functional magnetic resonance imaging (fMRI) to conventional anatomical MRI is a valuable step in the interpretation of fMRI activations. One of the main limits on the accuracy of this alignment arises from differences in the geometric distortion induced by magnetic field inhomogeneity. This paper describes an approach to the registration of echo planar image (EPI) data to conventional anatomical images which takes into account this difference in geometric distortion. We make use of an additional spin echo EPI image and use the known signal conservation in spin echo distortion to derive a specialized multimodality nonrigid registration algorithm. We also examine a plausible modification using log-intensity evaluation of the criterion to provide increased sensitivity in areas of low EPI signal. A phantom-based imaging experiment is used to evaluate the behavior of the different criteria, comparing nonrigid displacement estimates to those provided by a imagnetic field mapping acquisition. The algorithm is then applied to a range of nine brain imaging studies illustrating global and local improvement in the anatomical alignment and localization of fMRI activations.

Algorithms↗

PubMed2000

The angular gyrus in developmental dyslexia: task-specific differences in functional connectivity within posterior cortex.

Converging evidence from neuroimaging studies of developmental dyslexia reveals dysfunction at posterior brain regions centered in and around the angular gyrus in the left hemisphere. We examined functional connectivity (covariance) between the angular gyrus and related occipital and temporal lobe sites, across a series of print tasks that systematically varied demands on phonological assembly. Results indicate that for dyslexic readers a disruption in functional connectivity in the language-dominant left hemisphere is confined to those tasks that make explicit demands on assembly. In contrast, on print tasks that do not require phonological assembly, functional connectivity is strong for both dyslexic and nonimpaired readers. The findings support the view that neurobiological anomalies in developmental dyslexia are largely confined to the phonological-processing domain. In addition, the findings suggest that right-hemisphere posterior regions serve a compensatory role in mediating phonological performance in dyslexic readers.

Adolescent↗

PubMed2000

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&frasl;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 Broca's area, whereas semantic anomaly activated several other sites anteriorly and posteriorly, among them Wernicke's 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.

Adult↗

PubMed2000

Reproducibility and accuracy of gated SPECT for determination of left ventricular volumes and ejection fraction: experimental validation using MRI.

UNLABELLED: Quantitative gated SPECT (QGS) has been used for computation of left ventricular volumes and ejection fraction. This study evaluated, first, the effect of injected dose, time of imaging, and background activity on the reproducibility of QGS and, second, the accuracy of QGS, compared with cine MRI, for determining left ventricular volumes and ejection fractions in dogs with and without perfusion defects. METHODS: Sixteen dogs were subjected to either chronic occlusion of the circumflex artery (group I, no perfusion defect) or acute occlusion of the anterior descending coronary artery (group II, perfusion defect). Both groups underwent serial MRI and SPECT. RESULTS: ( QGS was very reproducible using the automated program (r = 0.99997). Correlation between left ventricular ejection fraction (LVEF) at 15 and 45 min was poor after the low-dose injection (r = 0.54; SE = 9%) and only fair after the high-dose injection (r = 0.77; SE = 5%). Correlation was poor in the presence of significant background activity (r = 0.36; SE = 12%). Correlation between QGS left ventricular volumes and MRI was good for group I (end-diastolic volume, r = 0.86; end-systolic volume, r = 0.81) and only fair for group II (end-diastolic volume, r = 0.66; end-systolic volume, r = 0.69). The overall LVEF correlation between QGS and MRI was poor (r = 0.51). QGS LVEF (mean +/- SD, 42% +/- 3%) overestimated MRI LVEF (29% +/- 2%). CONCLUSION: QGS provides a highly reproducible estimate of LVEF. However, QGS is affected by changes in background activity, time of imaging, and injected dose. In the presence of perfusion defects, QGS overestimated volume relative to MRI. The correlation between QGS- and MRI-derived LVEF was poor in this canine model.

Animals↗

PubMed1999

Effect of estrogen on brain activation patterns in postmenopausal women during working memory tasks.

CONTEXT: Preclinical studies suggest that estrogen affects neural structure and function in mature animals; clinical studies are less conclusive with many, but not all, studies showing a positive influence of estrogen on verbal memory in postmenopausal women. OBJECTIVE: To investigate the effects of estrogen on brain activation patterns in postmenopausal women as they performed verbal and nonverbal working memory tasks. DESIGN: Randomized, double-blind, placebo-controlled, crossover trial from 1996 through 1998. SETTING: Community volunteers tested in a hospital setting. PATIENTS: Forty-six postmenopausal women aged 33 to 61 years (mean [SD] age, 50.8 [4.7] years). INTERVENTION: Twenty-one-day treatment with conjugated equine estrogens, 1.25 mg/d, randomly crossed over with identical placebo and a 14-day washout between treatments. MAIN OUTCOME MEASURES: Brain activation patterns measured using functional magnetic resonance imaging during tasks involving verbal and nonverbal working memory. RESULTS: Treatment with estrogen increased activation in the inferior parietal lobule during storage of verbal material and decreased activation in the inferior parietal lobule during storage of nonverbal material. Estrogen also increased activation in the right superior frontal gyrus during retrieval tasks, accompanied by greater left-hemisphere activation during encoding. The latter pattern represents a sharpening of the hemisphere encoding/retrieval asymmetry (HERA) effect. Estrogen did not affect actual performance of the verbal and nonverbal memory tasks. CONCLUSIONS: Estrogen in a therapeutic dosage alters brain activation patterns in postmenopausal women in specific brain regions during the performance of the sorts of memory function that are called upon frequently during any given day. These results suggest that estrogen affects brain organization for memory in postmenopausal women.

Adult↗