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Biomedical subjects

J C Gore

Publications and source records attributed to J C Gore.

At least 73 records · Page 4Linked to original sources

Functional disruption in the organization of the brain for reading in dyslexia.

Learning to read requires an awareness that spoken words can be decomposed into the phonologic constituents that the alphabetic characters represent. Such phonologic awareness is characteristically lacking in dyslexic readers who, therefore, have difficulty mapping the alphabetic characters onto the spoken word. To find the location and extent of the functional disruption in neural systems that underlies this impairment, we used functional magnetic resonance imaging to compare brain activation patterns in dyslexic and nonimpaired subjects as they performed tasks that made progressively greater demands on phonologic analysis. Brain activation patterns differed significantly between the groups with dyslexic readers showing relative underactivation in posterior regions (Wernicke's area, the angular gyrus, and striate cortex) and relative overactivation in an anterior region (inferior frontal gyrus). These results support a conclusion that the impairment in dyslexia is phonologic in nature and that these brain activation patterns may provide a neural signature for this impairment.

Brain↗

Cortical dysfunction in schizophrenia during auditory word and tone working memory demonstrated by functional magnetic resonance imaging.

BACKGROUND: Verbal learning and memory deficits are among the most severe cognitive deficits observed in schizophrenia. We have demonstrated that such deficits do not extend to working memory for tones in a substantial number of patients even when verbal working memory is impaired. In this study we used functional magnetic resonance imaging to study the neural basis of this dissociation of auditory verbal and nonverbal working memory in individuals with schizophrenia. METHODS: While undergoing functional magnetic resonance imaging, 12 schizophrenic patients and 12 matched control subjects performed auditory Word Serial Position Task and Tone Serial Position Task. RESULTS: Both tasks produced activation in frontal cortex and temporal and parietal lobes of the cerebrum in both groups. While robust activation was observed in the left inferior frontal gyrus (areas 6, 44, and 45) in the control group during the Word Serial Position Task, activation in the patient group was much reduced in these areas and failed to show the same task-specific activation as in controls. Reduced activation in patients was not confined to the inferior frontal gyrus, but also extended to a medial area during the Tone Serial Position Task and to premotor and anterior temporal lobe areas during both tasks. CONCLUSIONS: These findings support the hypothesis that abnormalities in cortical hemodynamic response in the inferior frontal gyrus underlie the verbal working memory deficit in schizophrenia. The relationship of verbal working memory deficits to other cognitive functions suggests that abnormal functioning in the speech-related areas may reflect a critical substrate of a broad range of cognitive dysfunctions associated with schizophrenia.

Adult↗

A functional magnetic resonance imaging study of tic suppression in Tourette syndrome.

BACKGROUND: The inability to inhibit unwanted behaviors and impulses produces functional debility in a broad range of neuropsychiatric disorders. A potentially important model of impulse control is volitional tic suppression in Tourette syndrome. METHODS: Tic suppression was studied in 22 adult subjects with Tourette syndrome by using functional magnetic resonance imaging. Images acquired during periods of voluntary tic suppression were compared with images acquired when subjects allowed the spontaneous expression of their tics. The magnitudes of signal change in the images were then correlated with measures of the severity of tic symptoms. CONCLUSIONS: Significant changes in signal intensity were seen in the basal ganglia and thalamus and in anatomically connected cortical regions believed to subserve attention-demanding tasks. The magnitudes of regional signal change in the basal ganglia and thalamus correlated inversely with the severity of tic symptoms. These findings suggest that the pathogenesis of tics involves an impaired modulation of neuronal activity in subcortical neural circuits.

Adolescent↗

Functional MRI studies of auditory comprehension.

The location of brain regions essential for auditory language comprehension is an important consideration in the planning of neurosurgical procedures that involve resections within the dominant temporal lobe. Language testing during intraoperative and extraoperative cortical stimulation has been the primary method for localizing these regions; however, noninvasive alternatives using functional neuroimaging have been sought. Here we report on a study of 14 subjects who listened passively to alternating sentences spoken in their native English language and in unfamiliar Turkish while functional magnetic resonance images were acquired. The English sentences produced strong activation within the left superior temporal sulcus in all subjects. Lesser activation was seen in homotopic right hemisphere locations in several subjects. In addition to these posterior temporal activations, 8 subjects also showed activation to English sentences in the left inferior frontal gyrus. Turkish sentences evoked no coherent region of activation in any subject. As both the Turkish and English sentences were read by the same speaker, and were matched for length, volume, and intonation, we conclude that the activation pattern evoked by the English sentences reflects auditory comprehension. This conclusion is further supported by additional control studies that have shown a markedly different pattern of activation by pure tone frequency glides.

Acoustic Stimulation↗

Gadolinium-bearing red cells as blood pool MRI contrast agents.

Human and rat red blood cells (RBCs) were loaded with gadolinium DTPA dimeglumine using an osmotic pulse technique to create a blood pool contrast agent for MRI. The resulting packed red cells contained 30.9 +/- 3.3 (1 SD) mmol Gd/liter for humans and 24.7 +/- 3.5 (1 SD) mmol Gd/liter for rats. Longitudinal relaxation rate constant of human RBCs increased from 2.0 +/- 0.1 to 145.6 +/- 36.2 s(-1); the transverse relaxation rate constant increased from 6.8 +/- 1.2 to 562 +/- 410 s(-1). For rat RBCs, R1 increased from 1.45 +/- 0.15 to 84.8 +/- 23.9 s(-1); R2 increased from 7.1 +/- 0.64 to 247 +/- 158 s(-1). Affinity for oxygen was slightly reduced (control P50 = 22.3 +/- 2.3 versus experimental P50 = 27.3 +/- 1.3, P < 0.01), as was mechanical deformability. No drop in relaxivities was seen after 5 days of storage. The apparent volume of distribution was 0.0164 +/- 0.003 liter/kg, biologic half-life 4.38 +/- 0.34 h, and total plasma clearance 0.003 +/- 0.0006 liter/kg/h. Compared with Gd-DTPA "free" in the plasma, tissue enhancement from RBCs was initially lower but was much prolonged. Preparation is simple enough to be reproduced by most laboratories.

Animals↗

Asymmetric spin-echo imaging of magnetically inhomogeneous systems: theory, experiment, and numerical studies.

The ability of the asymmetric spin-echo (ASE) pulse sequence to provide different degrees of spin-echo (SE)-type and gradient-echo (GE)-type contrast when imaging media containing magnetic inhomogeneities is investigated. The dependence of the ASE signal on the size of magnetic field perturbers is examined using theory, computer simulations, and experiment. A theoretical prediction of the ASE signal is obtained using the Anderson-Weiss mean field theory, the results of which are qualitatively supported by computer simulations and experimental studies. It is shown that the ASE sequence can be used to tune the range of perturber sizes that provide the largest contributions to susceptibility contrast effects.

Artifacts↗

Quantification of intravascular and extravascular contributions to BOLD effects induced by alteration in oxygenation or intravascular contrast agents.

A simple model is presented that allows quantitative separation of the contributions of signals from water in blood and extravascular parenchyma due to changes in blood oxygenation, induced either by brain activation or by alteration of inspired oxygen. The separation is based on the progressive attenuation of the signals in the vasculature of different levels when bipolar field gradient pulses are applied. Diffusion-weighted spin-echo echo-planar imaging sequences were used to measure signal changes under various conditions in both animals and human volunteers. Normoxic-hyperoxic episodes were induced in rats before and after injection of a superparamagnetic iron oxide contrast agent. Signal changes produced by visual stimulation were measured in human volunteers, and in volunteers subject to alternating normoxic-hyperoxic episodes, and with administration of Gd-DTPA. Analysis of the results with our simple model suggests that the apparent diffusion coefficient increases and R2 (= 1/T2) decreases upon brain activation, with a large component from extravascular water related to the decrease in the blood deoxyhemoglobin concentration. Furthermore, this study suggests that apparent diffusion coefficient of the extravascular component alone may provide localization of neuronal activation.

Animals↗

Physiological basis for BOLD MR signal changes due to neuronal stimulation: separation of blood volume and magnetic susceptibility effects.

An NMR method is applied for separating blood volume and magnetic susceptibility effects in response to neuronal stimulation in a rat model. The method uses high susceptibility contrast agents to enhance blood volume induced signal changes. In the absence of exogenous agent, the dominant source of signal change on neuronal activation is associated with the signal increase from the blood oxygen level dependent (BOLD) effect. The relative negative contribution of blood volume changes to BOLD changes is maximally estimated to be 34%. The blood volume changes associated with median nerve stimulation (7 Hz) in the motor cortex are 26+/-7% and the corresponding blood susceptibility changes are 0.021+/-0.006 ppm. These methods can be applied to enhance the sensitivity of fMRI signal response and provide accurate quantitative measures of blood volume response to stimulation.

Animals↗

The role of specific side groups and pH in magnetization transfer in polymers.

The nature of water-macromolecule interactions in aqueous model polymers has been investigated using quantitative measurements of magnetization transfer. Cross-linked polymer gels composed of 94% water, 3% N,N'-methylene-bis-acrylamide, and 3% functional monomer (acrylamide, methacrylamide, acrylic acid, methacrylic acid, 2-hydroxyethyl-acrylate, or 2-hydroxyethyl-methacrylate) were studied. Water-macromolecule interactions were modified by varying the pH and specific functional group on the monomer. The magnitudes of the interactions were quantified by measuring the rate of proton nuclear spin magnetization exchange between the polymer matrix and the water. This rate was highly sensitive to the presence of carboxyl side groups on the macromolecule. However, the dependence of the rate on pH was not consistent with simple acid/base-catalyzed chemical exchange, and instead, the data suggest that multiequilibria proton exchange, a wide distribution in surface group pK values, and/or a macromolecular structural dependence on pH may play a significant role in magnetization transfer in polymer systems. These model polymer gels afford useful insights into the relevance of chemical composition and chemical dynamics on relaxation in tissues.

Acrylamides↗

Measurements of the temporal fMRI response of the human auditory cortex to trains of tones.

Averaged single trials (AST) allowed the functional magnetic resonance imaging (fMRI) response to auditory stimuli to be measured at high temporal (1 s) and spatial (0.1 cm3) resolution. Using this paradigm we investigated the transient signal response to 100-ms tone bursts in trains of between 100 ms and 25.5 s in total duration. We have demonstrated that the fMRI response to such auditory stimuli is approximately linear for trains of 6 s and longer, but that shorter stimuli produce signals that are larger than might be expected from the response to the longer stimuli. This nonlinear behavior can be modeled if an adaptive response to each stimulus is assumed. A study using a novel paradigm was also performed in order to study the influence of scanner noise during fMRI experiments on the auditory system response to tones. This study demonstrated that the temporal response to 700-ms tone stimuli is modified when performed in the presence of scanner gradient noise, the modification being a small but significant increase (P < 0.05) in the magnitude of the response. Finally the ability to measure the onset of functional activation using the AST method was examined. It was found, with the aid of computer simulation that a sampling rate of one image per second is adequate to distinguish temporal responses. Using the data acquired in this study, onset times were calculated for the auditory cortex, and these results are consistent with current models of functional activation.

Adult↗

Human amygdala activation during conditioned fear acquisition and extinction: a mixed-trial fMRI study.

Echoplanar functional magnetic resonance imaging (fMRI) was used in normal human subjects to investigate the role of the amygdala in conditioned fear acquisition and extinction. A simple discrimination procedure was employed in which activation to a visual cue predicting shock (CS+) was compared with activation to another cue presented alone (CS-). CS+ and CS- trial types were intermixed in a pseudorandom order. Functional images were acquired with an asymmetric spin echo pulse sequence from three coronal slices centered on the amygdala. Activation of the amygdala/periamygdaloid cortex was observed during conditioned fear acquisition and extinction. The extent of activation during acquisition was significantly correlated with autonomic indices of conditioning in individual subjects. Consistent with a recent electrophysiological recording study in the rat (Quirk et al., 1997), the profile of the amygdala response was temporally graded, although this dynamic was only statistically reliable during extinction. These results provide further evidence for the conservation of amygdala function across species and implicate an amygdalar contribution to both acquisition and extinction processes during associative emotional learning tasks.

Adolescent↗

Isometric and dynamic exercise studied with echo planar magnetic resonance imaging (MRI).

PURPOSE: The effect of different types of exercise upon echo planar (EP) magnetic resonance (MR) images was examined during and after both dynamic and isometric dorsi-flexion exercises at matched workloads and durations. METHODS: Healthy untrained subjects performed either dynamic exercise through a full range of motion and against a constant resistance or isometric exercise at the center of the range of motion and against a constant resistance at 25 or 70% their measured maximum voluntary contraction (MVC). EP MR images were acquired at 1.5 T every 4 s before (4 images), during (27 images), and after (29-65 images) exercise. A spin echo EP sequence was employed with TE = 30 ms, TR = 4000 ms, FOV = 20 x 40 cm, 64 x 128 matrix. The changes in proton transverse relaxation rate (deltaR2, [s(-1)]) relative to values obtained before exercise were calculated from individual images at different times during and after exercise. RESULTS: At both 70 and 25% of MVC, the maximum deltaR2 after dynamic exercise (-8.38+/-0.32 s(-1) (70%), -6.47+/-1.23s(-1) (25%)) was significantly greater (P < or = 0.05) than after isometric exercise (-5.91+/-0.67 s(-1) (70%), -3.80+/-0.87s(-1) (25%)). Throughout the period that recovery was monitored, the recovery patterns of deltaR2 following isometric and dynamic exercise at both workloads remained parallel. CONCLUSIONS: We conclude that exercise-induced changes in MR images are influenced not only by workload and exercise duration but also by the type of exercise, and we postulate that these differences result from the different physiological responses elicited by the different types of exercise.

Adult↗

Effect of muscle glycogen content on exercise-induced changes in muscle T2 times.

Effects of gastrocnemius glycogen (Gly) concentration on changes in transverse relaxation time (T2; ms) were studied after 5-min plantar flexion at 25% of maximum voluntary contraction (MVC). Gastrocnemius Gly, phosphorus metabolites, and T2 were measured in seven subjects by using interleaved 13C/31P magnetic resonance spectroscopy (MRS) at 4.7 T and magnetic resonance imaging (MRI; 1.5 T). After baseline MRS/MRI, subjects exercised for 5 min at 25% of MVC and were reexamined (MRS/MRI). Subjects then performed approximately 15 min of single-leg toe raises (50 +/- 2% of MVC), depleting gastrocnemius Gly by 43%. After a 1-h rest (for T2 return to baseline), subjects repeated the 5-min protocol, followed by a final MRI/MRS. After the initial 5-min protocol, T2 values increased by 5.9 +/- 0.8 ms (29.9 +/- 0.4 to 35.8 +/- 0.6 ms), whereas Gly did not change significantly (70.5 +/- 6.8 to 67.6 +/- 7.4 mM). After 15 min of toe raises, gastrocnemius Gly was reduced to 40.4 +/- 5.3 mM (P </= 0. 01), recovering to 45.8 +/- 5.3 mM (P </= 0.05) during a 1-h rest. After the second 5-min bout of plantar flexion (reduced Gly at 25% of MVC), T2 values increased by 5.0 +/- 0.8 ms (30.4 to 35.4 ms), whereas muscle Gly rose to 57.6 +/- 5.3 mM. We conclude that muscle Gly concentration per se does not affect exercise-induced T2 increases in the human gastrocnemius.

Adolescent↗

Dissociation of mnemonic and perceptual processes during spatial and nonspatial working memory using fMRI.

Neuroimaging studies in humans have consistently found robust activation of frontal, parietal, and temporal regions during working memory tasks. Whether these activations represent functional networks segregated by perceptual domain is still at issue. Two functional magnetic resonance imaging experiments were conducted, both of which used multiple-cycle, alternating task designs. Experiment 1 compared spatial and object working memory tasks to identify cortical regions differentially activated by these perceptual domains. Experiment 2 compared working memory and perceptual control tasks within each of the spatial and object domains to determine whether the regions identified in experiment 1 were driven primarily by the perceptual or mnemonic demands of the tasks, and to identify common brain regions activated by working memory in both perceptual domains. Domain-specific activation occurred in the inferior parietal cortex for spatial tasks, and in the inferior occipitotemporal cortex for object tasks, particularly in the left hemisphere. However, neither area was strongly influenced by task demands, being nearly equally activated by the working memory and perceptual control tasks. In contrast, activation of the dorsolateral prefrontal cortex and the intraparietal sulcus (IPS) was strongly task-related. Spatial working memory primarily activated the right middle frontal gyrus (MFG) and the IPS. Object working memory activated the MFG bilaterally, the left inferior frontal gyrus, and the IPS, particularly in the left hemisphere. Finally, activation of midline posterior regions, including the cingulate gyrus, occurred at the offset of the working memory tasks, particularly the shape task. These results support a prominent role of the prefrontal and parietal cortices in working memory, and indicate that spatial and object working memory tasks recruit differential hemispheric networks. The results also affirm the distinction between spatial and object perceptual processing in dorsal and ventral visual pathways.

Adult↗

Functional MR imaging of regional brain responses to pleasant and unpleasant odors.

BACKGROUND AND PURPOSE: Odors can elicit a range of behaviors and emotions. Our purpose was to identify regional activation of the human cerebral cortex in response to pleasant (positive hedonic value) and unpleasant (negative hedonic value) odors. METHODS: Thirteen neurologically normal adults underwent functional MR imaging of frontal and anterior temporal brain regions with a gradient-echo echo-planar technique. Eleven candidate regions of interest (ROIs) were identified on the first half of the data set based on t-map comparisons of signal intensities during administration of clementine (pleasant odor), isovaleric acid (unpleasant odor), and clear air (control odor). These ROIs were applied to the second half of the data set, and the number of voxels activated with the odorants was compared with the number of voxels activated during clear air trials, using independent t-tests. RESULTS: Clementine activated five cortical areas: Brodmann's area (BA) 8, BA 32 (lateralized to left), BA 46/9, BA 6 (lateralized to right), and the insula. Isovaleric acid activated four of the five regions without lateralization; no BA 8 activity was seen. Clementine produced more activity than isovaleric acid in the left insula, and isovaleric acid produced more activity than clementine in the left BA 6. No activation was detected in the orbitofrontal cortex or in the medial temporal lobes. Subjects rated clementine, isovaleric acid, and clear air as being pleasant, unpleasant, and neutral, respectively. CONCLUSION: Activation in frontal regions may represent brain processes linked to olfactory networks. There may be regional specialization based on odorant hedonic values.

Adult↗

Levels of categorization in visual recognition studied using functional magnetic resonance imaging.

BACKGROUND: Recent functional neuroimaging results implicate part of the ventral temporal lobe of the brain in face recognition, and have, together with neurophysiological findings, been used as evidence for a face-specific neural module in the brain. Experimental designs, however, have often failed to distinguish between the class of the object used as the stimulus (face or non-face) and the level of categorization at which the stimulus is recognized (the 'basic' level, such as 'bird', at which familiar objects are first recognized, or more subordinate levels - 'sparrow', for example - which require additional perceptual processing). We have used echo-planar functional magnetic resonance imaging to compare brain activation for the matching of non-face objects with subordinate-level and basic-level descriptors. RESULTS: The additional visual processing required to verify the subordinate level of a picture over its basic level was associated with activation of the fusiform and inferior temporal gyri (FIT) as well as the temporal poles. These areas correspond closely to those previously implicated in the processing of facial images. CONCLUSIONS: Our results indicate that areas of the ventral visual pathway that have been associated with face recognition are sensitive to manipulations of the categorization level of non-face objects. This idea offers an alternative to the dominant view that FIT may be organized according to conceptual categories, and our results establish the importance of manipulating task requirements when evaluating a 'neural module' hypothesis.

Brain Mapping↗

Three-dimensional visualization and measurement of conformal dose distributions using magnetic resonance imaging of BANG polymer gel dosimeters.

PURPOSE/OBJECTIVE: The measurement of complex dose distributions (those created by irradiation through multiple beams, multiple sources, or multiple source dwell positions) requires a dosimeter that can integrate the dose during a complete treatment. Integrating dosimeter devices generally are capable of measuring only dose at a point (ion chamber, diode, TLD) or in a plane (film). With increasing use of conformal dose distributions requiring shaped, noncoplanar beams, there will be an increased requirement for a dosimeter that can record and display a 3D dose distribution. The use of a 3D dosimeter will be required to confirm the accuracy of treatment plans produced by the current generation of 3D treatment-planning computers. METHODS AND MATERIALS: The use of a Fricke-infused gel and magnetic resonance imaging (MRI) to demonstrate the localization of stereotactic beams has been demonstrated (11). The recently developed BANG polymer gel dosimetry system (MGS Research, Inc., Guilford, CT), based on radiation-induced chain polymerization of acrylic monomers dispersed in a tissue-equivalent gel, surpasses the Fricke-gel method by providing accurate, quantitative dose distribution data that do not deteriorate with time (6, 9). The improved BANG2 formulation contains 3% N,N'-methylene-bisacrylamide, 3% acrylic acid, 1% sodium hydroxide, 5% gelatin, and 88% water, where all percentages are by weight. The gel was poured into volumetric flasks, of dimensions comparable to a human head. The gels were irradiated with complex beam arrangements, similar to those used for conformal radiation therapy. Images of the gels were acquired using a Siemens 1.5T imager and a Hahn spin-echo pulse sequence (90 degrees-tau-180 degrees-tau-acquire, for different values of tau). The images were transferred via network to a Macintosh computer for which a data analysis and display program was written. The program calculates R2 maps on the basis of multiple TE images, using a monoexponential nonlinear least-squares fit based on the Levenberg-Marquardt algorithm. The program also creates a dose-to-R2 calibration function by fitting a polynomial to a set of dose and R2 data points, obtained from gels irradiated in test tubes to known doses. This function can then be applied to any other R2 map, so that a dose map can be computed and displayed. RESULTS: Through exposure to known doses of radiation, the gel has been shown to respond linearly with dose in the range of 0 to 10 Gy, and its response is independent of the beam energy or modality. Dose distributions have been imaged in orthogonal planes, and can be displayed in a convenient form for comparison with isodose plans. The response of the gel is stable; the gel can be irradiated at any time after its manufacture, and imaging can be conducted any time following a brief interval after irradiation. CONCLUSION: The polymer gel dosimeter has been shown to be a valuable device for displaying three-dimensional dose distributions. The imaged dose distribution can be compared easily with calculated dose distributions, to validate a treatment planning system. In the future, gels may be prepared in anthropomorphic phantoms, to confirm unique patient dose distributions.

Gels↗

Reversible, reproducible reduction of brain water apparent diffusion coefficient by cortical electroshocks.

Rat brains were imaged after cortical electroshock pulse trains (1 ms pulses at 100 Hz) of varying durations (0.1-10 s), with diffusion-weighted echo planar imaging sequences at 2.0 T. The apparent water diffusion coefficient (ADC) decreased after either single or repeat electroshock trains. ADC reductions were observed within 6 s after the first shock. The size of the affected area of the brain increased in subsequent images during the 1st min after a 10-pulse (0.1 s) train, and also increased with the duration of electroshock trains. ADC reduction was reproducible in extent and time course after single 10-shock trains and was reversible. In the affected pixels the mean ADC reduction was 4% for a single shock train (0.1 s), and 7-8% for trains repeated once a minute, independent of electroshock train duration. The results indicate that neuronal activity associated with electrostimulation may be monitored with water diffusion measurements, and they may be useful for measuring the severity of seizure activity in patients with medically intractable epilepsy.

Animals↗