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Biomedical subjects

J C Gore

Publications and source records attributed to J C Gore.

At least 19 recordsLinked to original sources

Detection of radiation effects in polymer gel dosimeters using 129Xe NMR.

Polymer gel dosimeters consist of monomers, with or without cross-linking agents, dispersed in a gel. Upon exposure to ionizing radiation, polymerization proceeds within the gel matrix, thereby changing several measurable physical properties that can then be related quantitatively to absorbed dose. Several previous studies have examined how various nuclear magnetic resonance (NMR) properties, such as the relaxation rates of water protons, change with dose, and magnetic resonance imaging (MRI) has been used successfully to measure three-dimensional dose distributions in irradiated polymer gels. Here we report our first observations of the manner in which the chemical shift of xenon gas (129Xe) dissolved in a gel changes with absorbed dose, and we introduce the potential use of high resolution xenon NMR spectra for understanding better the dose response of gels. 129Xe possesses a large chemical shift range and xenon spectra are sensitive to subtle changes in the physical and chemical environments in which the gas is dissolved. For doses ranging from 0 Gy to 40 Gy we found that the mean chemical shift of 129Xe was linearly related to dose, and that the gel dosimeter could be described in terms of a two-component model undergoing fast exchange. We found no evidence of radiation damage to the gelatin matrix at doses between 0 Gy and 40 Gy. At 40 Gy, the fast-exchange model begins to break down, and distinct gelatin and poly(methacrylate) resonances are observed at higher doses. High resolution NMR measurements of xenon provide a novel method for probing radiation dose effects in irradiated polymer gels.

Dose-Response Relationship, Radiation↗

Differential anterior prefrontal activation during the recognition stage of a spatial working memory task.

Neuroimaging studies commonly show widespread activations in the prefrontal cortex during various forms of working memory and long-term memory tasks. However, the anterior prefrontal cortex (aPFC, Brodmann area 10) has been mainly associated with retrieval in episodic memory, and its role in working memory is less clear. We conducted an event-related functional magnetic resonance imaging study to examine brain activations in relation to recognition in a spatial delayed-recognition task. Similar to the results from previous findings, several frontal areas were strongly activated during the recognition phase of the task, including the aPFC, the lateral PFC and the anterior cingulate cortex. Although the aPFC was more active during the recognition phase, it was also active during the delay phase of the spatial working memory task. In addition, the aPFC showed greater activity in response to negative probes (non-targets) than to positive probes (targets). While our analyses focused on examining signal changes in the aPFC, other prefrontal regions showed similar effects and none of the areas were more active in response to the positive probes than to the negative probes. Our findings support the conclusion that the aPFC is involved in working memory and particularly in processes that distinguish target and non-target stimuli during recognition.

Adult↗

Tissue localization and regulation by juvenile hormone of human allergen Bla g 4 from the German cockroach, Blattella germanica (L.).

The German cockroach, Blattella germanica (L.), produces several potent protein aeroallergens, including Bla g 4, a approximately 20 kDa lipocalin. RT-PCR, Northern analyses and in situ hybridization showed that Bla g 4 is expressed only in the adult male reproductive system. Western blotting and ELISA with rBla g 4 antiserum detected immunoreactivity in the utricles and the conglobate gland, but not in other tissues of the male reproductive system. The Bla g 4 protein content of males increased from adult emergence to day 14, but during copulation Bla g 4 was depleted in the male and transferred to the female within the spermatophore. Topical application of juvenile hormone III stimulated Bla g 4 production by both conglobate gland and utricles.

Age Factors↗

Sustained mnemonic response in the human middle frontal gyrus during on-line storage of spatial memoranda.

The mapping of cognitive functions to neural systems is a central goal of cognitive neuroscience. On the basis of homology with lesion and physiological studies in nonhuman primates, Brodmann's area (BA) 46/9 in the middle frontal gyrus (MFG) has been proposed as the cortical focus for both the storage as well as processing components of working memory in the human brain, but the evidence on the segregation of these components and their exact areal localization has been inconsistent. In order to study this issue and increase the temporal resolution of functional mapping, we disambiguated the storage component of working memory from sensory and motor responses by employing functional magnetic resonance imaging (fMRI) in spatial delayed-response (DR) tasks with long delay intervals and different conditions of demand. We here show that BA 46 can support a sustained mnemonic response for as long as 24 sec in a high-demand task and the signal change in this area exceeded that in the other prefrontal areas examined. Our findings support a conservation of functional architecture between human and nonhuman primate in showing that the MFG is prominently engaged in the storage of spatial information.

Adult↗

Changes in rat cerebral blood volume due to modulation of the 5-HT(1A) receptor measured with susceptibility enhanced contrast MRI.

Brain blood volume changes in the rat in response to 5-HT(1A) agonist and antagonist administration were measured using susceptibility contrast enhanced magnetic resonance imaging (MRI). Administration of the 5-HT(1A) agonist 8-OH-DPAT resulted in decreases in fractional brain blood volumes. Administration of the 5-HT(1A) antagonist WAY-100635 following a dose of 8-OH-DPAT resulted in increases in fractional blood volumes greatest in hippocampus and cortex and smallest in thalamus and caudate-putamen. The magnitude of the regional increases in blood volumes paralleled the distribution of 5-HT(1A) receptors in the rat brain. Administration of WAY-100635 alone resulted in decreases in cortical blood volume and increases in cerebellar blood volume.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Regional brain and ventricular volumes in Tourette syndrome.

BACKGROUND: The pathophysiology of Tourette syndrome (TS) is thought to involve disturbances in cortico-striato-thalamo-cortical circuitry. The morphological characteristics of the cortical and associated white matter portions of these circuits have not been previously examined in TS subjects. METHODS: High-resolution anatomical magnetic resonance images were acquired in 155 TS and 131 healthy children and adults. The cerebrums and ventricles were isolated and then parcellated into subregions using standard anatomical landmarks. RESULTS: For analyses that included both children and adults, TS subjects were found to have larger volumes in dorsal prefrontal regions, larger volumes in parieto-occipital regions, and smaller inferior occipital volumes. Significant inverse associations of cerebral volumes with age were seen in TS subjects that were not seen in healthy controls. Sex differences in the parieto-occipital regions of healthy subjects were diminished in the TS group. The age-related findings were most prominent in TS children, whereas the diminished sex differences were most prominent in TS adults. Group differences in regional ventricular volumes were less prominent than in the cerebrum. Regional cerebral volumes were significantly associated with the severity of tic symptoms in orbitofrontal, midtemporal, and parieto-occipital regions. CONCLUSIONS: Broadly distributed cortical systems are involved in the pathophysiology of TS. Developmental processes, sexual dimorphisms, and compensatory responses in these cortical regions may help to modulate the course and severity of tic symptoms.

Adolescent↗

Dysprosium-bearing red cells as potential transverse relaxation agents for MRI.

The cytosol of intact human red blood cells was loaded with 28.1 +/- 3.4 mM of dysprosium DTPA-BMA using a hypoosmotic technique. When loaded cells were diluted with saline and control cells to give an average dysprosium concentration of 3.3 +/- 0.5 mM, the transverse relaxation rate constants R(*)(2) and R(2) increased. R(*)(2) increased from 7.5 +/- 0.9 sec(-1) to 356 +/- 50 sec(-1), and R(2) increased from 7.4 +/- 0.7 sec(-1) to 148 +/- 40 sec(-1). After lysing, R(*)(2) was 6.0 +/- 0.6 sec(-1) in the control and 13.4 +/- 1.5 sec(-1) in the mixture; R(2) was 6.4 +/- 1.1 sec(-1) and 9.8 +/- 2.4 sec(-1), respectively. Thus, the relaxivity effects were enhanced by sequestration of the dysprosium within intact red cells, and this effect was lost after lysis. At a circulating whole-blood concentration of 0.81 +/- 0.15 mM in rats, the liver signal intensity dropped 29.9% +/- 3.7% and kidney signal intensity dropped 19.4% +/- 8.7%. Dysprosium-loaded cells might be useful in the study of perfusion and tissue blood volume.

Animals↗

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↗

Neonatal auditory activation detected by functional magnetic resonance imaging.

The objective of this study was to detect auditory cortical activation in non-sedated neonates employing functional magnetic resonance imaging (fMRI). Using echo-planar functional brain imaging, subjects were presented with a frequency-modulated pure tone; the BOLD signal response was mapped in 5 mm-thick slices running parallel to the superior temporal gyrus. Twenty healthy neonates (13 term, 7 preterm) at term and 4 adult control subjects. Blood oxygen level-dependent (BOLD) signal in response to auditory stimulus was detected in all 4 adults and in 14 of the 20 neonates. FMRI studies of adult subjects demonstrated increased signal in the superior temporal regions during auditory stimulation. In contrast, signal decreases were detected during auditory stimulation in 9 of 14 newborns with BOLD response. fMRI can be used to detect brain activation with auditory stimulation in human infants.

Acoustic Stimulation↗

Mutual information analysis of the EEG in patients with Alzheimer's disease.

OBJECTIVE: Mutual information provides a measure of both the linear and nonlinear statistical dependencies between two time series. Cross-mutual information (CMI) is used to quantify the information transmitted from one time series to another, while auto mutual information (AMI) in a time series estimates how much on average the value of the time series can be predicted from values of the time series at preceding points. The aim of this study is to assess information transmission between different cortical areas in Alzheimer's disease (AD) patients by estimating the average CMI between EEG electrodes. METHODS: We recorded the EEG from 16 scale electrodes in 15 AD patients and 15 age-matched normal controls, and estimated the local, distant, and interhemispheric CMIs of the EEG in both groups. The rate of decrease (with increasing delay) of the AMI of the EEG was also measured to evaluate the complexity of the EEG in AD patients. RESULTS: The local CMI in AD subjects was lower than that in normal controls, especially over frontal and antero-temporal regions. A prominent decrease in information transmission between distant electrodes in the right hemisphere and between corresponding interhemispheric electrodes was detected in the AD patients. In addition, the AMIs throughout the cerebrums of the AD patients decreased significantly more slowly with delay than did the AMIs of normal controls. CONCLUSIONS: These results are consistent with previous findings that suggest the association of EEG abnormalities in AD patients with functional impairment of information transmission in long cortico-cortical connections.

Aged↗

Activation of the left amygdala to a cognitive representation of fear.

We examined the neural substrates involved when subjects encountered an event linked verbally, but not experientially, to an aversive outcome. This instructed fear task models a primary way humans learn about the emotional nature of events. Subjects were told that one stimulus (threat) represents an aversive event (a shock may be given), whereas another (safe) represents safety (no shock will be given). Using functional magnetic resonance imaging (fMRI), activation of the left amygdala was observed in response to threat versus safe conditions, which correlated with the expression of the fear response as measured by skin conductance. Additional activation observed in the insular cortex is proposed to be involved in conveying a cortical representation of fear to the amygdala. These results suggest that the neural substrates that support conditioned fear across species have a similar but somewhat different role in more abstract representations of fear in humans.

Amygdala↗

Polymer gels for magnetic resonance imaging of radiation dose distributions at normal room atmosphere.

Polymer gels whose NMR and optical properties change when irradiated offer unique advantages for measuring radiation dose distributions. To date, all acrylic polymer gel dosimeters must be manufactured, stored and irradiated in hypoxic conditions which severely limits their use and stability. A new formulation of acrylic dosimeter gel has been developed that responds well in normal atmosphere and which we have named MAGIC (Methacrylic and Ascorbic acid in Gelatin Initiated by Copper). To produce dosimeter gels, an aqueous solution of gelatin, open to the atmosphere, is mixed with methacrylic acid, copper(II) ions, ascorbic acid and hydroquinone. It is believed that the copper(II) and ascorbic acid form a complex with oxygen which (with radiolysis of water) serves as a free radical source for the initiation of the polymerization of methacrylic acid. At room air the water proton spin relaxation rate R2 in MAGIC gels is proportional to absorbed dose though the precise relationship depends on the composition of the gel and the initiating complex. For example, in the range 0-30 Gy the slope of the response of R2 versus dose at 20 MHz was 0.300, 0.519 and 0.681 s(-1) Gy(-1), respectively, when the concentration of MAA was 3, 6 and 9%. The slopes increased to 0.310, 0.567 and 0.868 s(-1) Gy(-1) at 85 MHz. An important determinant of the sensitivity to detect small dose changes is shown to be the slope-to-intercept ratio of the dose-response curve. These varied from 0.08 to 0.17, comparable to hypoxic gels described earlier. MAGIC gels can be manufactured and used much more easily than the previous formulations and can be imaged by magnetic resonance imaging or optical scanning, and thus they will likely be of considerable interest to radiation physicists.

Ascorbic Acid↗

Respiratory effects in human functional magnetic resonance imaging due to bulk susceptibility changes.

Functional magnetic resonance imaging relies on detecting small changes in the signal in the presence of noise from various sources. It has been shown that periodic variations in the signal at the respiratory frequency occur in the brain and various techniques have been proposed to remove them. However, the precise mechanism by which respiration affects the fMRI signal has not yet been proven. Here, we explore the nature of respiratory signal variations and the artefacts they produce in brain images. Our results demonstrate conclusively that bulk susceptibility variations in the lungs during respiration cause variations in the static magnetic field within the brain tissue. These variations in field strength and homogeneity lead to a shift of the image and a shading of image intensity in the phase encoding direction. These artefacts, if left uncorrected, may lead to the production of spurious activations and/or decreased statistical significance of true activations in fMRI. In addition, these results suggest that respiration effects may not necessarily be well characterized as simple additive noise and that an alternative model based on the physical origins of susceptibility variations may be more appropriate.

Brain↗

Studies of magnetization transfer and relaxation in irradiated polymer gels--interpretation of MRI-based dosimetry.

Magnetization transfer and NMR relaxation rates were measured for water protons in two types of polymer gels developed for radiation dosimetry with MRI in order to quantify the contributions of different relaxation processes to the radiation response in such gels. Measurements included the rate of magnetization transfer between proton pools and the ratio of the sizes of exchanging pools, R1 and R2. A model of relaxation in irradiated gels is presented to explain their properties. The model incorporates three proton pools: free water, macromolecular and interfacial. Two pools are insufficient to model the data. In these systems, radiation-induced polymerization appears to increase the size of a solid-like macromolecular proton pool but does not affect the rate constant of magnetization transfer per proton from macromolecular protons to the free water protons. The relation between R1 and the pool size ratio is consistent with free water exchanging with a macromolecular pool with an R1 of approximately 8 Hz. In addition, the rate of magnetization transfer is not limited by the rate of chemical exchange between the free water and the interfacial protons, and magnetization transfer most probably occurs via labile proton exchange rather than via bound water molecules.

Acrylamide↗

Hemispheric dominance of cortical activity evoked by focal electrogustatory stimuli.

Functional magnetic resonance imaging was used to observe cortical hemodynamic responses to electric taste stimuli applied separately to the right and left sides of the tongue tip. In 11 right-handed normal adults activation occurred primarily in the insular cortex, superior temporal lobe, inferior frontal lobe, including premotor regions, and in inferior parts of the postcentral gyrus. Unexpectedly, the location and laterality of activation were largely identical regardless of the side of the tongue stimulated. Activation in the superior insula, the presumed location of primary gustatory cortex, was predominantly, but not exclusively, in the right hemisphere, whereas central (more inferior) insular activations were more evenly bilateral. Right hemispheric dominance of activation also occurred in premotor regions (Brodmann areas 6 and 44), whereas left hemispheric dominance occurred only in the superior temporal cortex (Brodmann areas 22/42). The electric taste-evoked hemodynamic response pattern was more consistent with activation of the gustatory system than activation of somatosensory systems. The results suggest that the sites for cortical processing of electric taste information are dependent on hemispheric specialization.

Adult↗

Functional magnetic resonance imaging of cocaine craving.

OBJECTIVE: Identification of brain activity associated with craving is important for understanding the neurobiology of addiction. METHOD: Brain activity was measured in cocaine addicts and healthy subjects by functional magnetic resonance imaging (fMRI) while the subjects watched videotapes designed to elicit happy feelings, sad feelings, or the desire to use cocaine. The subjects indicated the onset of drug craving or emotional response, allowing comparison of groups before and after such feelings. RESULTS: Robust activation of the anterior cingulate was evident in patients watching cocaine-cue tapes but not in patients watching happy or sad tapes or in healthy subjects under any condition. Anterior cingulate activation preceded the reported onset of craving and was evident in patients who did not report craving. In contrast, patients showed less activation than healthy subjects during the cocaine-cue tapes in areas of the frontal lobes. After the reported onset of craving, cocaine-dependent subjects showed greater activity than healthy subjects in regions that are more active in healthy subjects when they watch sad tapes than when they watch happy tapes, suggesting a physiologic link between cocaine-cue responses and normal dysphoric states. Dynamic aspects of regional brain activations, but not the location of activations, were abnormal in cocaine-dependent subjects watching sad tapes, suggesting more general affective dysregulation. Patients showed low activation of sensory areas during initial viewing of all videotapes, suggesting generalized alteration in neuroresponsiveness. CONCLUSIONS: Cocaine cues lead to abnormally high cingulate and low frontal lobe activation in cocaine addicts. Addicts also show more general abnormalities in affect-related brain activation.

Adult↗

Functional MR imaging of regional brain activation associated with the affective experience of pain.

OBJECTIVE: Current models propose that the experience of pain includes both sensory and affective components. Our purpose was to use functional MR imaging to determine areas of the brain engaged by the affective dimension of pain. SUBJECTS AND METHODS: Twelve healthy adults underwent functional MR imaging using a gradient-echo echoplanar technique while a cold pressor test, consisting of cold and pain tasks, was applied first to one foot and then to the other. The cold task involved the application of cold water (14-20 degrees C) that was not at a painful level. For the pain task, the water temperature was then lowered to a painful temperature (8-14 degrees C) and subsequently to the pain threshold (3-8 degrees C). Images acquired at room temperature before the cold and pain tasks served as a baseline task. Composite maps of brain activation were generated by comparing the baseline task with the cold task and the cold task with the pain task. The significance of signal changes was estimated by randomization of individual activation maps. RESULTS: Cold-related activation (p < 0.01) was found in the postcentral gyrus bilaterally, laterally, and inferiorly to the primary motor-sensory area of the foot and at a site near the second somatosensory site. Activation also occurred in the frontal lobe (the bilateral middle frontal gyri and the right inferior frontal gyrus), the left anterior insula, the left thalamus, and the superior aspect of the anterior cingulate gyrus (seen at one slice location). Pain-related activation (p < 0.01) included the anterior cingulate gyrus (seen at four slice locations); the superior frontal gyrus, especially on the right; and the right cuneus. CONCLUSION: Compared with the basic sensory processing of pain, the affective dimension of pain activates a cortical network that includes the right superior frontal gyrus, the right cuneus, and a large area of the anterior cingulate gyrus.

Adult↗

Automated measurement of latent morphological features in the human corpus callosum.

Our objective was to develop a novel factor-based analysis of the morphology of the corpus callosum and assess its applicability to the study of normal development, intelligence, and other subject characteristics. The contour of the corpus callosum was defined in the midsagittal planes of the MRI scans of 325 subjects, 6 to 88 years of age. The contours were coregistered, rescaled, and resampled to 50 points that were then entered into a principal components analysis with varimax rotation. The analysis yielded 8 factors for the contours of 138 healthy subjects. A second analysis of contours from 187 subjects in a patient group extracted 8 similar factors. Correlations of factor scores with conventional measures of callosum shape supported the construct validity of the assignment of morphological features to each of the factors. Correlations of factor scores with age, sex, handedness, ventricular volume, and IQ demonstrated the predictive validity of the factor structure and helped to define the neural correlates of these subject characteristics. We conclude that factor-based measures capture latent morphological features of the corpus callosum that are reliable and valid. Future studies will determine whether these novel measures are more closely related to neurobiologically important features of the corpus than are conventional measures of callosum size and shape.

Adolescent↗