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John C Gore

Publications and source records attributed to John C Gore.

At least 19 recordsLinked to original sources

Hypoglycemia reduces the blood-oxygenation level dependent signal in primary auditory and visual cortex: a functional magnetic resonance imaging study.

Studies of the effects of hypoglycemia on the brain using neurocognitive testing have suggested that mainly complex functions subserved by secondary and tertiary cortex are affected by mild to moderate hypoglycemia and that intensively treated patients with Type I diabetes mellitus (T1DM) may have altered sensitivity to the central nervous system effects of hypoglycemia. Functional magnetic resonance imaging provides a sensitive, regionally-specific probe of possible neurophysiologic changes related to hypoglycemia in the brain. Eleven intensively-treated T1DM patients and 11 matched non-diabetic controls took part in a 2-day protocol in which functional magnetic resonance imaging (MRI) was used to measure changes in the patterns of brain activation produced by simple auditory and visual stimuli in different conditions. On one day, participants were euglycemic the entire time. On the other day, an initial 50-min euglycemic period was followed by a 50-min hypoglycemic period. Results indicated that hypoglycemia reduced the amplitude of the blood-oxygenation level dependent response in primary auditory and visual cortex to simple auditory and visual stimuli. The latency and duration of the transient hemodynamic response function were not affected. Responses to hypoglycemia were similar in diabetic and non-diabetic participants. These results suggest that mild to moderate hypoglycemia may alter the balance of blood flow and oxygen extraction when glucose levels are lowered. Intensively-treated T1DM, with its attendant frequent hypoglycemic episodes, did not seem to alter hypoglycemic responses in primary visual and auditory cortex.

Acoustic Stimulation↗

Task demand modulation of steady-state functional connectivity to primary motor cortex.

Correlations in blood oxygen level-dependent (BOLD) MRI signals from separate areas within the human brain have been used as a measure of functional connectivity. Steady-state measures of interregional correlations are particularly useful because they do not depend on the specific design of a task nor on subtracting conditions in a blocked design task. However, the conditions under which such correlations are measured may influence these indices of functional connectivity. The aim of this study was to investigate the influence of task demand on interregional correlations within the motor system. Specifically, tapping rates in audibly paced finger-tapping tasks were controlled and varied between runs in order to observe their effects on interregional correlations to contralateral primary motor cortex (PM). Regions of interest included the supplementary motor area, ipsilateral cerebellum, ipsilateral auditory cortex, and a control region. It was found that tapping rate was a significant factor in determining the mean correlation of some regions to PM, and that correlations measured during tapping in general increased relative to resting state. Furthermore, analysis of the percent of voxels in each region significantly correlated to PM suggested that changes in the mean correlation of that region to PM could be accounted for by changes in the fraction of significantly correlated voxels within a region. This provides insight into the manner in which steady-state correlations are modified in response to different task demands and further evidence that low-frequency fluctuations in BOLD signals reflect functional connectivity.

Acoustic Stimulation↗

Brain connectivity related to working memory performance.

Several brain areas show signal decreases during many different cognitive tasks in functional imaging studies, including the posterior cingulate cortex (PCC) and a medial frontal region incorporating portions of the medial frontal gyrus and ventral anterior cingulate cortex (MFG/vACC). It has been suggested that these areas are components in a default mode network that is engaged during rest and disengaged during cognitive tasks. This study investigated the functional connectivity between the PCC and MFG/vACC during a working memory task and at rest by examining temporal correlations in magnetic resonance signal levels between the regions. The two regions were functionally connected in both conditions. In addition, performance on the working memory task was positively correlated with the strength of this functional connection not only during the working memory task, but also at rest. Thus, it appears these regions are components of a network that may facilitate or monitor cognitive performance, rather than becoming disengaged during cognitive tasks. In addition, these data raise the possibility that the individual differences in coupling strength between these two regions at rest predict differences in cognitive abilities important for this working memory task.

Adult↗

5-Hydroxytryptamine2C receptor contribution to m-chlorophenylpiperazine and N-methyl-beta-carboline-3-carboxamide-induced anxiety-like behavior and limbic brain activation.

Activation of 5-hydroxytryptamine2C (5-HT(2C)) receptors by the 5-HT(2) receptor agonist m-chlorophenylpiperazine (m-CPP) elicits anxiety in humans and anxiety-like behavior in animals. We compared the effects of m-CPP with the anxiogenic GABA(A) receptor inverse agonist N-methyl-beta-carboline-3-carboxamide (FG-7142) on both anxiety-like behavior and regional brain activation using functional magnetic resonance imaging (fMRI) in the rat. We also determined whether the selective 5-HT(2C) receptor antagonist SB 242084 [6-chloro-2,3-dihydro-5-methyl-N-[6-[(2-methyl-3-pyridinyl)oxy]-3-pyridinyl]-1H-indole-1-carboxyamide dihydrochloride] would blunt m-CPP or FG-7142-induced neuronal activation. Both m-CPP (3 mg/kg i.p.) and FG-7142 (10 mg/kg i.p.) elicited anxiety-like behavior when measured in the social interaction test, and pretreatment with SB 242084 (1 mg/kg i.p.) completely blocked the behavioral effects of both anxiogenic drugs. Regional brain activation in vivo in response to anxiogenic drug challenge was determined by blood oxygen level-dependent (BOLD) fMRI using a powerful 9.4T magnet. Region of interest analyses revealed that m-CPP and FG-7142 significantly increased BOLD signals in brain regions that have been linked to anxiety, including the amygdala, dorsal hippocampus, and medial hypothalamus. These BOLD signal increases were blocked by pretreatment with SB 242084. In contrast, injection of m-CPP and FG-7142 resulted in BOLD signal decreases in the medial prefrontal cortex that were not blocked by SB 242084. In conclusion, the brain activation signals produced by anxiogenic doses of both m-CPP and FG-7142 are mediated at least partially by the 5-HT(2C) receptor, indicating that this receptor is a key component in anxiogenic neural circuitry.

Aminopyridines↗

Integration of quantitative DCE-MRI and ADC mapping to monitor treatment response in human breast cancer: initial results.

PURPOSE: The objective of this study was to assess changes in the water apparent diffusion coefficient (ADC) and in pharmacokinetic parameters obtained from the fast-exchange regime (FXR) modeling of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) during neoadjuvant chemotherapy in breast cancer. MATERIALS AND METHODS: Eleven patients with locally advanced breast cancer underwent MRI examination prior to and after chemotherapy but prior to surgery. A 1.5-T scanner was used to obtain T1, ADC and DCE-MRI data. DCE-MRI data were analyzed by the FXR model returning estimates of K(trans) (volume transfer constant), v(e) (extravascular extracellular volume fraction) and tau(i) (average intracellular water lifetime). Histogram and correlation analyses assessed parameter changes post-treatment. RESULTS: Significant (P < .05) changes or trends towards significance (P < .10) were seen in all parameters except tau(i), although there was qualitative reduction in tau(i) values post-treatment. In particular, there was reduction (P < .035) in voxels with K(trans) values in the range 0.2-0.5 min(-1) and a decrease (P < .05) in voxels with ADC values in the range 0.99 x 10(-3) to 1.35 x 10(-3) mm2/s. ADC and v(e) were negatively correlated (r = -.60, P < .02). Parameters sensitive to water distribution and geometry (T(1), v(e), tau(i) and ADC) correlated with a multivariable linear regression model. CONCLUSION: The analysis presented here is sensitive to longitudinal changes in breast tumor status; K(trans) and ADC are most sensitive to these changes. Relationships between parameters provide information on water distribution and geometry in the tumor environment.

Antineoplastic Agents↗

Measurement of thermal diffusivity by magnetic resonance imaging.

Nuclear magnetic resonance (NMR) may be used for monitoring temperature changes within samples based on measurements of relaxation times, the diffusion coefficient of liquids, proton resonance frequency or phase shifts. Such methods may be extended to the explicit measurement of the thermal diffusivity of materials by NMR imaging. A method based on measuring nuclear spin phase shifts or changes in the equilibrium nuclear magnetization has been developed for measuring transient thermal diffusion effects and thermal diffusivity with potential applications in NMR thermotherapy and materials science. In this method, a thermal pulse is applied to a medium, and the resultant temporal variations of the nuclear spin phase or of the magnitude of the nuclear magnetization produced by the thermal pulse are monitored at a spatial distance. The results obtained on common fluids agree well with the data from other methods.

Diffusion↗

Effects of hypoglycemia on human brain activation measured with fMRI.

Functional magnetic resonance imaging (fMRI) was used to measure the effects of acute hypoglycemia caused by passive sensory stimulation on brain activation. Visual stimulation was used to generate blood-oxygen-level-dependent (BOLD) contrast, which was monitored during hyperinsulinemic hypoglycemic and euglycemic clamp studies. Hypoglycemia (50 +/- 1 mg glucose/dl) decreased the fMRI signal relative to euglycemia in 10 healthy human subjects: the fractional signal change was reduced by 28 +/- 12% (P < .05). These changes were reversed when euglycemia was restored. These data provide a basis of comparison for studies that quantify hypoglycemia-related changes in fMRI activity during cognitive tasks based on visual stimuli and demonstrate that variations in blood glucose levels may modulate BOLD signals in the healthy brain.

Adult↗

The use of magnetic resonance imaging (MRI) in the study of manganese neurotoxicity.

Manganese (Mn), an element found in many foods, is an important and essential nutrient for proper health and maintenance. It is toxic in high doses, however, and exposure to excessive levels can result in the onset of a neurological disorder similar to, but distinct from, Parkinson's disease. Historically, Mn neurotoxicity was most commonly associated with various occupations, such as Mn mining, welding and steel production. More recently, increases in both blood and brain Mn levels have been observed in persons with liver disease or those receiving prolonged parenteral nutrition. Additionally, rodent data suggest that iron deficiency and anemia may be risk factors for Mn neurotoxicity. Clinically, brain Mn accumulation can be monitored in vivo using non-invasive magnetic resonance imaging (MRI) due to the paramagnetic nature of this element. Indeed, MRI has been used in a variety of settings to evaluate the brain Mn deposition in various populations. This review focuses on the use of MRI technology in studies related specifically to Mn neurotoxicity. Thus, we will examine reports using MRI to confirm brain Mn accumulation in human populations, and conclude with data from non-human primate and rodent models of Mn neurotoxicity.

Animals↗

Integration of fMRI, NIROT and ERP for studies of human brain function.

Different methods of assessing human brain function possess specific advantages and disadvantages compared to others, but it is believed that combining different approaches will provide greater information than can be obtained from each alone. For example, functional magnetic resonance imaging (fMRI) has good spatial resolution but poor temporal resolution, whereas the converse is true for electrophysiological recordings (event-related potentials or ERPs). In this review of recent work, we highlight a novel approach to combining these modalities in a manner designed to increase information on the origins and locations of the generators of specific ERPs and the relationship between fMRI and ERP signals. Near infrared imaging techniques have also been studied as alternatives to fMRI and can be readily integrated with simultaneous electrophysiological recordings. Each of these modalities may in principle be also used in so-called steady-state acquisitions in which the correlational structure of signals from the brain may be analyzed to provide new insights into brain function.

Brain↗

Improved fiber tractography with Bayesian tensor regularization.

Diffusion tensor tractography suffers from the effects of noise and partial volume averaging (PVA). For reliable reconstruction of fiber pathways, tracking algorithms that are robust to these artifacts are called for. To meet this need, the present study establishes a novel Bayesian regularization framework for fiber tracking that takes into account the effects of noise and PVA, thereby improving tracking accuracy and precision. With this framework, the propagation of a fiber path follows an optimal vector determined by Bayes decision rule; the probability functions involved are modeled on the basis of multivariate normal distributions of diffusion tensor elements, which allows the optimal solution with maximum a posteriori probability to be derived analytically. Parameters for the probability functions are estimated from the uncertainty of tensor elements and the variance among tensors within an oriented sampling volume weighted by fractional anisotropy. Experiments with Monte Carlo simulations, synthetic, and in vivo human diffusion tensor data demonstrate that this specialized scheme enhances the immunity of fiber tracking to noise and PVA, and hence enables fibers to be more faithfully reconstructed.

Adult↗

Connectivity-behavior analysis reveals that functional connectivity between left BA39 and Broca's area varies with reading ability.

Correlations between temporal fluctuations in MRI signals may reveal functional connectivity between brain regions within individual subjects. Such correlations would be especially useful indices of functional connectivity if they covary with behavioral performance or other subject variables. This study investigated whether such a relationship could be demonstrated in the context of the reading circuit in the brain. The method proved sufficiently powerful to reveal significant correlations between the reading abilities of subjects and the strength of their functional connection between left Brodmann's area 39 and Broca's area during reading. This suggests that the disconnection of the angular gyrus previously reported for dyslexic readers is part of a larger continuum in which poor (but nonimpaired readers) also show reduced connectivity to the region. In addition, it illustrates the potential power of paradigms that examine correlations between behavior and functional brain connections.

Adult↗

Repeatability of a reference region model for analysis of murine DCE-MRI data at 7T.

PURPOSE: To test the repeatability of a reference region (RR) model for the analysis of dynamic contrast-enhanced MRI (DCE-MRI) in a mouse model of cancer at high field. MATERIALS AND METHODS: Seven mice were injected with 10(6) 4T1 mammary carcinoma cells and imaged eight to 10 days later on a Varian 7.0T scanner. Two DCE-MRI studies were performed for each mouse (separated by 2.5 hours). The RR model was used to analyze the data, and returned estimates on the perfusion-permeability index (Ktrans) for the RR and the tissue of interest (TOI), as well as the extravascular extracellular volume fraction (ve) for the TOI. RESULTS: When the first injection was compared with the second injection, all parameters tested were highly correlated (r2=0.90, 0.62, 0.82 for the RR Ktrans, TOI Ktrans, and TOI ve, respectively, with P<0.001 for all). To observe a statistically significant change (at the 5% level) in a treatment study with seven animals in each group, log10 changes of 0.084 and 0.077 in the tumor Ktrans and ve, respectively, are required. CONCLUSION: If a reliable arterial input function (AIF) is unavailable, the RR model is a reasonable alternative to measuring MRI contrast-agent (CA) kinetics in mouse models of cancer at high field.

Algorithms↗

Temporal diffusion spectroscopy: theory and implementation in restricted systems using oscillating gradients.

The theory of temporal diffusion spectra is reviewed. In contrast to q-space spectroscopy, which measures the displacement spectrum of spins in a spatial domain, the spectral density of the velocity correlation function (VCF) in the temporal domain is considered. It is demonstrated that casting diffusion in this domain may facilitate measurements of microscopic geometry and the decomposition of the diffusion signal into components due to disperse flow and restricted diffusion. An oscillating gradient (OG) method of diffusion spectroscopy was developed and implemented. Microscopic pore sizes, surface-to-volume ratios (S/Vs), and diffusion path tortuosities were extracted from model systems using this method. Cases are discussed in which this type of experiment may allow the characterization of pore geometry when spatial domain experiments fail. OGs may be combined with imaging sequences to map complex patterns of diffusion and flow. Moreover, scalar apparent diffusion coefficient (ADC) measurements in complex biological systems may be subtly dependent on specific pulse sequence parameters. Thus, scalar ADC measurements using gradient pulses with different frequency spectra may give different results. Conversely, the frequency dependence of motion-sensitizing gradient pulses may be exploited to deduce the origin of ADC changes.

Diffusion Magnetic Resonance Imaging↗

Correlation between estimates of tumor perfusion from microbubble contrast-enhanced sonography and dynamic contrast-enhanced magnetic resonance imaging.

OBJECTIVE: We compared measurements of tumor perfusion from microbubble contrast-enhanced sonography (MCES) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in an animal tumor model. METHODS: Seven mice were implanted with Lewis lung carcinoma cells on their hind limbs and imaged 14 days later with a Philips 5- to 7-MHz sonography system (Philips Medical Systems, Andover, MA) and a Varian 7.0-T MRI system (Varian, Inc, Palo Alto, CA). For sonographic imaging 100 microL of a perfluoropropane microbubble contrast agent (Definity; Bristol-Myers Squibb Medical Imaging, Billerica, MA) was injected and allowed to reach a pseudo steady state, after which a high-mechanical index pulse was delivered to destroy the microbubbles within the field of view, and the replenishment of the microbubbles was imaged for 30 to 60 seconds. The MRI included acquisition of a T(10) map and 35 serial T(1)-weighted images (repetition time, 100 milliseconds; echo time, 3.1 milliseconds; alpha, 30 degrees ) after the injection of 100 microL of 0.2-mmol/kg gadopentetate dimeglumine (Magnevist; Berlex, Wayne, NJ). Region-of-interest and voxel-by-voxel analyses of both data sets were performed; microbubble contrast-enhanced sonography returned estimates of microvessel cross-sectional area, microbubble velocity, and mean blood flow, whereas DCE-MRI returned estimates of a perfusion-permeability index and the extravascular extracellular volume fraction. RESULTS: Comparing similar regions of tumor tissue seen on sonography and MRI, region-of-interest analyses revealed a strong (r(2) = 0.57) and significant relationship (P < .002) between the estimates of perfusion obtained by the two modalities. CONCLUSIONS: Microbubble contrast-enhanced sonography can effectively depict intratumoral heterogeneity in preclinical xenograft models when voxel-by-voxel analysis is performed, and this analysis correlates with similar DCE-MRI measurements.

Animals↗

Preliminary evidence for medication effects on functional abnormalities in the amygdala and anterior cingulate in bipolar disorder.

RATIONALE: Abnormal amygdala and frontocortical responses to emotional stimuli are implicated in bipolar disorder (BD) and have been proposed as potential treatment targets. OBJECTIVES: The aim of this study was to investigate amygdala and frontocortical responses to emotional face stimuli in BD and the influences of mood-stabilizing medications on these responses. METHODS: Functional magnetic resonance imaging was performed while 17 BD participants (5 unmedicated) and 17 healthy comparison (HC) participants viewed faces with happy, sad, fearful, or neutral expressions. RESULTS: The group by stimulus-condition interaction was significant (p<0.01) for amygdala activation, with the greatest effects in the happy face condition. Relative to HC, amygdala increases were greater in unmedicated BD, but lower in medicated BD. Rostral anterior cingulate (rAC) activation was decreased in unmedicated BD compared to HC; however, BD participants taking medication demonstrated rAC activation similar to HC participants. CONCLUSIONS: Although the sample sizes were small, these preliminary results suggest that BD is associated with increased amygdala and decreased rAC response to emotional faces. The findings also provide preliminary evidence that mood-stabilizing medications may reverse abnormalities in BD in the response of an amygdala-frontal neural system to emotional stimuli.

Adult↗

Simultaneous measurement of D and T2 using the distant dipolar field.

The presence of long-range dipolar fields in liquids is known to introduce a non-linear term in the Bloch-Torrey equations which is responsible for many interesting effects in nuclear magnetic resonance as well as in magnetic resonance imaging. We show here, for the first time, that the diffusion coefficient D and the spin-spin relaxation time T2 can be obtained simultaneously from the time evolution profile of the long-range dipolar field refocused signal. In a COSY Revamped by Z-asymmetric Echo Detection sequence, the analytical first-order approximation solution of the Bloch-Torrey equations modified to include the effect of the distant dipolar field is used to demonstrate the technique in an experiment using doped water.

Diffusion↗

Absolute pitch: music and beyond.

"Perfect pitch," known in the scientific literature as "absolute pitch" (AP), is a rare phenomenon that has fascinated musicians and scientists alike for over a century. There has been a great deal of conflict in the literature between advocates of the two main theories on the etiology of AP: some believe that AP is learned early in life through intensive musical training, whereas others believe AP to be largely innate. Both theories are alike, however, in considering AP to be exclusively a musical phenomenon. We propose a paradigm shift by presenting here a new model of AP, one that is predicated on two principles: (1) that AP may be relatively independent of musical experience; and (2) that there are different types of AP, each of which can be ascribed to discrete neurobiological mechanisms. We also review data from a diverse series of experiments that were designed to test explicitly both the predictions of our model and a series of historical myths about AP. In each case, the data strongly support our model. We conclude with a general discussion on the nature of AP, the relevance of these findings for other areas of research, and future directions of study.

Acoustic Stimulation↗

Reduction of noise in diffusion tensor images using anisotropic smoothing.

To improve the accuracy of tissue structural and architectural characterization with diffusion tensor imaging, a novel smoothing technique is developed for reducing noise in diffusion tensor images. The technique extends the traditional anisotropic diffusion filtering method by allowing isotropic smoothing within homogeneous regions and anisotropic smoothing along structure boundaries. This is particularly useful for smoothing diffusion tensor images in which direction information contained in the tensor needs to be restored following noise corruption and preserved around tissue boundaries. The effectiveness of this technique is quantitatively studied with experiments on simulated and human in vivo diffusion tensor data. Illustrative results demonstrate that the anisotropic smoothing technique developed can significantly reduce the impact of noise on the direction as well as anisotropy measures of the diffusion tensor images.

Algorithms↗