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K Ugurbil

Publications and source records attributed to K Ugurbil.

At least 55 records · Page 3Linked to original sources

Human hippocampal long-term sustained response during word memory processing.

Temporal behavior of activation associated with the neural substrate of human memory function was investigated during and after an auditorily instructed word memory task using multislice functional magnetic resonance imaging. The hippocampal formation, which is involved in human memory function, displayed a long-term sustained response that persisted significantly (approximately 90 s) beyond the duration of the memory task. This sustained period was approximately two-fold longer than the duration of the post-task activation observed in auditory areas and Broca's area, which are involved in the phonological loop of the verbal working memory. These observations suggest that the hippocampal memory processing involves sustained activation in the transitional function for the long-term memory over the working memory period.

Adult↗

Mapping of lateral geniculate nucleus activation during visual stimulation in human brain using fMRI.

Functional magnetic resonance imaging has been successfully used to map the activation in the lateral geniculate nucleus (LGN) in both hemispheres as well as the primary visual cortex (V1) during a checkerboard visual stimulation. The average blood oxygenation level dependent (BOLD) change in LGN was less than that in V1. However, the BOLD temporal responses were similar between LGN and V1. The activation in the pulvinar nucleus during visual perception was also detected, and its activated location could be separated from LGN in 3D images. The LGN activation between intersubject and intrasubject multiple trials was compared. The results demonstrate that fMRI can reliably and robustly detect small subcortical nucleus activation in the human brain.

Adult↗

Spatial and temporal differentiation of fMRI BOLD response in primary visual cortex of human brain during sustained visual simulation.

The blood oxygenation level dependent (BOLD) response during sustained visual stimulation has been studied by several groups using fMRI with controversial conclusions. This issue was investigated for the human brain at high (4 Tesla) magnetic field strength using a flashing goggle at 8 Hz. The results demonstrate that the overall BOLD response in the primary visual cortex has an initial overshoot after the onset of visual stimulation and an undershoot after the termination of visual stimulation. A significant and positive BOLD response, however, remains constant between the initial and terminal transient responses. The temporal BOLD responses in the primary visual cortex were spatially dependent. The regions identified as draining veins in images displayed proportionately larger initial and terminal transient responses, whereas regions devoid of such vessels and associated mainly with parenchyma exhibited a more time-independent BOLD response. These results reveal that the BOLD effect and, presumably, the uncoupling between cerebral blood flow and cerebral metabolic rate of oxygen consumption, are maintained in the primary visual cortex during sustained visual stimulation, and the temporal characteristics of the BOLD effect are spatially dependent.

Humans↗

Detecting natural abundance carbon signal of NAA metabolite within 12-cm3 localized volume of human brain using 1H-[13C] NMR spectroscopy.

NMR spectroscopy has been applied extensively to study metabolism noninvasively in the human brain and other tissues. However, it usually suffers from poor signal-to-noise ratio due to low NMR sensitivity and low metabolite concentrations. In this study, the technique of proton-observe-carbon-edited (POCE) NMR spectroscopy combined with a single-shot localization sequence was used to detect the natural abundance carbon signal of the amino acid N-acetyl aspartate from a 12-cm3 localized volume in the occipital lobe of humans at 4 T. The results suggest that NMR spectroscopy is sensitive enough to detect signals from low concentration metabolites (< 60 nmol/g) from small volumes in the human brain within several minutes of data acquisition. This reveals that in vivo NMR spectroscopy is a promising technique for detecting small metabolite changes and low traces of 13C isotopic labeling for dynamic metabolism studies aimed at investigating physiological and pathological questions.

Aspartic Acid↗

Activation of visuomotor systems during visually guided movements: a functional MRI study.

The dorsal stream is a dominant visuomotor pathway that connects the striate and extrastriate cortices to posterior parietal areas. In turn, the posterior parietal areas send projections to the frontal primary motor and premotor areas. This cortical pathway is hypothesized to be involved in the transformation of a visual input into the appropriate motor output. In this study we used functional magnetic resonance imaging (fMRI) of the entire brain to determine the patterns of activation that occurred while subjects performed a visually guided motor task. In nine human subjects, fMRI data were acquired on a 4-T whole-body MR system equipped with a head gradient coil and a birdcage RF coil using a T2*-weighted EPI sequence. Functional activation was determined for three different tasks: (1) a visuomotor task consisting of moving a cursor on a screen with a joystick in relation to various targets, (2) a hand movement task consisting of moving the joystick without visual input, and (3) a eye movement task consisting of moving the eyes alone without visual input. Blood oxygenation level-dependent (BOLD) contrast-based activation maps of each subject were generated using period cross-correlation statistics. Subsequently, each subject's brain was normalized to Talairach coordinates, and the individual maps were compared on a pixel by pixel basis. Significantly activated pixels common to at least four out of six subjects were retained to construct the final functional image. The pattern of activation during visually guided movements was consistent with the flow of information from striate and extrastriate visual areas, to the posterior parietal complex, and then to frontal motor areas. The extensive activation of this network and the reproducibility among subjects is consistent with a role for the dorsal stream in transforming visual information into motor behavior. Also extensively activated were the medial and lateral cerebellar structures, implicating the cortico-pontocerebellar pathway in visually guided movements. Thalamic activation, particularly of the pulvinar, suggests that this nucleus is an important subcortical target of the dorsal stream.

Animals↗

Functional magnetic resonance imaging of motor, sensory, and posterior parietal cortical areas during performance of sequential typing movements.

We investigated the activation of sensory and motor areas involved in the production of typing movements using functional magnetic resonance imaging (fMRI). Eleven experienced typists performed tasks, in which the spatial and temporal requirements as well as the number of digits involved were varied. These included a simple uni-digit repetitive task, a uni-digit sequential task, a dual-digit sequential task, a multi-digit sequential task, and typing text from memory. We found that the production of simple repetitive keypresses with the index finger primarily involved the activation of contralateral primary motor cortex (M1), although a small activation of the supplementary motor area (SMA) and other regions was sometimes observed as well. The sequencing of keypresses involved bilateral M1 and a stronger activation of the SMA and to a lesser extent the premotor area, cingulate gyrus, caudate, and lentiform nuclei. However, the activation of these areas did not exclusively depend on the complexity of the movements, since they were often activated during more simple movements, such as alternating two keypresses repeatedly. Somatosensory and parietal regions were also found to be activated during typing sequences. The activation of parietal areas did not exclusively depend on the spatial requirements of the task, since similar activation was observed during movements within intra-personal space (finger-thumb opposition) and may instead be related to the temporal requirements of the task. Our findings suggest that the assembly of well-learned, goal-directed finger movement sequences involves the SMA and other secondary motor areas as well as somatosensory and parietal areas.

Adult↗

Steady-state cerebral glucose concentrations and transport in the human brain.

Understanding the mechanism of brain glucose transport across the blood-brain barrier is of importance to understanding brain energy metabolism. The specific kinetics of glucose transport have been generally described using standard Michaelis-Menten kinetics. These models predict that the steady-state glucose concentration approaches an upper limit in the human brain when the plasma glucose level is well above the Michaelis-Menten constant for half-maximal transport, Kt. In experiments where steady-state plasma glucose content was varied from 4 to 30 mM, the brain glucose level was a linear function of plasma glucose concentration. At plasma concentrations nearing 30 mM, the brain glucose level approached 9 mM, which was significantly higher than predicted from the previously reported Kt of approximately 4 mM (p < 0.05). The high brain glucose concentration measured in the human brain suggests that ablumenal brain glucose may compete with lumenal glucose for transport. We developed a model based on a reversible Michaelis-Menten kinetic formulation of unidirectional transport rates. Fitting this model to brain glucose level as a function of plasma glucose level gave a substantially lower Kt of 0.6 +/- 2.0 mM, which was consistent with the previously reported millimolar Km of GLUT-1 in erythrocyte model systems. Previously reported and reanalyzed quantification provided consistent kinetic parameters. We conclude that cerebral glucose transport is most consistently described when using reversible Michaelis-Menten kinetics.

Adult↗

On the characteristics of functional magnetic resonance imaging of the brain.

In this review we discuss various recent topics that characterize functional magnetic resonance imaging (fMRI). These topics include a brief description of MRI image acquisition, how to cope with noise or signal fluctuation, the basis of fMRI signal changes, and the relation of MRI signal to neuronal events. Several observations of fMRI that show good correlation to the neurofunction are referred to. Temporal characteristics of fMRI signals and examples of how the feature of real time measurement is utilized are then described. The question of spatial resolution of fMRI, which must be dictated by the vascular structure serving the functional system, is discussed based on various fMRI observations. Finally, the advantage of fMRI mapping is shown in a few examples. Reviewing the vast number of recent fMRI application that have now been reported is beyond the scope of this article.

Animals↗

Localized in vivo 13C-NMR of glutamate metabolism in the human brain: initial results at 4 tesla.

Using optimized administration of 13C-labeled glucose, the time course of the specific activity of glucose was measured directly by in vivo 13C-NMR in the human brain at 4 Tesla. Subsequent label incorporation was measured at the C2, C3 and C4 positions of both glutamate and the well-resolved C2, C3 and C4 resonances of glutamine and at the C2 and C3 positions of aspartate. GABA was clearly observed for the first time in vivo, suggesting a substantial GABA turnover in the normal human visual cortex. Likewise, lactate C3 labeled with an estimated active pool size on the order of 0.5 mM. A model of cerebral glutamate metabolism is proposed which predicts that glutamatergic action ('neurotransmission'), pyruvate carboxylase flux, TCA cycle activity, glucose consumption and exchange across the mitochondrial membrane can be assessed simultaneously in the human brain.

Aspartic Acid↗

Time-resolved fMRI of mental rotation.

Time-resolved fMRI seeks to elucidate neuronal activity during a single execution of a mental task, which corresponds typically to a timescale of seconds. However, this is also the timescale of the hemodynamic response, which delays and blurs the signal in time. In order to distinguish the temporal characteristics of the neuronal activity from that of the hemodynamic response, which is often vaguely known, we recorded a set of fMRI time courses under conditions of a varying behavioral parameter, and correlated this parameter to the width of the fMRI response. For the task under investigation, the mental rotation of three-dimensional objects, we found that the activation in the parietal lobe is related to an aspect of the task that is described by the reaction time (for example, the very act of mental rotation), and not only to aspects of the task that are constant from trial to trial, such as the visual presentation at the beginning or the decision at the end of the task.

Brain Mapping↗

Relationships between myocardial bioenergetic and left ventricular function in hearts with volume-overload hypertrophy.

BACKGROUND: Left ventricular (LV) hypertrophy secondary to volume overload can result in alterations in myocardial bioenergetics and LV dysfunction. This study examined whether bioenergetic abnormalities contribute to the pump dysfunction. METHODS AND RESULTS: Severe mitral regurgitation (MR) was produced in 10 dogs by disruption of the chordal apparatus. Hemodynamics and ventricular function were examined 11.7 months later under baseline conditions and during treadmill exercise. Myocardial high-energy phosphates were measured by using magnetic resonance spectroscopy at rest, during coronary vasodilation with adenosine, and during oxidative stress induced by rapid pacing and dobutamine. Chronic MR caused a 30% increase in LV mass and a 65% increase in LV volume. In MR animals, the hemodynamic and LV function were normal at rest, but abnormalities developed during beta-blockade and exercise. Myocardial creatine phosphate-to-ATP ratios were significantly lower in each layer across the LV wall in MR hearts than normal hearts. Myocardial blood flow and coronary reserve were normal in MR hearts. Moreover, hyperperfusion did not correct the abnormal bioenergetics. Despite altered bioenergetics at rest, the MR hearts tolerated rapid pacing and dobutamine infusion well. CONCLUSIONS: In volume-overloaded LV hypertrophied hearts, alterations in myocardial high-energy phosphate levels do not induce abnormal mechanical performance at rest but may be related to a decreased contractile reserve during exercise.

Adenosine Triphosphate↗

Functional magnetic resonance imaging of the human brain.

The current technical and methodological status of functional magnetic resonance imaging (fMRI) is reviewed. The mechanisms underlying the effects of deoxyhemoglobin concentration and cerebral blood flow changes are discussed, and methods for monitoring these changes are described and compared. Methods for post-processing fMRI data are outlined. Potential problems and solutions related to vessels and motion are discussed in detail.

Brain↗

Imaging H2(17)O distribution in a phantom and measurement of metabolically produced H2(17)O in live mice by proton NMR.

Previously we suggested a method for indirect detection of H2(17)O via a combination of 1H spin-echo sequence and 17O decoupling. The method is based on the shortening of the water proton T2 due to the residual spin-spin coupling with the 17O nucleus, and on our finding that this shortening is abolished by applying an radio frequency field at the 17O resonance frequency. In the present work we demonstrate how the method can be used for imaging low concentrations of H2(17)O, and report for the first time an application of this method to in vivo detection of H2(17)O in live newborn mice, where the H2(17)O was introduced either directly i.p. or by inhalation of 17O2 where it was formed by oxidative metabolic activity.

Animals↗

Experimental determination of the BOLD field strength dependence in vessels and tissue.

High resolution functional MRI (fMRI) experiments were performed in human visual cortex at 0.5, 1.5, and 4 T to determine the blood oxygenation level dependent (BOLD) field strength response within regions of obvious venous vessels and cortical gray matter ("tissue"). T2*-weighted FLASH images were collected in single- and multi-echo mode and used to determine the intrinsic BOLD parameters, namely, signal-to-noise ratio (psi), the apparent transverse relaxation rate (R2*) and the change in R2* (deltaR2*) between the activated and baseline states. The authors find the average percentage signal change (deltaS/S, measured at TE = T2*) to be large in vessels (13.3 +/- 2.3%, 18.4 +/- 4.0%, and 15.1 +/- 1.2%) compared with that in tissue (1.4 +/- 0.7%, 1.9 +/- 0.7%, and 3.3 +/- 0.2%) at 0.5, 1.5, and 4 T, respectively. The signal-to-noise ratio in optimized, fully relaxed proton density weighted gradient echo images was found to increase linearly with respect to the static magnetic field strength (B0). The predicted upper bound on BOLD contrast-to-noise ratio (deltaS/R)max as a function of field strength was calculated and found to behave less than linearly in voxels containing vessels larger than the voxel itself and greater than linearly in voxels containing a mixture of capillaries and veins/venules with a diameter less than that of the voxel.

Humans↗

Increase of creatine kinase activity in the visual cortex of human brain during visual stimulation: a 31P magnetization transfer study.

31P magnetic resonance spectroscopy was used to investigate changes in high energy phosphate levels and creatine kinase (CK) kinetics induced in the human visual cortex during photic stimulation. CK kinetics was evaluated by measuring the apparent unidirectional rate constant (kf) in the "forward" direction (i.e., in the direction of ATP synthesis from phosphocreatine). kf increased 34% in the visual cortex areas during stimulation without significant changes of steady-state concentration of high energy phosphate compounds, indicating that CK turnover is elevated during increased neuronal activity.

Adenosine Triphosphate↗

Myocardial perfusion reserve: assessment with multisection, quantitative, first-pass MR imaging.

PURPOSE: To demonstrate the feasibility of determining myocardial blood flow changes and the myocardial perfusion reserve with magnetic resonance (MR) first-pass imaging, to validate the MR results by means of comparison with radiolabeled microsphere flow measurements in an animal model, and to compare the coronary flow reserve with the perfusion reserve at MR imaging in patients with hemodynamically nonsignificant coronary lesions and angina. MATERIALS AND METHODS: Arrhythmia-insensitive, first-pass, multisection, T1-weighted MR imaging with contrast agent enhancement was performed in eight pigs with acute ischemia and in eight adult patients (six women, two men). In the pigs, microsphere flow measurements were obtained in parallel with the MR measurements. In the patients, the coronary flow reserve was measured with an intracoronary Doppler flow ultrasound probe for comparison with the MR perfusion reserve. RESULTS: In the animal studies, there was linear correlation between MR perfusion indexes and the microsphere flow measurements (r = .88, P < .01). In the patients, the regional perfusion reserve matched the coronary flow reserve (linear regression with a slope of 1.02 +/- 0.09, r = .80). CONCLUSION: The myocardial perfusion reserve can be quantified with first-pass MR imaging. In patients with microvascular dysfunction, the myocardial perfusion reserve matches the reduced coronary flow reserve.

Animals↗