Biomedical subjects

K Uğurbil

Publications and source records attributed to K Uğurbil.

At least 19 recordsLinked to original sources

PubMed2002

Cerebellum activation associated with performance change but not motor learning.

The issue of whether the cerebellum contributes to motor skill learning is controversial, principally because of the difficulty of separating the effects of motor learning from changes in performance. We performed a functional magnetic resonance imaging investigation during an implicit, motor sequence-learning task that was designed to separate these two processes. During the sequence-encoding phase, human participants performed a concurrent distractor task that served to suppress the performance changes associated with learning. Upon removal of the distractor, participants showed evidence of having learned. No cerebellar activation was associated with the learning phase, despite extensive involvement of other cortical and subcortical regions. There was, however, significant cerebellar activation during the expression of learning; thus, the cerebellum does not contribute to learning of the motor skill itself but is engaged primarily in the modification of performance.

Brain↗

PubMed2001

Localized cerebral blood flow response at submillimeter columnar resolution.

Functional magnetic resonance imaging (fMRI) has been widely used for imaging brain functions. However, the extent of the fMRI hemodynamic response around the active sites, at submillimeter resolution, remains poorly understood and controversial. With the use of perfusion-based fMRI, we evaluated the hemodynamic response in the cat visual cortex after orientation-specific stimuli. Activation maps obtained by using cerebral blood flow fMRI measurements were predominantly devoid of large draining vein contamination and reproducible at columnar resolution. Stimulus-specific cerebral blood flow responses were spatially localized to individual cortical columns, and columnar layouts were resolved. The periodic spacing of orientation columnar structures was estimated to be 1.1 +/- 0.2 mm (n = 14 orientations, five animals), consistent with previous findings. The estimated cerebral blood flow response at full width at half-maximum was 470 microm under single-stimulus conditions without differential subtraction. These results suggest that hemodynamic-based fMRI can indeed be used to map individual functional columns if large-vessel contributions can be minimized or eliminated.

Animals↗

PubMed2001

Functional magnetic resonance imaging of visual object construction and shape discrimination : relations among task, hemispheric lateralization, and gender.

We studied the brain activation patterns in two visual image processing tasks requiring judgements on object construction (FIT task) or object sameness (SAME task). Eight right-handed healthy human subjects (four women and four men) performed the two tasks in a randomized block design while 5-mm, multislice functional images of the whole brain were acquired using a 4-tesla system using blood oxygenation dependent (BOLD) activation. Pairs of objects were picked randomly from a set of 25 oriented fragments of a square and presented to the subjects approximately every 5 sec. In the FIT task, subjects had to indicate, by pushing one of two buttons, whether the two fragments could match to form a perfect square, whereas in the SAME task they had to decide whether they were the same or not. In a control task, preceding and following each of the two tasks above, a single square was presented at the same rate and subjects pushed any of the two keys at random. Functional activation maps were constructed based on a combination of conservative criteria. The areas with activated pixels were identified using Talairach coordinates and anatomical landmarks, and the number of activated pixels was determined for each area. Altogether, 379 pixels were activated. The counts of activated pixels did not differ significantly between the two tasks or between the two genders. However, there were significantly more activated pixels in the left (n = 218) than the right side of the brain (n = 161). Of the 379 activated pixels, 371 were located in the cerebral cortex. The Talairach coordinates of these pixels were analyzed with respect to their overall distribution in the two tasks. These distributions differed significantly between the two tasks. With respect to individual dimensions, the two tasks differed significantly in the anterior--posterior and superior--inferior distributions but not in the left--right (including mediolateral, within the left or right side) distribution. Specifically, the FIT distribution was, overall, more anterior and inferior than that of the SAME task. A detailed analysis of the counts and spatial distributions of activated pixels was carried out for 15 brain areas (all in the cerebral cortex) in which a consistent activation (in > or = 3 subjects) was observed (n = 323 activated pixels). We found the following. Except for the inferior temporal gyrus, which was activated exclusively in the FIT task, all other areas showed activation in both tasks but to different extents. Based on the extent of activation, areas fell within two distinct groups (FIT or SAME) depending on which pixel count (i.e., FIT or SAME) was greater. The FIT group consisted of the following areas, in decreasing FIT/SAME order (brackets indicate ties): GTi, GTs, GC, GFi, GFd, [GTm, GF], GO. The SAME group consisted of the following areas, in decreasing SAME/FIT order : GOi, LPs, Sca, GPrC, GPoC, [GFs, GFm]. These results indicate that there are distributed, graded, and partially overlapping patterns of activation during performance of the two tasks. We attribute these overlapping patterns of activation to the engagement of partially shared processes. Activated pixels clustered to three types of clusters : FIT-only (111 pixels), SAME-only (97 pixels), and FIT + SAME (115 pixels). Pixels contained in FIT-only and SAME-only clusters were distributed approximately equally between the left and right hemispheres, whereas pixels in the SAME + FIT clusters were located mostly in the left hemisphere. With respect to gender, the left-right distribution of activated pixels was very similar in women and men for the SAME-only and FIT + SAME clusters but differed for the FIT-only case in which there was a prominent left side preponderance for women, in contrast to a right side preponderance for men. We conclude that (a) cortical mechanisms common for processing visual object construction and discrimination involve mostly the left hemisphere, (b) cortical mechanisms specific for these tasks engage both hemispheres, and (c) in object construction only, men engage predominantly the right hemisphere whereas women show a left-hemisphere preponderance.

Adult↗

PubMed2000

Effect of acute hyperglycemia on visual cortical activation as measured by functional MRI.

To determine whether acute hyperglycemia changes the hyperemic response to functional activation of brain, the area and magnitude of the activation were measured in healthy volunteers maintained at euglycemia and then at hyperglycemia using the hyperglycemic clamp technique. Activation of the visual cortex (8-16 Hz) was assessed by functional MRI with blood oxygenation level dependent (BOLD) contrast using a 4 Tesla magnet and a multi-slice echo-planar imaging sequence (TE = 30 msec, TR = 1.5 sec). At euglycemia (4.8 +/- 0.2 mM, mean +/- SEM, n = 6), the number of activated pixels in the occipital lobe was 79 +/- 10 and the intensity of activation was 4.5 +/- 0.5%. During hyperglycemia (plasma glucose 300% of control), the number of activated pixels was 90 +/- 20% of control and the BOLD activation was 3.5 +/- 0.3%, respectively. The change in BOLD signal was below 0.2%/mM plasma glucose. This study demonstrates that acute hyperglycemia is without substantial effect on the size and intensity of activation of the occipital cortex. The results further suggest that fluctuations in blood glucose within the physiologic range are without effect on the functional activation of the cerebral cortex measured by BOLD fMRI.

Adult↗

PubMed2000

Spatiotemporal dynamics of the BOLD fMRI signals: toward mapping submillimeter cortical columns using the early negative response.

The existence of the early-negative blood-oxygenation-level-dependent (BOLD) response is controversial and its practical utility for mapping brain functions with columnar spatial specificity remains questionable. To address these issues, gradient-echo BOLD fMRI studies were performed at 4.7 T and 9.4 T using the well-established orientation column model in the cat visual cortex. A robust transient early-negative BOLD response was consistently observed in anesthetized cat (-0.35 +/- 0.09%, mean +/- SD, n = 8 at 2.9 +/- 0.5 sec poststimulus onset for 4.7 T, TE = 31 ms; -0.29 +/- 0.10%, n = 4 at 3.0 +/- 0.8 sec poststimulus onset for 9.4 T, TE = 12 ms). In addition to its temporal evolution, the BOLD response also evolved dynamically in the spatial domain. The initially spatially localized early-negative signal appeared to dynamically drain from the active sites toward large vessels, followed by a wave of the delayed positive signal, which exhibited similar spatiotemporal dynamics. Only the early-negative BOLD response within 2 sec of the stimulus onset (not the entire dip) yielded columnar layouts without differential subtraction. The functional maps of two orthogonal orientations using the first 2-sec dip were indeed complementary. On the other hand, the delayed positive BOLD response appeared diffused and extended beyond the active sites. It was thus less suitable to resolve columnar layouts. These results have implications for the design and interpretation of the BOLD fMRI at columnar resolution. Magn Reson Med 44:231-242, 2000.

Animals↗

PubMed2000

Magnetic resonance studies of brain function and neurochemistry.

In the short time since its introduction, magnetic resonance imaging (MRI) has rapidly evolved to become an indispensable tool for clinical diagnosis and biomedical research. Recently, this methodology has been successfully used for the acquisition of functional, physiological, and biochemical information in intact systems, particularly in the human body. The ability to map areas of altered neuronal activity in the brain, often referred to as functional magnetic resonance imaging (fMRI), is probably one of the most significant recent achievements that rely on this methodology. This development has permitted the examination of functional specialization in human and animal brains with unprecedented spatial resolution, as demonstrated by mapping at the level of orientation and ocular dominance columns in the visual cortex. These functional imaging studies are complemented by the ability to study neurochemistry using magnetic resonance spectroscopy, allowing the determination of metabolic processes that support neurotransmission and neurotransmission rates themselves.

Animals↗

PubMed1999

Functional mapping in the human brain using high magnetic fields.

An avidly pursued new dimension in magnetic resonance imaging (MRI) research is the acquisition of physiological and biochemical information non-invasively using the nuclear spins of the water molecules in the human body. In this trial, a recent and unique accomplishment was the introduction of the ability to map human brain function non-invasively. Today, functional images with subcentimetre resolution of the entire human brain can be generated in single subjects and in data acquisition times of several minutes using 1.5 tesla (T) MRI scanners that are often used in hospitals for clinical purposes. However, there have been accomplishments beyond this type of imaging using significantly higher magnetic fields such as 4 T. Efforts for developing high magnetic field human brain imaging and functional mapping using MRI (fMRI) were undertaken at about the same time. It has been demonstrated that high magnetic fields result in improved contrast and, more importantly, in elevated sensitivity to capillary level changes coupled to neuronal activity in the blood oxygenation level dependent (BOLD) contrast mechanism used in fMRI. These advantages have been used to generate, for example, high resolution functional maps of ocular dominance columns, retinotopy within the small lateral geniculate nucleus, true single-trial fMRI and early negative signal changes in the temporal evolution of the BOLD signal. So far these have not been duplicated or have been observed as significantly weaker effects at much lower field strengths. Some of these high-field advantages and accomplishments are reviewed in this paper.

Brain↗

PubMed1999

Transmural metabolic heterogeneity at high cardiac work states.

This study compared the transmural distribution of high-energy phosphate (HEP) depletion during oxidative stress induced by pacing- and dobutamine-induced tachycardia in myocardium perfused by a flow-limiting coronary stenosis. Myocardial blood flow (MBF) was measured with radioactive microspheres. Creatine phosphate (CrP), ATP, and P(i) were measured with transmurally localized (31)P NMR spectroscopy. In normal dogs a hydraulic occluder was used to produce a left anterior descending coronary artery stenosis, which maintained constant flow measured with a Doppler probe. Tachycardia was induced by rapid pacing (200 beats/min, n = 11) or by dobutamine infusion (20 micrograms . kg(-1). min(-1) iv, n = 13) to produce a similar heart rate. In the presence of stenosis, pacing and dobutamine caused similar reductions of subendocardial (Endo)-to-subepicardial (Epi) MBF ratios (0.66 +/- 0.06 vs. 0.63 +/- 0.08, respectively). Stenosis plus pacing caused a decrease of the CrP-to-ATP ratio (CrP/ATP) in Endo from 2.00 +/- 0.07 to 1.65 +/- 0. 08 (P < 0.05) with no significant change in Epi. Stenosis plus dobutamine caused HEP changes across the left ventricular wall, which were most marked in the outer myocardial layer (Epi CrP/ATP decreased from 2.33 +/- 0.11 to 1.67 +/- 0.12; Endo CrP/ATP decreased from 1.99 +/- 0.09 to 1.64 +/- 0.12). Thus HEP changes during oxidative stress that are produced by pacing parallel the pattern of hypoperfusion and are most severe in the subendocardium. In contrast, in response to inotropic stimulation, the transmural metabolic changes did not correspond to the pattern of the hypoperfusion.

Animals↗

PubMed1999

Oxygen delivery does not limit cardiac performance during high work states.

This study tested the hypothesis that the loss of myocardial high-energy phosphates (HEP), which occurs during high cardiac work states [J. Zhang, D. J. Duncker, Y. Xu, Y. Zhang, G. Path, H. Merkle, K. Hendrich, A. H. L. From, R. Bache, and K. Uğurbil. Am. J. Physiol. 268: (Heart Circ. Physiol. 37): H1891-H1905, 1995], is not the result of insufficient intracellular O(2) availability. To evaluate the state of myocardial oxygenation, the proximal histidine signal of deoxymyoglobin (Mb-delta) was determined with (1)H nuclear magnetic resonance spectroscopy (MRS), whereas HEP were examined with (31)P MRS. Normal dogs (n = 11) were studied under basal conditions and during combined infusion of dobutamine and dopamine (20 micrograms . kg(-1). min(-1) iv each), which increased rate-pressure products to >50,000 mmHg. beats. min(-1). Creatine phosphate (CP) was expressed as CP/ATP, and myocardial myoglobin desaturation was normalized to the Mb-delta resonance present during total coronary artery occlusion. This Mb-delta resonance appeared at 71 parts per million downfield from the water resonance. CP/ATP decreased from 2. 22 +/- 0.12 during the basal state to 1.83 +/- 0.09 during the high work state (P < 0.01), whereas DeltaP(i)/CP increased from 0 to 0.21 +/- 0.04 (P < 0.01). Despite these HEP changes, Mb-delta remained undetectable. In contrast, when a coronary stenosis was applied to produce a similar decrease in CP/ATP, Mb-delta reached 0.38 +/- 0.10 of the value present during total coronary occlusion. These data demonstrate that Mb-delta is readily detected in vivo during limitation of coronary blood flow sufficient to cause a decrease of myocardial CP/ATP. However, similar HEP changes that occur at high work states in the absence of coronary occlusion are not associated with a detectable Mb-delta resonance. The findings support the hypothesis that the myocardial HEP changes observed at high work states are not due to inadequate O(2) availability to the mitochondria and emphasize the limitations of interpreting HEP alterations in the absence of knowing the level of myocyte oxygenation.

Animals↗

PubMed1998

Simultaneous oxygenation and perfusion imaging study of functional activity in primary visual cortex at different visual stimulation frequency: quantitative correlation between BOLD and CBF changes.

A relationship between regional cerebral blood flow (CBF) and blood oxygenation level dependent (BOLD) changes in the primary visual cortex (V1) at varied visual stimulation frequency has been examined quantitatively using the multislice FAIR technique. A linear correlation in the common activation areas between functional BOLD and CBF maps was observed. This supports the hypothesis that the task-stimulated BOLD changes in microvasculature are correlated with the CBF changes that presumably reflect the degree of neuronal activity. The linear correlation coefficients for intrasubject comparisons are more significant than those for intersubject comparisons. This suggests that using intrasubject comparisons for quantitative studies of neuronal activity related to different task stimuli and task performances should be more reliable than using intersubject comparisons.

Brain Mapping↗

PubMed1998

Resolution improvements in in vivo 1H NMR spectra with increased magnetic field strength.

The measurement of cerebral metabolites using highly homologous localization techniques and similar shimming methods was performed in the human brain at 1.5 and 4 T as well as in the dog and rat brain at 9.4 T. In rat brain, improved resolution was achieved by shimming all first- and second-order shim coils using a fully adiabatic FASTMAP sequence. The spectra showed a clear improvement in spectral resolution for all metabolite resonances with increased field strength. Changes in cerebral glutamine content were clearly observed at 4 T compared to 1.5 T in patients with hepatic encephalopathy. At 9.4 T, glutamine H4 at 2.46 ppm was fully resolved from glutamate H4 at 2.37 ppm, as was the potential resonance from gamma-amino-butyric acid at 2.30 ppm and N-acetyl-aspartyl-glutamate at 2.05 ppm. Singlet linewidths were found to be as low as 6 Hz (0.015 ppm) at 9.4 T, indicating a substantial decrease in ppm linewidth with field strength. Furthermore, the methylene peak of creatine was partially resolved from phosphocreatine, indicating a close to 1:1 relationship in gray matter. We conclude that increasing the magnetic field strength increases spectral resolution also for 1H NMR, which can lead to more than linear sensitivity gains.

Adult↗

PubMed1998

Effects of movement predictability on cortical motor activation.

Humans have the ability to make motor responses to unpredictable visual stimuli, and do so as a matter of course on a daily basis. We used functional magnetic resonance imaging (fMRI) to examine the neural substrate of this behavior in six cortical motor areas. We found that five of these areas (premotor, cingulate, supplementary motor area, pre-supplementary motor area, and superior parietal lobule) showed increased activation in association with an unpredictable behavior compared to a predictable one; only the motor cortex remained unchanged. There was also a quantitative relation between the response time and functional activation in the premotor and cingulate cortex. There was less activation across all the motor areas with repetition of the motor tasks. With the exception of the pre-supplementary motor area, all areas were significantly lateralized, with a greater volume of activation in the hemisphere contralateral to the performing hand. In addition, a left hemisphere dominance was found in the activation of motor cortex and supplementary motor areas. Our results suggest that activation in motor areas is differentially and quantitatively related to higher order aspects of motor behavior such as movement predictability.

Adult↗

PubMed1997

Detection of 13C-labeled metabolites in the in vivo canine heart by B1 insensitive heteronuclear coherent polarization transfer and comparison of signal enhancement with NOE.

A recently developed adiabatic coherent polarization transfer enhancement technique [H. Merkle, H. Wei, M. Garwood, K. Uğurbil. J. Magn. Reson, 99, 480-494 (1992)] was employed to perform 13C spectroscopy in the intact canine heart in vivo during [2-13C]-acetate infusion into the left descending coronary artery, the results were compared with 13C spectra obtained with conventionally employed nuclear Overhauser enhancement. The results demonstrate that both methods can be performed by using surface coils to obtain in vivo 13C spectra and that coherent polarization transfer provides better enhancement than NOE for [2-13C]-acetate but not for short T2 compounds.

Acetates↗

PubMed1997

The nature of spatiotemporal changes in cerebral hemodynamics as manifested in functional magnetic resonance imaging.

The nature of changes in rapidly acquired magnetic resonance images of the brain was studied by using a denoising method and spectral techniques optimally suited to short time series. It was found that the stimulus related changes have a complex spatiotemporal structure even for simple visual stimuli. Apart from a low frequency window, the non-stimulus-related changes were found to correspond in detail to either breathing or heartbeat, although these two sources show different patterns of spatial coherence in the image. At low frequencies, oscillations with frequencies around 0.1 Hz were observed, also with nontrivial space-time structure, which are likely to be vasomotor in origin.

Blood Vessels↗

PubMed1997

Limitations of temporal resolution in functional MRI.

In fMRI, images can be collected in a very short time; therefore, high temporal resolution is possible in principle. However, the temporal resolution is limited by a blurred intrinsic hemodynamic response and a finite signal-to-noise ratio. To determine the upper limit of temporal resolution in a single area during repeated tasks, motor cortex activity was investigated during visually instructed finger movements. Without averaging, a sequence of four single-finger movements with an execution time of approximately 2 s can be resolved when the delay time between consecutive sequences is at least 3 s. The hemodynamic response time is constant for each subject, but not among different subjects. The temporal resolution can be better when the signal from spatially distinct regions is examined. For a series of experiments involving a visually instructed delayed cued finger movement task with a well-defined, independently determined, variable delay time, time courses in the motor area are distinct from each other in two experiments if the difference in delay time is as little as 2 s. The activation in the visual area due to the presentation of the task serves here as an internal time reference. By comparing a set of fMRI time courses in multiple distinct areas, serial neural processing may be investigated.

Brain↗

PubMed1997

Evaluation of the early response in fMRI in individual subjects using short stimulus duration.

Optical imaging studies have provided evidence of an initial increase in deoxyhemoglobin following the onset of neuronal stimulation/activation and demonstrated that this initial increase could be spatially more specific to the site of neuronal activity. These studies also raised the possibility of improving the specificity of fMRI by selective mapping of this early response. Previous MR studies reported the observation of this early response but were limited in scope and not in full agreement. This paper presents a more extensive study that (a) demonstrates the initial signal decrease in individual subjects and (b) examines its dependence on stimulus duration and subject. Binocular visual stimulation experiments were performed on 14 subjects using echo-planar imaging (EPI) with high temporal resolution. An initial signal decrease was consistently observed in regions that were more localized than those displaying the delayed positive response. In agreement with previous fMRI and optical imaging findings, the maximum signal decrease was 1-2% and occurred at approximately 2 s after the onset of the stimulus, depending on the subject. For stimulus longer then 3.0 s, the temporal dynamics and the amount of signal change of the early response was essentially independent of the stimulus duration, while the delayed response and the post-stimulus undershoot increased both in terms of magnitude and rise time as the duration of the stimulus increased; this observation is concordant with the recent optical imaging study.

Brain↗

PubMed1997

Comparison of blood oxygenation and cerebral blood flow effects in fMRI: estimation of relative oxygen consumption change.

The most widely-used functional magnetic resonance imaging (fMRI) technique is based on the blood oxygenation level dependent (BOLD) effect, which requires at least partial uncoupling between cerebral blood flow (CBF) and oxygen consumption changes during increased mental activity. To compare BOLD and CBF effects during tasking, BOLD and flow-sensitive alternating inversion recovery (FAIR) images were acquired during visual stimulation with red goggles at a frequency of 8 Hz in an interleaved fashion. With the FAIR technique, absolute and relative CBF changes were determined. Relative oxygen consumption changes can be estimated using the BOLD and relative CBF changes. In gray matter areas in the visual cortex, absolute and relative CBF changes in humans during photic stimulation were 31 +/- 11 SD ml/100 g tissue/min and 43 +/- 16 SD % (n = 12), respectively, while the relative oxygen consumption change was close to zero. These findings agree extremely well with previous results using positron emission tomography. The BOLD signal change is not linearly correlated with the relative CBF increase across subjects and negatively correlates with the oxygen consumption change. Caution should be exercised when interpreting the BOLD percent change as a quantitative index of the CBF change, especially in inter-subject comparisons.

Blood Volume↗

PubMed1997

Ocular dominance in human V1 demonstrated by functional magnetic resonance imaging.

Very high resolution functional magnetic resonance imaging (fMRI) at a 4 Tesla (T) magnetic field was used to map ocular dominance regions in the human visual cortical layers using the blood oxygen level dependent (BOLD) contrast mechanism. The fMRI response from primary visual cortex (V1) exhibited a distribution of ocular dominance reminiscent of the single-cell recordings of Hubel and Wiesel. Pixels could be grouped into seven categories varying from left-only response to binocular-only response to right-only responses. Nonspecific responses were found in the MRI-visible draining veins as well as in the parenchyma. Although large vessel BOLD signals are easily detectable, regardless of field strength, they demonstrate a fMRI response to photic input that could not be used to distinguish ocular dominance. The difference in BOLD response between a region activated by one eye and that activated by the other is only 2.9% on average. This necessitates the use of a difference paradigm to visualize the regions of ocular dominance accurately. The data show that BOLD-based fMRI is sensitive to neuronal activity in cortical columns when using differential techniques, opening up the possibility of mapping specialized populations of neurons in humans that are not accessible to electrophysiological or other methods of invasive mapping.

Adult↗