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K R Thulborn

Publications and source records attributed to K R Thulborn.

At least 19 recordsLinked to original sources

Stimulus-response incompatibility activates cortex proximate to three eye fields.

We used functional magnetic resonance imaging (fMRI) to investigate cortical activation during the performance of three oculomotor tasks that impose increasing levels of cognitive demand. (1) In a visually guided saccade (VGS) task, subjects made saccades to flashed targets. (2) In a compatible task, subjects made leftward and rightward saccades in response to foveal presentation of the uppercase words "LEFT" or "RIGHT." (3) In a mixed task, subjects made rightward saccades in response to the lowercase word "left" and leftward saccades in response to the lowercase word "right" on incompatible trials (60%). The remaining 40% of trials required compatible responses to uppercase words. The VGS and compatible tasks, when compared to fixation, activated the three cortical eye fields: the supplementary eye field (SEF), the frontal eye field (FEF), and the parietal eye field (PEF). The mixed task, when compared to the compatible task, activated three additional cortical regions proximate to the three eye fields: (1) rostral to the SEF in medial frontal cortex; (2) rostral to the FEF in dorsolateral prefrontal cortex (DLPFC); (3) rostral and lateral to the PEF in posterior parietal cortex. These areas may contribute to the suppression of prepotent responses and in holding novel visuomotor associations in working memory.

Adult↗

Maturation of widely distributed brain function subserves cognitive development.

Cognitive and brain maturational changes continue throughout late childhood and adolescence. During this time, increasing cognitive control over behavior enhances the voluntary suppression of reflexive/impulsive response tendencies. Recently, with the advent of functional MRI, it has become possible to characterize changes in brain activity during cognitive development. In order to investigate the cognitive and brain maturation subserving the ability to voluntarily suppress context-inappropriate behavior, we tested 8-30 year olds in an oculomotor response-suppression task. Behavioral results indicated that adult-like ability to inhibit prepotent responses matured gradually through childhood and adolescence. Functional MRI results indicated that brain activation in frontal, parietal, striatal, and thalamic regions increased progressively from childhood to adulthood. Prefrontal cortex was more active in adolescents than in children or adults; adults demonstrated greater activation in the lateral cerebellum than younger subjects. These results suggest that efficient top-down modulation of reflexive acts may not be fully developed until adulthood and provide evidence that maturation of function across widely distributed brain regions lays the groundwork for enhanced voluntary control of behavior during cognitive development.

Adolescent↗

Transplantation of cultured human neuronal cells for patients with stroke.

Transplantation of cultured neuronal cells is safe in animal models and improves motor and cognitive deficits in rats with stroke. The authors studied the safety and feasibility of human neuronal cellular transplantation in patients with basal ganglia stroke and fixed motor deficits, including 12 patients (aged 44 to 75 years) with an infarct 6 months to 6 years previously (stable for at least 2 months). Serial evaluations (12 to 18 months) showed no adverse cell-related serologic or imaging-defined effects. The total European Stroke Scale score improved in six patients (3 to 10 points), with a mean improvement 2.9 points in all patients (p = 0. 046). Six of 11 PET scans at 6 months showed improved fluorodeoxyglucose uptake at the implant site. Neuronal transplantation is feasible in patients with motor infarction.

Adult↗

Developmental and lesion effects in brain activation during sentence comprehension and mental rotation.

The development of neurocognitive networks was examined in 2 cognitive paradigms: auditory sentence comprehension and mental rotation of alphanumeric stimuli. Patterns of brain activation were measured with whole brain echoplanar functional magnetic resonance imaging at 3 Tesla in 5 adults (20-28 years old), 7 children (9-12 years old), and 6 pediatric patients (9-12 years old) with perinatal strokes or periventricular hemorrhages. Healthy children and adults activated similar neurocognitive networks, but there were developmental differences in the distribution of activity across these networks. In the sentence task, children showed more activation in the inferior visual area suggesting an imagery strategy rather than a linguistic strategy for sentence processing. Furthermore, consistent use of a sentence comprehension strategy, whether correct or incorrect as compared to chance performance, was associated with greater activation in the inferior frontal area (Broca's) in both children and pediatric patients. In the mental rotation task, healthy adults showed more activation in the superior parietal and middle frontal areas and less activation in the supramarginal gyrus, suggesting adults were primarily engaged in visual-spatial manipulation and less engaged in the recognition of noncanonical views of stimuli. The pediatric patients showed patterns of activation consistent with organization of cognitive processing into homologous areas of the contralateral hemisphere.

Adult↗

Effects of stereotactic radiosurgery on an animal model of hippocampal epilepsy.

OBJECTIVE: Stereotactic radiosurgery has been shown in small clinical series to reduce or abolish seizures in patients with lesion-related or idiopathic epilepsy. The radiation dose necessary to eliminate epileptogenesis is unknown, and the histological and metabolic effects of radiosurgery remain undefined. We hypothesized that in a rat model of kainic acid-induced hippocampal epilepsy, radiosurgery could provide a significant reduction in seizure frequency while limiting biochemical and structural histological damage to the brain. METHODS: Kainic acid (8 g) was injected into the rat hippocampus using stereotactic targeting. Focal seizures so generated were identified with scalp and depth electroencephalography (EEG). Epileptic rats were randomized to a control group (n = 20) and to radiosurgery groups in which maximum doses of 20, 40, 60, or 100 Gy (8-9 animals per group) were administered. Over a 42-day period, seizure frequency was determined by direct observation for 8 hours per week. Scalp EEG was performed weekly in all animals. Magnetic resonance imaging (MRI) studies (T1- and T2-weighted water-proton and quantitative sodium images) were obtained on Days 7, 21, and 42. RESULTS: As compared with the control group, treated animals showed significant reductions in the number of seizures during each successive week after 20-Gy radiosurgery (P = 0.01-0.002). When we combined the number of seizures observed in the latter half of the study (Weeks 4-6), we found a significant reduction in seizures after 20-Gy (P = 0.007), 40-Gy (P = 0.03), 60-Gy (P = 0.03), and 100-Gy (P = 0.03) radiosurgery as compared with control animals. Increasing doses of radiosurgery correlated with higher percentages of rats that became seizure-free by EEG criteria. MRI-determined total sodium concentration in the injected hippocampus was 49.8+/-3 mmol/L, compared with 42.8 mmol/L on the contralateral side (within normal limits). This significant increase in sodium concentration was present in control rats (because of the kainic acid) and did not change with increasing radiosurgery dose. No parenchymal effects from radiosurgery were identified after 20, 40, and 60 Gy, and only two rats had necrosis at 100 Gy. All animals showed hippocampal injury from kainic acid by proton MRI and histological examination. CONCLUSION: In this rat hippocampal epilepsy model, stereotactic radiosurgery was followed by a significant dose-dependent reduction in the frequency of observed and EEG-defined seizures. These effects were not accompanied by increased radiation-induced structural or metabolic brain injury as assessed by proton and sodium MRI or histological examination. The role of radiosurgery as a new, nondestructive surgical therapy for idiopathic epilepsy warrants further investigation.

Animals↗

Functional MR imaging using a visually guided saccade paradigm for comparing activation patterns in patients with probable Alzheimer's disease and in cognitively able elderly volunteers.

BACKGROUND AND PURPOSE: Alzheimer's disease is associated with progressive visuospatial dysfunction. This study used functional MR (fMR) imaging with an eye movement paradigm to investigate differences in visuospatial cognition between patients with probable Alzheimer's disease (pAD) and cognitively able elderly volunteers. METHODS: Using established, although imperfect, clinical criteria, patients with pAD (n = 18) and cognitively able elderly volunteers (n = 10) were selected for study. All patients underwent echo-planar fMR imaging at 1.5 T. The visually guided saccade paradigm consisted of alternating periods (30 s) of central fixation and visually guided saccades to a target appearing randomly along the horizontal meridian. Activation maps were derived using a voxelwise t test, comparing the signal intensities between the two steady-state conditions. The activation patterns were characterized by Talairach coordinates, activation volumes, and laterality ratios (LRs). RESULTS: Statistically significant differences existed between the activation patterns of the patients with pAD and those of the volunteers. In contrast to the control group, a left-dominant parietal activation pattern and enhanced prefrontal cortical activation were observed in most patients with pAD. CONCLUSION: Within the limitations of the imperfect clinical standard of reference, the reduction in right parietal activation producing the left-dominant LR for the intraparietal sulcus may reflect the progressive dysfunction in spatial attention associated with Alzheimer's disease, considering the known parietal lobe involvement in this function and the disease. The high specificity of a positive intraparietal sulcal LR measured by fMR imaging may have a role in detecting and monitoring Alzheimer's disease.

Aged↗

Retinotopic mapping of lateral geniculate nucleus in humans using functional magnetic resonance imaging.

Subcortical nuclei in the thalamus, which play an important role in many functions of the human brain, provide challenging targets for functional mapping with neuroimaging techniques because of their small sizes and deep locations. In this study, we explore the capability of high-resolution functional magnetic resonance imaging at 4 Tesla for mapping the retinotopic organization in the lateral geniculate nucleus (LGN). Our results show that the hemifield visual stimulation only activates LGN in the contralateral hemisphere, and the lower-field and upper-field visual stimulations activate the superior and inferior portion of LGN, respectively. These results reveal a similar retinotopic organization between the human and nonhuman primate LGN and between LGN and the primary visual cortex. We conclude that high-resolution functional magnetic resonance imaging is capable of functional mapping of suborganizations in small nuclei together with cortical activation. This will have an impact for studying the thalamocortical networks in the human brain.

Adult↗

Cortical networks subserving pursuit and saccadic eye movements in humans: an FMRI study.

High-field (3 Tesla) functional magnetic resonance imaging (MRI) was used to investigate the cortical circuitry subserving pursuit tracking in humans and compare it to that for saccadic eye movements. Pursuit performance, relative to visual fixation, elicited activation in three areas known to contribute to eye movements in humans and in nonhuman primates: the frontal eye field, supplementary eye field, and intraparietal sulcus. It also activated three medial regions not previously identified in human neuroimaging studies of pursuit: the precuneus and the anterior and posterior cingulate cortices. All six areas were also activated during saccades. The spatial extent of activation was similar for saccades and pursuit in all but two regions: spatial extent was greater for saccades in the superior branch of the frontal eye field and greater for pursuit in posterior cingulate cortex. This set of activations for smooth pursuit parallels the network of oculomotor areas characterized in nonhuman primates and complements recent studies showing that common cortical networks subserve oculomotor functions and spatial attention in humans.

Adolescent↗

Experimentally verified, theoretical design of dual-tuned, low-pass birdcage radiofrequency resonators for magnetic resonance imaging and magnetic resonance spectroscopy of human brain at 3.0 Tesla.

A new theoretical method is presented for designing frequency responses of double-tuned, low-pass birdcage coils. This method is based on Kirchhoff's equations through a nonsymmetric matrix algorithm and extended through a modification of the corresponding eigenvalue system from a single-tuned mode. Designs from this method are verified for sodium/proton, dual-tuned, double-quadrature, low-pass birdcage coils at 1.5 Tesla and 3.0 Tesla and then are used to design dual-tuned, double-quadrature, lithium/proton and phosphorus/proton birdcage coils for 3.0 Tesla. All frequencies show experimental deviations of less than 3% from theory under unloaded conditions. The frequency shifts caused by loading and radiofrequency shielding are less than 1 MHz and can be compensated readily by adjustment of variable capacitors. Applications to human neuroimaging and spectroscopy are demonstrated.

Brain↗

Quantitative tissue sodium concentration mapping of the growth of focal cerebral tumors with sodium magnetic resonance imaging.

Tissue sodium concentration (TSC), as determined by in vivo 23Na magnetic resonance imaging (MRI) and the ex vivo classical 22Na radionuclide dilution assay (RDA), has been compared in a rat model of a focal glioma. The 23Na MRI method used a three-dimensional, twisted projection acquisition scheme at short echo time to minimize signal losses from relaxation of transverse magnetization. Calibration standards within the field of view allowed quantification of the sodium signal in terms of a TSC after correction for B1 nonuniformity and tissue water concentration. The 23Na MRI method measured focally increased TSC values in tumors that were equivalent statistically to the destructive 22Na RDA method. The noninvasive 23Na MRI method provided a quantitative means with which to monitor focal brain tumor growth.

Animals↗

Visual feedback to stabilize head position for fMRI.

Head motion is a common cause of technical failure in functional magnetic resonance imaging. A simple visual alignment system has been developed to provide visual feedback to the subject about his or her head position. The subject is able to readjust his or her head position accurately during a study, should motion occur. This sighting system is incorporated into a visor that fits onto the commercial head coil. The accuracy of correcting head motion and activation maps obtained with this device are demonstrated. The cognitive workload of using the alignment system does not significantly alter the activation pattern associated with eye movement paradigms.

Biofeedback, Psychology↗

An integrated head immobilization system and high-performance RF coil for fMRI of visual paradigms at 1.5 T.

A flexible quadrature radiofrequency coil that maximizes the signal-to-noise ratio over the field of view of the human brain has been integrated into a head immobilization and visor system for fMRI at 1.5 T. Head motion is reduced by the visor that incorporates a head clamp and a simple visual sighting system that provides feedback on head position. This system is demonstrated in serial images by correction of deliberate head motions. The sensitivity at the cortical surface of fMRI using blood oxygenation level dependent contrast is increased significantly above that of the commercial rigid volume RF coil under the same acquisition conditions. This improved performance is demonstrated using visual activation and eye movement paradigms.

Artifacts↗

Time course of fMRI-activation in language and spatial networks during sentence comprehension.

Functional neuroimaging previously has been considered to provide inadequate temporal resolution to study changes of brain states as a function of cognitive computations; however, we have obtained evidence of differential amounts of brain activity related to high-level cognition (sentence processing) within 1.5 s of stimulus onset. The study used an event-related paradigm with high-speed echoplanar functional magnetic resonance imaging (fMRI) to trace the time course of the brain activation in the temporal and parietal regions as participants comprehended single sentences describing a spatial configuration. Within the first set of images, on average 1 s from when the participant begins to read a sentence, there was significant activation in a key cortical area involved in language comprehension (the left posterior temporal gyrus) and visuospatial processing (the left and right parietal regions). In all three areas, the amount of activation during sentence comprehension was higher for negative sentences than for their affirmative counterparts, which are linguistically less complex. The effect of negation indicates that the activation in these areas is modulated by the difficulty of the linguistic processing. These results suggest a relatively rapid coactivation in both linguistic and spatial cortical regions to support the integration of information from multiple processing streams.

Adult↗

Functional organization of activation patterns in children: whole brain fMRI imaging during three different cognitive tasks.

1. Patterns of brain activation were measured with whole brain echo-planar functional magnetic resonance imaging (fMRI) at 3.0 Tesla in healthy children (N = 6) and in one child with a left-hemisphere encephalomalacic lesion as sequellae from early stroke. 2. Three cognitive tasks were used: auditory sentence comprehension, verb generation to line drawings, and mental rotation of alphanumeric stimuli. 3. There was evidence for significant bilateral activation in all three cognitive tasks for the healthy children. Their patterns of activation were consistent with previous functional imaging studies with adults. 4. The child with a left-hemisphere stroke showed evidence of homologous organization in the non-damaged hemisphere.

Adult↗

Clinical rationale for very-high-field (3.0 Tesla) functional magnetic resonance imaging.

The recent development of integrating very-high-field magnets (3.0 T) into clinical scanners was driven by the demonstration that both functional and anatomic information can be derived reliably at high spatial and temporal resolution. As very-high-field magnetic resonance imaging now approaches its entry into the clinical arena with a product by one major scanner manufacturer that is to be considered for Food and Drug Administration clearance, it is timely to consider the clinical applications that are likely to make such new technology significant in medical imaging. The rationale for very high field is based on the mechanism of blood oxygenation level-dependent contrast and the need for reliable functional studies on individual patients. The use of functional magnetic resonance imaging in the setting of presurgical planning is demonstrated in a number of different clinical scenarios. Such cases covering both pediatric and adult patients indicate that 3.0-T functional magnetic resonance imaging has an important role in neuroradiology.

Adolescent↗

Comprehensive MR imaging protocol for stroke management: tissue sodium concentration as a measure of tissue viability in nonhuman primate studies and in clinical studies.

PURPOSE: To investigate sodium magnetic resonance (MR) imaging for monitoring tissue viability in stroke. MATERIALS AND METHODS: A comprehensive MR imaging protocol used to measure apparent diffusion coefficient and perfusion parameters was extended to include sodium imaging. Tissue sodium concentration was estimated by using a two-compartment model. This protocol lasted less than 45 minutes. These parameters were followed over the first 6 hours in a nonhuman primate model (n = 2) of acute embolic stroke without or with thrombolytic therapy. This protocol was used in patients in whom acute (< 24 hours, n = 11) or nonacute (> or = 24 hours, n = 31) stroke was ultimately confirmed. RESULTS: The animal model showed abnormal diffusion and perfusion parameters in the lesion immediately after embolization, and these remained abnormal for over 6 hours. Tissue sodium concentration increased with time (5.7 mmol/L/h) unless halted with thrombolytic therapy. Regions with sodium concentrations over 70 mmol/L were histochemically verified as being infarcted. In patients in whom stroke older than 6 hours was clinically confirmed, sodium concentrations over 70 mmol/L were found in the appropriate brain regions. CONCLUSION: Tissue sodium concentration provides a sensitive measure of tissue viability that is complementary to the diagnostic role of diffusion and perfusion imaging for ischemic insult.

Adult↗

Plasticity of language-related brain function during recovery from stroke.

BACKGROUND AND PURPOSE: This study was undertaken to correlate functional recovery from aphasia after acute stroke with the temporal evolution of the anatomic, physiological, and functional changes as measured by MRI. METHODS: Blood oxygenation level-dependent contrast and echo-planar MRI were used to map language comprehension in 6 normal adults and in 2 adult patients during recovery from acute stroke presenting with aphasia. Perfusion, diffusion, sodium, and conventional anatomic MRI were used to follow physiological and structural changes. RESULTS: The normal activation pattern for language comprehension showed activation predominately in left-sided Wernicke's and Broca's areas, with laterality ratios of 0.8 and 0.3, respectively. Recovery of the patient confirmed as having a completed stroke affecting Broca's area occurred rapidly with a shift of activation to the homologous region in the right hemisphere within 3 days, with continued rightward lateralization over 6 months. In the second patient, in whom mapping was performed fortuitously before stroke, recovery of a Wernicke's aphasia showed a similar increasing rightward shift in activation recruitment over 9 months after the event. CONCLUSIONS: Recovery of aphasia in adults can occur rapidly and is concomitant with an activation pattern that changes from left to a homologous right hemispheric pattern. Such recovery occurs even when the stroke evolves to completion. Such plasticity must be considered when evaluating stroke interventions based on behavioral and neurological measurements.

Adult↗