Evaluation Of MEG As A Current Source Imaging Technique
Yoshio Okada, Professor
University Of New Mexico Albuquerque Health Sciences Ctr, Financial Srvs Div. Albuquerque, Nm 87131
Grant 2R01NS030968-07A1 from National Institute Of Neurological Disorders And Stroke IRG: ZRG1
Abstract: The proposed study is a direct outgrowth of the research carried out over the past six years using a neonatal piglet model. Our research strongly indicates that the advantage of Magnetoencephalography (MEG) over Electroencephalography (EEG) should be clearest in an area that has thus far received little attention in non-invasive studies of brain functions, i.e. in the area of human neonatal brain research. Unlike the adults, the skull of the infants has fontanels and sutures which may be abnormally large in pathological cases. Our previous and ongoing studies imply that these openings should highly distort EEG, but not MEG signals. Moreover, the size of the fontanels and sutures as well as thickness of the scalp and skull change with age. These factors confer advantages to MEG, since it is insensitive to the skull, and by the same token to the scalp as well. In addition, the infant s skull and scalp are thin (2 mm for skull and 1 mm for scalp at birth). This makes it possible to measure the cortical activity with an exquisite sensitivity and spatial resolution at a distance of 3-4 mm from the brain surface using a special MEG sensor such as the microSQUID available in our laboratory and the babySQUID being developed by us with an SBIR phase I support. We will compare MEG and EEG in our piglet model in order to help develop the application of MEG in assessing brain functions of infants in both health and disease. The scalp and skull appear to be "transparent" to MEG signals since the signals above the scalp, skull and cortex are very similar unlike EEG. EEG signals are clearly distorted by defects in the skull such as a hole mimicking the fontanel in infants. Experimental and theoretical studies will be carried out to provide understanding of how the distortion is produced, and how the skull and scalp differentially attenuate EEG signals produced by sources at different depths. The insensitivity of MEG to skull defects will be quantitatively assessed by comparing the somatic evoked magnetic field (SEF) on the scalp and cortex, and (2) by evaluating how well the cortical SEF can be predicted from scalp SEF. The sensitivity of MEG measurements will be evaluated in a developmental study, by measuring the signal-to-noise ratio of SEFs as a function of age, so that the results can be used to extrapolate the signals expected from human infants using the babySQUID. Our ongoing study has shown that the sensitivity of the microSQUID is sufficiently high to measure the synchronized population spikes due to thalamocortical axonal terminals and excitatory cortical neurons. It is undoubtedly extremely important if such signals can be seen in infants. Thus, we will solidify this finding. The spatial resolution will be evaluated by obtaining an estimate of the current distribution in the cortex with a simple technique and the estimated active areas will be verified with intracortical recordings. The current imaging technique will be also used to test whether it can reveal a mass lesion in the cortex as a relatively silent area and the surrounding penumbra as an area of hyperexcitability in a current image of spontaneous activity over the cortex. We hope to use these results as the basis for planning an infant study which will be started as soon as the babySQUID becomes available.
Keywords: biomagnetism measurement, brain electrical activity, brain imaging /visualization /scanning, brain mapping, developmental neurobiology, magnetoencephalography, technology /technique development, age difference, biological model, brain disorder diagnosis, cell population study, computational neuroscience, electroencephalography, evoked potential, image enhancement, neuron, superconductivity, bioimaging /biomedical imaging, excitatory aminoacid, histology, magnetic resonance imaging, newborn animal, picrotoxin, swine, weanling animal
Project start date: 1993-08-01
Project end date: 2005-05-31
2R01NS030968-07A1 (2001): $306693
Sponsored Links Excellgen http://Excellgen.com
EVALUATION OF MEG AS A CURRENT SOURCE IMAGING TECHNIQUE
Yoshio Okada, Professor
Neurologyuniversity Of New Mexico
health Sciences Ctr, Financial Srvs Div.
albuquerque, Nm 87131
Grant 2R01NS030968-04 from National Institute Of Neurological Disorders And Stroke IRG: NEUA
Abstract: The proposed research is a direct extension of the research carried out in the previous 3 years. The capacity of magnetoencephalography (MEG) in identifying active tissues in the porcine brain will be evaluated in order to establish a solid empirical basis for interpreting MEG signals from gyrencephalic brains including the human brain. We will determine the subcortical generator responsible for the novel somatic evoked field (SEF) found to be generated by a structure deeper than the thalamus. This generator appears to be the spinal division of the trigeminal -nuclei that carries nociceptive information. If so, we will be demonstrating a capability of MEG with important clinical applications, i.e., the capability of detecting subcortical activities related to pain. Field potentials within the brain associated with this response were quite distinct from those associated with presumably cutaneous responses. We will use mechanical and electrical stimuli to stimulate the cutaneous and nociceptive pathways, and verify the differences in the pathways activated with depth recordings. The cortical areas receiving projections from these two pathways will be found with MEG and ECoG. Our ablation results indicated that the three areas (two areas in the primary somatosensory area (51) and one area in the secondary somatosensory area, 511) can be distinguished with MEG. We will also test whether multiple areas of activation found within the coronal 51 area correspond to areas 3b, 1 and 2 of the primate. In addition to the study of cortical projections from the peripheral afferents, we will study the cortico-cortical connections to determine whether MEG is useful for measuring such connections. The connections between the cortical areas identified from the above study will be investigated by electronically stimulating one area and recording induced activities in connected cortical areas within and across the hemispheres. Our MEG sensor is sensitive enough to record induced, time-locked by phase-unlocked cortical responses during single epochs from a specific cortical areas. Thus, we expect to be able to study the cortical connections. If this is feasible, we will be demonstrating a new capability of MEG for studying brain functions. Finally, we will use MEG to estimate the size of active tissue from the magnitude of SEF for early cortical responses and also by applying a linear estimating algorithm which has been shown to be capable of estimating not only size but also shape of active tissue in a sulcus on stimulated data. If this is the case for empirical data, we can demonstrate that size and perhaps shape of active tissue may be estimated with MEG
Keywords: brain electrical activity, evaluation /testing, magnetoencephalography brain disorder diagnosis, computational neuroscience, diagnosis design /evaluation, mathematical model, partial seizure, temporal lobe /cortex disorder human tissue, swine
Project start date: 1993-08-01
Project end date: 2000-01-31
2R01NS030968-04 (1997): $227944
Grants awarded to Yoshio Okada
PHYSIOLOGICAL BASES OF MAGNETOENCEPHALOGRAPHY
Yoshio Okada, Professor
Neurologyuniversity Of New Mexico
health Sciences Ctr, Financial Srvs Div.
albuquerque, Nm 87131
Grant 2R01NS021149-14 from National Institute Of Neurological Disorders And Stroke IRG: NEUA
Abstract: We will continue our effort to understand the genesis of magnetoencephalographic (MEG) signals in terms of the modern concepts of dendritic and somatic electrophysiology in order to help interpret MEG signals from the human brain in disease and health. Our work has characterized the MEG signals produced by guinea pig hippocampal slicers. Intracellular and extracellular field potential data was well as MEG signals were obtained after systematically blocking the various ligand-gated and voltage-and calcium-sensitive channels. This has brought our research to a new stage where it is possible to make some quantitative comparisons between the three types of signals and those generated by a mathematical model (Traub model) of CA3. The model we have used contains 100 excitatory cells and 20 inhibitory cells, each excitatory cell having two types of excitatory and inhibitory receptors and six different voltage- and calcium-sensitive conductances. We will Extend the Traub model to predict no only intracellular potentials, but also field potentials and MEG signals. Our modeling work has shown that the Traub model can be extended to make some quantitatively accurate predictions. We will first apply the extended model to account for the three sets of data collected thus far and identify the aspects of the data that are well explained by the model and those that are not. The comparisons will be used to revise the model to better account for the three data sets simultaneously. The revision will, for example include changes in the distribution of the channel densities and receptor site along the dendrites and addition of new channels. As the model is improved, it should be possible to infer with increasing levels of confidence the role of different types of currents in generating the MEG signals. Experimental analyses of this issue are often ambiguous even with the use of selective channel blockers. A mathematical model helps us clarity their roles since the currents can be separately calculated. On the basis of our work, we expect that the calcium conductance plays an important role in generating MEG signals and field potentials. The comparison will also be used as the basis for specifying a new set of experiments that will best characterize the role of individual channels in generating MEG signals. In one series of study, we will characterize the signals generated with synaptic transmissions blocked and the pyramidal cells directly excited. We will also combine the model and experiments to understand the MEG signals underlying spontaneous activities such as the gamma-oscillations discovered in the hippocampal slices. Our preliminary study indicates that such oscillation scan be recorded in our preparations
Keywords: biological signal transduction, brain electrical activity, computational neuroscience, magnetoencephalography, neurophysiology biomagnetism, dendrite, electric field, evoked potential, hippocampus, magnetic field, mathematical model, membrane channel, neural transmission, neuropharmacology, pyramidal cell guinea pig, single cell analysis, tissue /cell culture
Project start date: 1985-03-01
Project end date: 2002-06-30
2R01NS021149-14 (1998): $285885
5R01NS021149-17 (2001): $233483
5R01NS021149-16 (2000): $226683
5R01NS021149-15 (1999): $256759
5R01NS021149-22 (2008): $0
5R01NS021149-21 (2007): $276276
5R01NS021149-20 (2006): $284528
5R01NS021149-19 (2005): $291375
2R01NS021149-18 (2004): $291375
5R01NS021149-11 (1995): $189937
Sponsored Links Excellgen http://Excellgen.com
2R01NS021149-10 (1994): $180287
5R01NS021149-13 (1997): $205437
INTEGRATIVE PROGRAM IN CNS PATHOPHYSIOLOGY RESEARCH
Yoshio Okada, Professor
University Of New Mexico Health Sciences Ctr, Financial Srvs Div. Albuquerque, Nm 87131
Grant 5P20RR015636-05 from National Center For Research Resources IRG: ZRR1
Abstract: This is an application for the Institutional Development Award (IdeA) to establish a Center for Biomedical Research Excellence (COBRE) at the University of New Mexico (UNM) for carrying our research in CNS injury and pathophysiology using an integrative approach with a neuroimaging focus. One goal is to strengthen our existing unique neuroimaging facilities so that they become integrated into a state-of-the- art Center for applying functional neuroimaging techniques in brain research. UNM has developed a unique niche in neuroimaging over the past ten years with strengths in a number of areas including Magnetoencephalography (MEG), Magnetic Resonance Spectroscopy (MRS), and Optimal Imaging. We are also in the process of constructing an Electron Paramagnetic Resonance (EPR) facility for non-invasive measurements of free radicals in in vivo preparations. Four pieces of major equipment requested for the core of this COBRE would substantially strengthen our Center, enabling us to complete at the national level in various areas of neuroimaging applications. This includes the upgrades of an existing 4.7T MR scanner and in vivo EPR spectrometer for animal studies, and a photodiode array and a two-photon laser scanning microscope for cellular optimal imaging studies using in vitro and in vivo preparations. Our second goal is to utilize this research environment for increasing the productivity and quality of research of our faculty, especially the junior faculty members, so that we can increase the number of funded investigators at the regular individual NIH grant (R01) level. At UNM there is a group of successful senior investigators with active regular individual NIH grant (RO1) level. At UNM there is a group of senior investigators with active RO1-level funding in the area of CNS injury and pathophysiology with a neuroimaging focus who can establish a collaborative research team that can service to create an exciting and stimulating environment for fostering faculty development. The increase in the number of active investigators at our institution over the past decade makes the COBRE an ideal vehicle for faculty development. We have identified four promising junior faculty members working in the area of CNS injury and pathophysiology who can be directly helped with support from this IdeA grant to become independent scientists from R01- level funding. The COBRE Director and the senior investigator our team will serve as the mentors. The proposed research by these mentored investigators is multi-disciplinary and integrative, designed to produce a useful systematic longitudinal characterization of each type of pathophysiology and to provide new insights into the possible mechanisms of brain injury and recovery. To help create a stimulating research milieu, we propose to initiate a formal seminar series on neuro- pathophysiology, to annually organize a mini-symposium on timely thematic topics, and to administer a visiting scientist program. We have also formed a national advisory committee consisting of prominent scientists in our field who can guide us in the development of our COBRE, The progress of the junior faculty members in their scientific work will be monitored according to our mentorship program.
Keywords: central nervous system disorder, neuropathology, clinical research
Project start date: 2001-02-23
Project end date: 2006-01-31
5P20RR015636-05 (2005): $1951898
5P20RR015636-04 (2004): $1897587
5P20RR015636-03 (2003): $2045117
5P20RR015636-02 (2002): $1913708
1P20RR015636-01 (2001): $1927346
CORTICAL CURRENT IMAGING IN HUMAN INFANTS WITH BABYSQUID
Yoshio Okada
University Of New Mexico, Main Campus Preaward, Albuquerque, Nm 87131
Grant 5R21NS057614-02 from National Institute Of Neurological Disorders And Stroke
Abstract: This exploratory project will evaluate the usefulness of a newly developed instrument called baby SQUID for assessing brain functions in human infants. The baby SQUID is a high-resolution magnetoencephalography (MEG) system designed to detect cortical activity in infants with an unprecedented level of sensitivity and spatial resolution. An array of 76 MEG sensors can be placed 6 mm from the scalp, rather than -20 mm as in conventional MEGs. Since the combined thickness of scalp and skull is -4 mm in neonates, MEG signals can be measured at 10 mm, rather than 25 mm, from brain surface. Since MEG signals fall off as a square of distance, they should be as much as 5 times stronger for the baby SQUID compared to conventional MEG systems. In the next phase of development, the gap will be reduced from 6 mm to 3 mm so that the signals would be about 10 times stronger. The spatial resolution is about 3-4 times higher than the conventional systems because of the smaller gap and higher sensor density (12-14 mm channel spacing instead of 30-40 mm for adult MEGs). Preliminary results show that spontaneous activity can be measured clearly with high SNR and evoked activity can be measured with very little signal averaging from healthy infants. Unlike EEG, MEG signals are not distorted by the fontanels and sutures in the skull. This property of MEG greatly simplifies the interpretation of the signals. Due to these characteristics of MEG and baby SQUID, it is possible to perform a cortical current imaging (CCI). Instead of the dipole approach, our simulation study shows that the baby SQUID provides images of the cortical neuronal current distribution. We propose to use the CCI to determine cortical activity in healthy infants and infants with cerebral palsy (CP) and with neocortical epilepsy. Aim 1 will characterize the spontaneous activity from different regions of the brain with a focus on elucidating the basis of localized spindles seen in healthy babies. We predict that the generators can be identified due to the high sensitivity and spatial resolution. Aim 2 will measure spontaneous and somatically evoked activity in CP infants with hemiparesis. The evoked response will localize the projection areas of different parts of the body. Preliminary studies have shown a profound level of plasticity in both the affected and unaffected cortices. We predict that the spontaneous activity from these specific projection areas, identified by the CCI, is abnormal in the unaffected as well as affected side. Aim 3 will measure the epileptiform activity in infants with neocortical epilepsy. We predict that the CCI will be able to distinguish functionally discrete areas in the zone producing the spikes. Human brain development is an area of biomedical research that is still in its infancy because of difficulties in finding tools that are safe and yet powerful. We believe that this project, if successful, will open new windows into brain development in healthy infants as well as infants with various neurological disorders
Keywords: 0-11 years old; 21+ years old; 4-Aminobutanoic Acid; 4-Aminobutyric Acid; Adult; Affect; Aminalon; Aminalone; Appearance; Area; Beds; Biomedical Research; Birth; Body part; Bone structure of cranium; Brain; Brain region; Butanoic acid, 4-amino-; Cell Communication and Signaling; Cell Signaling; Cerebral Palsy; Characteristics; Child; Child Youth; Children (0-21); Cranium; Delta Wave; Delta Wave sleep; Depressed mood; Development; EEG; Electrical Resistance; Electroencephalography; Encephalon; Encephalons; Epilepsy; Epileptic Seizures; Epileptics; Evolution; GABA; Head; Hemipareses; Human; Human, Adult; Human, Child; Human, General; Image; Infant; Infarction; Intracellular Communication and Signaling; Invasive; Investigators; Life; Localized; Magnetoencephalography; Man (Taxonomy); Man, Modern; Measurement; Measures; Nerve Cells; Nerve Unit; Nervous; Nervous System Diseases; Nervous System, Brain; Neural Cell; Neurocyte; Neurologic Disorders; Neurological Disorders; Neurons; Noise; Operation; Operative Procedures; Operative Surgical Procedures; Parturition; Patients; Pattern; Perinatal; Phase; Programs (PT); Programs [Publication Type]; Property; Property, LOINC Axis 2; Research Personnel; Researchers; Resistance, Electric; Resolution; Scalp; Scalp structure; Seizure Disorder; Side; Signal Transduction; Signal Transduction Systems; Signaling; Skull; Sleep; Slow-Wave Sleep; Source; Squid; Surface; Surgical; Surgical Interventions; Surgical Procedure; Surgical sutures; Sutures; System; System, LOINC Axis 4; Theta Rhythm; Thick; Thickness; Time; adult human (21+); base; biological signal transduction; children; cranium; density; depressed; design; designing; epilepsia; epileptiform; epileptogenic; falls; gamma-Aminobutyric Acid; hemiparetic; imaging; improved; infancy; infantile; infarct; instrument; magnetic field; neocortical; neonate; nervous system disorder; neural; neurological disease; neuronal; next generation; programs; prototype; relating to nervous system; response; sadness; sensor; simulation; surgery; tool; youngster
Project start date: 2007-06-01
Project end date: 2010-05-31
Budget start date: 1-JUN-2008
Budget end date: 31-MAY-2010
PFA/PA: PA-03-107
5R21NS057614-02 (2008): $0
1R21NS057614-01 (2007): $196875
FUNCTIONS OF FRONTAL LOBE IN SHORT TERM MEMORY
Yoshio Okada, Professor
Physics And Astronomyuniversity Of New Mexico
health Sciences Ctr, Financial Srvs Div.
albuquerque, Nm 87131
Grant 1F06TW002063-01 from Fogarty International Center IRG: BNS
Abstract: The study of electrophysiology of higher brain functions has become possible with the successful development of a 122-channel whole-head MEG (magnetoencephalography) system for non-invasively measuring the magnetic field outside the human head (Lounasmaa et al., IBRO NEWS, 21(2), 1993). In the proposed study we will utilize this whole-head system to detect spontaneous MEG signals from the frontal lobe of healthy volunteers during an alert rest period, during a short-term memory task, and finally again during a rest period. The memory task will consist of a presentation of a set of items to be remembered (i.e. spatial positions of items in the visual field, tone of differing pitches or words presented either visually or auditorily), followed by a retention period, and finally by a test phase where old and new items will be presented to test recognition memory. The coherence of spontaneous MEG activity will be measured to detect activities in the frontal lobe during the rest and retention periods. Localized changes in the coherence pattern will indicate the involvement of the frontal lobe in short-term memory. Asymmetry of the coherence pattern across the hemispheres will be also examined. Temporal kinetics of cortical involvement will be inferred from temporal changes in the coherence pattern during the retention period. Unlikely in previous studies of coherence, we will also examine the source coherence by solving for the source covariance matrix from the MEG covariance maori and test for the source activities in the frontal region during a retention interval. This study may open a new area of application for MEG namely in measuring functions of the associative areas of both healthy people and patients with neurological diseases
1F06TW002063-01 (1994): $8890
Sponsored Links Excellgen http://Excellgen.com
A STUDY OF THE NEURAL BASES OF MAGNETOENCEPHALOGRAM
Yoshio Okada, Professor
New York University Office Of Sponsored Programs New York, Ny 100122331
Grant 5R01NS021149-03 from National Institute Of Neurological Disorders And Stroke IRG: NEUA
Abstract: The relationship between current sources in a brain tissue and the magnetic field outside the brain will be studied directly on isolated brain preparations as well as on partially intact preparations in order to provide a firm basis for the interpretation of the extracranial magnetic field of the brain (MEG). The relationship of the MEG has been inferred on the basis of theoretical results that hold for model sources and volume conductors, but has not been directly determined, since the research has been limited to human MEGs. To directly study the relationship, a current source will be set up in the cerebellum of turtles and guinea pigs immersed in a Ringer solution and it will be characterized in terms of the distribution of "current-sources" and "current-sinks" in the active tissue by applying the current source-density (CSD) analysis. Then the magnetic field outside the brain tissue will be calculated by applying the law of Biot and Savart to each current element represented by a current source-sink pair. Finally the computed field will be compared with the actual field. The comparison should reveal whether the external field is indeed due solely to the component of the current in the active tissue tangential to the outer boundary of the volume conductor, without any contribution from the normal component of the current or from sources set up by the volume current, as commonly assumed today. Inversely, the location and size of single and multiple sources will be estimated from measured fields and compared with those determined with the CSD analysis in order to evaluate the accuracy of source localization based on point source and distributed source models that incorporate the assumptions about the relative contributions of tangential and normal current sources and sources set up by the volume current.
Keywords: BRAIN ELECTRICAL ACTIVITY, MAGNETOENCEPHALOGRAPHY, DIAGNOSTIC QUALITY-STANDARDS, ELECTRICITY-MAGNETISM, MAGNETIC FIELDS, NEUROLOGY A STUDY SECTION, brain electrical activity, BRAIN, RHOMBENCEPHALON, CEREBELLUM, DIAGNOSTIC TESTS, NON-INVASIVE, NEUROPHYSIOLOGY (GENERAL), MAMMALS, RODENTS, HYSTRICOMORPHA, GUINEA PIGS, REPTILES, TURTLES
Project start date: 1985-03-01
Project end date: 1988-02-29
Evaluation Of MEG As A Current Source Imaging Technique
Yoshio Okada, Professor
University Of New Mexico Albuquerque Health Sciences Ctr, Financial Srvs Div. Albuquerque, Nm 87131
Grant 5R01NS030968-10 from National Institute Of Neurological Disorders And Stroke IRG: ZRG1
Abstract: The proposed study is a direct outgrowth of the research carried out over the past six years using a neonatal piglet model. Our research strongly indicates that the advantage of Magnetoencephalography (MEG) over Electroencephalography (EEG) should be clearest in an area that has thus far received little attention in non-invasive studies of brain functions, i.e. in the area of human neonatal brain research. Unlike the adults, the skull of the infants has fontanels and sutures which may be abnormally large in pathological cases. Our previous and ongoing studies imply that these openings should highly distort EEG, but not MEG signals. Moreover, the size of the fontanels and sutures as well as thickness of the scalp and skull change with age. These factors confer advantages to MEG, since it is insensitive to the skull, and by the same token to the scalp as well. In addition, the infant s skull and scalp are thin (2 mm for skull and 1 mm for scalp at birth). This makes it possible to measure the cortical activity with an exquisite sensitivity and spatial resolution at a distance of 3-4 mm from the brain surface using a special MEG sensor such as the microSQUID available in our laboratory and the babySQUID being developed by us with an SBIR phase I support. We will compare MEG and EEG in our piglet model in order to help develop the application of MEG in assessing brain functions of infants in both health and disease. The scalp and skull appear to be "transparent" to MEG signals since the signals above the scalp, skull and cortex are very similar unlike EEG. EEG signals are clearly distorted by defects in the skull such as a hole mimicking the fontanel in infants. Experimental and theoretical studies will be carried out to provide understanding of how the distortion is produced, and how the skull and scalp differentially attenuate EEG signals produced by sources at different depths. The insensitivity of MEG to skull defects will be quantitatively assessed by comparing the somatic evoked magnetic field (SEF) on the scalp and cortex, and (2) by evaluating how well the cortical SEF can be predicted from scalp SEF. The sensitivity of MEG measurements will be evaluated in a developmental study, by measuring the signal-to-noise ratio of SEFs as a function of age, so that the results can be used to extrapolate the signals expected from human infants using the babySQUID. Our ongoing study has shown that the sensitivity of the microSQUID is sufficiently high to measure the synchronized population spikes due to thalamocortical axonal terminals and excitatory cortical neurons. It is undoubtedly extremely important if such signals can be seen in infants. Thus, we will solidify this finding. The spatial resolution will be evaluated by obtaining an estimate of the current distribution in the cortex with a simple technique and the estimated active areas will be verified with intracortical recordings. The current imaging technique will be also used to test whether it can reveal a mass lesion in the cortex as a relatively silent area and the surrounding penumbra as an area of hyperexcitability in a current image of spontaneous activity over the cortex. We hope to use these results as the basis for planning an infant study which will be started as soon as the babySQUID becomes available.
Keywords: biomagnetism measurement, brain electrical activity, brain imaging /visualization /scanning, brain mapping, developmental neurobiology, magnetoencephalography, technology /technique development, age difference, biological model, brain disorder diagnosis, cell population study, computational neuroscience, electroencephalography, evoked potential, image enhancement, neuron, superconductivity, bioimaging /biomedical imaging, excitatory aminoacid, histology, magnetic resonance imaging, newborn animal, picrotoxin, swine, weanling animal
Project start date: 1993-08-01
Project end date: 2006-05-31
5R01NS030968-10 (2004): $315000
5R01NS030968-09 (2003): $315000
PHYSIOLOGICAL BASES OF MAGNETOENCEPHALOGRAPHY
Yoshio Okada, Professor
University Of New Mexico Albuquerque Health Sciences Ctr, Financial Srvs Div. Albuquerque, Nm 87131
Grant 5R01NS021149-09 from National Institute Of Neurological Disorders And Stroke IRG: NEUA
Abstract: The proposed study extends our previous work on the physiological basis of magnetoencephalography (MEG) carried out with support from NINDS. The usefulness of MEG as a non-invasive technique depends very much on whether it can be used to determine the distribution of neuronal currents in the brain that reflect abnormal as well as normal neuronal activity. Our previous results with an in vitro cerebellar preparation indicated that the magnetic evoked field (MEF) may be directly related to intracellular currents produced by active neurons with the strong contribution coming from dendritic currents. These results have motivated our proposal here to determine the MEF that can be produced by different types of currents in the dendrites. The concept of post- synaptic currents has undergone dramatic transformations in the past twenty years with the discoveries of active conductances in the dendrites that can produce spikes in dendrites. These discoveries call for a re-examination of the role of dendritic currents in the generation of magnetic field as well as evoked potential. For this purpose we have received an instrumentation grant from National Science Foundation and installed a 4-channel, high-resolution magnetometer (muSQUID) that has a sensitivity of as much as 30-300 times the sensitivity of the more conventional, superconducting sensor we have used in our earlier studies. Its sensitivity enables us to see the MEF produced by a tissue as small as 1 mm3 without averaging with a bandwidth of 1 kHz. Our plan is to measure the MEF produced by the pyramidal cells in the longitudinal slice of the CA3 of the guinea pig hippocampus in the presence of various selective channel blockers and to interpret the MEF with the aid of the mathematical model developed by R. Traub of IBM. Traub model incorporates six active conductances (gNa, gCa, gk(DR), gA, gK(C), and gK(AHP) and NMDA-and quisqualate-channels within each cell and connects such cell with excitatory synaptic connections. This model and its earlier versions have been successfully used to account for intracellular potential in CA3. Based on this analysis we expect to be able to determine the relative contributions of these conductances to the MEF and, by extrapolation, to the evoked potential as well. The second series of study will evaluate the ability of MEG to determine the underlying current distribution. The usefulness of MEG will be limited unless one addresses this issue of MEG as a current-imaging tool. Therefore, we shift out approach from that of the earliest studies in biomagnetism which addressed the issue of accuracy of localization of the current dipole generation of MEF, and consider whether one can correctly infer the distribution of cortical activity based solely on measured external MEFs. Our plan is to produce simple and complex patterns of activation in the somatosensory cortex of a juvenile swine with a transcutaneous stimulation of the somatic afferents, measure the MEF directly over the exposed intact dura of this large brain (6x4x4 cm), then solve the inverse problem with minimum norm estimation algorithms and estimate the current distribution over the epidural and cortical surfaces. The prediction will be verified directly with a set of epi-and intracortical potential recordings over each of predicted active areas and with pharmacological manipulations.
Keywords: biomagnetism, brain electrical activity, magnetic field, magnetoencephalography, neuropharmacology, neurophysiology, cadmium, calcium channel blocker, carbachol, dendrite, diagnosis quality /standard, electric field, evoked potential, excitatory aminoacid, hippocampus, lidocaine, manganese, mathematical model, membrane channel, membrane permeability, membrane potential, neural conduction, noninvasive diagnosis, norepinephrine, picrotoxin, pyramidal cell, pyridine, somesthetic sensory cortex, superconductivity, tetraethylammonium compound, tetrodotoxin, computer processing of laboratory data, digital imaging, electrode, guinea pig, histology, swine
Project start date: 1985-03-01
Project end date: 1994-04-30
5R01NS021149-09 (1993): $135226
2R01NS021149-08 (1992): $150534
EVALUATION OF MEG AS A CURRENT SOURCE IMAGING TECHNIQUE
Yoshio Okada, Professor
Neurologyuniversity Of New Mexico
health Sciences Ctr, Financial Srvs Div.
albuquerque, Nm 87131
Grant 5R01NS030968-02 from National Institute Of Neurological Disorders And Stroke IRG: NEUA
Abstract: The proposed research will examine the usefulness of magnetoencephalography (MEG) as a technique for visualizing neuronal activity in the form of current patterns in the brain. Electric current is an important modality for imaging functions of the brain, since it reflects neuronal activity with a millisecond time resolution. However, there are still very few validation studies of MEG as a current source imaging technique using an animal model that is directly comparable to the human brain. We, therefore, propose to rigorously evaluate the accuracy of MEG in identification of electrically active neuronal tissues in a gyrencephalic brain. MEG will be evaluated in comparison with electroencephalography (EEG), since MEG and EEG are closely related complementary techniques for inferring current source distributions. The MEG and EEG will be evaluated by studying the somatic evoked fields (SEFs) and potentials (SEPs) of an in vivo swine preparation that has a large, well-developed gyrencephalic brain. the somatosensory cortex receiving projections from the snout will be activated by electrical stimulations of the afferents. The resulting SEF will be measured over the exposed intact scalp (with hairs removed), intact skull and intact dura at a measurement distance of 2 mm from each of these surfaces, using a high-resolution, 4-channel superconducting MEG sensor. The SEP will be also measured from the same animal over the scalp, exposed skull, and exposed cortex at nearly 100 locations, using a multi-channel array of electrodes. The active sites will be deduced during the experiment and intracortical electrodes will be inserted at inferred active locations in the cortex to determine whether there are polarity reversals in the laminar field potential profile. Preliminary experiments indicate that these measurements are feasible within the same preparation. The accuracy of localization will be evaluated not only with electrocorticogram (ECoG) and the intracortical recordings, but also with pharmacological and surgical lesions of the active sites or surrounding presumably non-active regions. In some experiments extracellular unit recordings will be carried out. After these measurements, the brain will be photographed and the shape of the dorsal surface of the brain will be determined with a laser-beam scanner for the purpose of calibrating the histological 3-D reconstruction of the brain and, in some cases, for calibrating the 3-D reconstruction of the MRI image of the brain. At the end of the experiment the animal will be euthanized and the perfused brain will be removed for a 3-D histological reconstruction to correlate with the locations of active sites deduced from the MEG and EEG measurements. Such comparisons will be carried out on the normal brain and on brains with lesions in the cortex to infer the effect of mass lesions on the accuracy of source localization in human MEG studies. Various algorithms will be evaluated for their accuracy in identifying locations of single and multiple active sites, since our preparation is ideal for direct evaluations. The algorithms to be tested will include not only the conventional single and multiple dipole models, but also the multiple signal classification (MUSIC) method and covariance methods employing Wiener filter
Keywords: brain electrical activity, brain scanning, evaluation /testing, magnetoencephalography, somesthetic sensory cortex biological model, dura mater, evoked potential, experimental brain lesion, magnetic field, scalp, skull, somatic afferent nerve digital imaging, electroencephalography, electronic stimulator, magnetic resonance imaging, photography, swine
Project start date: 1993-08-01
Project end date: 1996-07-31
5R01NS030968-02 (1994): $149557
1R01NS030968-01A1 (1993): $139402
3R01NS030968-06S1 (2000): $61168
5R01NS030968-06 (1999): $225414
Sponsored Links Excellgen http://Excellgen.com
5R01NS030968-05 (1998): $219745
ADMIN: PROGRAM IN CNS PATHOPHYSIOLOGY RESEARCH
Yoshio Okada, Professor
University Of New Mexico Health Sciences Ctr, Financial Srvs Div. Albuquerque, Nm 87131
Grant 5P20RR015636-030005 from National Center For Research Resources IRG: ZRR1
Abstract: SUBPROJECT NOT AVAILABLE
PHYSIOLOGICAL BASES OF MAGNETOENCEPHALOGRAPHY
Yoshio Okada, Professor
University Of New Mexico Albuquerque Health Sciences Ctr, Financial Srvs Div. Albuquerque, Nm 87131
Grant 5R01NS021149-07 from National Institute Of Neurological Disorders And Stroke IRG: NEUA
Abstract: As in our previous application, the general aim of this proposal is to study the physiological basis of magnetoencephalograms (MEGs) in order to help interpret non-invasively obtained human MEGs. Continuing and extending our previous work, we propose (1) to elucidate the nature of the currents that may give rise to the MEG, (2) to characterize the relationship between the MEG and its underlying currents in different structures of a mammalian brain and (3) to characterize the magnetic field associated with spreading depression (SD) and anoxia. Specifically, we will determine the relative contributions intraneuronal, extracellular and glial currents to the MEG in the isolated turtle cerebellum by, first of all, constructing a mathematical model that incorporates various ionic conductances in a model neuron, K+-mediated currents in the ependymal glia and ionic currents in the extracellular space and them comparing its predictions to the MEGs data to be obtained in a series of experiments in which Na-, K- and Ca-conductances and (K+) are manipulated. We will also evaluate the relative the contributions to the MEG Na- and Ca- conductances in the neuronal soma and dendrites of isolated turtle cerebellum and guinea-pig cerebellar slice by manipulating ionic composition of the bathing medium and blocking one type of conductance and then measuring the MEG due to these conductances separately. Issue two will be addressed by comparing the MEG-current relationships in the slice preparations of the primary sensorimotor cortex and its thalamocortical radiation fibers, hippocampus, cerebellum and thalamus of the guinea pig. Slice preparations are chosen, for they enable us to orient the principal core conductors horizontally in the bathing medium medium just below the detector in order to maximize the MEG as to these conductors. Regarding SD and anoxia, our work indicates that a strong magnetic field is produced during the initial stage of SD in turtle cerebellum unlike the extracellular potential which often outlasts the MEG. We will test whether this difference temporal waveform is due to a strong transcortical current in the initiation stage of and whether such a strong current is produced during the anoxic depolarization as suggested by various lines of indirect evidence. Also the origin of dc potential during and anoxia will be studied by evaluating roles of the spatial buffer mechanism and Nernst potential in producing such a potential. Furthermore, the MEG associated with the transversal current at the propagating wavefront of SD will be measured. These results taken together will be used to interpret the MEG to be measured from intact during SD and anoxia.
Keywords: BRAIN ELECTRICAL ACTIVITY, MAGNETOENCEPHALOGRAPHY, DIAGNOSTIC QUALITY-STANDARDS, DIAGNOSTIC TESTS, NON-INVASIVE, ELECTRICITY-MAGNETISM, MAGNETIC FIELDS, biomagnetism, brain electrical activity, neurophysiology, BIOLOGICAL TRANSPORT, MEMBRANE PERMEABILITY AND TRANSPORT, ANIMALS, CHORDATES, BIRDS, CHICKENS, ANIMALS, CHORDATES, MAMMALS, RODENTS, HYSTRICOMORPHA, GUINEA PIGS, ANIMALS, CHORDATES, MAMMALS, RODENTS, MYOMORPHA, RATS (LABORATORY), ANIMALS, CHORDATES, REPTILES, TURTLES
Project start date: 1985-03-01
Project end date: 1991-11-30
Yoshio Okada
Moment Technologies, Llc
Project start date: 2011-08-01
Project end date: 2012-01-31
Integrative Program In CNS Pathophysiology Research
Yoshio Okada, Professor
University Of New Mexico Health Sciences Ctr, Financial Srvs Div. Albuquerque, Nm 87131
Grant 5P20RR015636-07 from National Center For Research Resources IRG: ZRR1
Keywords: brain disorder, neuropathology
Project start date: 2001-02-23
Project end date: 2011-02-28
5P20RR015636-07 (2007): $2101891
2P20RR015636-06 (2006): $2175103
3P20RR015636-04S1 (2004): $97715
EVALUATION OF MEG AS A CURRENT SOURCE IMAGING TECHNIQUE
Yoshio Okada, Professor
Neurologyuniversity Of New Mexico
health Sciences Ctr, Financial Srvs Div.
albuquerque, Nm 87131
Grant 3R01NS030968-05S1 from National Institute Of Neurological Disorders And Stroke IRG: NEUA
Project start date: 1993-08-01
Project end date: 2000-01-31
3R01NS030968-05S1 (1998): $68852
Sponsored Links Excellgen http://Excellgen.com
PHYSIOLOGICAL BASES OF MAGNETOENCEPHALOGRAPHY
Yoshio Okada, Professor
University Of New Mexico Albuquerque Health Sciences Ctr, Financial Srvs Div. Albuquerque, Nm 87131
Grant 5R01NS021149-12 from National Institute Of Neurological Disorders And Stroke IRG: NEUA
Project start date: 1985-03-01
Project end date: 1998-04-30
5R01NS021149-12 (1996): $197536
EVALUATION OF MEG AS A CURRENT SOURCE IMAGING TECHNIQUE
Yoshio Okada, Professor
University Of New Mexico
health Sciences Ctr, Financial Srvs Div.
albuquerque, Nm 87131
Grant 3R01NS030968-01A1S1 from National Institute Of Neurological Disorders And Stroke IRG: NEUA
Project start date: 1993-08-01
Project end date: 1996-07-31
3R01NS030968-01A1S1 (1993): $31682