Normative High-frequency MEG Database for Children (MEG)
Recruitment status was: Recruiting
The objective of this study is to characterize the normal neuromagnetic profile of sensorimotor, auditory, visual, and language cortices in children and adults using magnetoencephalography (MEG). We hope to build the world's first high-frequency MEG data for the developing brain. High-frequency neuromagnetic signals are associated with high-frequency oscillations (HFOs), ripple, fast ripple or high-gamma activation in the brain.
MEG is a new powerful tool for noninvasively measuring neuromagnetic signals originating from the brain. Since MEG can detect neuromagnetic signals with high spatial and temporal resolution, many brain properties can be studied. For pediatric purposes, MEG can (1) evaluate the functionalities of the sensorimotor, auditory, visual, and language systems non-invasively during normal maturation; (2) identify abnormalities in these functionalities that occur with neurological or neurodevelopmental disorders; and (3) provide a pre-operative "functional map" for neurosurgeons to improve surgical outcomes and decrease morbidity and mortality.
Previously MEG has been used to provide a single three-dimensional point that estimates the 'center' of cortical regions [1,2]. In this study three new techniques will be used to extend the usefulness of MEG beyond this point-like estimate of a cortical primary sensory input or motor output region. The three new techniques are independent component analysis, S-transform, and magnetic spatial filtering. The three new techniques for data analysis will be used in conjunction with non-invasive MEG data collection. The three techniques will provide us with the following important information about the brain: (1) the patterns of synchronization and de-synchronization of evoked cortical activation and (2) the volumetric extent of these active sensorimotor, auditory, visual and language cortices in children and adults. This approach may lead to a new way to study the brain functions in normal children and in children with various brain disorders.
|Study Design:||Time Perspective: Prospective|
|Official Title:||Localizing Sensorimotor, Auditory, Visual and Language Cortices With Magnetoencephalography|
|Study Start Date:||November 2006|
|Estimated Study Completion Date:||July 2012|
|Estimated Primary Completion Date:||July 2012 (Final data collection date for primary outcome measure)|
This normative study recruit healthy children.
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I. PURPOSE OF STUDY The purpose of this study is to characterize neuromagnetic activation in 0-3,000 Hz in normal children and adults using our state of the art MEG system. MEG is an instrument that allows for quantitative measurement of brain function with very high temporal and spatial resolution (see Appendix A). Conventional MEG data analysis methods focus on the magnetic signal in the time domain. In order to extend the usefulness of MEG, we will use three advanced signal-processing techniques to focus on the magnetic signal in the frequency domain. Our MEG system combined with the three advanced signal-processing techniques may open new windows to understanding development of the brain.
Specifically, we propose to study sensorimotor, auditory, visual and language evoked magnetic fields in normal children. Since the maturation of the brain may be associated with changes in the neuromagnetic signals generated in the sensorimotor, auditory, visual and language systems, one group of adults will be included to clarify the maturational changes. The normative data of the proposed study would be essential for identification of the abnormalities of the brain in various disorders; such data will be the foundation for development of clinical applications in children with MEG. The following aims and exploratory hypothesis will be probed:
Specific Aim 1. To characterize the evoked sensorimotor, auditory, visual and language evoked magnetic responses The working hypothesis for this aim is that at least one magnetic response will be identified in the averaged magnetic waveforms following sensorimotor, auditory, visual and language stimulation. The latency and amplitude of the evoked magnetic responses can be quantitatively measured and normal, age-adjusted ranges determined. Statistical comparisons between children and adults and across pediatric age ranges will be performed. Furthermore, we will characterize the neuromagnetic activation in each subgroup in children to estimate the maturational changes of the brain.
The hypotheses for this aim are all exploratory, as our intent is to gather normative data. The following are hypotheses with which we will probe our data:
- The neuromagnetic responses evoked by sensorimotor, auditory and visual stimulation be simple patterns.
- The neuromagnetic responses evoked by language stimulation would be a complex pattern.
- Among the four modalities, for latencies and amplitudes, sensorimotor evoked magnetic response will have the smallest coefficient of variation and language evoked responses will have the largest.
We have the hardware, software, techniques and skills to quantitatively measure and statistically compare the evoked magnetic responses. The MEG results in normal children will provide a foundation for future studies in diseased populations of children.
Specific Aim 2. To volumetrically localize the neuromagnetic spectral distributions evoked by sensorimotor, auditory, visual and language stimulation The working hypothesis for this aim is that the three-dimensional distribution of neuromagnetic spectral power can reveal the focal changes around sensorimotor, auditory, visual and language cortices in children. The development of the multichannel MEG system makes it possible to simultaneously record the neuromagnetic activation of the entire cortex. The newest magnetic signal processing techniques have the ability to reconstruct the three-dimensional neuromagnetic activation (see Appendix A, Figure 6, for an example). The frequency-spectral profile can provide novel information about the specific neural activation patterns in eloquent cortex. This exploratory aim will use the same data recorded for Specific Aim 1.
The hypotheses for this aim are:
- Each eloquent brain area (sensorimotor, auditory, visual and language cortex) may be associated with one or more specific frequency bands. The spectral power of certain frequency bands may increase at specific brain areas.
- High frequency oscillation can be identified in all the four modalities; however, the three-dimensional distributions of the high frequency oscillation are different across the modalities. The high frequency components may be identified before the conventional magnetic responses.
- Synchronization and de-synchronization can be observed in sensorimotor, auditory, visual and language systems. However, the frequency bands and regions are different among the four modalities.
The three techniques can measure in a reliable, non-biased, and quantitative magnetic manner, signals in the frequency domain. Since conventional MEG data analysis methods focus on magnetic signal in the time domain, the present study can provide a novel neuromagnetic profile of the brain in children. The new objective neuromagnetic parameters will enable us to quantitatively evaluate the brain function and maturation in normal children and possibly in children with brain disorders in the future.
Specific Aim 3. To quantitatively estimate neuromagnetic maturational changes in sensorimotor, auditory, visual and language systems in children The working hypothesis for this aim is that MEG combined with the three new signal processing techniques can reveal the maturational change of sensorimotor, auditory, visual and language systems in children. The proposed research focuses on children. We will recruit one group of adults as a reference, so that we can differentiate the neuromagnetic maturational change from inter-individual variation. Since most of the previous MEG reports [3,4] on functional brain mapping focus on adults, the MEG data from the adult group also allow us to compare our results with the results from other MEG sites. With the three new signal-processing techniques as well as the conventional methods, this study will provide quantitative data to estimate the maturational changes of the brain. This exploratory aim will use the same data recorded for Specific Aims 1 and 2.
The hypotheses for this aim are:
- In normal children, sensorimotor, auditory, visual evoked magnetic responses change linearly with age. However, language evoked magnetic responses may change nonlinearly due to the development of lateralization.
- The neuromagnetic differences between girls and boys may be observed in auditory, visual and language systems. However, this phenomenon may be only observable over certain ages.
- The maturational changes of the brain may be associated with frequency changes in normal children. The development of the brain in childhood through adulthood can be then quantitatively monitored using MEG.
Once we complete the studies for specific aim 1 and aim 2, we will address this aim. We consider that this aim can be directly addressed because we will have all the data, analysis software and hardware available. The maturational neuromagnetic results will enable us to objectively evaluate the brain function in various age groups. We consider that the results will contribute to the clinical management of children with developmental brain disorders.
II. SIGNIFICANCE OF STUDY IN RELATION TO HUMAN HEALTH Many disorders of cerebral function are associated with abnormal patterns of brain activity, which can be assessed using neurophysiology. Neurophysiologic measures can thus provide insight into the underlying biology of both normal and diseased brain.
MEG is an evolving, noninvasive technology which allows for very precise spatial and temporal measurements of neurophysiological function (see Appendix A). MEG measures very weak magnetic fields originating from the human brain . Its time resolution is under 1 millisecond, significantly shorter than that of functional magnetic resonance imaging (fMRI), and its spatial discrimination is 2-3 mm for sources in the cerebral cortex, much better than electroencephalography (EEG) [6,7]. MEG provides unique neurophysiologic data not obtainable by other neuroimaging techniques. The three advanced signal-processing methods can reveal aspects of neuronal function that previously could not be obtained by conventional MEG data analysis methods, such as averaging or dipole modeling.
We propose to use these MEG signal-processing techniques to characterize the normal neuromagnetic profile of children. Recent changes in the software which we employ in this study do not pose any additional risk to study participants. This study focuses on functional brain mapping using MEG in normal children. These maps will then be available for comparison to children with epilepsy and other neurological disorders.
For clinical purposes, there are at least two very valuable roles for MEG, functional mapping and determination of the locations of epileptic foci [3,4]. Neurosurgeons frequently face the dilemma of deciding whether operating to remove an epileptogenic region will cause greater harm than the pathology itself. This dilemma is greatest when there is reason to believe that the eloquent cortex involved is critical to either motor skills or speech skills. MEG can solve this problem by localizing critical brain regions and providing a "brain map" to guide the surgeons [3,4]. The "brain map" is also called magnetic source imaging (MSI). MSI is a combination of functional data derived from MEG recording co-registered with structural magnetic resonance imaging (MRI). MSI shows the anatomical location of the functional brain activity.
Functional brain mapping for children with intractable epilepsy is necessary to reduce surgical morbidity and has broad clinical applicability for several reasons. First, the prevalence, morbidity, and mortality of childhood epilepsy are high, and seizures in about 40% of patients cannot be controlled adequately by medication alone. In these patients, surgical treatment must be considered. Second, the spectrum of prenatally and postnatally acquired lesions in children with intractable seizures often creates difficulty in localization of epileptic regions using conventional EEG. Third, epileptogenic tissue is commonly not distinguishable from normal cortex in the operating room, making surgery guided by simple intraoperative visual inspection problematic and accurate pre-surgical anatomic localization critical. Fourth, the standard additional approach to intraoperative localization, which is electrocorticography (ECoG), is more invasive and risky. To record ECoG, the electrodes have to be placed directly on the brain. Disadvantages of the current approach include need for a craniotomy, risks of surgical complications like infection and intracerebral hemorrhage, and time delays during the operative procedure itself. In contrast, MEG is a non-invasive outpatient procedure. It reduces risk, time and expense for the patients.
In summary, the outcome of the proposed research will be significant. First of all, the normal MEG data obtained in this study will be the basis for identification of the abnormalities in various brain disorders in children. Second, the three new signal-processing methods can open new windows to understanding the brain function. Third, gaining greater experience with data acquisition and statistical analysis with this relatively new clinical tool will help us establish standardized routines for clinical applications. Moreover, the results of the present study can be directly transferred to epilepsy surgery to produce improved surgical outcomes.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00600717
|United States, Ohio|
|Cincinnati, Ohio, United States, 45229|
|Study Director:||Jing Xiang, Ph.D M.D.||Children's Hospital Medical Center, Cincinnati|
|Study Director:||Douglas Rose, M.D||Children's Hospital Medical Center, Cincinnati|