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.
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