Pamela Murphy

Fetal MEG redistribution by projection operators

The fetal magnetoencephalogram (fMEG) is measured in the presence of large interference from the maternal and fetal magnetocardiograms. This interference can be efficiently attenuated by orthogonal projection of the corresponding spatial vectors. However, the projection operators redistribute the fMEG signal among sensors. Although redistribution can be readily accounted for in the forward solution, visual interpretation of the fMEG signal topography is made difficult. We have devised a general, model-independent method for correction of the redistribution effect that utilizes the assumption that we know in which channels the fMEG should be negligible (such channels are distant from the known fetal head position). In a simplified case where the fMEG can be explained by equivalent current dipoles, the correction can also be obtained from fitting the dipoles to the fMEG signal. The corrected fMEG signal topography then corresponds to the dipole forward solution, but without orthogonal projection. We illustrate the redistribution correction on an example of experimentally measured flash evoked fMEG.

Development of auditory evoked fields in human fetuses and newborns: A longitudinal MEG study

OBJECTIVE To investigate the maturation of the auditory cortex by non-invasive recording of auditory evoked magnetic fields in human fetuses and newborns with the relatively novel and completely non-invasive technology of MEG. METHODS Serial recordings were performed every 2 weeks on 18 fetuses beginning from week 27 of gestational age until term with a follow-up recording on the newborn. Auditory stimulation consisted of tone bursts in an oddball design with standard tones and deviant tones. RESULTS In 52 of 63 fetal and in all of the neonatal recordings an auditory evoked magnetic field was obtained. A decrease in latency with increasing age of the subjects was observed in the combined analysis of fetuses and neonates. CONCLUSIONS With advanced study using MEG, 83% of the measurements showed auditory evoked fields in fetuses that correspond with existing literature in electrophysiology in the past. These findings indicate that MEG is a technique that can be used to investigate maturation of the auditory cortex based on auditory evoked fields in fetuses and neonates. SIGNIFICANCE Maturational changes have been examined in the past. With the use of this novel technique, applied to a serial study, it is possible to trace the development of auditory responses in utero and newborns.

Human fetal brain imaging by magnetoencephalography: verification of fetal brain signals by comparison with fetal brain models.

Fetal magnetoencephalogram (fMEG) is measured in the presence of a large interference from maternal and fetal magnetocardiograms (mMCG and fMCG). This cardiac interference can be successfully removed by orthogonal projection of the corresponding spatial vectors. However, orthogonal projection redistributes the fMEG signal among channels. Such redistribution can be readily accounted for in the forward solution, and the signal topography can also be corrected. To assure that the correction has been done properly, and also to verify that the measured signal originates from within the fetal head, we have modeled the observed fMEG by two extreme models where the fetal head is assumed to be either electrically transparent or isolated from the abdominal tissue. Based on the measured spontaneous, sharp wave, and flash-evoked fMEG signals, we have concluded that the model of the electrically isolated fetal head is more appropriate for fMEG analysis. We show with the help of this model that the redistribution due to projection was properly corrected, and also, that the measured fMEG is consistent with the known position of the fetal head. The modeling provides additional confidence that the measured signals indeed originate from within the fetal head.

Optimal reduction of MCG in fetal MEG recordings

Recording fetal magnetoencephalographic (fMEG) signals in-utero is a demanding task due to biological interference, especially maternal and fetal magnetocardiographic (MCG) signals. A method based on orthogonal projection of MCG signal space vectors (OP) was evaluated and compared with independent component analysis (ICA). The evaluation was based on MCG amplitude reduction and signal-to-noise ratio of fetal brain signals using exemplary datasets recorded during ongoing studies related to auditory evoked fields. The results indicate that the OP method is the preferable approach for attenuation of MCG and for preserving the fetal brain signals in fMEG recordings

Analysis of uterine contractions: a dynamical approach

The development of suitable techniques for quantifying mechanical and electrophysiological aspects of uterine contractions has been an active area of research. The uterus is a physiological system consisting of a large number of interacting muscle cells. The activity of these cells evolves with time, a trait characteristic of a dynamical system. While such complex physiological systems are non-linear by their very nature, whether this non-linearity is exhibited in the external recording is far from trivial. Traditional techniques such as spectral analysis have been used in the past, but these techniques implicitly assume that the process generating the contractions is linear and hence may be biased. In this tutorial review, a systematic approach using a hierarchy of surrogate algorithms is used to determine the nature of the process generating the contractions produced during labor. The results reveal that uterine contractions are probably generated by non-linear processes. The contraction segments were obtained through simultaneous recordings of the electrical and magnetic signals corresponding to the electrophysiological activity of the uterus and then analyzed. The electrical activity was recorded by placement of non-invasive electrodes onto the maternal abdomen and magnetic activity was recorded non-invasively using a superconducting quantum interference device (SQUID).

A fast algorithm for detecting contractions in uterine electromyography

Discusses a method of higher-order zero crossings, which was found to be an effective tool for signal analysis. This method mirrors the spectral characteristics of certain Gaussian and non-Gaussian processes. The authors use this method to discriminate between contraction segments interspersed in a uterine EMG recorded from the abdominal surface. They also describe a schematic circuit that can be implemented for fast on-line detection of contraction segments.

Neonatal and fetal response decrement of evoked responses: A MEG study

OBJECTIVE To investigate the response decrements of visual evoked responses (VER) in newborns and assess the applicability of this paradigm to fetuses in magnetoencephalographic (MEG) recordings. METHODS Twelve newborns with no known risks or complications participated at chronological ages between 6 and 22days. They constituted the follow-up group to a prenatal study conducted on a sample of 25 fetuses whose gestational age (GA) varied between 29 and 37weeks at the time of recording. Trains of four light flashes with an interstimulus interval of 2s followed by 10s without stimulation were delivered to record VER. RESULTS Nine of the 12 newborns responded to the stimulation and showed response decrements in amplitude from the first to the last light flash. Furthermore, the response latency increased significantly from the first to the last stimulus. The remaining three recordings were discontinued early. Even though the prenatal visual evoked response rate was only 29%, the fetuses exhibited a response decrement after the first stimulus. CONCLUSIONS The amplitude of VERs can be used to elicit a response decrement in newborns and, with limitations, even in fetuses. This paradigm might be a useful tool for a direct non-invasive assessment of neonatal and prenatal brain development and CNS functioning. SIGNIFICANCE The proposed method might be a first step towards an early detection of developmental deficits in newborns and fetuses.

Habituation of visual evoked responses in neonates and fetuses: A MEG study

In this study we aimed to develop a habituation paradigm that allows the investigation of response decrement and response recovery and examine its applicability for measuring the habituation of the visually evoked responses (VERs) in neonatal and fetal magnetoencephalographic recordings. Two paradigms, one with a long and one with a short inter-train interval (ITI), were developed and tested in separate studies. Both paradigms consisted of a train of four light flashes; each train being followed by a 500Hz burst tone. Healthy pregnant women underwent two prenatal measurements and returned with their babies for a neonatal investigation. The amplitudes of the neonatal VERs in the long-ITI condition showed within-train response decrement. An increased response to the auditory dishabituator was found confirming response recovery. In the short-ITI condition, neonatal amplitude decrement could not be demonstrated while response recovery was present. In both ITI conditions, the response rate of the cortical responses was much lower in the fetuses than in the neonates. Fetal VERs in the long-ITI condition indicate amplitude decline from the first to the second flash with no further decrease. The long-ITI paradigm might be useful to investigate habituation of the VERs in neonates and fetuses, although the latter requires precaution.

Bootstrap significance of low SNR evoked response

In order to obtain adequate signal to noise ratio (SNR), stimulus-evoked brain signals are averaged over a large number of trials. However, in certain applications, e.g. fetal magnetoencephalography (MEG), this approach fails due to underlying conditions (inherently small signals, non-stationary/poorly characterized signals, or limited number of trials). The resulting low SNR makes it difficult to reliably identify a response by visual examination of the averaged time course, even after pre-processing to attenuate interference. The purpose of this work was to devise an intuitive statistical significance test for low SNR situations, based on non-parametric bootstrap resampling. We compared a two-parameter measure of p-value and statistical power with a bootstrap equal means test and a traditional rank test using fetal MEG data collected with a light flash stimulus. We found that the two-parameter measure generally agreed with established measures, while p-value alone was overly optimistic. In an extension of our approach, we compared methods to estimate the background noise. A method based on surrogate averages resulted in the most robust estimate. In summary we have developed a flexible and intuitively satisfying bootstrap-based significance measure incorporating appropriate noise estimation.

TESTING FOR NONLINEARITY OF THE CONTRACTION SEGMENTS IN UTERINE ELECTROMYOGRAPHY

In this report, we test for possible nonlinearity of the contraction segments interspersed in a uterine electromyography (EMG), recorded externally with abdominal electrodes. There have been several reports in which the uterine contractility had been assumed to be an auto-regressive process and others have hypothesized it as a nonlinear process and possibly chaotic. The surrogate data testing was used successfully to detect nonlinear behavior of physiological systems. However, there have been case studies, which discuss spurious identification of nonrandom structures. The proper choice of the null hypothesis and discriminant statistics plays a crucial role in the surrogate data testing. We have chosen the approximate entropy as the discriminant statistic for our tests. The null hypothesis addressed here is that the uterine contraction is a linearly correlated noise transformed by a nonlinear function. We applied the Amplitude Adjusted Fourier Transform (AAFT) and the Iterated Amplitude Adjusted Fourier Transform (IAAFT) tests to the uterine contraction data. The Kolmogorov Smirnov (D) statistics identified the discriminant values of the surrogates to be from a Gaussian distribution. Parametric testing showed a very low significance value, (~2σ), which indicated the absence of nonrandom structure in the contraction segment.