P Murphy

University of Tuebingen, Tübingen, Baden-Wuerttemberg, Germany

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Publications (41)101.73 Total impact

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    ABSTRACT: 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.
    Developmental cognitive neuroscience. 03/2012; 2(3):303-16.
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    ABSTRACT: Using non-invasive fetal magnetoencephalography (fMEG), we investigated spontaneous brain activity in 28 fetuses diagnosed with intrauterine growth restriction (IUGR) and compared the results to 47 normal-growth fetuses. The fetal gestational age ranged from 28 to 39 weeks with post-natal recordings obtained on 17 of the IUGR fetuses. Power spectrum was computed and was divided into four frequency bands. A significant difference in the relative spectral power in delta, theta and beta bands (P<0.01) was observed only in the 28-32 week gestation age group with alpha band showing a similar trend (P=0.054). This observation suggests that growth restriction may have a more pronounced effect on the fetal brain in early gestation. Larger population studies could reveal the potential value of fMEG as an additional surveillance tool for growth-restricted fetuses.
    Early human development 10/2011; 88(6):451-4. · 2.12 Impact Factor
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    ABSTRACT: Fetal magnetoencephalography (fMEG) recordings are contaminated by maternal and fetal magnetocardiography (MCG) signals and by other biological and environmental interference. Currently, all methods for the attenuation of these signals are based on a time-domain approach. We have developed and tested a frequency dependent procedure for removal of MCG and other interference from the fMEG recordings. The method uses a set of reference channels and performs subtraction of interference in the frequency domain (SUBTR). The interference-free frequency domain signals are converted back to the time domain. We compare the performance of the frequency dependent approach with our present approach for MCG attenuation based on orthogonal projection (OP). SUBTR has an advantage over OP and similar template approaches because it removes not only the MCG but also other small amplitude biological interference, avoids the difficulties with inaccurate determination of the OP operator, provides more consistent and stable fMEG results, does not cause signal redistribution, and if references are selected judiciously, it does not reduce fMEG signal amplitude. SUBTR was found to perform well in simulations and on real fMEG recordings, and has a potential to improve the detection of fetal brain signals. The SUBTR removes interference without the need for a model of the individual interference sources. The method may be of interest for any sensor array noise reduction application where signal-free reference channels are available.
    NeuroImage 09/2011; 59(3):2475-84. · 6.25 Impact Factor
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    ABSTRACT: The purpose of fetal magnetoencephalography (fMEG) is to record and analyze fetal brain activity. Unavoidably, these recordings consist of a complex mixture of bio-magnetic signals from both mother and fetus. The acquired data include biological signals that are related to maternal and fetal heart function as well as fetal gross body and breathing movements. Since fetal breathing generates a significant source of bio-magnetic interference during these recordings, the goal of this study was to identify and quantify the signatures pertaining to fetal breathing movements (FBM). The fMEG signals were captured using superconducting quantum interference devices (SQUIDs) The existence of FBM was verified and recorded concurrently by an ultrasound-based video technique. This simultaneous recording is challenging since SQUIDs are extremely sensitive to magnetic signals and highly susceptible to interference from electronic equipment. For each recording, an ultrasound-FBM (UFBM) signal was extracted by tracing the displacement of the boundary defined by the fetal thorax frame by frame. The start of each FBM was identified by using the peak points of the UFBM signal. The bio-magnetic signals associated with FBM were obtained by averaging the bio-magnetic signals time locked to the FBMs. The results showed the existence of a distinctive sinusoidal signal pattern of FBM in fMEG data.
    Physiological Measurement 02/2011; 32(2):263-73. · 1.50 Impact Factor
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    ABSTRACT: Analysis of fetal magnetoencephalographic brain recordings is restricted by low signal to noise ratio (SNR) and non-stationarity of the sources. Beamformer techniques have been applied to improve SNR of fetal evoked responses. However, until now the effect of non-stationarity was not taken into account in detail, because the detection of evoked responses is in most cases determined by averaging a large number of trials. We applied a windowing technique to improve the stationarity of the data by using short time segments recorded during a flash-evoked study. In addition, we implemented a random field theory approach for more stringent control of false-positives in the statistical parametric map of the search volume for the beamformer. The search volume was based on detailed individual fetal/maternal biometrics from ultrasound scans and fetal heart localization. Average power over a sliding window within the averaged evoked response against a randomized average background power was used as the test z-statistic. The significance threshold was set at 10% over all members of a contiguous cluster of voxels. There was at least one significant response for 62% of fetal and 95% of newborn recordings with gestational age (GA) between 28 and 45 weeks from 29 subjects. We found that the latency was either substantially unchanged or decreased with increasing GA for most subjects, with a nominal rate of about − 11 ms/week. These findings support the anticipated neurophysiological development, provide validation for the beamformer model search as a methodology, and may lead to a clinical test for fetal cognitive development.
    NeuroImage 01/2010; · 6.25 Impact Factor
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    ABSTRACT: The processing of rapidly presented stimuli has been shown to be a precursor for the perception of speech in infants, long before they learn to speak. However, the onset and early development of rapid temporal processing (RTP) skills is not yet well understood. The main goal of this study was to assess the development of RTP skills during the prenatal and early postnatal stages of life. Tone pairs were presented in two difficulties (long and short) and event-related magnetic fields were recorded using MEG. Pregnant women (22) (gestational ages between 29 and 38 weeks') participated in the fetal study and 15 returned for a neonatal follow-up study between 2 and 38 days after delivery or 38 and 44 weeks gestational age (GA). In the postnatal follow-up study, a trend towards two peaks with increasing chronological and gestational age was observed in the longer tone pair. However, no such trend was evident in neonatal responses to the short tone pairs or in fetal recordings. Neonates showed a gradual trend to successful processing of the longer tone pair with increasing age. By 22 days of chronological age, the infants processed this tone pair successfully, as indicated by two-peak waveforms. Therefore, the first 3 weeks of life could be critical for the development of RTP. This study is a first approach towards the assessment of early RTP development. The results provide promising indications for future studies, which might lead to an early detection of deficits in speech perception and therefore prevent further language impairments.
    Brain & development 11/2009; 32(8):642-57. · 1.74 Impact Factor
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    ABSTRACT: Fetal magnetoencephalography (fMEG) is used to study neurological functions of the developing fetus by measuring magnetic signals generated by electrical sources within the fetal brain. For this aim either auditory or visual stimuli are presented and evoked brain activity or spontaneous activity is measured at the sensor level. However a limiting factor of this approach is the low signal to noise ratio (SNR) of recorded signals. To overcome this limitation, advanced signal processing techniques such as spatial filters (e.g., beamformer) can be used to increase SNR. One crucial aspect of this technique is the forward model and, in general, a simple spherical head model is used. This head model is an integral part of a model search approach to analyze the data due to the lack of exact knowledge about the location of the fetal head. In the present report we overcome this limitation by a coregistration of volumetric ultrasound images with fMEG data. In a first step we validated the ultrasound to fMEG coregistration with a phantom and were able to show that the coregistration error is below 2 cm. In the second step we compared the results gained by the model search approach to the exact location of the fetal head determined on pregnant mothers by ultrasound. The results of this study clearly show that the results of the model search approach are in accordance with the location of the fetal head.
    NeuroImage 09/2009; 49(2):1469-78. · 6.25 Impact Factor
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    ABSTRACT: The design, safety analysis and performance of a fetal visual stimulation system suitable for fetal and neonatal magnetoencephalography studies are presented. The issue of fetal, neonatal and maternal safety is considered and the maximum permissible exposure is computed for the maternal skin and the adult eye. The risk for neonatal eye exposure is examined. It is demonstrated that the fetus, neonate and mother are not at risk.
    Physiological Measurement 02/2009; 30(1):N1-10. · 1.50 Impact Factor
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    ABSTRACT: We propose to use cross-correlation function to determine significant fetal and neonatal evoked responses (ERs). We quantify ERs by cross-correlation between the stimulus time series and the recorded brain signals. The statistical significance of the correlation is calculated by surrogate analysis. For validation of our approach we investigated a model which mimics the generation of ERs. The model assumes a fixed latency of the ER and contains two parameters, epsilon and lambda. Whether or not the system responds to a given stimulus is controlled by epsilon. The amount to which the system is excited from the base line (background activity) is governed by lambda. We demonstrate the technique by applying it to auditory evoked responses from four fetuses (21 records) between 27 and 39 weeks of gestational age and four neonates (eight records). The method correctly identified the ER and the latency incorporated in the model. A combined analysis of fetuses and neonates data resulted in a significant negative correlation between age and latency. The analysis of ER, especially for fetal and newborn recordings, should be based on advanced data analysis including the assessment of the significance of responses. The negative correlation between age and latency indicates the neurological maturation. The proposed method can be used to objectively assess the ER in fetuses and neonates.
    NeuroImage 09/2008; 43(3):521-7. · 6.25 Impact Factor
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    ABSTRACT: The world's first magnetoencephalography (MEG) system specifically designed for fetal and newborn assessment has been installed at the University of Arkansas for Medical Sciences. This noninvasive system called SARA (SQUID Array for Reproductive Assessment) consists of 151 primary superconducting sensors that detect biomagnetic fields from the human body. Since the installation of SARA, significant progress has been made toward the ultimate goal of developing a clinical neurological assessment tool for the developing fetus. Using appropriate analysis techniques, cardiac and brain signals are recorded and studied to gain new understanding of fetal maturation. It is clear from our investigations that a combination of assessment protocols including both fetal heart and brain activity is necessary for the development of a comprehensive new method of fetal neurological testing. We plan to implement such a test protocol for fetuses at high risk for neurological impairment due to certain maternal risk factors and/or fetal diagnostic findings.
    Seminars in Perinatology 08/2008; 32(4):263-8. · 2.81 Impact Factor
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    ABSTRACT: 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. 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. 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. 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. The proposed method might be a first step towards an early detection of developmental deficits in newborns and fetuses.
    Clinical Neurophysiology 05/2008; 119(4):796-804. · 3.14 Impact Factor
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    ABSTRACT: 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.
    Journal of Neuroscience Methods 03/2008; 168(1):265-72. · 2.11 Impact Factor
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    ABSTRACT: Using detrended fluctuation analysis (DFA), we studied the scaling properties of the time instances (occurrence) of the fetal breathing, gross-body, and extremity movements scored on a second by second basis from the recorded ultrasound measurements of 49 fetuses. The DFA exponent α of all the three movements of the fetuses varied between 0.63 and 1.1. We found an increase in α obtained for the movement due to breathing as a function of the gestational age while this trend was not observed for gross-body and extremity movements. This trend was argued as the indication of the maturation of lung and functional development of respiratory aspect of the fetal central nervous system. This result may be useful in discriminating normal fetuses from high-risk fetuses.
    Physica A: Statistical Mechanics and its Applications 01/2008; 386(1):231-239. · 1.68 Impact Factor
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    ABSTRACT: Flash-evoked responses can be recorded from the fetus in utero. However, a standard analysis approach based on orthogonal projection (OP) to attenuate maternal and fetal cardiac signals leads to a spatial redistribution of the signal. This effect prevents the correlation of source location with a known fetal head location in some cases and the signal-to-noise ratio (SNR) is sometimes limited such that the response latency is difficult to determine. We used a modified beamformer model search analysis to avoid the redistribution shortcoming and to improve the SNR. We included a statistical test for residual interference in the average and quantified significance of the evoked response with a bootstrap method. Selected source locations compared favorably to fetal head locations estimated from ultrasound exams. The evoked response time course was found to have a significant post-trigger peak with a latency between about 180 and 770 ms in more than 90% of the subject measurements. These results confirm that the combined application of a beamformer model search and bootstrap significance test provides a validation of the flash-evoked response observed in OP processed fetal MEG channels.
    Physics in Medicine and Biology 11/2007; 52(19):5803-13. · 2.70 Impact Factor
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    ABSTRACT: The purpose of this study was to compare cardiac dynamics of high-risk and low-risk fetuses using beat to beat variability. This study obtained 214 fetal magnetocardiography recordings from a group of high-risk fetuses with maternal conditions associated with placental insufficiency with the risk of developing intrauterine growth restriction or were already diagnosed with intrauterine growth restriction. For purpose of comparison, another 136 recordings were obtained from low-risk fetuses. The cardiac beat-to-beat intervals computed as RR intervals were analyzed from both groups using the mean and median interval, standard deviation of normal-to-normal intervals, root mean square of the successive differences, and the fraction of the normal-to-normal intervals (pNNx) that differ by more than the chosen tolerance level of 'x' milliseconds from the previous normal-to-normal intervals. Tests for significance between high-risk and low-risk fetuses were calculated using an independent samples t test within the following gestational age groups, 27-30 weeks, 31-35 weeks, and 36-40 weeks. The root mean square of the successive differences, and the pNNx showed a significant difference between the low-risk and high-risk fetuses in the 31-35-week and the 36-40-week divisions. In the 31-35-week age division, low-risk fetuses had significantly lower root mean square of the successive differences, and pNN values than the high risk, but in the 36-40-week division, the low-risk fetuses had significantly higher root mean square of the successive differences, and pNN values. Cardiac dynamics for fetuses of mothers at risk for placental insufficiency mature quicker than fetuses not at risk for placental insufficiency.
    American journal of obstetrics and gynecology 07/2007; 196(6):572.e1-7; discussion 572.e7. · 3.28 Impact Factor
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    ABSTRACT: Non-invasive technique such as magneto-encephalography (MEG), initially pioneered to study human brain signals, has found many other applications in medicine. SQUID(1) Array for Reproductive Assessment (SARA) is a unique non-invasive scanning-device developed at the University of Arkansas for Medical Sciences (UAMS) that can detect fetal brain and other signals. The fetal magneto-encephalography (fMEG) signals often have many bio-magnetic signals mixed in. Examples include the movement of the fetus or muscle contraction of the mother. As a result, the recorded signals may show unexpected patterns, other than the target signal of interest. These "interventions" make it difficult for a physician to assess the exact fetal condition, including its response to various stimuli. We propose using intervention analysis and spatial-temporal auto-regressive moving-average (STARMA) modeling to address the problem. STARMA is a statistical method that examines the relationship between the current observations as a linear combination of past observations as well as observations at neighboring sensors. Through intervention analysis, the change in a pattern due to "interfering" signals can be accounted for. When these interferences are "removed," the end product is a "template" time series, or a typical signal from the target of interest. In this research, a "universal" template is obtained. The template is then used to detect intervention in other datasets by the method of template matching. By this method, it is possible to detect if there is an intervention in any dataset. It will assist physicians in monitoring the actual signal generated by fetal brain and other organs of interest.
    Journal of Neuroscience Methods 06/2007; 162(1-2):333-45. · 2.11 Impact Factor
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    ABSTRACT: The mismatch negativity (MMN) response elicited to auditory stimuli is an indicator for cognitive function of sound discrimination in humans. MMN was successfully recorded in previous studies in newborns and fetuses (33-40 weeks of gestation) with magnetoencephalography (MEG). The aim of our study was to perform systematic serial MMN recordings on fetuses starting at 28 weeks of gestation with a follow up recording within 2 weeks after birth. The recording of weak magnetic fields from the fetal brain were performed with the 151 channel MEG system called SARA (SQUID Array for Reproductive Assessment). Two tone bursts were presented in a sequence of a standard complex tone of 500 Hz intermixed with a deviant complex tone of 750 Hz in 12% of the stimuli, inter-stimulus interval 800+/-100 ms. Eighteen pregnant women between 28th and 39th gestational weeks participated in the study. Measurements were performed every two weeks and once after delivery. The averaged evoked responses to standard and deviant tones were obtained and subtraction between them was calculated. A successful detection of response to the frequency change was found in 66% of the fetal data and 89% of the neonatal data. Responses to the standard tone were detected in 56% of all records. In the 28-39 week gestational age group, the discriminative brain responses to tone frequency change could be detected as early as 28 weeks. Although not statistically significant, a decrease in latency was observed with increase in gestational age. The ability of the fetus to detect changes in sounds is a prerequisite to normal development for cognitive function; related to language learning and clinical aspects of auditory disorders.
    Early Human Development 04/2007; 83(3):199-207. · 2.02 Impact Factor
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    ABSTRACT: Fetal brain signals produce weak magnetic fields at the maternal abdominal surface. In the presence of much stronger interference these weak fetal fields are often nearly indistinguishable from noise. Our initial objective was to validate these weak fetal brain fields by demonstrating that they agree with the electromagnetic model of the fetal brain. The fetal brain model is often not known and we have attempted to fit the data to not only the brain source position, orientation and magnitude, but also to the brain model position. Simulation tests of this extended model search on fetal MEG recordings using dipole fit and beamformers revealed a region of ambiguity. The region of ambiguity consists of a family of models which are not distinguishable in the presence of noise, and which exhibit large and comparable SNR when beamformers are used. Unlike the uncertainty of a dipole fit with known model plus noise, this extended ambiguity region yields nearly identical forward solutions, and is only weakly dependent on noise. The ambiguity region is located in a plane defined by the source position, orientation, and the true model centre, and will have a diameter approximately 0.67 of the modelled fetal head diameter. Existence of the ambiguity region allows us to only state that the fetal brain fields do not contradict the electromagnetic model; we can associate them with a family of models belonging to the ambiguity region, but not with any specific model. In addition to providing a level of confidence in the fetal brain signals, the ambiguity region knowledge in combination with beamformers allows detection of undistorted temporal waveforms with improved signal-to-noise ratio, even though the source position cannot be uniquely determined.
    Physics in Medicine and Biology 03/2007; 52(3):757-76. · 2.70 Impact Factor
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    ABSTRACT: The assessment of the neurological integrity of the human fetus in utero is a technically challenging problem. New brain imaging devices can substantially improve our capabilities to describe functional brain activity in the fetus. It has been well established by fetal behavioral studies and investigations in preterm and term newborns that the brain is functional in utero. The major effort required to perform effective neurological functional investigations is designation of an integrated approach to neurological assessment and the generation of normative data. Currently, it is possible to record evoked brain activity elicited by auditory and visual stimulation from the fetus. In addition, there is growing evidence that spontaneous brain activity can be recorded in the fetus. This paper explores the current status of the brain-imaging field for fetal investigations and currently available data.
    Seminars in Fetal and Neonatal Medicine 01/2007; 11(6):430-6. · 3.51 Impact Factor
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    ABSTRACT: We have evaluated a newly implemented optical stimulator in a fetal MEG system for effectiveness of eliciting fetal flash evoked response using 29 normal, low-risk fetuses. MEG recordings were performed with a 151 channel array conforming to the maternal abdomen. Interference from maternal and fetal heart was attenuated by orthogonal projection and stimulus events were averaged to improve SNR after rejection of data segments with fetal motion. The responses identified by visual examination of the averaged time courses were subjected to validation by a significance measure based on a bootstrap confidence interval computation. The second generation stimulator increased comfort and ease of placement between the maternal abdomen and sensor array while delivering greater optical power to the fetus. After discarding 2 measurements for excessive artifact, averaged evoked responses with good baseline above background noise levels were observed in 24 recordings resulting in a detection rate of 89%; 26% greater than previously reported by our group using a first generation stimulator. Use of the new fetal visual stimulation delivery system resulted in an increased detection rate of fetal flash evoked response and the bootstrap significance measure provided some validation of results.
    International Congress Series 01/2007; 1300:749-752.

Publication Stats

395 Citations
101.73 Total Impact Points

Institutions

  • 2005–2012
    • University of Tuebingen
      • Institute of Medical Psychology and Behavioral Neurobiology
      Tübingen, Baden-Wuerttemberg, Germany
  • 2004–2012
    • University of Arkansas for Medical Sciences
      • Department of Obstetrics and Gynecology
      Little Rock, Arkansas, United States
  • 1995–2011
    • University of Arkansas at Little Rock
      • • Graduate Institute of Technology (GIT)
      • • Department of Applied Sciences
      Little Rock, AR, United States