Search

Background: Auditory steady-state responses (ASSRs) are ongoing evoked brain responses to continuous auditory stimuli that play a role for auditory processing of complex sounds and speech perception. Transient auditory event-related responses (AERRs) have previously been recorded using fetal magnetoencephalography (fMEG) but involve different neurological pathways. Previous studies in children and adults demonstrated that the cortical components of the ASSR are significantly affected by state of consciousness and by maturational changes in neonates and young infants. To our knowledge, this is the first study to investigate ASSRs in human fetuses., Methods: 47 fMEG sessions were conducted with 24 healthy pregnant women in three gestational age groups (30-32 weeks, 33-35 weeks and 36-39 weeks). The stimulation consisted of amplitude-modulated (AM) tones with a duration of one second, a carrier frequency (CF) of 500 Hz and a modulation frequency (MF) of 27 Hz or 42 Hz. Both tones were presented in a random order with equal probability adding up to 80-100 repetitions per tone. The ASSR across trials was quantified by assessing phase synchrony in the cortical signals at the stimulation frequency., Results and Conclusion: Ten out of 47 recordings were excluded due to technical problems or maternal movements. Analysis of the included 37 fetal recordings revealed a statistically significant response for the phase coherence between trials for the MF of 27 Hz but not for 42 Hz. An exploratory subgroup analysis moreover suggested an advantage in detectability for fetal behavioral state 2F (active asleep) compared to 1F (quiet asleep) detected using fetal heart rate. In conclusion, this pilot study is the first description of a method to detect human ASSRs in fetuses. The findings warrant further investigations of the developing fetal brain., Competing Interests: The authors have declared that no competing interests exist.

Background and Aims: In-utero exposure to opioids including buprenorphine (BUP) has been shown to affect fetal activity, specifically heart-rate variability (FHRV) and fetal movement (FM). Our objective was to extract simultaneous recordings of fetal cardiac and brain-related activity in BUP-maintained and non-opioid exposed pregnant women using a novel non-invasive biomagnetic technique., Design: A pilot study was conducted, recording and analyzing biomagnetic data from fetuses of BUP-maintained and non-opioid exposed pregnant women. Signals were acquired with the non-invasive 151-channel SARA (SQUID-Array for Reproductive Assessment) system. Advanced signal-processing techniques were applied to extract fetal heart and brain activity., Setting: University of Arkansas for Medical Sciences (UAMS, Little Rock, Arkansas, USA)., Participants: Eight BUP-maintained pregnant women from UAMS Women's Mental Health Program between gestational ages (GA) of 29-37 weeks who were treated with 8-24 mg of BUP daily. Sixteen pregnant women with no known opioid exposure in the same GA range were also included., Measurements: Outcome measures from the fetal heart and brain signals included: heart rate (FHR), FM, FHR accelerations, FHR-FM coupling, FHRV, fetal behavioral states (FBS) and power spectral density (PSD) of spontaneous brain activity. These measures were analyzed at three GA intervals., Findings: Fetal heart and brain activity parameters were extracted and quantified successfully from 18 non-opioid and 16 BUP recordings. Overall analysis in both groups show that: FHR and FM ranged from 131 to 141 beats per minute (b.p.m.) and 5 to 11 counts, respectively. In the 35-37 weeks GA, the coupling duration (~9 s) was the shortest, while three of the FHRV parameters were the highest. The PSD of brain activity revealed highest power in 0.5-4 Hz bandwidth. Transitions in FBS from quiet to active sleep were > 50% of sessions., Conclusions: This pilot study showed that a novel biomagnetic technique allows simultaneous quantification of cardiac and brain activities of a group of buprenorphine-exposed and non-exposed fetuses in the third trimester., (© 2018 Society for the Study of Addiction.)

Objective: To identify quantitative MEG indices of spontaneous brain activity for fetal neurological maturation in normal pregnancies and examine the effect of fetal state on these indices., Methods: Spontaneous MEG brain activity was examined in 22 low-risk fetal recordings with gestational age (GA) ranging from 30 to 37 weeks. As major quantitative characteristics of spontaneous activity, burst duration (BD) and interburst interval (IBI) were studied in correlation with GA and fetal state., Results: IBI showed a decrease with gestational age (-0.21 s/week, P=0.0031). This trend was only maintained in the quiet-sleep state. With respect to BD, no significant trends were detected with GA and state., Conclusion: IBI can be quantified as a fetal brain maturational parameter. The decrease in IBI over gestation was similar to the trend reported in the preterm neonatal EEG studies. Quiet sleep could be the optimal state to study such MEG maturational indices., Significance: With further investigation, indices extracted from spontaneous fetal brain activity may serve as an early warning for fetal neurological distress., (Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Aim: Fetal magnetography enables the recording of biomagnetic fetal signals, including fetal heart and fetal brain signals. These signals allow the determination of fetal behavioral states and functional brain signals with auditory evoked responses (AER). In the current study, we investigated how the behavioral state influences the AER and how stimulation affects fetal state., Methods: One hundred and four fetuses in three age groups (28-31 weeks, 32-35 weeks and 36-41 weeks) were recorded with and without auditory stimulation. Both sessions were scored for fetal states. The AER latency was determined for each state separately. Forty-five additional subjects were recorded with two sessions of 10 min without stimulation to investigate a possible time effect on state changes., Results: The state distribution was significantly different between stimulation and no stimulation conditions. The AER latencies were significantly shorter in active sleep (P=0.013) and active wakefulness (P=0.004) compared to quiet sleep., Conclusion: Auditory stimulation has an effect on fetal states. The state information should be taken into account for the analysis of AER latencies.

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., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

The fetal brain remains inaccessible to neurophysiological studies. Magnetoencephalography (MEG) is being assessed to fill this gap. We performed 40 fetal MEG (fMEG) recordings with gestational ages (GA) ranging from 30 to 37 weeks. The data from each recording were divided into 15 second epochs which in turn were classified as continuous (CO), discontinuous (DC), or artifact. The fetal behavioral state, quiet or active sleep, was determined using previously defined criteria based on fetal movements and heart rate variability. We studied the correlation between the fetal state, the GA and the percentage of CO and DC epochs. We also analyzed the spectral edge frequency (SEF) and studied its relation with state and GA. We found that the odds of a DC epoch decreased by 6% per week as the GA increased (P = 0.0036). This decrease was mainly generated by changes during quiet sleep, which showed 52% DC epochs before a 35 week GA versus 38% after 35 weeks (P = 0.0006). Active sleep did not show a significant change in DC epochs with GA. When both states were compared for MEG patterns within each GA group (before and after 35 weeks), the early group was found to have more DC epochs in quiet sleep (54%) compared to active sleep (42%) (P = 0.036). No significant difference in DC epochs between the two states was noted in the late GA group. Analysis of SEF showed a significant difference (P = 0.0014) before and after a 35 week GA, with higher SEF noted at late GA. However, when both quiet and active sleep states were compared within each GA group, the SEF did not show a significant difference. We conclude that fMEG shows reproducible variations in gross features and frequency content, depending on GA and behavioral state. Fetal MEG is a promising tool to investigate fetal brain physiology and maturation., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: 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., Methodology: 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)., Results: 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., Conclusions: 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., Significance: 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., (Copyright 2009 Elsevier B.V. All rights reserved.)

The fetal magnetoencephalogram (fMEG) is measured in the presence of large interference from maternal and fetal magnetocardiograms (mMCG and fMCG). These cardiac interferences can be attenuated by orthogonal projection (OP) technique of the corresponding spatial vectors. However, the OP technique redistributes the fMEG signal among the channels and also leaves some cardiac residuals (partially attenuated mMCG and fMCG) due to loss of stationarity in the signal. In this paper, we propose a novel way to extract and localize the neonatal and fetal spontaneous brain activity by using independent component analysis (ICA) technique. In this approach, we perform ICA on a small subset of sensors for 1-min duration. The independent components obtained are further investigated for the presence of discontinuous patterns as identified by the Hilbert phase analysis and are used as decision criteria for localizing the spontaneous brain activity. In order to locate the region of highest spontaneous brain activity content, this analysis is performed on the sensor subsets, which are traversed across the entire sensor space. The region of the spontaneous brain activity as identified by the proposed approach correlated well with the neonatal and fetal head location. In addition, the burst duration and the inter-burst interval computed for the identified discontinuous brain patterns are in agreement with the reported values.

The discontinuous patterns in neonatal magnetoencephalographic (MEG) data are quantified with a novel Hilbert phase (HP) based approach. The expert neurologists' scores were used as the gold standard. The performance of this approach was analyzed using a receiver operating characteristic (ROC) curve, and it was compared with two other approaches, namely spectral ratio (SR) and discrete wavelet transform (DWT) that have been proposed for the detection of discontinuous patterns in neonatal EEG. The area under the ROC curve (AUC) was used as a performance measure. AUCs obtained for SR, HP, and DWT were 0.87, 0.80, and 0.56, respectively. Although the performance of HP was lower than SR, it carries information about the frequency content of the signal that helps to distinguish brain patterns from artifacts such as cardiac residuals. Based on this property, the HP approach was extended to fetal MEG data. Further, using the frequency property of the HP approach, burst duration and interburst interval were computed for the discontinuous patterns detected and they are in agreement with reported values.

SQUID Array for Reproductive Assessment is a unique magnetoencephalography device designed for the noninvasive recording of fetal brain activity. In this article, we provide a general overview of the technology and its potential application to fetal medicine. A large number of studies that have been conducted and published describing this device since it was brought into operation are referenced throughout the article.

Objective: The purpose of this study was to investigate fetal brain development of growth-restricted fetuses with auditory evoked responses (AER) that were recorded by the noninvasive magnetoencephalographic technique., Study Design: Serial fetal recordings that started at 27 weeks of gestation were conducted on a fetal magnetoencephalographic device that was especially designed for obstetric assessment. Fifteen normotrophic fetuses were compared with 14 hypotrophic fetuses. After birth, 10 of the hypotrophic fetuses were diagnosed with asymmetric growth restriction; 4 fetuses were classified as symmetrically small for gestational age., Results: Fetal AER latencies in both groups showed an average developmental decrease of 12.74 msec/wk (P = .0035). Hypotrophic fetuses had longer age-adjusted latencies compared with normotrophic fetuses, with a difference of 73.5 msec (P = .034). The subgroup of symmetrically growth-restricted fetuses showed the longest latencies for age, with a difference from the normotrophic fetuses of 120.0 msec (P = .045)., Conclusion: The results indicate that biomagnetically recorded AER can be used to monitor functional brain development in growth-restricted fetuses.

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.

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.

Objective: Utilizing a MEG-based device specifically designed to study the fetus, we investigated the presence of salient patterns in spontaneous fetal brain activity., Methods: We performed 91 MEG recordings from 30 fetuses at various gestational ages. The tracings were evaluated and compared to the well-established electroencephalographic (EEG) features in premature infants. Also, we looked at the correlation of the gestational age (GA) on the occurrence of these patterns and complexes., Results: We were able to identify specific patterns and track changes in fetal brain activity starting at 28 weeks of gestation. The patterns and trends were similar to the established EEG features in premature infants at comparable ages. Of the 30 fetuses, 18 (60%) had at least one recording with discontinuity, 7 (23%) had sharp transients, and 8 (27%) had delta brush activity. Further there was a decrease in the presence of discontinuous patterns after 35 weeks., Conclusions: We have shown that fetal spontaneous brain activity features can be recorded and identified using MEG technique. The observation of more discontinuity at early gestational ages is consistent with the overall pattern of maturation seen in EEGs of premature infants., Significance: With refinements, this method can aid in understanding the maturation process of fetal brain activity and further develop as a tool for fetal neurological evaluation.

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.

Objective: To describe magnetoencephalography (MEG) recordings in a cohort of healthy neonates., Methods: We performed MEG and single channel EEG concomitantly in 21 healthy newborns. MEG and EEG signals were reviewed for gross comparison of general patterns and individual waveform characteristics. Spectral analysis was performed to quantify the signals., Results: Our MEG recordings showed patterns comparable to classical neonatal EEG. Seventy-nine percent of the subjects exhibited the 'continuous polyfrequency activity' at some point in their recording. Sixty-three percent had the 'continuous slow' pattern, and 47% had the 'trace alternant' pattern. Spectral analysis revealed maximal power at frequencies of less than 4 Hz (delta band) in both MEG and EEG with a decline towards higher frequencies., Conclusions: Neonatal MEG is feasible and shares the basic EEG features and frequency content, with predominant activity in the slow frequency delta band. The latter corresponds to reports from earlier neonatal EEG studies., Significance: MEG may prove to be useful in studies of neonatal brain functions.

Past studies have shown the feasibility of recording fetal evoked responses to external stimuli using a non-invasive technique called magnetoencephalography (MEG). These studies were all performed using either auditory or visual stimuli and showed a fairly low detection rate for each modality, thus making this technology currently unreliable for fetal clinical applications. This study is based on the hypothesis that a multimodal approach of applying both auditory and visual stimulation paradigms in successive recording sessions could improve the probability of obtaining a fetal evoked response. A total of 34 studies were performed on 11 normal healthy fetuses at different stages of gestation starting as early as 28 weeks with a 151-channel fetal MEG system. The success rate of obtaining a response to either (or both) stimuli from a study at a given gestation age was 91%. All the 11 fetuses showed a response at least once over the gestation period the recordings were performed. A multimodal testing approach can improve the ability of the MEG technique to reliably monitor the functional development of the fetal brain.

Multimodal testing is the key to successful fetal neurological assessment. New mutichannel SQUID (Superconducting Quantum Interference Device) sensor devices can now be used to effectively record fetal auditory evoked responses (fAER) and visual evoked responses (VER), spontaneous brain activity, and heart activity. In this paper, we review the current progress in the area of fetal magnetoencephalography (fMEG) and also present an overview of the studies performed using a system called SARA that is specifically designed for fetal MEG studies. With the capability of recording spontaneous and evoked magnetic fields, we believe the monitoring of the neurological status of the fetus can be effectively implemented and can encourage the development of new strategies of intervention for the high-risk fetus.

Statistically valid detection of evoked responses from magnetoencephalographic (MEG) sensors is complicated by temporal autocorrelation. By decorrelating time series and transforming them toward normality, the discrete wavelet transform (DWT) allows the analyst to test for an association between stimulus and sensor time series with appropriate degrees of freedom. Eswaran et al. (Neurosci. Lett. 2002a;331:128-32) used a 151-channel fetal MEG system to obtain serial recordings from 10 pregnant subjects. There were 3-8 recordings per subject. In each recording session, the fetus was stimulated by 500Hz and 1KHz tones with a relative frequency of 80-20%, respectively. In this new analysis of the same data, the fetal MEG signals were compared to two different stimulus waveforms: the frequent tone and the Novel stimulus, defined as a change in pitch. WaveDetect was developed to determine whether there was a significant association between the stimuli and the MEG traces. This test is performed by taking the DWT of each series and then computing the Spearman correlation between the wavelet coefficients for an appropriate scale. A significant response (i.e., correlated stimulus-sensor pair) was detected from each patient. This result suggests that the combination of serial recordings and WaveDetect may ensure reliable detection of auditory evoked responses.

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.

We investigated the feasibility of recording visual evoked brain activity in the human fetus by use of non-invasive magnetoencephalography (MEG). Each recording lasted 6 min and consisted of a sequence of 180 flashes with 33 ms duration delivered 2 s apart over the maternal abdomen. Four of ten fetuses included showed a response; the ranges of amplitude and latency of peak response were 15-30 x 10(-15) Tesla and 180-390 ms, respectively. Six fetuses showed no discernible response. With improvement, this method could aid in the testing of fetal neurological status throughout pregnancy.

The development of the human brain in utero is normally regarded as a dynamic process involving mainly structural and quantitative changes in neurons and their distribution. However, it is generally accepted that a parallel development of functional specialization occurs in certain areas of the brain, especially in the primary cortex. Nearly all knowledge of functional fetal brain development has been obtained from various animal studies rather than human studies. These studies show that the primary sensory areas like auditory, visual, and somatosensory cortex show a basic function similar to that of a fully developed brain. It has been specifically shown that the visual system develops during fetal life and becomes functional before birth. Several studies have demonstrated the feasibility of using visual evoked response (VER) recordings on preterm human infants to follow the functional development of the visual system. With the advent of the noninvasive technique of magnetoencephalography (MEG), human fetal VER recordings are now possible thus providing the opportunity to track its functional development with gestation. We present and discuss the results of VER recordings in human fetuses starting at 28 weeks of gestation performed using a 151-channel MEG system. [Copyright &y& Elsevier]