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Fetal auditory evoked responses detected by magnetoencephalography
Fetal auditory evoked responses detected by magnetoencephalography Ronald T. Wakai, Phi), a Arthur C. Leuthold, MS, a and Chester B. Martin, MD b
Madison, Wisconsin Magnetoencephalography was used to noninvasively record auditory evoked responses from fetuses in utero at 34 to 37 weeks' gestation. The recordings were similar to auditory evoked responses from neonates at age 7 to 14 days. (AM J OBSTETGYNECOL1996;174:1484-6.)
Key words: Fetal magnetoencephalography, fetal auditory evoked response, fetal brain activity
Intrauterine evaluation of fetal brain function has been a long-standing objective of basic and clinical research in perinatology. For the human fetus the main approach has been indirect; researchers have studied outputs of brain function such as fetal heart rate variability and fetal body and breathing movements. The fetal electroencephalogram has been recorded during labor after rupture of the fetal membranes, but before labor the human fetal brain is largely inaccessible for study of its electrical activity. Techniques for imaging brain function such as positron emission tomography, single-photon emission computed tomography, and fetal magnetic resonance imaging pose potential hazards to the fetus and are generally considered not suitable for fetal research. We have investigated magnetoencephalography as an alternative method for assessing fetal brain function. Magnetoencephalography is potentially an ideal technology because it records neuronal activity directly, has high temporal resolution, and is completely safe and noninvasive. Because of the unique properties of magnetic signal transmission, fetal magnetic signals are considerably less affected by signal attenuation and maternal interference than are fetal electric signals recorded from the maternal surface? Only one group has previously published fetal magnetoencephalography recordings. 2'~These data consisted of fetal auditory evoked responses to 1 kHz tone bursts and spontaneous fetal brain activity, recorded with a singlechannel magnetometer. Only a few subjects were studied and the quality of the recordings was not high. Despite considerable interest generated by these data, no follow-up study by any group has been published since this initial report. In this communication we present magnetic auditory evoked response recordings of improved From the Departments' of Medical Physics~ and Obstetricsand Gyneeology,~ University of Wisconsin-Madison, Received for publication June 27, 1995; revised September 19, 1995; accepted September28, 1995. Reprint requests: Ronald Wakai, PAD, 1530 Medical Sciences Cent~ 1300 UniversityAve., Madison, WI53706. Copyright 9 1996 by Mosby-YearBook, Inc. 0002-9378/96 $5.00 + 0 6/1/69631 1484
100 fT
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I
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I
0.4 s
Fig. 1. Auditory evoked responses from four different subjects at 37 (A), 34 (B), 35 (C), and 36 (D) weeks' gestation (1 fl" = 10-15 T). The stimulus occurs at time zero (0.0 s).
quality from fetuses and neonates; a multichannel magnetometer was used. The experimental protocol was reviewed and approved by the institutional human subjects committee before commencement of the study. Detection of the fetal auditory evoked response was attempted in 14 uncomplicated pregnancies at 36 to 40 weeks' gestation. Recordings were made in an eddy-current-shielded room, with a 7-channel SQUID (model 607 Neuromagnetometer, Biomagnetie Technologies, San Diego) gradiometer. The magnetic field resolution of each channel was 20 t T / H z ~
Wakai, Leuthold, and Martin 1485
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B . . . . Fig. 2. A, Six-channel fetal auditory evoked responses from subject at 36 weeks' gestation. Shown are two separate measurements taken from similar probe positions. The posiuons of the waveforms reflect the physical arrangement of the detection coils--a central coil surrounded by six others, spaced equally on a circle with 2.0 cm center-to-center separation. One of the channels ,a-as not working during this recording. A notch filter was applied to remove environmental interference near 10 Hz. B, Sevenchannel neonatal auditory evoked response at age 10 days from same subject as in Fig. 2, A. Phase reversal of the signal is seen between the left and right channels.
( l i T = 10 .25 T). P l a c e m e n t o f t h e m a g n e t o m e t e r was g u i d e d by u l t r a s o n o g r a p h y , w h i c h was u s e d to locate t h e fetal a u d i t o r y canal a n d e x t e r n a l c a n t h u s . Typically, the fetal scalp was 3 to 5 c m below t h e m a t e r n a l surface. T h e a u d i t o r y stimulus was a b r i e f t o n e b u r s t o f 1.5 kHz fre-
q u e n c y a n d 20 msec d u r a t i o n , delivered f r o m a small s p e a k e r p l a c e d a p p r o x i m a t e l y 1.5 m f r o m t h e subject. T h e s o u n d intensity in air was 100 dB for fetal r e c o r d i n g s a n d 60 dB for n e o n a t a l r e c o r d i n g s . O n e h u n d r e d 0.5s e c o n d trials (0.1 s e c o n d b e f o r e stimulus, 0.4 s e c o n d after
1486 Wakai,Leuthold,and Martin
stimulus) were collected with a random intertrial interval of 2 seconds' mean duration. The analog passband was 1 to 50 Hz, and the signal was digitized at 128 Hz. Some recordings showed interference from the fetal magnetocardiogram, and a computer algorithm was implemented to detect and remove fetal complexes. The auditory evoked responses were averaged and digitally filtered with a 2 to 20 Hz passhand. Four of 14 fetal subjects showed distinct auditory evoked responses with latencies near 200 msec (Figs. 1 and 2, A). Other prominent deflections were sometimes seen at shorter and, more often, at longer latencies but were less consistent between subjects. The quality of the recordings was limited by environmental noise, as well as low signal amplitude. Even in the best recordings signal amplitude was only 100 IT, compared with 400 iT in typical adult recordings. Two of these subjects and four others were studied 7 to 14 days after birth, and all showed neonatal auditory evoked responses similar to the fetal auditory evoked responses. Although probe placement was relatively consistent and optimal for the neonatal recordings, the amplitudes of the neonatal auditory evoked responses were low and showed considerable intersubject variability, ranging from <100 IT to approximately 200 IT. The low amplitude implies that the current-dipole moment is significantly less than for adults, whereas the variability may reflect differences in brain development or state. Spatial variation of the signal was investigated in several neonatal subjects by mapping the signal over the frontal and parietal regions. Phase inversion of the signal was
May 1996 Amj ObstetOynecol
seen between anterior and posterior probe positions, compatible with a source in the auditory cortex. In one subject it was possible to observe phase inversion at a single probe placement (Fig. 2, B). Failure to detect fetal auditory evoked responses can be caused by immaturity of the fetal brain, movement or unfavorable position or orientation of the fetal head, low sound intensity in the womb, or other causes. In addition, the magnetometer used in this study was designed for adult studies. The use of detectors developed specifically for fetal magnetoencephalography can be expected to significantly enhance the success rate of detection and to extend the window of observation earlier in pregnancy. Despite these difficulties, we have shown that under favorable circumstances the magnetic fetal auditory evoked response can be detected with good signal-to-noise ratio and is similar in form to neonatal auditory evoked responses. Magnetoencephalography is a potential technology for detecting the activity of the human fetal brain noninvasively, to study its normal development and pathophysiologic characteristics. REFERENCES
1. Wakai RT, Wang M, Martin C. Spatiotemporal properties of the fetal magnetocardiogram. AMJ OBST~TGmECOL1994;170: 770-6. 2. Blum T, Saling E, Bauer R. First magnetoencephalographic recordings of the brain activity of a human fetus. BrJ Obstet Gynaecol 1985;92:1224-9. 3. Blum T, Bauer R, Arabin B, Reckel S, Saling E. Prenatally recorded auditory evoked neuromagnetic field of the human fetus. In: Barber C, Blum T, eds. Volume 3: evoked potentials. Boston: Butterworth, 1987:13642.
Madison, Wisconsin Magnetoencephalography was used to noninvasively record auditory evoked responses from fetuses in utero at 34 to 37 weeks' gestation. The recordings were similar to auditory evoked responses from neonates at age 7 to 14 days. (AM J OBSTETGYNECOL1996;174:1484-6.)
Key words: Fetal magnetoencephalography, fetal auditory evoked response, fetal brain activity
Intrauterine evaluation of fetal brain function has been a long-standing objective of basic and clinical research in perinatology. For the human fetus the main approach has been indirect; researchers have studied outputs of brain function such as fetal heart rate variability and fetal body and breathing movements. The fetal electroencephalogram has been recorded during labor after rupture of the fetal membranes, but before labor the human fetal brain is largely inaccessible for study of its electrical activity. Techniques for imaging brain function such as positron emission tomography, single-photon emission computed tomography, and fetal magnetic resonance imaging pose potential hazards to the fetus and are generally considered not suitable for fetal research. We have investigated magnetoencephalography as an alternative method for assessing fetal brain function. Magnetoencephalography is potentially an ideal technology because it records neuronal activity directly, has high temporal resolution, and is completely safe and noninvasive. Because of the unique properties of magnetic signal transmission, fetal magnetic signals are considerably less affected by signal attenuation and maternal interference than are fetal electric signals recorded from the maternal surface? Only one group has previously published fetal magnetoencephalography recordings. 2'~These data consisted of fetal auditory evoked responses to 1 kHz tone bursts and spontaneous fetal brain activity, recorded with a singlechannel magnetometer. Only a few subjects were studied and the quality of the recordings was not high. Despite considerable interest generated by these data, no follow-up study by any group has been published since this initial report. In this communication we present magnetic auditory evoked response recordings of improved From the Departments' of Medical Physics~ and Obstetricsand Gyneeology,~ University of Wisconsin-Madison, Received for publication June 27, 1995; revised September 19, 1995; accepted September28, 1995. Reprint requests: Ronald Wakai, PAD, 1530 Medical Sciences Cent~ 1300 UniversityAve., Madison, WI53706. Copyright 9 1996 by Mosby-YearBook, Inc. 0002-9378/96 $5.00 + 0 6/1/69631 1484
100 fT
C
I
0.0
I
I
0.2
I
0.4 s
Fig. 1. Auditory evoked responses from four different subjects at 37 (A), 34 (B), 35 (C), and 36 (D) weeks' gestation (1 fl" = 10-15 T). The stimulus occurs at time zero (0.0 s).
quality from fetuses and neonates; a multichannel magnetometer was used. The experimental protocol was reviewed and approved by the institutional human subjects committee before commencement of the study. Detection of the fetal auditory evoked response was attempted in 14 uncomplicated pregnancies at 36 to 40 weeks' gestation. Recordings were made in an eddy-current-shielded room, with a 7-channel SQUID (model 607 Neuromagnetometer, Biomagnetie Technologies, San Diego) gradiometer. The magnetic field resolution of each channel was 20 t T / H z ~
Wakai, Leuthold, and Martin 1485
Volume 174, Number 5 Am J Obstet Oynecol
.
.
.
.
..2oo L t
t
I
t
"0
200
0.0
0.2
0.4
time (see)
A
....
[
LU 0.0
0.2
0.4
time (sec)
B . . . . Fig. 2. A, Six-channel fetal auditory evoked responses from subject at 36 weeks' gestation. Shown are two separate measurements taken from similar probe positions. The posiuons of the waveforms reflect the physical arrangement of the detection coils--a central coil surrounded by six others, spaced equally on a circle with 2.0 cm center-to-center separation. One of the channels ,a-as not working during this recording. A notch filter was applied to remove environmental interference near 10 Hz. B, Sevenchannel neonatal auditory evoked response at age 10 days from same subject as in Fig. 2, A. Phase reversal of the signal is seen between the left and right channels.
( l i T = 10 .25 T). P l a c e m e n t o f t h e m a g n e t o m e t e r was g u i d e d by u l t r a s o n o g r a p h y , w h i c h was u s e d to locate t h e fetal a u d i t o r y canal a n d e x t e r n a l c a n t h u s . Typically, the fetal scalp was 3 to 5 c m below t h e m a t e r n a l surface. T h e a u d i t o r y stimulus was a b r i e f t o n e b u r s t o f 1.5 kHz fre-
q u e n c y a n d 20 msec d u r a t i o n , delivered f r o m a small s p e a k e r p l a c e d a p p r o x i m a t e l y 1.5 m f r o m t h e subject. T h e s o u n d intensity in air was 100 dB for fetal r e c o r d i n g s a n d 60 dB for n e o n a t a l r e c o r d i n g s . O n e h u n d r e d 0.5s e c o n d trials (0.1 s e c o n d b e f o r e stimulus, 0.4 s e c o n d after
1486 Wakai,Leuthold,and Martin
stimulus) were collected with a random intertrial interval of 2 seconds' mean duration. The analog passband was 1 to 50 Hz, and the signal was digitized at 128 Hz. Some recordings showed interference from the fetal magnetocardiogram, and a computer algorithm was implemented to detect and remove fetal complexes. The auditory evoked responses were averaged and digitally filtered with a 2 to 20 Hz passhand. Four of 14 fetal subjects showed distinct auditory evoked responses with latencies near 200 msec (Figs. 1 and 2, A). Other prominent deflections were sometimes seen at shorter and, more often, at longer latencies but were less consistent between subjects. The quality of the recordings was limited by environmental noise, as well as low signal amplitude. Even in the best recordings signal amplitude was only 100 IT, compared with 400 iT in typical adult recordings. Two of these subjects and four others were studied 7 to 14 days after birth, and all showed neonatal auditory evoked responses similar to the fetal auditory evoked responses. Although probe placement was relatively consistent and optimal for the neonatal recordings, the amplitudes of the neonatal auditory evoked responses were low and showed considerable intersubject variability, ranging from <100 IT to approximately 200 IT. The low amplitude implies that the current-dipole moment is significantly less than for adults, whereas the variability may reflect differences in brain development or state. Spatial variation of the signal was investigated in several neonatal subjects by mapping the signal over the frontal and parietal regions. Phase inversion of the signal was
May 1996 Amj ObstetOynecol
seen between anterior and posterior probe positions, compatible with a source in the auditory cortex. In one subject it was possible to observe phase inversion at a single probe placement (Fig. 2, B). Failure to detect fetal auditory evoked responses can be caused by immaturity of the fetal brain, movement or unfavorable position or orientation of the fetal head, low sound intensity in the womb, or other causes. In addition, the magnetometer used in this study was designed for adult studies. The use of detectors developed specifically for fetal magnetoencephalography can be expected to significantly enhance the success rate of detection and to extend the window of observation earlier in pregnancy. Despite these difficulties, we have shown that under favorable circumstances the magnetic fetal auditory evoked response can be detected with good signal-to-noise ratio and is similar in form to neonatal auditory evoked responses. Magnetoencephalography is a potential technology for detecting the activity of the human fetal brain noninvasively, to study its normal development and pathophysiologic characteristics. REFERENCES
1. Wakai RT, Wang M, Martin C. Spatiotemporal properties of the fetal magnetocardiogram. AMJ OBST~TGmECOL1994;170: 770-6. 2. Blum T, Saling E, Bauer R. First magnetoencephalographic recordings of the brain activity of a human fetus. BrJ Obstet Gynaecol 1985;92:1224-9. 3. Blum T, Bauer R, Arabin B, Reckel S, Saling E. Prenatally recorded auditory evoked neuromagnetic field of the human fetus. In: Barber C, Blum T, eds. Volume 3: evoked potentials. Boston: Butterworth, 1987:13642.