Natural Science Forum / Biology / Biology / November 2007

surely we can now discern with acuracy the first moment of
consciousness...

article taken from lancet, 2002...

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
[15-30310.sup.-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.

Lancet 2002; 360: 779-80

Technological developments during the past decade have enabled direct
investigation of the functional development of the fetal brain. Two
techniques that have been used to study fetal brain activity are
magnetoencephalography (MEG) (1) and functional magnetic resonance
imaging (functional MRI). (2) These techniques have been used to study
the cortical response to auditory stimuli. For a more complete
assessment of the functional development of the brain, additional
senses need to be tested.

There have been only a few studies of visual evoked response in human
fetuses, and all have focused on non-specific changes such as heart
rate, body movements, and eye movements. (3,4) We investigated the
feasibility of non-invasive MEG recording of the visual evoked fetal
brain activity by use of a 151-channel SQUID (superconducting quantum
interference device) system called SARA (SQUID array for reproductive
assessment). SARA was designed to study aspects of maternal and fetal
physiology.

The 151 sensors in SARA are arranged in a concave array. The mother
being assessed sits and leans forward against the smooth surface of
the array, allowing the SQUID sensors to receive signals from the
entire maternal abdomen. To reduce the effects of environmental noise,
SARA is installed in a magnetically shielded room (Vakuumschmelze;
Hanau, Germany).

A flash stimulus was used to elicit the visual evoked response. The
light source, located outside the shielded room, uses a light emitting
diode (LED) array (Opto Technology, Wheeling, USA; model
OTL630A-5-10-66-E, wavelength -625 nm). A 77 m long fibre-optic cable
channels the light flash from the LED array (outside the shielded
room) to the maternal abdomen. The peak illumination at the exit of
the fibre-optic cable measured over a 33 ms duration light pulse was
8800 lux. The light pulse was considered safe for the fetus, since it
was of short duration, contained no short wavelength radiation, and
had an intensity much lower than sunlight on a bright day (about 100
000 lux).

MEG data were recorded in a continuous mode at a sampling rate of 312
Hz. The light stimulus was a sequence of 33 ms duration flash with
mean interstimulus interval of 2 s (+/-50 ms randomisation). The onset
time of each light stimulus was recorded with MEG data. Each recording
session lasted 6 min and consisted of 180 flashes. Interfering
maternal and fetal heart signal components were removed by application
of a spatial-filter-based null-projection algorithm. The evoked
responses were obtained by averaging extracted time slices from the
continuous data set from 02 s before onset of the stimulus to 08 s
after onset. The results were band-pass filtered between 05 and 10
Hz.

Before doing the MEG recordings, we measured the distance from the
fetal eye to maternal skin and noted the fetal head and eye positions
by ultrasonography. We excluded fetuses who had an eye-maternal skin
distance greater than 3 cm or their head facing down or away from the
anterior abdominal surface. We screened 17 low-risk fetuses, from 28
to 36 weeks' gestational age, of which 10 were positioned adequately
and were included. The University of Arkansas for Medical Sciences
Human Research Advisory Committee approved the protocol, which was
discussed with each patient and their written consent obtained.

Figure 1B shows an overlay of recordings from six channels recording
averaged visual evoked response to about 180 flash stimuli in a fetus
at 36 weeks' gestation. The positive and negative deflections showing
the phase reversal of the signals indicate a dipolar magnetic field
pattern. The contour map (figure 1A) shows the dipolar field pattern
over the fetal head at 180 ms. Reproducibility of the signal is shown
(figure 1C) by comparison of the split averages obtained from the
first (90 stimuli) and second (90 stimuli) halves of the trial. Figure
1D shows maximum averaged evoked response from a single channel with
the corresponding plus-minus average (figure 1E). The comparison of
these two figures gives the measure of the signal-to-noise ratio.
Figure 2 shows the response from four fetuses with gestational ages of
28, 29, 31, and 36 weeks, respectively. These single channel plots are
averaged over 180 trials showing either the positive or negative
deflection in each case. The ranges of maximum amplitude (positive or
negative) and the corresponding latency of these responses were
[15-30310.sup.-15] Tesla and 180-390 ms, respectively. The magnetic
response is comparable in morphology and latency to the electrical
visual evoked response for preterm infants (for gestational age <34
weeks P2=180-249 ms [positive peak], N3=256-316 ms [negative peak];
for gestational age 34-36 weeks P2=150-280 ms, N3=228-372 ms). (5) The
latency of the fetal response fell with increasing gestational age and
began to approach the adult latency. The remaining six fetuses showed
no evident response.

[FIGURES 1-2 OMITTED]

In this preliminary study, we have shown that brain activity to visual
stimuli can be recorded by use of MEG in human fetuses. Further
studies with improved stimulation protocols and light delivery
mechanisms will increase the success rate of the technique. Serial
recordings of visual evoked brain activity in conjunction with
auditory evoked brain activity will be a new method to study the
neurological development of the fetus.

Contributors All authors contributed to study conception, data
analysis, writing, and interpretation of this paper.

Conflict of interest statement None declared.

Acknowledgments

This work was supported by National Institutes of Health grant
1R01NS36277. The sponsors of the study had no role in study design,
data collection, data analysis, data interpretation, or writing of the
report.

(1) Blum T, Saling E, Bauer R. First magneto encephalographic
recordings of the brain activity of the human fetus. Br J Obstet
Gynaecol 1985; 92: 1224-29.

(2) Hykin J, Moore R, Duncan K, et al. Fetal brain activity
demonstrated by functional magnetic resonance imaging. Lancet 1999;
354: 645-46.

(3) Peleg D, Goldman JA. Fetal heart rate acceleration in response to
light stimulation as a clinical measure of fetal well-being: a
preliminary report. J Perinat Med 1980; 8: 38-41.

(4) Kiuchi M, Nagata N, Ikeno S, Terakawa N. The relationship between
the response to external light stimulation and behavioural states in
the human fetus: how it differs from vibroacoustic stimulation. Early
Hum Dev 2000; 58: 153-65.

(5) Shepherd AJ, Saunders KJ, McCulloch DL, Dutton GN. Prognostic
value of flash visual evoked potentials in preterm infants. Dev Med
Child Neurol 1999; 41: 9-15.

Department of Obstetrics and Gynecology, University of Arkansas for
Medical Sciences, 4301 W Markham, Slot 518, Little Rock, AR 72205, USA
(H Eswaran PhD, H Preissl PhD, P Murphy BSN, C L Lowery MD); Graduate
Institute of Technology, University of Arkansas at Little Rock, Little
Rock (H Eswaran, J D Wilson MS); MEG Center, Institute of Medical
Psychology and Behavioral Neurobiology, University of Tubingen,
Tubingen, Germany (H Preissl); CTF Systems, Port Coquitlam, British
Columbia, Canada (S E Robinson PhD, J Vrba PhD); and Department of
Pediatrics and Neurology, Children's Hospital Medical Center
Cincinnati, Cincinnati, OH, USA (D F Rose MD)

Correspondence to: Dr C. L. Lowery (e-mail: LoweryCurtisL@uams.edu)