A pilot study: Auditory steady-state responses (ASSR) can be measured in human fetuses using fetal magnetoencephalography (fMEG)

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, with the present study it was possible to detect human fetal ASSRs for the first time. These findings warrant further investigations of the developing fetal brain.

[1]  R. Draganova,et al.  Fetal auditory evoked responses to onset of amplitude modulated sounds. A fetal magnetoencephalography (fMEG) study , 2018, Hearing Research.

[2]  Hubert Preissl,et al.  Neuromagnetic signatures of syllable processing in fetuses and infants provide no evidence for habituation. , 2016, Early human development.

[3]  H. Preissl,et al.  Functional brain development in growth‐restricted and constitutionally small fetuses: a fetal magnetoencephalography case–control study , 2015, BJOG : an international journal of obstetrics and gynaecology.

[4]  R. Draganova,et al.  Heart rate variability parameters and fetal movement complement fetal behavioral states detection via magnetography to monitor neurovegetative development , 2015, Front. Hum. Neurosci..

[5]  Hubert Preissl,et al.  Magnetoencephalographic Signatures of Numerosity Discrimination in Fetuses and Neonates , 2014, Developmental neuropsychology.

[6]  H. Preissl,et al.  Fetal behavioral states are stable over daytime – evidence by longitudinal and cross-sectional fetal biomagnetic recordings , 2014, Journal of perinatal medicine.

[7]  H. Preissl,et al.  Maternal insulin sensitivity is associated with oral glucose-induced changes in fetal brain activity , 2014, Diabetologia.

[8]  Moriah E. Thomason,et al.  Functional plasticity before the cradle: A review of neural functional imaging in the human fetus , 2013, Neuroscience & Biobehavioral Reviews.

[9]  Hubert Preissl,et al.  Sensitivity to Auditory Spectral Width in the Fetus and Infant – An fMEG Study , 2013, Front. Hum. Neurosci..

[10]  H. Preissl,et al.  Is there a relationship between fetal brain function and the fetal behavioral state? A fetal MEG-study , 2013, Journal of perinatal medicine.

[11]  S. Muthukumaraswamy.  High-frequency brain activity and muscle artifacts in MEG/EEG: a review and recommendations , 2013, Front. Hum. Neurosci..

[12]  Hubert Preissl,et al.  Auditory habituation in the fetus and neonate: an fMEG study. , 2013, Developmental science.

[13]  Robert Burkard,et al.  The Auditory Steady-State Response: Generation, Recording, and Clinical Applications , 2009 .

[14]  Hubert Preissl,et al.  Delayed maturation of auditory-evoked responses in growth-restricted fetuses revealed by magnetoencephalographic recordings. , 2008, American journal of obstetrics and gynecology.

[15]  D. Hoyer,et al.  Human fetal heart rate variability-characteristics of autonomic regulation in the third trimester of gestation , 2008, Journal of perinatal medicine.

[16]  Renaud Jardri,et al.  Fetal cortical activation to sound at 33 weeks of gestation: A functional MRI study , 2008, NeuroImage.

[17]  Hubert Preissl,et al.  Integrated Approach for Fetal QRS Detection , 2008, IEEE Transactions on Biomedical Engineering.

[18]  Hubert Preissl,et al.  Serial magnetoencephalographic study of fetal and newborn auditory discriminative evoked responses. , 2007, Early human development.

[19]  F. Linthicum,et al.  The human auditory system: A timeline of development , 2007, International journal of audiology.

[20]  S. Kuwada,et al.  Optimizing the Stimuli to Evoke the Amplitude Modulation Following Response (AMFR) in Neonates , 2006, Ear and hearing.

[21]  Dirk Hoyer,et al.  Permutation entropy improves fetal behavioural state classification based on heart rate analysis from biomagnetic recordings in near term fetuses , 2006, Medical and Biological Engineering and Computing.

[22]  Hubert Preissl,et al.  Development of auditory evoked fields in human fetuses and newborns: A longitudinal MEG study , 2005, Clinical Neurophysiology.

[23]  Terence W Picton,et al.  Recording Auditory Steady-State Responses in Young Infants , 2004, Ear and Hearing.

[24]  Hubert Preissl,et al.  Fetal MEG redistribution by projection operators , 2004, IEEE Transactions on Biomedical Engineering.

[25]  Terence W. Picton,et al.  Frequency specificity of 40-Hz auditory steady-state responses , 2003, Hearing Research.

[26]  Hubert Preissl,et al.  Noninvasive antepartum recording of fetal S-T segment with a newly developed 151-channel magnetic sensor system. , 2003, American journal of obstetrics and gynecology.

[27]  T. Picton,et al.  Human auditory steady-state responses: Respuestas auditivas de estado estable en humanos , 2003, International journal of audiology.

[28]  Hubert Preissl,et al.  Short-term serial magnetoencephalography recordings offetal auditory evoked responses , 2002, Neuroscience Letters.

[29]  Terence W. Picton,et al.  Temporal integration in the human auditory cortex as represented by the development of the steady-state magnetic field , 2002, Hearing Research.

[30]  R. Wakai,et al.  Improved neuromagnetic detection of fetal and neonatal auditory evoked responses , 2001, Clinical Neurophysiology.

[31]  R. Mühler,et al.  Amplitude modulation following responses in awake and sleeping humans - a comparison for 40 Hz and 80 Hz modulation frequency , 2001, Scandinavian audiology. Supplementum.

[32]  Almut Engelien,et al.  A combined functional in vivo measure for primary and secondary auditory cortices , 2000, Hearing Research.

[33]  Terence W. Picton,et al.  Frequency‐Specific Audiometry Using Steady‐State Responses , 1996, Ear and hearing.

[34]  R. Dobie,et al.  Amplitude-modulation following response (AMFR): Effects of modulation rate, carrier frequency, age, and state , 1993, Hearing Research.

[35]  G M Clark,et al.  A comparison of steady-state evoked potentials to modulated tones in awake and sleeping humans. , 1991, The Journal of the Acoustical Society of America.

[36]  T W Picton,et al.  Human Auditory Steady‐State Response During General Anesthesia , 1990, Anesthesia and analgesia.

[37]  S Makeig,et al.  Inconsistency of auditory middle latency and steady-state responses in infants. , 1986, Electroencephalography and clinical neurophysiology.

[38]  S. Schulze,et al.  Fetal behavioural states and controlled sound stimulation. , 1985, Early human development.

[39]  H. Prechtl,et al.  Are there behavioural states in the human fetus? , 1982, Early human development.

[40]  S. Makeig,et al.  A 40-Hz auditory potential recorded from the human scalp. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[41]  B. Ross,et al.  Introduction to Technical Principles of Auditory Steady-state Response Testing 11 the Stimulus-response Relationship in Auditory Steady-state Response Testing 55 Neural Generators of the Auditory Steady-state Responses 83 Clinical Application of Auditory Steady-state Responses 119 Behavioural Thresh , 2008 .

[42]  Jan Wouters,et al.  Clinical application of auditory steady-state responses , 2006 .

[43]  H. Preissl,et al.  Fetal magnetoencephalography: viewing the developing brain in utero. , 2005, International review of neurobiology.

[44]  M. Scherg,et al.  Intracerebral Sources of Human Auditory Steady-State Responses , 2004, Brain Topography.

[45]  G M Clark,et al.  Auditory steady-state evoked potential in newborns. , 1994, British journal of audiology.

[46]  Y. Koike,et al.  Effects of aging on amplitude-modulation following response. , 1994, Acta oto-laryngologica. Supplementum.

[47]  M Maurizi,et al.  40-Hz steady-state responses in newborns and in children. , 1990, Audiology : official organ of the International Society of Audiology.

[48]  C. Oliver,et al.  Sound environment of the fetal sheep. , 1990, American journal of obstetrics and gynecology.

[49]  S. Makeig,et al.  Dynamic Changes in Steady-State Responses , 1988 .

[50]  T. Melnechuk,et al.  Dynamics of Sensory and Cognitive Processing by the Brain , 1988, Springer Series in Brain Dynamics.

[51]  D. Querleu,et al.  Fetal hearing. , 1988, European journal of obstetrics, gynecology, and reproductive biology.

[52]  T Suzuki,et al.  An evaluation of 40-Hz event-related potentials in young children. , 1984, Audiology : official organ of the International Society of Audiology.