Investigating frequency-tagging in fetal MEG: Evidence against the “Smeared Stimulus Hypothesis”

Poster No:

1021 

Submission Type:

Abstract Submission 

Authors:

Joel Frohlich1, Julia Moser2,3, Katrin Sippel1, Hubert Preissl1

Institutions:

1IDM/fMEG Center of the Helmholtz Center Munich at the University of Tübingen, University of Tübingen, Tübingen, Baden-Württemberg, 2Masonic Institute for the Developing Brain, University of Minnesota, Minneapolis, MN, 3Institute of Child Development, University of Minnesota, Minneapolis, MN

First Author:

Joel Frohlich, PhD  
IDM/fMEG Center of the Helmholtz Center Munich at the University of Tübingen, University of Tübingen
Tübingen, Baden-Württemberg

Co-Author(s):

Julia Moser, PhD  
Masonic Institute for the Developing Brain, University of Minnesota|Institute of Child Development, University of Minnesota
Minneapolis, MN|Minneapolis, MN
Katrin Sippel, PhD  
IDM/fMEG Center of the Helmholtz Center Munich at the University of Tübingen, University of Tübingen
Tübingen, Baden-Württemberg
Hubert Preissl  
IDM/fMEG Center of the Helmholtz Center Munich at the University of Tübingen, University of Tübingen
Tübingen, Baden-Württemberg

Introduction:

Fetal magnetoencephalography (fMEG) uses superconducting magnetometers for the non-invasive detection of fetal cortical signals after 25 weeks gestation. A recent review (Dehaene-Lambertz 2024) suggested that fetuses may perceive trains of repetitive stimuli with brief (e.g., < 1000 ms) interstimulus intervals as a single stimulus due to the coarse temporal scale of prenatal perception (henceforth: "Smeared Stimulus Hypothesis"), perhaps explaining anomalous results in a prior fMEG study from our lab of fetal prediction errors (Moser et al. 2021). Herein, we seek to test this hypothesis by looking for frequency-tagging in fMEG, which takes place when neural responses are evoked by each stimulus in a periodic train or sequence.

Methods:

We applied a frequency-tagging analysis to our previously published data (Moser et al. 2021) which the Smeared Stimulus Hypothesis seeks to explain. These fMEG data were recorded with sequences of four tones with 600 ms between tone onsets (Fig. 1). To check that our results generalize to other periodic auditory stimuli, we also analyzed fMEG data from a statistical learning task which exposed fetuses to a constant stream of 3 random tones per second (Fig. 1). In both datasets, fMEG data were recorded from 156 channels at 610.35 Hz. After excluding fetuses with noisy data, we analyzed trial-averaged fMEG responses from 41 recordings in 29 fetuses (first dataset, 25 - 39 weeks gestation) and 31 recordings in 31 fetuses (second dataset, 31 - 38 weeks gestation). Maternal and fetal R-peaks were detected to estimate and subtract cardiac activity from the data. Channels containing cortical signals were then selected based on in-house methods for further processing. Signals were Butterworth bandpass filtered 0.5 - 10 Hz prior to analysis. In the first dataset, we averaged all fetal cortical signals across trials (-200 to 2400 ms after first tone), channels, and recordings, and we then looked for evidence of frequency-tagging by measuring the SNR of the grand-average according to the method outlined by Liu-Shuang et al. (2014) at 1.67 Hz. In the second dataset, we averaged 4000 ms windows of data for the first 5 minutes of the recording, as prior work in infants (Heering and Rossion, 2015) showed this duration to be sufficient and, moreover, durations past 5 minutes were thought likely to produce habituation. We then followed the same procedure as above, looking for frequency tagging at 3.0 Hz. In all cases, we computed the grand-averaged signal's amplitude spectrum (0.5 - 8 Hz) using Morlet wavelets with 0.05 Hz frequency resolution. The amplitude spectrum was then whitened to remove the 1/f background. In addition to z-scoring the SNR values across frequency bins, we also computed 1000 temporally misaligned signal averages for each dataset (maximum 500 ms jitter) and derived a null distribution of SNRs for non-parametric testing.
Supporting Image: fMEG_and_stimuli.png
   ·Figure 1
 

Results:

Grand-averaged amplitude spectra are shown in Fig.2. In the first dataset, parametric testing yielded trends for both the first (P = 0.084) and second (P = 0.063) datasets. Non-parametric testing rejected the null hypothesis for the first dataset (P = 0.005), but not the second dataset (P = 0.25).
Supporting Image: whitened_fMEG_amplitude_spectrum.png
   ·Figure 2
 

Conclusions:

This is the first ever analysis of frequency-tagging in fetal MEG data. Parametric testing appears more sensitive to the center-frequency of the tagged response, whereas nonparametric testing appears more sensitive to the overall size of the tagged response. Because the second dataset used a continuous sequence of stimuli, fetuses may have habituated to the stimuli (see Muenssinger et al. 2013), resulting in null finding; by contrast, the first dataset included 1000 ms silent intervals between sequences, which may have counteracted fetal habituation. Though our results are mixed, non-parametric testing in the first dataset challenges the Smeared Stimulus Hypothesis with evidence that fetuses respond to individual tones within a stimulus sequence.

Higher Cognitive Functions:

Higher Cognitive Functions Other

Lifespan Development:

Normal Brain Development: Fetus to Adolescence 1

Neuroanatomy, Physiology, Metabolism and Neurotransmission:

Normal Development

Novel Imaging Acquisition Methods:

MEG 2

Perception, Attention and Motor Behavior:

Consciousness and Awareness

Keywords:

Cognition
Consciousness
Cortex
Development
Learning
MEG
NORMAL HUMAN
Perception
Other - frequency-tagging

1|2Indicates the priority used for review

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Provide references using APA citation style.

Dehaene-Lambertz, G. (2024). Perceptual awareness in human infants: What is the evidence?. Journal of Cognitive Neuroscience, 36(8), 1599-1609. https://doi.org/10.1162/jocn_a_02149

de Heering, A., & Rossion, B. (2015). Rapid categorization of natural face images in the infant right hemisphere. eLife, 4, e06564. https://doi.org/10.7554/eLife.06564

Liu-Shuang, J., Norcia, A. M., & Rossion, B. (2014). An objective index of individual face discrimination in the right occipito-temporal cortex by means of fast periodic oddball stimulation. Neuropsychologia, 52, 57-72. https://doi.org/10.1016/j.neuropsychologia.2013.10.022

Muenssinger, J., Matuz, T., Schleger, F., Kiefer‐Schmidt, I., Goelz, R., Wacker‐Gussmann, A., Birbaumer, N., & Preissl, H. (2013). Auditory habituation in the fetus and neonate: an fMEG study. Developmental Science, 16(2), 287-295. https://doi.org/10.1111/desc.12025

Moser, J., Schleger, F., Weiss, M., Sippel, K., Semeia, L., & Preissl, H. (2021). Magnetoencephalographic signatures of conscious processing before birth. Developmental Cognitive Neuroscience, 49, 100964. https://doi.org/10.1016/j.dcn.2021.100964

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