Music and brain studies on newborns: an fMRI, NIRS and EEG-ABR multimodal discussion

Prof. Efthymios Papatzikis: Electrophysiology on the Newborn Brainstem: Studying the Musical Auditory Brainstem Response

Petra S Hüppi MD: Music enhances brain development in preterm infants

Dr. Artur C. Jaschke, PhD: Neonatal Music Therapy and cerebral Oxygenation in extremely and very preterm infants

Electrophysiology on the Newborn Brainstem: Studying the Musical Auditory Brainstem Response

Papatzikis,E.; Elhalik,M.; Inocencio, S.A.M.; Agapaki, M.; Selvan, R.N.; Muhammed, F.S.; Haroon, N.A.; Dash, S.K..; Bezoni, A.

Neuroscientific studies showing how music exposure is beneficial for the brain have driven the academic and clinical research interest to focus on earlier stages of development and more specifically on newborns. In this context, a small number of studies have successfully managed to discuss early electrophysiological evidence exploring the perinatal therapeutic, restorative and developmental potential of music and complex sounds. These studies have mostly shown an interest on cortical regions, employing either amplitude integrated electroencephalography (aEEG), magnetoencephalography (MEG) or Event-Related Potentials (ERPs). However, at a subcortical level, and more specifically at the level of the brainstem, there is still quite a void on available electrophysiological knowledge and evidence. Considering that the brainstem is the primary neuronal system-gate letting sound in the brain, a crucial question arises: is music still a good candidate to facilitate positive neuronal activation - seen in the newborn context as maturation - when compared to other sound-related stimuli? Trying to answer this question, we followed a randomized control trial (RCT) approach and measured 25 healthy full-term newborns (APGAR score 8 and above) in the first 10 days postpartum. We formed two different experimental groups and employed the click-ABR method to study brainstem activation pre and post a seven days intervention application. For the intervention, we used an aligned - as of tempo (bpm), frequencies (high-low extremes) and sound intensity/volume production (dB) - profile of music and story-telling constructs, offering to newborns a 20 minutes-long passive listening experience during breastfeeding. Recording and analyzing the results at a preliminary level, we describe (a) the Δ of the peak V latencies and (b) the Δ of the inter-peak (V-III; V-I) latencies pre and post intervention, and we demonstrate, in our results, a slight preponderance of music to language. We further discuss signal-amplitude related observations and extent the findings to future investigations.

Prof. Efthymios Papatzikis

Music enhances brain development in preterm infants

Lara Lordier, PhD, Serafeim Loukas, PhD, Manuela Filippa, PhD, Joana De Almeida MD PhD, Petra S Hüppi MD

Division of Development and Growth, Dept of Pediatrics, University Childrens Hospital, University of Geneva, petra.huppi@hcuge.ch

Music is known to induce emotions and activate associated memories, including musical memories. In adults, it is well known that music activates both working memory and limbic networks. We have recently studied the effects of a music intervention on the brain networks in prematurely born newborns and have discovered that as early as during the newborn period, familiar music is processed differently from unfamiliar music (Lordier et al., 2018). In addition this daily music intervention lead to improved resting state functional connectivity in the preterm infants with music compared to control preterm infants (Lordier et al., 2019) and a more mature brain structural maturation of fronto-limbic pathways (Sa de Almeida et al., 2020). Musical memory engrams go beyond the immediate processing of a music stimulus. The brain architecture binding the multisensory music percepts in newborns, as well as the creation of the first extra-uterine musical memories, are still unknown. Using a connectome-based framework, we further describe resting-state functional connectivity (RS-fc) modulation after music listening in three groups of newborn infants, in preterm infants exposed to music during their Neonatal-Intensive-Care-Unit stay, in control preterm, and full-term infants. We observed a modulation of the RS-fc between brain regions known to be implicated in music and emotions processing, immediately following music listening in all newborn infants. In the music exposed group, we found increased RS-fc between brain regions known to be implicated in familiar and emotionally arousing music and multisensory processing, and therefore important for memory retrieval and associative memory. Finally, we demonstrate a positive correlation between the occurrence of the prior music exposure and increased RS-fc in brain regions implicated in multisensory and emotional processing, indicating strong engagement of musical memories; and a negative correlation with the Default Mode Network, indicating disengagement due to the aforementioned cognitive processing (Loukas et al., 2021). Our results describe the modulatory effect of music listening on subsequent brain resting-state functional connectivity in newborns that demonstrates brain correlates of musical memory engrams in preterm infants

Lordier, L., Loukas, S., Grouiller, F., Vollenweider, A., Vasung, L., Meskaldij, D. E., . . . Huppi, P. S. (2018). Music processing in preterm and full-term newborns: A psychophysiological interaction (PPI) approach in neonatal fMRI. Neuroimage. doi:10.1016/j.neuroimage.2018.03.078

Lordier, L., Meskaldji, D. E., Grouiller, F., Pittet, M. P., Vollenweider, A., Vasung, L., . . . Huppi, P. S. (2019). Music in premature infants enhances high-level cognitive brain networks. Proc Natl Acad Sci U S A, 116(24), 12103-12108. doi:10.1073/pnas.1817536116

Loukas, S., Lordier, L., Meskaldji, D. E., Filippa, M., Sa de Almeida, J., Van De Ville, D., & Huppi, P. S. (2021). Musical memories in newborns: A resting-state functional connectivity study. Hum Brain Mapp. doi:10.1002/hbm.25677

Sa de Almeida, J., Lordier, L., Zollinger, B., Kunz, N., Bastiani, M., Gui, L., . . . Huppi, P. S. (2020). Music enhances structural maturation of emotional processing neural pathways in very preterm infants. Neuroimage, 207, 116391. doi:10.1016/j.neuroimage.2019.116391

Petra S Hüppi MD

Neonatal Music Therapy and cerebral Oxygenation in extremely and very preterm infants

Music therapy is a novel intervention that may minimize neonatal stress. The mechanism of action is still largely unknown. We hypothesized that one mechanism of action regards altered brain oxygenation (either due to altered cerebral perfusion or altered cerebral oxygen consumption). We measured cerebral oxygenation before, during and after music therapy sessions using Near-Infrared Spectroscopy (NIRS). We extracted data on cerebral oxygen saturation (rcSO2) and calculated cerebral fractional tissue oxygen extraction (cFTOE). In addition, we measured heart rate. We included 20 infants, receiving 44 music therapy sessions. Median gestational age was 27 weeks, the majority were males. We identified two distinct reactions: in one group rcSO2 increased and cFTOE decreased during therapy compared with before therapy, whereas in the other group rcSO2 decreased and cFTOE increased during therapy compared with before therapy. The first may indicate a sedative effect, whereas the second may reflect a hyperalert state. The observed changes in heart rate may contribute to these observations through altered cerebral perfusion. The clinical significance of these two distinct reactions for music processing and (future) neurological functioning in these infants warrants further investigation.

Artur C. Jaschke, PhD

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