Abstract

Cognitive and neurobehavioral problems are among the most severe adverse outcomes in very preterm infants. Such neurodevelopmental impairments may be mitigated through nonpharmacological interventions such as creative music therapy (CMT), an interactive, resource- and needs-oriented approach that provides individual social contact and musical stimulation. The aim was to test the feasibility of a study investigating the role of CMT and to measure the short- and medium-term effects of CMT on structural and functional brain connectivity with MRI. In this randomized, controlled clinical pilot feasibility trial, 82 infants were randomized to either CMT or standard care. A specially trained music therapist provided CMT via infant-directed humming and singing in lullaby style. To test the short-term effects of CMT on brain structure and function, diffusion tensor imaging data and resting-state functional imaging data were acquired. Clinical feasibility was achieved despite moderate parental refusal mainly in the control group after randomization. 40 infants remained as final cohort for the MRI analysis. Structural brain connectivity appears to be moderately affected by CMT, structural connectomic analysis revealed increased integration in the posterior cingulate cortex only. Lagged resting-state MRI analysis showed lower thalamocortical processing delay, stronger functional networks, and higher functional integration in predominantly left prefrontal, supplementary motor, and inferior temporal brain regions in infants treated with CMT. This trial provides unique evidence that CMT has beneficial effects on functional brain activity and connectivity in networks underlying higher-order cognitive, socio-emotional, and motor functions in preterm infants. Our results indicate the potential of CMT to improve long-term neurodevelopmental outcomes in children born very preterm.

Highlights

  • Very preterm birth is associated with a higher prevalence of neurodevelopmental impairments

  • Our results indicate the potential of creative music therapy (CMT) to improve long-term neurodevelopmental outcomes in children born very preterm

  • After 32 infants were excluded due to relocation to other hospitals and parental withdrawal in the control group (Fig. 2), MRI data were acquired in 49 infants (May 2015-April 2018)

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Summary

Introduction

Very preterm birth is associated with a higher prevalence of neurodevelopmental impairments. Among the most common adverse outcomes are deficits in executive functions and behavioral problems (Twilhaar et al, 2018). These impairments persist from early childhood into adolescence and adulthood (Nosarti et al, 2007; Wehrle et al, 2018). Separation from mothers can Abbreviations: AAL, Automated Anatomical Labeling; CMT, creative music therapy; DT-MRI, diffusion tensor magnetic resonance imaging; EPI, echo-planar imaging; FA, fractional anisotropy; FD, framewise displacement; FDR, false discovery rate; fMRI, functional magnetic resonance imaging; ICA, independent component analysis; NICU, neonatal intensive care unit; NIRS, near infrared spectroscopy; ODF, orientation distribution function; PMCC, product moment correlation coefficient; ROI, region of interest; rsfMRI, resting-state functional magnetic resonance imaging; SC, structural connectivity strength; TBSS, tract-based spatial statistics; TCLP, thalamocortical lag projection; TE, echo time; TFCE, threshold-free cluster enhancement; TR, repetition time

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