Simultaneous EEG-fMRI investigation of sound sequence processing in human neonates

The ability to detect sensory regularities and their violations (i.e. deviance) is fundamental for learning and the orientation of attention across the lifespan. This starts from the prenatal period, where the environment is rich in regular patterns and deviations of auditory stimulation which likely provides the basis for the emergence of early learning capacities. Following birth, EEG recordings of brain activity have demonstrated that neonates detect violations of regularity and show a robust mismatch response to deviant auditory stimuli. However, it is unknown how this processing is integrated across wider regions within emergent brain networks. To gain comprehensive insight into both the temporal and spatial properties of the processing underlying sensory deviance detection in the neonatal brain, we acquired simultaneous EEG and fMRI data in sleeping neonates during an auditory oddball paradigm. A mismatch response was identified with EEG when a deviant sound appeared after a sequence of identical sounds but not when a sound was omitted, suggesting encoding of deviances that violated local sequence regularity, but not global sequence structure. Simultaneous fMRI demonstrated engagement of distributed cortical networks during sound sequence processing, encompassing temporal, sensori-motor, and inferior frontal cortices, as well as subcortical regions including the thalamus and hippocampus. Deviance detection was associated with activity in the superior and ventromedial (hippocampus and parahippocampus) parts of the temporal lobe, and the precentral gyrus. Together, these findings suggest that neonatal brain detects deviance in sound sequences through the encoding of local regularities, supported by distinct processing pathways within sensory and limbic systems. These insights help advance our understanding of early auditory learning mechanisms, with implications for understanding how atypical developmental trajectories may emerge in these substrates.