Neurophysiological basis of hemodynamic responses in the developing human brain before the time of normal birth

Neurovascular coupling that links neural activity to localized increases in blood flow is essential both for brain function and to prevent tissue injury. In the healthy human brain, this underlies an association between the duration of EEG microstates, which represent coordinated and metastable activation of neuronal ensembles, and increases in hemodynamic activity. However, in early human life it is not clear whether neurovascular coupling is functional as the underlying physiological mechanisms may be too immature to effectively support it. Here, we combined MRI compatible robotics with simultaneous EEG and fMRI data acquisition in 13 preterm infants to assess whether the relationship between neural activity and hemodynamic responses is present in this critical period of early life. Passive sensorimotor stimulation elicited both a distinct sequence of four EEG microstates and a significant rise in the blood oxygen level dependent (BOLD) fMRI signal in the left primary sensorimotor cortex. Furthermore, EEG microstate duration was significantly related to BOLD response amplitude. These results suggest that effective neurovascular coupling is present in the human brain even before the normal time of birth and reveal a complex relationship between EEG and fMRI signals underpinned by patterns of activity across distinct neural ensembles. ### Competing Interest Statement The authors have declared no competing interest.