Neurochemical-hemodynamic-electrophysiological coupling in the neonatal brain: a multimodal MRS-fMRI-EEG...

Inhibitory and excitatory neurotransmitter levels are linked to fast neuronal oscillations and infra-slow hemodynamic fluctuations, suggesting a shared excitation-inhibition (E/I) regulatory framework across measures. However, these relationships may differ in early development, when both excitatory and inhibitory cortical systems are undergoing substantial functional and structural maturation. Consequently, we hypothesize different functional coupling between neurochemical, electrophysiological, and hemodynamic proxies of E/I signaling in healthy full-term neonates compared to what has been observed in adults.

Twenty-five healthy full-term neonates (mean postmenstrual age at study = 40.1 ± 1.4 weeks) underwent multimodal MRI and electroencephalography (EEG) recordings during natural resting-state to provide proxy measures of neural excitation and inhibition. These included frontal and occipital MRS measures of γ-aminobutyric acid (GABA+) and Glx (glutamate + glutamine) levels, and their ratio; EEG source-reconstructed power spectra decomposed into periodic beta (13-30 Hz) and gamma (30-45 Hz) features (center frequency and peak amplitude), relative to total band power and an aperiodic exponent; and infra-slow fMRI BOLD fluctuations (0.01-0.08 Hz) using amplitude of low-frequency fluctuations (mean and fractional ALFF). Crossmodal relationships were assessed using partial correlations controlling for age.

Occipital GABA+ was negatively correlated with beta relative power (r = -0.64, p = 0.01) and fractional ALFF (r = -0.55, p = 0.048), while mean ALFF was negatively correlated with gamma center frequency (r = -0.99, p = 0.02). These relationships were not observed in the frontal cortex. Instead, frontal Glx positively correlated with beta peak amplitude (r = 0.87, p < 0.01) and negatively correlated with beta (r = -0.78, p = 0.02) and gamma (r = -0.79, p = 0.02) relative power, potentially reflecting the existence of regionally distinct maturational trajectories.

Together, these preliminary findings suggest that commonly used neurochemical, oscillatory, and hemodynamic proxy measures of cortical excitatory and inhibitory processes may show only modest correspondence at birth, consistent with ongoing and hierarchal cortical development, leading to complex and asynchronous relationships between these measures.