Electroencephalogram (EEG) network-level excitation-inhibition in GRIN2B-related neurodevelopmental disorders: a pilot case-control series

Background: Loss of function (LoF) variants in GRIN2B lead to neurodevelopmental delay, which is expected to be mediated by alterations in the excitation-inhibition (E/I) balance resulting from reduced activity of the N-Methyl-D-Aspartate receptor. To test this hypothesis, we use quantitative electroencephalogram to provide insights into network-level estimates of the excitation-inhibition ratio. Methods: a single-center, case-control pilot study was conducted. Eyes-open rest EEG recordings were obtained from children with GRIN2B LoF variants (n = 5, aged 3-12.7; 2 females) who participated in an L-Serine intervention trial and compared to age-and gender-matched typically developing children (TDC) (n = 35, aged 4.3-12.8; 15 females). High-frequency resolution analyses (1-45 Hz) of spectral power and long-range temporal correlations measured by detrended fluctuation analyses (DFA) were performed. The functional E/I ratio (fE/I) was also computed. We used source modeling to identify the brain regions showing aberrant activity in GRIN2B neurodevelopmental disorder (NDD) brain dynamics. Statistical differences were tested by applying bootstrapping analyses. Results: The patients harboring pathogenic GRIN2B LoF variants showed elevated absolute and relative power compared to the control group in the 1-4 Hz range across all brain regions. The GRIN2B group had elevated DFA values almost across all frequencies and brain regions, whereas the fE/I marker was lower at frequencies from 4-13 Hz compared to the TDC group (P < 0.05). Conclusions: our findings indicate that quantitative EEG is strongly affected in GRIN2B and might be a valuable tool for measuring E/I imbalances and evaluating changes resulting from pharmacological interventions.