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This study aimed to develop a time–frequency method for measuring directional interactions over time and frequency from scalp-recorded electroencephalographic (EEG) signals in a way that is less affected by volume conduction and amplitude scaling. We modified the time-varying generalized partial directed coherence (tv-gPDC) method, by orthogonalization of the strictly causal multivariate autoregressive model coefficients, to minimize the effect of mutual sources. The novel measure, generalized orthogonalized PDC (gOPDC), was tested first using two simulated models with feature dimensions relevant to EEG activities. We then used the method for assessing event-related directional information flow from flash-evoked responses in neonatal EEG. For testing statistical significance of the findings, we followed a thresholding procedure driven by baseline periods in the same EEG activity. The results suggest that …