EEG Phase-Amplitude Coupling Strength and Phase Preference: Association with Age over the First Three Years after Birth

Abstract

Phase-amplitude coupling (PAC), the coupling of the phase of slower electrophysiological oscillations with the amplitude of faster oscillations, is thought to facilitate dynamic integration of neural activity in the brain. Though the brain undergoes dramatic change and development during the first few years of life, how PAC changes through this developmental period has not been extensively studied. Here, we examined PAC through electroencephalography (EEG) data collected during an awake, eyes-open EEG collection paradigm in 98 children between the ages of 3 months and 3 years. We employed non-parametric clustering methods to identify areas of significant PAC across a range of frequency pairs and electrode locations, and examined how PAC strength and phase preference develops in these areas. We found that PAC, primarily between the alpha-beta and gamma frequencies, was positively correlated with age from early infancy to early childhood (p = 2.035 x 10 -6 ). Additionally, we found gamma over anterior electrodes coupled with the rising phase of the alpha-beta waveform, while gamma over posterior electrodes coupled with the falling phase of the alpha-beta waveform; this regionalized phase preference became more prominent with age. This opposing trend may reflect each region's specialization towards feedback or feedforward processing, respectively, suggesting opportunities for back translation in future studies. Significance StatementThe brain undergoes significant development during infancy and early childhood, enabling the emergence of higher-level cognition. Phase-amplitude coupling (PAC) is thought to support the integration of information within the brain. Our data suggest PAC increases from 3 months to 3 years of age. We additionally report the anterior and posterior electrodes show opposing forms of PAC; this regional phase preference also increases with age of EEG collection. These findings help set the stage for future analyses of PAC in young children with neurodevelopmental disorders, in which development of biomarkers during early life is a burgeoning field and measures of cross-frequency coupling may offer new promise.

Cortical Cross-Frequency Coupling Is Affected by in utero Exposure to Antidepressant Medication

“…Prior literature has generally considered that the PAC is a ubiquitous property of the early neuronal network activity ( Vanhatalo et al, 2005 ; Li et al, 2017 ; Moghimi et al, 2020 ), while any spatial differences in the PAC mechanisms have been only studied in older infants ( Mariscal et al, 2021 ). Our present findings could not be explained with studies on older human subjects because cortical mechanisms underlying EEG signal characteristics, including PAC, will change after neonatal period ( Vanhatalo and Kaila, 2006 ; Simpson et al, 2011 ; Molnár et al, 2020 ; Wallois et al, 2021 ).…”

“…Second, the measures should examine functional interactions within local and large-scale neuronal networks. Third, the measures should estimate the interplay between neural oscillations at different frequencies, which underpins the intrinsic mechanisms guiding the early brain networking ( Vanhatalo et al, 2005 ; Tokariev et al, 2016b ; Mariscal et al, 2021 ). All these requirements can be met by studying cortical activity—estimated from reconstruction of the scalp-recorded EEG—and analysis of phase-phase correlations (PPC) for remote cortico-cortical interactions, and phase-amplitude coupling (PAC) for local interactions.…”

Phase-Amplitude Coupling in Autism Spectrum Disorder: Results from the Autism Biomarkers Consortium for Clinical Trials

“…We primarily evaluated PAC metrics across three brain regions: the anterior (FP1, FP2, F3, F4, F7, F8, Fz), posterior (O1, O2, T5, T6, Pz), and whole (all 10-20 channels) brain. These regions were chosen based on prior studies showing that PAC often differs in anterior versus posterior channels (18,19). PAC was evaluated in three specific frequency range pairs following the canonical wavebands: theta (4-6 Hz) and gamma (28-56 Hz), alpha (8-12 Hz) and gamma (28-56 Hz), and low beta (14-20 Hz) and gamma (44-56 Hz).…”

“…We evaluated associations of whole brain PAC of theta-gamma, alpha-gamma, and beta-gamma activity with IQ via the DAS-2 and two behavioral domains frequently associated with ASD, social communication (SC) and restricted interests and repetitive behaviors (RRB), as measured by the Social Responsiveness Scale (SRS-2). Because PAC has been shown to change with age (18), we also evaluated PAC association with age and subsequently included age as an independent variable in regression analyses with SC, RRB, and IQ. Associations were run for the full sample (combining ASD and TD groups) and for the ASD group alone.…”

“…First, we identified regions of significant PAC in frequency space within each of 18 channels for the ASD and TD groups separately. We employed the clustering procedure detailed in (18). In summary, a t-test was used to compare the raw MI values and the surrogate MI values (each an average of 200 iterations) from all participants of a diagnostic group.…”