Impact of aging on theta-gamma phase-amplitude coupling during learning: A multivariate analysis

Aging is associated with cognitive decline and memory impairment, but the underlying neural mechanisms remain unclear. Phase-amplitude coupling (PAC) between mid-frontal theta and occipital gamma is a proposed marker for the parallel storage of multiple items in working memory. However, prior research has mainly focused on young adults, with only a few studies in aging populations. Moreover, these studies typically used univariate PAC methods, which are susceptible to spurious estimates due to EEG nonstationarities and often assess PAC at individual electrodes, potentially overlooking the broader functional significance of PAC in coordinating neural activity across distant brain regions. To address these limitations, we applied multivariate PAC (mPAC) using generalized eigendecomposition (GED), which avoids confounds from non-sinusoidal waveforms and captures coupling across distributed brain regions. EEG was recorded from 113 younger and 117 older healthy adults during a sequence learning paradigm (6423 repetitions, 55,944 stimuli), where participants learned a fixed visual sequence over repeated observations, allowing us to track mPAC throughout incremental learning. Younger adults learned significantly faster than older adults. In both groups, mPAC increased with learning and distinguished fast from slow learners. However, older participants showed overall reduced mPAC, suggesting compromised parallel storage in working memory. Crucially, stratification analysis revealed that mPAC effects persisted across performance groups matched for mid-frontal theta power, indicating that theta amplitude alone does not explain the observed effects. These findings shed light on the age-related differences in memory formation processes and may guide interventions to enhance memory performance in older adults and slow learners.