A fundamental issue in cognitive neuroscience is how the brain encodes others' actions and intentions. In recent years, a potential advance in our knowledge on this issue is the discovery of mirror neurons in the motor cortex of the nonhuman primate. These neurons fire to both execution and observation of specific types of actions. Researchers use this evidence to fuel investigations of a human mirror system, suggesting a common neural code for perceptual and motor processes. Among the methods used for inferring mirror system activity in humans are changes in a particular frequency band in the electroencephalogram (EEG) called the mu rhythm. Mu frequency appears to decrease in amplitude (reflecting cortical activity) during both action execution and action observation. The current meta-analysis reviewed 85 studies (1,707 participants) of mu that infer human mirror system activity. Results demonstrated significant effect sizes for mu during execution (Cohen's d = 0.46, N = 701) as well as observation of action (Cohen's d = 0.31, N = 1,508), confirming a mirroring property in the EEG. A number of moderators were examined to determine the specificity of these effects. We frame these meta-analytic findings within the current discussion about the development and functions of a human mirror system, and conclude that changes in EEG mu activity provide a valid means for the study of human neural mirroring. Suggestions for improving the experimental and methodological approaches in using mu to study the human mirror system are offered.

BACKGROUND: DNA methylation (DNAm) is a developmentally dynamic epigenetic process; yet, most epigenome-wide association studies (EWAS) have examined DNAm at only one timepoint or without systematic comparisons between timepoints. Thus, it is unclear whether DNAm alterations during certain developmental periods are more informative than others for health outcomes, how persistent epigenetic signals are across time, and whether epigenetic timing effects differ by outcome. METHODS: We applied longitudinal meta-regression models to published meta-analyses from the PACE consortium that examined DNAm at two timepoints-prospectively at birth and cross-sectionally in childhood-in relation to the same child outcome (ADHD symptoms, general psychopathology, sleep duration, BMI, asthma). These models allowed systematic comparisons of effect sizes and statistical significance between timepoints. Furthermore, we tested correlations between DNAm regression coefficients to assess the consistency of epigenetic signals across time and outcomes. Finally, we performed robustness checks, estimated between-study heterogeneity, and tested pathway enrichment. RESULTS: Our findings reveal three new insights: (i) across outcomes, DNAm effect sizes are consistently larger in childhood cross-sectional analyses compared to prospective analyses at birth; (ii) higher effect sizes do not necessarily translate into more significant findings, as associations also become noisier in childhood for most outcomes (showing larger standard errors in cross-sectional vs prospective analyses); and (iii) DNAm signals are highly time-specific, while also showing evidence of shared associations across health outcomes (ADHD symptoms, general psychopathology, and asthma). Notably, these observations could not be explained by sample size differences and only partly to differential study-heterogeneity. DNAm sites changing associations were enriched for neural pathways. CONCLUSIONS: Our results highlight developmentally-specific associations between DNAm and child health outcomes, when assessing DNAm at birth vs childhood. This implies that EWAS results from one timepoint are unlikely to generalize to another. Longitudinal studies with repeated epigenetic assessments are direly needed to shed light on the dynamic relationship between DNAm, development and health, as well as to enable the creation of more reliable and generalizable epigenetic biomarkers. More broadly, this study underscores the importance of considering the time-varying nature of DNAm in epigenetic research and supports the potential existence of epigenetic timing effects on child health.