AbstractAn outstanding issue in our understanding of human brain development is whether sensitive periods exist for higher-order processes (e.g., emotion regulation) that depend on the prefrontal cortex. Evidence from rodent models suggests that there is a sensitive period before puberty when acoustic stimuli, like music, shape medial prefrontal cortex (mPFC) responses that regulate affect in the context of acute stress in adulthood. The present study examined whether a homologous sensitive period for the mPFC occurs during human childhood. In the context of acute stress, adult behavioral preferences were observed only for music experienced during childhood, not preschool or adolescent periods. Childhood music increased mPFC activation and modulated connectivity with the amygdala, which was associated with enhanced emotion regulation and lowered autonomic arousal. Moreover, the timing of this sensitive period could be moved by early-life stress. These findings indicate that childhood is a sensitive period for mPFC encoding of regulatory stimuli.Sensitive periods are developmental moments of heightened neuroplasticity when experiences shape brain function and behavior with lasting effects (1). They are fundamental to human cortical ontogeny, and yet, the timing and nature of sensitive periods for human prefrontal cortex functions remain unknown (2–8). In the rodent, Yang and colleagues have shown that the medial prefrontal cortex (mPFC) exhibits a sensitive period during the prepubertal juvenile period, with heightened responsivity to complex auditory stimuli (i.e., music) (9). Specifically, initial exposure to music during the open (juvenile) sensitive period or a pharmacologically re-opened sensitive period in adulthood was followed by that music uniquely producing a behavioral preference in adulthood, increasing mPFC activity, and reducing anxiety-like behavior. This finding and others converging on the same prepubertal period of plasticity in the rodent (9, 10) may have important implications for human development; the complementary prepubertal period in humans (i.e., school-age childhood) also exhibits developmentally-unique mPFC circuitry phenotypes (11–17) that make childhood a strong candidate for a human mPFC sensitive period. Here, we used Billboard music chart data to identify age-specific exposures to pop songs to test whether music shapes human mPFC responses during a childhood sensitive period as in the rodent. To parallel the approach used in the rodent, we examined whether (i) music experienced during childhood uniquely produced a behavioral preference under stress, (ii) childhood music enhanced emotion regulation behaviorally and physiologically, (iii) mPFC activity was enhanced by childhood music, and mPFC circuitry mediated emotion regulation benefits of childhood music, and (iv) whether the timing of this putative sensitive period could be shifted by early adversity.
The Response of the ERK/MAPK Cascade to Acute Stress in the Medial Prefrontal Cortex of Chronically Stressed Rats
