Age-dependent changes in prefrontal intrinsic connectivity.

The prefrontal cortex continues to mature after puberty and into early adulthood, mirroring the time course of maturation of cognitive abilities. However, the way in which prefrontal activity changes during peri- and postpubertal cortical maturation is largely unknown. To address this question, we evaluated the developmental stage of peripubertal rhesus monkeys with a series of morphometric, hormonal, and radiographic measures, and conducted behavioral and neurophysiological tests as the monkeys performed working memory tasks. We compared firing rate and the strength of intrinsic functional connectivity between neurons in peripubertal vs. adult monkeys. Notably, analyses of spike train cross-correlations demonstrated that the average magnitude of functional connections measured between neurons was lower overall in the prefrontal cortex of peripubertal monkeys compared with adults. The difference resulted because negative functional connections (indicative of inhibitory interactions) were stronger and more prevalent in peripubertal compared with adult monkeys, whereas the positive connections showed similar distributions in the two groups. Our results identify changes in the intrinsic connectivity of prefrontal neurons, particularly that mediated by inhibition, as a possible substrate for peri- and postpubertal advances in cognitive capacity.