Adolescence as a neurobiological critical period for the development of higher-order cognition

Abstract

The transition from adolescence to adulthood is characterized by improvements in higher-order cognitive abilities and corresponding refinements of the structure and function of the brain regions that support them. Whereas the neurobiological mechanisms that govern early development of sensory systems are well-understood, the mechanisms that drive developmental plasticity of association cortices, such as prefrontal cortex (PFC), during adolescence remain to be explained. In this review, we synthesize neurodevelopmental findings at the cellular, circuit, and systems levels in PFC and evaluate them through the lens of established critical period (CP) mechanisms that guide early sensory development. We find remarkable correspondence between these neurodevelopmental processes and the mechanisms driving CP plasticity, supporting the hypothesis that adolescent development is driven by CP mechanisms that guide the rapid development of neurobiology and cognitive ability during adolescence and their subsequent stability in adulthood. Critically, understanding adolescence as a CP not only provides a mechanism for normative adolescent development, it provides a framework for understanding the role of experience and neurobiology in the emergence of psychopathology that occurs during this developmental period.

Keywords: Adolescence; Cognition; Critical period; Development; Dopamine; GABA; Parvalbumin; Prefrontal cortex.

Figure 1

A critical period model of adolescent development. Adolescence begins with the onset of puberty and a concomitant increase in dopamine (DA) availability. Increases in DA motivate exploratory behavior and heightened reward reactivity which, in turn, promote the experience accumulation necessary to shape experience-dependent plasticity. DA, puberty, novel experience may jointly function to trigger critical period activity through their interaction with neurobiological factors that facilitate critical period (CP) plasticity. These facilitating factors include changes in NMDA signaling and receptor concentrations that promote experience-dependent plasticity, increased levels of brain-derived neurtrophic factor (BDNF), and maturation of GABAergic inhibitory circuitry (particularly parvalbumin positive (PV) interneurons). The maturation of inhibitory circuitry has important functional consequences including a reduction in the excitation-to-inhibition balance (E/I balance) and facilitation of high-frequency oscillatory capability of local circuits. As the critical period progresses, age-related increases in critical period braking factors, including myelination and PNN formation, begin to restrict further plasticity to close the CP window and stabilize circuits into adulthood. This stabilization leads to consistent and reliable circuit function and communication which underlies the stabilization of trial-to-trial cognitive ability that is characteristic of mature higher-order cognitive function. Note: Developmental curves are schematics meant to summarize prior work. Blue and red curves represent the development of facilitating and braking factors, respectively. Shaded grey area reflects the adolescent period.

Figure 2

The development of GABAergic interneuron subtypes in prefrontal cortex through adolescence. The development of parvalbumin (PV) interneurons is an essential factor for critical period development. Here we show findings from studies of PV development in the prefrontal cortex (PFC) in three different species (A-C top panels). Developmental trajectories for calretinin (CR) interneurons are also provided (A-C lower panel) to highlight the specificity of PV increases during adolescence. A) PV protein expression significantly increases from childhood (white) to adolescence (grey) and adulthood (black)in the medial PFC of healthy rats (top panel). In contrast, CR protein expression decreases over the same period (bottom panel). Data is adapted from (Caballero et al., 2014). B) Parvalbumin mRNA levels increase with age throughout adolescence in the healthy macaque monkey PFC (top panel), while CR mRNA levels either remain stable or decrease (bottom panel). Data is adapted from (Hoftman et al., 2015). C) PV mRNA expression, assessed postmortem, increases from childhood to adulthood in the human dorsolateral PFC (top panel) while CR mRNA expression decreases (bottom panel). Triangles = females; circles = males. Representative mRNA expression profiles for PV, CR and calbindin (CB) interneuron subtypes (bottom panel) indicate a possible peak in PV during adolescence while CR and CB decrease. Data adapted from (Fung et al., 2010). Panels A-C indicate increasing ratios of PV to CR expression in PFC across rat, non-human primate, and human species. D) Approximate windows for adolescence in the species represented in this figure (Kilb, 2012; Piekarski et al., 2017; Spear, 2000; Zehr et al., 2005).

Figure 3

Development of cortical dopamine during adolescence. This schematic summarizes rodent and non-human primate evidence for the dynamic and multifaceted development of the mesocortical dopamine system during adolescence. Dopamine innervation of PFC, including fiber volume, fiber length, density of varicosities and appositions, and dopamine concentration increase throughout adolescence and either decrease (Rosenberg and Lewis, 1995) or stabilize (Benes et al., 1996; Lambe et al., 2000; Leslie et al., 1991; Willing et al., 2017) during the transition to adulthood. D1 and D2 receptor densities peak during adolescence or early adulthood in non-human primates and D1 expression is stably greater than D2 expression across adolescence (Lidow et al., 1991; Lidow and Rakic, 1992). The peak may be less pronounced in rodent studies (e.g. Andersen et al., 2000; Tarazi and Baldessarini, 2000). Dopamine transporter increases from late childhood to adulthood in rodent PFC and cingulate cortex (Coulter et al., 1996).