Developmental changes in prefrontal cortex (PFC) excitatory (glutamatergic, Glu) and inhibitory (gamma- aminobutryic acid, GABA) neurotransmitter balance (E:I) have been identified during human adolescence, potentially reflecting a critical period of plasticity that supports the maturation of PFC-dependent cognition. Animal models implicate increases in dopamine (DA) in regulating changes in PFC E:I during critical periods of development, however, mechanistic relationships between DA and E:I have not been studied in humans. Here, we used high field (7T) echo planar imaging (EPI) in combination with Magnetic Resonance Spectroscopic Imaging (MRSI) to assess the role of basal ganglia tissue iron—reflecting DA neurophysiology—in longitudinal trajectories of dorsolateral PFC Glu, GABA, and their relative levels (Glu:GABA) and working memory performance from adolescence to adulthood in 153 participants (ages 10–32 years old, 1–3 visits, 272 visits total). Using generalized additive mixed models (GAMMs) that capture linear and non-linear developmental processes, we show that basal ganglia tissue iron increases during adolescence, and Glu:GABA is biased towards heightened Glu relative to GABA early in adolescence, decreasing into adulthood. Critically, variation in basal ganglia tissue iron was linked to different age-related trajectories in Glu:GABA and working memory. Specifically, individuals with higher levels of tissue iron showed a greater degree of age-related declines in Glu and Glu:GABA, resulting in lower Glu relative to GABA (i.e., higher GABA relative to Glu) in young adulthood. Variation in tissue iron additionally moderated working memory trajectories, as higher levels of tissue iron were associated with steeper age-related improvements and better performance into adulthood. Our results provide novel evidence for a model of critical period plasticity whereby individual differences in DA may be involved in fine-tuning PFC E:I and PFC-dependent cognitive function at a critical transition from adolescence into adulthood.

在人类青春期，已经确定了前额叶皮层 （PFC） 兴奋性（谷氨酸能，Glu）和抑制性（γ-氨基丁酸，GABA）神经递质平衡 （E：I） 的发育变化，这可能反映了支持 PFC 依赖性认知成熟的可塑性的关键时期。动物模型表明，在发育的关键时期，多巴胺 （DA） 的增加与调节 PFC E：I 的变化有关，然而，尚未在人类中研究 DA 和 E：I 之间的机制关系。在这里，我们使用高场 （7T） 回波平面成像 （EPI） 与磁共振光谱成像 （MRSI） 相结合来评估基底神经节组织铁的作用——反映 DA 神经生理学——在背外侧 PFC Glu、GABA 及其相对水平 （Glu：GABA） 和从 153 名参与者（年龄 10-32 岁， 1-3 次访问，总共 272 次访问）。使用捕捉线性和非线性发育过程的广义加性混合模型 （GAMM），我们表明基底神经节组织铁在青春期增加，并且 Glu：GABA 偏向于青春期早期相对于 GABA 的 Glu 升高，直到成年期下降。至关重要的是，基底神经节组织铁的变化与 Glu：GABA 和工作记忆中不同的年龄相关轨迹有关。具体来说，组织铁水平较高的个体表现出更大程度的 Glu 和 Glu：GABA 与年龄相关的下降，导致在成年早期 Glu 相对于 GABA 较低（即，GABA 相对于 Glu 较高）。 组织铁的变化还调节了工作记忆轨迹，因为更高水平的组织铁与更陡峭的年龄相关改善和成年后更好的表现相关。我们的结果为关键期可塑性模型提供了新的证据，其中 DA 的个体差异可能参与从青春期到成年的关键过渡期微调 PFC E：I 和 PFC 依赖性认知功能。