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In Vivo Neuroimaging Evidence of Prefrontal Cortex Dysfunction in Adolescents With Substance Use: A Systematic Review

Sep 2026 · NeuroRegulation · 0 citations · 22 references
Substance Abuse Treatment and Outcomes

TL;DR

Evidence suggests that adolescent substance use is linked with structural, functional, and neurochemical alterations in the PFC, which may further affect executive functioning and impulse control.

Abstract

Background. Adolescence marks a critical phase for neurodevelopment, particularly in the prefrontal cortex (PFC), which underpins executive function and impulse control. This period coincides with the vulnerability to substance use, which has a significant impact on brain maturation. In vivo neuroimaging techniques provide valuable insights into the structural and functional alterations in the PFC associated with adolescent substance use. This review aims to synthesize the available literature focusing on the PFC dysfunction in adolescent substance users. Methods. A comprehensive search was conducted across peer-reviewed, Scopus-indexed databases, including PubMed, Web of Science, and Google Scholar. Eligible studies included adolescents aged 10–19 years with reported substance use like alcohol, nicotine, cannabis, opioids, stimulants, or polysubstance use, assessed via structural or functional neuroimaging techniques (MRI, fMRI, DTI, PET). Data were extracted on study design, sample characteristics, imaging modalities, and findings related to PFC dysfunction. Results. Sixteen studies met the inclusion criteria. Structural MRI studies reported reduced cortical thickness and gray matter volume in the dorsolateral and orbitofrontal regions among the cannabis and alcohol users. Functional imaging studies consistently showed the hypoactivation of PFC circuits during executive function tasks, along with the altered resting-state connectivity within the default mode and reward networks. Conclusion. This evidence suggests that adolescent substance use is linked with structural, functional, and neurochemical alterations in the PFC, which may further affect executive functioning and impulse control. Thus, it highlights the need for longitudinal studies to understand the neurodevelopmental vulnerabilities and highlight the importance of early prevention and intervention strategies targeting adolescent substance users.

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