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Puberty is a critical developmental period characterized by increases in exploration and experimentation, supported by changes in functional interactions of mesocorticolimbic circuitry. Although changing dynamics within mesocorticolimbic connections among the prefrontal cortex, amygdala, and nucleus accumbens help adolescents manage increasingly complex demands important for adult independence, they may additionally confer neuropsychiatric risk during this period. Questions remain regarding how puberty influences the development of the mesocorticolimbic circuitry that supports motivational traits.

Investigators including Amar Ojha, PhD (Postdoctoral scholar, University of Connecticut; former graduate student, University of Pittsburgh); Neil Jones, PhD (Associate Professor of Psychiatry and Psychology); and Cecile Ladouceur, PhD (Professor of Psychiatry and Psychology), examined resting-state functional connectivity in 126 young adolescents over two years and assessed sensitivity to reward and punishment via questionnaires. The longitudinal study was designed to examine puberty-specific influences on these relationships.

In a paper published in Neuropsychopharmacology, the investigators reported that fronto-striatal resting-state functional connectivity was associated with reward sensitivity, but both fronto-striatal and fronto-amygdala resting-state functional connectivity were linked to punishment sensitivity. Puberty moderated several associations in male but not female adolescents. 

In addition, in early puberty stronger fronto-striatal resting-state functional connectivity related to higher punishment sensitivity in male adolescents, but by late puberty, stronger fronto-amygdala resting-state functional connectivity was related to higher punishment sensitivity. 

Testosterone levels moderated the association between anterior ventromedial prefrontal cortex- nucleus accumbens resting-state functional connectivity and reward sensitivity, such that weaker resting-state functional connectivity related to higher reward sensitivity in males with lower testosterone levels, after controlling for age and pubertal status.

“We often define early adolescence by age, such as ‘turning double-digits,’ but our findings show that puberty is an important factor to consider for understanding neuropsychiatric risk and resilience. It affects circuits involved in emotion and motivation in ways that can increase vulnerability for anxiety, depression or substance use disorders, and these effects differ between boys and girls,” said Dr. Ladouceur, senior author of the study. “Because puberty opens a period of heightened brain plasticity, it provides a critical window for prevention. But we must move beyond a one-size-fits-all approach and take into consideration the teen’s biological development.” 

Mesocorticolimbic connectivity and motivational sensitivity: sex-specific effects of puberty in early adolescence
Ojha A, Henry TR, Jones NP, Shirtcliff EA, Ladouceur CD.
Neuropsychopharmacology. (2026). https://doi.org/10.1038/s41386-026-02378-2