Neural response to reward uncertainty in adolescents with mood and anxiety symptoms

Neuropsychopharmacology. 2026 Apr 23. doi: 10.1038/s41386-026-02412-3. Online ahead of print.

ABSTRACT

Adolescence represents a critical neurodevelopmental period of high vulnerability to the onset of psychiatric conditions. Altered processing of uncertain reward outcomes likely contributes to this vulnerability, yet remains poorly understood. Addressing this knowledge gap, we sought to use the fMRI Reward Flanker Task, originally developed by our group, to examine neural responses to uncertain rewards and their clinical associations. To fully capture clinical correlates, we recruited adolescents with mood and anxiety symptoms ranging from low to high severity, including healthy controls (HC). Participants were 84 psychotropic-medication-free adolescents (15.3 ± 2.1 years; 62% female; 17 HC); all completed diagnostic and dimensional symptom assessments. Neuroimaging data were preprocessed using Human Connectome Project pipelines. Analyses examined participant-level neural responses to uncertain reward expectancy and attainment, adjusted for age, sex, and multiple comparisons. Across the whole sample, uncertain versus certain cues activated the default network and suppressed the fronto-parietal control network. Neural responses during expectancy to uncertain reward were intermediate between responses to certain reward and non-reward stimuli. Outcome attainment following uncertain cues activated stronger neural responses in reward and salience regions compared to reward cues. Anhedonia severity correlated with default network activation during uncertain outcome attainment. Anxiety severity correlated with blunted striatal responses during uncertain vs. certain non-reward expectancy. Exploratory group comparisons revealed that adolescents with mood and anxiety symptoms versus HC showed blunted striatal responses during uncertain versus non-reward expectancy and hyperactivation in visual and default network areas during attainment following uncertain cues. Together, these findings support the role of uncertain reward processing in adolescent mood and anxiety psychopathology.

PMID:42026240 | DOI:10.1038/s41386-026-02412-3