Brain Signatures During Reward Anticipation Predict Persistent Attention-Deficit/Hyperactivity Disorder Symptoms

Children experiencing attention-deficit/hyperactivity disorder (ADHD) symptoms may retain symptoms into adulthood, but little is known about the underlying mechanism.To identify biomarkers of persistent ADHD symptom development, we carried out whole-brain analyses of neuroimaging data during the anticipation phase of the Monetary-Incentive-Delay (MID) task in 1,368 adolescents recruited by the IMAGEN Consortium at age 14 years, whose behavioral measurements were followed up longitudinally at age 16. In particular, we focused on comparing individuals with persistent high ADHD symptoms at both ages 14 and 16 years to unaffected control individuals, but also exploring which individuals demonstrating symptom remission (with high ADHD symptoms at age 14 but much reduced at age 16).We identified reduced activations in the medial frontal cortex and the thalamus during reward anticipation as neuro-biomarkers for persistent ADHD symptoms across time. The genetic relevance of the above findings was further supported by the associations of the polygenic risk scores of ADHD with both the persistent and control status and the activations of both brain regions. Furthermore, in an exploratory analysis, the thalamic activation might also help to distinguish persons with persistent ADHD from those remitted in both an exploratory sample (odds ratio = 9.43, p < .001) and an independent generalization sample (odds ratio = 4.64, p = .003).Using a well-established and widely applied functional magnetic resonance imaging task, we have identified neural biomarkers that could discriminate ADHD symptoms that persist throughout adolescence from controls and potentially those likely to remit during adolescent development as well.