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J Clin Psychiatry. 2017 Jul;78(7):e790-e796. doi: 10.4088/JCP.15m10624.

Stimulant Treatment Trajectories Are Associated With Neural Reward Processing in Attention-Deficit/Hyperactivity Disorder.

Author information

UMCG/Accare Kinder en Jeugdpsychiatrie, 9700VB Groningen, The Netherlands.
Department of Psychiatry, University Medical Center Groningen, Groningen, The Netherlands.
Department of Clinical, Neuro, and Developmental Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Donders Institute for Brain, Cognition and Behaviour, Department of Cognitive Neuroscience, Radboud University Medical Center, Nijmegen, The Netherlands.
Department of Psychology, Leiden University, Leiden, The Netherlands.
Departments of Psychiatry and of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, New York, USA.
K. G. Jebsen Centre for Research on Neuropsychiatric Disorders, Department of Biomedicine, University of Bergen, Bergen, Norway.



The past decades have seen a surge in stimulant prescriptions for the treatment of attention-deficit/hyperactivity disorder (ADHD). Stimulants acutely alleviate symptoms and cognitive deficits associated with ADHD by modulating striatal dopamine neurotransmission and induce therapeutic changes in brain activation patterns. Long-term functional changes after treatment are unknown, as long-term studies are scarce and have focused on brain structure. In this observational study (2009-2012), we investigated associations between lifetime stimulant treatment history and neural activity during reward processing.


Participants fulfilling DSM-5 criteria for ADHD (N = 269) were classified according to stimulant treatment trajectory. Of those, 124 performed a monetary incentive delay task during magnetic resonance imaging, all in their nonmedicated state (nEARLY&INTENSE = 51; nLATE&MODERATE = 49; nEARLY&MODERATE = 9; nNAIVE = 15; mean age = 17.4 years; range, 10-26 years). Whole-brain analyses were performed with additional focus on the striatum, concentrating on the 2 largest treatment groups.


Compared to the late-and-moderate treatment group, the early-and-intense treatment group showed more activation in the supplementary motor area and dorsal anterior cingulate cortex (SMA/dACC) during reward outcome (cluster size = 8,696 mm³; PCLUSTER < .001). SMA/dACC activation of the control group fell in between the 2 treatment groups. Treatment history was not associated with striatal activation during reward processing.


Our findings are compatible with previous reports of acute increases of SMA/dACC activity in individuals with ADHD after stimulant administration. Higher SMA/dACC activity may indicate that patients with a history of intensive stimulant treatment, but currently off medication, recruit brain regions for cognitive control and/or decision-making upon being rewarded. No striatal or structural changes were found.

[Indexed for MEDLINE]

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