Functional connectivity in cortico-subcortical brain networks underlying reward processing in attention-deficit/hyperactivity disorder.
Many patients with attention-deficit/hyperactivity disorder (ADHD) display aberrant reward-related behavior. Task-based fMRI studies have related atypical reward processing in ADHD to altered BOLD activity in regions underlying reward processing such as ventral striatum and orbitofrontal cortex. However, it remains unclear whether the observed effects are region-specific or related to changes in functional connectivity of networks supporting reward processing. Here we use resting-state fMRI to comprehensively delineate the functional connectivity architecture underlying aberrant reward processing in ADHD.



We assessed resting-state functional connectivity of four networks that support reward processing. These networks showed high spatial overlap with the default mode, fronto-parietal, lateral visual, and salience networks, yet only activity within the salience network was effectively sensitive to reward value. We parcelled these networks into their functional cortical and subcortical subregions and obtained functional connectivity matrices by computing Pearson correlations between the regional time series. We compared functional connectivity within each of the four networks between participants with ADHD and controls, and related functional connectivity to dimensional ADHD symptom scores across all participants (N= 444; age range: 8.5-30.5; mean age: 17.7).



We did not observe significant ADHD-related alterations in functional connectivity of the salience network, which included key reward regions. Instead, levels of inattention symptoms modulated functional connectivity of the default-mode and fronto-parietal networks, which supported general task processing.



The present study does not corroborate previous childhood evidence for functional connectivity alterations between key reward processing regions in adolescents and young adults with ADHD. Our findings could point to developmental normalization or indicate that reward-processing deficits result from functional connectivity alterations in general task-related networks.
Department of Cognitive Neuroscience, Radboud University Medical Center, Nijmegen, The Netherlands; Donders Institute for Brain, Cognition and Behavior, Radboud University, Nijmegen, The Netherlands.
Marianne
M
Oldehinkel
Department of Cognitive Neuroscience, Radboud University Medical Center, Nijmegen, The Netherlands; Donders Institute for Brain, Cognition and Behavior, Radboud University, Nijmegen, The Netherlands; Centre for Functional MRI of the Brain (FMRIB), University of Oxford, Oxford, United Kingdom.
Christian F
CF
Beckmann
Donders Institute for Brain, Cognition and Behavior, Radboud University, Nijmegen, The Netherlands; Radboud University Medical Center, Departments of Human Genetics and Psychiatry, Nijmegen, The Netherlands.
Barbara
B
Franke
University of Groningen, University Medical Center Groningen, Department of Psychiatry, Groningen, The Netherlands.
Catharina A
CA
Hartman
University of Groningen, University Medical Center Groningen, Department of Psychiatry, Groningen, The Netherlands.
Pieter J
PJ
Hoekstra
Vrije Universiteit Amsterdam, Clinical Neuropsychology Section, Amsterdam, The Netherlands.
Jaap
J
Oosterlaan
Vrije Universiteit Amsterdam, Clinical Neuropsychology Section, Amsterdam, The Netherlands.
Dirk
D
Heslenfeld
Department of Cognitive Neuroscience, Radboud University Medical Center, Nijmegen, The Netherlands; Donders Institute for Brain, Cognition and Behavior, Radboud University, Nijmegen, The Netherlands; Karakter Child and Adolescent Psychiatry University Centre, Nijmegen, The Netherlands.
Jan K
JK
Buitelaar
Donders Institute for Brain, Cognition and Behavior, Radboud University, Nijmegen, The Netherlands.
Maarten
M
Mennes
D000293:Adolescent; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000000981:diagnostic imaging / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000503:physiopathology*; D002648:Child; D015331:Cohort Studies; D005260:Female; D059907:Functional Neuroimaging / Q000379:methods*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009415:Nerve Net / Q000000981:diagnostic imaging / Q000503:physiopathology*; D012201:Reward; D066328:Ventral Striatum / Q000000981:diagnostic imaging / Q000503:physiopathology*; D055815:Young Adult
ADHD; Default mode network; Fronto-parietal network; Functional connectivity; Functional parcellation; Resting-state fMRI; Reward