Orbitofrontal signaling of future reward is associated with hyperactivity in attention-deficit/hyperactivity disorder
Open accessAbstract
Alterations in motivated behavior are a hallmark of attention-deficit/hyperactivity disorder (ADHD), one of the most common psychiatric disorders in children and adolescents. The orbitofrontal cortex (OFC) plays a key role in controlling goal-directed behavior, but the link between OFC dysfunction and behavioral deficits in ADHD, particularly in adolescence, remains poorly understood. Here we used advanced high-resolution functional magnetic resonance imaging (fMRI) of the human OFC in adolescents with ADHD and typically developing (TD) controls (N = 39, age 12–16, all male except for one female per group) to study reward-related OFC responses and how they relate to behavioral dysfunction in ADHD. During fMRI data acquisition, participants performed a simple decision-making task, allowing us to image expectation-related responses to small and large monetary outcomes. Across all participants, we observed significant signal increases to large versus small expected rewards in the OFC. These responses were significantly enhanced in ADHD relative to TD participants. Moreover, stronger reward-related activity was correlated with individual differences in hyperactive/impulsive symptoms in the ADHD group, whereas high cognitive ability was associated with normalized OFC responses. These results provide evidence for the importance of OFC dysfunctions in the neuropathology of ADHD, highlighting the role of OFC-dependent goal-directed control mechanisms in this disorder. SIGNIFICANCE STATEMENT Attention-deficit/hyperactivity disorder (ADHD) is characterized by alterations in motivated behavior which can be understood as diminished goal-directed control. The orbitofrontal cortex (OFC) plays a key role in controlling goal-directed behavior, but its potential contribution to ADHD symptomatology remains poorly understood. Using high-resolution fMRI, we show that adolescent ADHD patients display enhanced OFC signaling of future rewards and that these increased reward-related responses are correlated with the severity of hyperactivity/impulsivity. These findings suggest that an inability to adequately evaluate future outcomes may translate into maladaptive behavior in ADHD patients. They also challenge the idea that dysfunctions in dopaminergic brain areas are the sole contributor to reward-related symptoms in ADHD and point to a central contribution of goal-directed control circuits in hyperactivity.
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Some OFC neurons respond to outcome value, and others to expected value; humans with ADHD have increased sensitivity to future rewards.
“These investigations show that some OFC neurons respond to outcome value (e.g. the taste of food), and others to expected value (or future rewards), and interestingly humans with ADHD have increased sensitivity to these future rewards (Tegelbeckers et al., 2018).”
From The orbitofrontal cortex: reward, emotion and depression (2020) · cites this paper as Tegelbeckers et al., 2018
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Cites
An Integrative Theory of Prefrontal Cortex Function
Miller, E. K., & Cohen, J. D. (2001) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.24.1.167 · Cited by 12,803 · see citing works
KAUFMAN, J., BIRMAHER, B., BRENT, D., RAO, U., FLYNN, C., MORECI, P., WILLIAMSON, D., & RYAN, N. (1997) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/00004583-199707000-00021 · Cited by 10,148 · see citing works
(1991) · Medical Entomology and Zoology · Cited by 8,071 · see citing works
Ashburner, J., & Friston, K. J. (2005) · NeuroImage · doi:10.1016/j.neuroimage.2005.02.018 · Cited by 7,507 · see citing works
The worldwide prevalence of ADHD: a systematic review and metaregression analysis
Polanczyk, G., de Lima, M. S., Horta, B. L., Biederman, J., & Rohde, L. A. (2007) · American Journal of Psychiatry · doi:10.1176/ajp.2007.164.6.942 · Cited by 5,346 · see citing works
(1991) · Cited by 3,844 · see citing works
Circular analysis in systems neuroscience: the dangers of double dipping
Kriegeskorte, N., Simmons, W. K., Bellgowan, P. S. F., & Baker, C. I. (2009) · Nature Neuroscience · doi:10.1038/nn.2303 · Cited by 2,696 · see citing works
Attention-deficit/hyperactivity disorder is characterized by a delay in cortical maturation
Shaw, P., Eckstrand, K., Sharp, W., Blumenthal, J., Lerch, J. P., Greenstein, D., Clasen, L., Evans, A., Giedd, J., & Rapoport, J. L. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0707741104 · Cited by 1,819 · see citing works
Neurons in the orbitofrontal cortex encode economic value
Padoa-Schioppa, C., & Assad, J. A. (2006) · Nature · doi:10.1038/nature04676 · Cited by 1,598 · see citing works
Encoding Predictive Reward Value in Human Amygdala and Orbitofrontal Cortex
Gottfried, J. A., O'Doherty, J., & Dolan, R. J. (2003) · Science · doi:10.1126/science.1087919 · Cited by 1,165 · see citing works
Toward systems neuroscience of ADHD: a meta-analysis of 55 fMRI studies
Cortese, S., Kelly, C., Chabernaud, C., Proal, E., Di Martino, A., Milham, M. P., & Castellanos, F. X. (2012) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2012.11101521 · Cited by 1,067 · see citing works
sagvolden, T., johansen, E. B., aase, H., & russell, V. A. (2005) · Behavioral and Brain Sciences · doi:10.1017/s0140525x05000075 · Cited by 1,035 · see citing works
Working Memory and Intelligence: The Same or Different Constructs?
Ackerman, P. L., Beier, M. E., & Boyle, M. O. (2005) · Psychological Bulletin · doi:10.1037/0033-2909.131.1.30 · Cited by 969 · see citing works
Sonuga-Barke, E. J. S. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2004.09.008 · Cited by 962 · see citing works
Orbitofrontal cortex and its contribution to decision-making.
Wallis, J. D. (2007) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.30.051606.094334 · Cited by 938 · see citing works
Why IQ is not a covariate in cognitive studies of neurodevelopmental disorders
DENNIS, M., FRANCIS, D. J., CIRINO, P. T., SCHACHAR, R., BARNES, M. A., & FLETCHER, J. M. (2009) · Journal of the International Neuropsychological Society · doi:10.1017/s1355617709090481 · Cited by 875 · see citing works
Optimized EPI for fMRI studies of the orbitofrontal cortex
Deichmann, R., Gottfried, J. A., Hutton, C., & Turner, R. (2003) · NeuroImage · doi:10.1016/s1053-8119(03)00073-9 · Cited by 821 · see citing works
Volkow, N. D., Wang, G.-J., Fowler, J. S., Logan, J., Gerasimov, M., Maynard, L., Ding, Y.-S., Gatley, S. J., Gifford, A., & Franceschi, D. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-02-j0001.2001 · Cited by 770 · see citing works
Contrasting Roles of Basolateral Amygdala and Orbitofrontal Cortex in Impulsive Choice
Winstanley, C. A., Theobald, D. E. H., Cardinal, R. N., & Robbins, T. W. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.5606-03.2004 · Cited by 675 · see citing works
Hyperactivity and Delay Aversion—I. The Effect of Delay on Choice
Sonuga‐Barke, E. J. S., Taylor, E., Sembi, S., & Smith, J. (1992) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.1992.tb00874.x · Cited by 578 · see citing works
What the orbitofrontal cortex does not do
Stalnaker, T. A., Cooch, N. K., & Schoenbaum, G. (2015) · Nature Neuroscience · doi:10.1038/nn.3982 · Cited by 531 · see citing works
Krause, K.-H., Dresel, S. H., Krause, J., Kung, H. F., & Tatsch, K. (2000) · Neuroscience Letters · doi:10.1016/s0304-3940(00)01040-5 · Cited by 521 · see citing works
Cubillo, A., Halari, R., Smith, A., Taylor, E., & Rubia, K. (2012) · Cortex · doi:10.1016/j.cortex.2011.04.007 · Cited by 505 · see citing works
Scheres, A., Milham, M. P., Knutson, B., & Castellanos, F. X. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.04.042 · Cited by 499 · see citing works
Tripp, G., & Wickens, J. R. (2009) · Neuropharmacology · doi:10.1016/j.neuropharm.2009.07.026 · Cited by 492 · see citing works
Weiskopf, N., Hutton, C., Josephs, O., & Deichmann, R. (2006) · NeuroImage · doi:10.1016/j.neuroimage.2006.07.029 · Cited by 488 · see citing works
Working memory is (almost) perfectly predicted by g.
COLOM, R. (2004) · Intelligence · doi:10.1016/j.intell.2003.12.002 · Cited by 436 · see citing works
Plichta, M. M., & Scheres, A. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2013.07.012 · Cited by 424 · see citing works
Rudebeck, P. H., & Murray, E. A. (2014) · Neuron · doi:10.1016/j.neuron.2014.10.049 · Cited by 405 · see citing works
Prefrontal mechanisms of behavioral flexibility, emotion regulation and value updating
Rudebeck, P. H., Saunders, R. C., Prescott, A. T., Chau, L. S., & Murray, E. A. (2013) · Nature Neuroscience · doi:10.1038/nn.3440 · Cited by 383 · see citing works
Abnormal Functional Connectivity in Children with Attention-Deficit/Hyperactivity Disorder
Tomasi, D., & Volkow, N. D. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.11.003 · Cited by 363 · see citing works
Luman, M., Tripp, G., & Scheres, A. (2010) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2009.11.021 · Cited by 335 · cited 1× · see citing works
“tional and reward processes are a hallmark of ADHD (Sagvolden et al., 2005; Luman et al., 2010).”
BackgroundReward anticipation and outcomes in adult males with attention-deficit/hyperactivity disorder
Ströhle, A., Stoy, M., Wrase, J., Schwarzer, S., Schlagenhauf, F., Huss, M., Hein, J., Nedderhut, A., Neumann, B., Gregor, A., et al. (2008) · NeuroImage · doi:10.1016/j.neuroimage.2007.09.044 · Cited by 323 · see citing works
Rubia, K., Smith, A. B., Halari, R., Matsukura, F., Mohammad, M., Taylor, E., & Brammer, M. J. (2009) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2008.08020212 · Cited by 322 · see citing works
The neural code of reward anticipation in human orbitofrontal cortex
Kahnt, T., Heinzle, J., Park, S. Q., & Haynes, J.-D. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0912838107 · Cited by 274 · see citing works
Self-citationCo‐occurrence of ADHD and low IQ has genetic origins
Kuntsi, J., Eley, T. C., Taylor, A., Hughes, C., Asherson, P., Caspi, A., & Moffitt, T. E. (2004) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.20076 · Cited by 267 · see citing works
Fusar-Poli, P., Rubia, K., Rossi, G., Sartori, G., & Balottin, U. (2012) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2011.11060940 · Cited by 260 · see citing works
Identity-specific coding of future rewards in the human orbitofrontal cortex
Howard, J. D., Gottfried, J. A., Tobler, P. N., & Kahnt, T. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1503550112 · Cited by 222 · see citing works
Self-citationSpencer, T. J., Biederman, J., Madras, B. K., Faraone, S. V., Dougherty, D. D., Bonab, A. A., & Fischman, A. J. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.03.036 · Cited by 185 · see citing works
Costa Dias, T. G., Wilson, V. B., Bathula, D. R., Iyer, S. P., Mills, K. L., Thurlow, B. L., Stevens, C. A., Musser, E. D., Carpenter, S. D., Grayson, D. S., et al. (2013) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2012.10.015 · Cited by 180 · see citing works
Howard, J. D., & Kahnt, T. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.3473-16.2017 · Cited by 131 · see citing works
Self-citationOrbitofrontal reward sensitivity and impulsivity in adult attention deficit hyperactivity disorder
Wilbertz, G., Tebartz van Elst, L., Delgado, M. R., Maier, S., Feige, B., Philipsen, A., & Blechert, J. (2012) · NeuroImage · doi:10.1016/j.neuroimage.2011.12.011 · Cited by 125 · see citing works
Orbitofrontal neurons infer the value and identity of predicted outcomes
Stalnaker, T. A., Cooch, N. K., McDannald, M. A., Liu, T., Wied, H. M., & Schoenbaum, G. M. (2014) · Nature Communications · doi:10.1038/ncomms4926 · Cited by 123 · see citing works
von Rhein, D., Cools, R., Zwiers, M. P., van der Schaaf, M., Franke, B., Luman, M., Oosterlaan, J., Heslenfeld, D. J., Hoekstra, P. J., Hartman, C. A., et al. (2015) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2015.02.012 · Cited by 108 · see citing works
Stoy, M., Schlagenhauf, F., Schlochtermeier, L., Wrase, J., Knutson, B., Lehmkuhl, U., Huss, M., Heinz, A., & Ströhle, A. (2011) · Psychopharmacology · doi:10.1007/s00213-011-2166-y · Cited by 91 · see citing works
Heidemann, R. M., Ivanov, D., Trampel, R., Fasano, F., Meyer, H., Pfeuffer, J., & Turner, R. (2012) · Magnetic Resonance in Medicine · doi:10.1002/mrm.24156 · Cited by 90 · see citing works
Learning-Related Human Brain Activations Reflecting Individual Finances
Tobler, P. N., Fletcher, P. C., Bullmore, E. T., & Schultz, W. (2007) · Neuron · doi:10.1016/j.neuron.2007.03.004 · Cited by 85 · see citing works
Differences in feedback- and inhibition-related neural activity in adult ADHD
Dibbets, P., Evers, E. A. T., Hurks, P. P. M., Marchetta, N. D. J., & Jolles, J. (2009) · Brain and Cognition · doi:10.1016/j.bandc.2009.01.001 · Cited by 58 · see citing works
van Hulst, B. M., de Zeeuw, P., Bos, D. J., Rijks, Y., Neggers, S. F. W., & Durston, S. (2016) · Journal of Child Psychology and Psychiatry · doi:10.1111/jcpp.12643 · Cited by 45 · see citing works
Sonuga‐Barke, E. J. S. (2011) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.2011.02444.x · Cited by 43 · see citing works
Differential reward processing in subtypes of adult attention deficit hyperactivity disorder
Edel, M.-A., Enzi, B., Witthaus, H., Tegenthoff, M., Peters, S., Juckel, G., & Lissek, S. (2013) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2012.09.026 · Cited by 42 · see citing works
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The orbitofrontal cortex: reward, emotion and depression
Rolls, E. T., Cheng, W., & Feng, J. (2020) · Brain Communications · doi:10.1093/braincomms/fcaa196 · Cited by 474 · see citing works
Lukito, S., Norman, L., Carlisi, C., Radua, J., Hart, H., Simonoff, E., & Rubia, K. (2020) · Psychological Medicine · doi:10.1017/s0033291720000574 · Cited by 248 · see citing works
The neurobehavioral mechanisms of motivational control in attention-deficit/hyperactivity disorder
Ceceli, A. O., Natsheh, J. Y., Cruz, D., & Tricomi, E. (2020) · Cortex · doi:10.1016/j.cortex.2020.02.009 · Cited by 9 · see citing works
- Authors
- Tegelbeckers, J., Kanowski, M., Krauel, K., Haynes, J.-D., Breitling, C., Flechtner, H.-H., & Kahnt, T.
- Affiliations
- Northwestern University (US)
- Otto-von-Guericke-Universität Magdeburg (DE)
- Center for Behavioral Brain Sciences (DE)
- Humboldt-Universität zu Berlin (DE)
- Corresponding author
- Tegelbeckers, Jana
- Kahnt, Thorsten
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2018-06-28
- Volume
- 38
- Issue
- 30
- Pages
- 6779-6786
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6067073
- OpenAlex
- W2810281965
- Cited by
- 31
- References
- 51
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 3 · 2023: 6 · 2022: 4 · 2021: 6 · 2020: 5 · 2019: 2
- FWCI
- 2.56
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Journal of Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- attention deficit hyperactivity disorder, orbitofrontal cortex, reward processing, hyperactivity/impulsivity, goal-directed behavior, motivated behavior, adolescents, financial decision-making, individual differences, cognitive ability, dopaminergic circuits
- MeSH terms
- Adolescent, Attention Deficit Disorder with Hyperactivity, Brain, Child, Female, Humans, Impulsive Behavior, Magnetic Resonance Imaging, Male, Motivation, Reward, Signal Transduction, Prefrontal Cortex
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