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Reward anticipation-related neural activation following cued reinforcement in adults with psychotic psychopathology and biological relatives

Published online by Cambridge University Press:  10 January 2024

Caroline Demro
Affiliation:
Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, MN, USA Department of Psychology, University of Minnesota, Minneapolis, MN, USA
Elijah Lahud
Affiliation:
Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, MN, USA
Philip C. Burton
Affiliation:
College of Liberal Arts, University of Minnesota, Minneapolis, MN, USA
John R. Purcell
Affiliation:
Minneapolis Veterans Affairs Health Care System, Minneapolis, MN, USA
Joe J. Simon
Affiliation:
Department of General Internal Medicine and Psychosomatics, Centre for Psychosocial Medicine, Heidelberg, Germany
Scott R. Sponheim*
Affiliation:
Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, MN, USA Department of Psychology, University of Minnesota, Minneapolis, MN, USA Minneapolis Veterans Affairs Health Care System, Minneapolis, MN, USA
*
Corresponding author: Scott R. Sponheim; Email: sponh001@umn.edu

Abstract

Background

Schizophrenia is associated with hypoactivation of reward sensitive brain areas during reward anticipation. However, it is unclear whether these neural functions are similarly impaired in other disorders with psychotic symptomatology or individuals with genetic liability for psychosis. If abnormalities in reward sensitive brain areas are shared across individuals with psychotic psychopathology and people with heightened genetic liability for psychosis, there may be a common neural basis for symptoms of diminished pleasure and motivation.

Methods

We compared performance and neural activity in 123 people with a history of psychosis (PwP), 81 of their first-degree biological relatives, and 49 controls during a modified Monetary Incentive Delay task during fMRI.

Results

PwP exhibited hypoactivation of the striatum and anterior insula (AI) during cueing of potential future rewards with each diagnostic group showing hypoactivations during reward anticipation compared to controls. Despite normative task performance, relatives demonstrated caudate activation intermediate between controls and PwP, nucleus accumbens activation more similar to PwP than controls, but putamen activation on par with controls. Across diagnostic groups of PwP there was less functional connectivity between bilateral caudate and several regions of the salience network (medial frontal gyrus, anterior cingulate, AI) during reward anticipation.

Conclusions

Findings implicate less activation and connectivity in reward processing brain regions across a spectrum of disorders involving psychotic psychopathology. Specifically, aberrations in striatal and insular activity during reward anticipation seen in schizophrenia are partially shared with other forms of psychotic psychopathology and associated with genetic liability for psychosis.

Type
Original Article
Copyright
Copyright © U.S. Federal Government and University of Minnesota, 2024. To the extent this is a work of the US Government, it is not subject to copyright protection within the United States. Published by Cambridge University Press

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References

Andreasen, N. C. (1984). Scale for the Assessment of Positive Symptoms (SAPS). Iowa City: University of Iowa.Google Scholar
Andreasen, N. C. (1989). Scale for the Assessment of Negative Symptoms (SANS). The British Journal of Psychiatry, 155, 5358.CrossRefGoogle Scholar
Blanchard, J. J., & Cohen, A. S. (2006). The structure of negative symptoms within schizophrenia: Implications for assessment. Schizophrenia Bulletin, 32(2), 238245. doi: 10.1093/schbul/sbj013CrossRefGoogle ScholarPubMed
Caballero-Gaudes, C., & Reynolds, R. C. (2017). Methods for cleaning the BOLD fMRI signal. Neuroimage, 154, 128149. doi: 10.1016/j.neuroimage.2016.12.018CrossRefGoogle ScholarPubMed
Centanni, S. W., Janes, A. C., Haggerty, D. L., Atwood, B., & Hopf, F. W. (2021). Better living through understanding the insula: Why subregions can make all the difference. Neuropharmacology, 198, 108765. doi: 10.1016/j.neuropharm.2021.108765CrossRefGoogle ScholarPubMed
Chung, Y. S., & Barch, D. (2015). Anhedonia is associated with reduced incentive cue related activation in the basal ganglia. Cognitive, Affective, & Behavioral Neuroscience, 15(4), 749767. doi: 10.3758/s13415-015-0366-3CrossRefGoogle ScholarPubMed
Cisler, J. M., Bush, K., & Steele, J. S. (2014). A comparison of statistical methods for detecting context-modulated functional connectivity in fMRI. Neuroimage, 84, 10421052. doi: 10.1016/j.neuroimage.2013.09.018CrossRefGoogle ScholarPubMed
Clementz, B. A., Sweeney, J. A., Hamm, J. P., Ivleva, E. I., Ethridge, L. E., Pearlson, G. D., … Tamminga, C. A. (2016). Identification of distinct psychosis biotypes using brain-based biomarkers. American Journal of Psychiatry, 173(4), 373384. doi: 10.1176/appi.ajp.2015.14091200CrossRefGoogle ScholarPubMed
Cox, R. W., Chen, G., Glen, D. R., Reynolds, R. C., & Taylor, P. A. (2017). FMRI clustering in AFNI: False-positive rates redux. Brain Connectivity, 7(3), 152171. doi: 10.1089/brain.2016.0475CrossRefGoogle ScholarPubMed
Cuthbert, B. N. (2014). The RDoC framework: Facilitating transition from ICD/DSM to dimensional approaches that integrate neuroscience and psychopathology. World Psychiatry, 13(1), 2835. doi: 10.1002/wps.20087CrossRefGoogle ScholarPubMed
De Leeuw, M., Kahn, R. S., & Vink, M. (2015). Fronto-striatal dysfunction during reward processing in unaffected siblings of schizophrenia patients. Schizophrenia Bulletin, 41(1), 94103. doi: 10.1093/schbul/sbu153CrossRefGoogle ScholarPubMed
Demro, C., Mueller, B. A., Kent, J. S., Burton, P. C., Olman, C. A., Schallmo, M. P., … Sponheim, S. R. (2021). The psychosis human connectome project: An overview. NeuroImage, 241, 118439. doi: 10.1016/j.neuroimage.2021.118439CrossRefGoogle ScholarPubMed
Dowd, E. C., Frank, M. J., Collins, A., Gold, J. M., & Barch, D. M. (2016). Probabilistic reinforcement learning in patients with schizophrenia: relationships to anhedonia and avolition. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 1(5), 460473. doi: 10.1016/j.bpsc.2016.05.005Google ScholarPubMed
Eklund, A., Nichols, T. E., & Knutsson, H. (2016). Cluster failure: Why fMRI inferences for spatial extent have inflated false-positive rates. Proceedings of the National Academy of Sciences, 113(28), 79007905. doi: 10.1073/pnas.1602413113CrossRefGoogle ScholarPubMed
Elliott, R., Friston, K. J., & Dolan, R. J. (2000). Dissociable neural responses in human reward systems. Journal of Neuroscience, 20(16), 61596165. doi: 10.1523/JNEUROSCI.20-16-06159.2000CrossRefGoogle ScholarPubMed
First, M. B., Spitzer, R. L., Gibbon, M., & Williams, J. B. W. (2002). Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Patient Edition (SCID-I/NP, 11/2002 revision). New York, NY: Biometrics Research Department, New York State Psychiatric Institution.Google Scholar
Frost, K. H., & Strauss, G. P. (2016). A review of anticipatory pleasure in schizophrenia. Current Behavioral Neuroscience Reports, 3, 232247. doi: 10.1007/s40473-016-0082-5CrossRefGoogle ScholarPubMed
Fuentes-Claramonte, P., Garcia-Leon, M. A., Salgado-Pineda, P., Ramiro, N., Soler-Vidal, J., Torres, M. L., … Pomarol-Clotet, E. (2023). Do the negative symptoms of schizophrenia reflect reduced responsiveness to reward? Examination using a reward prediction error (RPE) task. Psychological Medicine, 53(15), 71067115. doi: 10.1017/S0033291723000521CrossRefGoogle ScholarPubMed
Gradin, V. B., Waiter, G., O'Connor, A., Romaniuk, L., Stickle, C., Matthews, K., … Steele, J. D. (2013). Salience network-midbrain dysconnectivity and blunted reward signals in schizophrenia. Psychiatry Research: Neuroimaging, 211(2), 104111. doi: 10.1016/j.pscychresns.2012.06.003CrossRefGoogle ScholarPubMed
Green, M. F., Hellemann, G., Horan, W. P., Lee, J., & Wynn, J. K. (2012). From perception to functional outcome in schizophrenia: Modeling the role of ability and motivation. Archives of General Psychiatry, 69(12), 12161224. doi: 10.1001/archgenpsychiatry.2012.652CrossRefGoogle ScholarPubMed
Greve, D. N., Mueller, B. A., Liu, T., Turner, J. A., Voyvodic, J., Yetter, E., … Glover, G. (2011). A novel method for quantifying scanner instability in fMRI. Magnetic Resonance in Medicine, 65(4), 10531061. doi: 10.1002/mrm.22691CrossRefGoogle ScholarPubMed
Grimm, O., Heinz, A., Walter, H., Kirsch, P., Erk, S., Haddad, L., … Meyer-Lindenberg, A. (2014). Striatal response to reward anticipation: evidence for a systems-level intermediate phenotype for schizophrenia. JAMA Psychiatry, 71(5), 531539. doi: 10.1001/jamapsychiatry.2014.9CrossRefGoogle ScholarPubMed
Hanssen, E., Van der Velde, J., Gromann, P. M., Shergill, S. S., De Haan, L., Bruggeman, R., … Van Atteveldt, N . (2015). Neural correlates of reward processing in healthy siblings of patients with schizophrenia. Frontiers in Human Neuroscience, 9, 504. doi: 10.3389/fnhum.2015.00504CrossRefGoogle ScholarPubMed
Hoaglin, D. C., & Iglewicz, B. (1987). Fine tuning some resistant rules for outlier labeling. Journal of American Statistical Association, 82(400), 11471149.CrossRefGoogle Scholar
Johnson, S. L., Mehta, H., Ketter, T. A., Gotlib, I. H., & Knutson, B. (2019). Neural responses to monetary incentives in bipolar disorder. Neuroimage: Clinical, 24, 102018. doi: 10.1016/j.nicl.2019.102018CrossRefGoogle ScholarPubMed
Jones, T. B., Bandettini, P. A., Kenworthy, L., Case, L. K., Milleville, S. C., Martin, A., & Birn, R. M. (2010). Sources of group differences in functional connectivity: An investigation applied to autism spectrum disorder. Neuroimage, 49(1), 401414. doi: 10.1016/j.neuroimage.2009.07.051CrossRefGoogle ScholarPubMed
Juckel, G. (2016). Inhibition of the reward system by antipsychotic treatment. Dialogues in Clinical Neuroscience, 18(1), 109114. doi: 10.31887/DCNS.2016.18.1/gjuckelCrossRefGoogle ScholarPubMed
Kieslich, K., Valton, V., & Roiser, J. P. (2022). Pleasure, reward value, prediction error and anhedonia. Current Topics in Behavioral Neurosciences, 58, 281304. doi: 10.1007/7854_2021_295CrossRefGoogle ScholarPubMed
Kirschner, M., Cathomas, F., Manoliu, A., Habermeyer, B., Simon, J. J., Seifritz, E., … Kaiser, S. (2020). Shared and dissociable features of apathy and reward system dysfunction in bipolar I disorder and schizophrenia. Psychological Medicine, 50(6), 936947. doi: 10.1017/S0033291719000801CrossRefGoogle Scholar
Klawonn, A. M., & Malenka, R. C. (2018). Nucleus accumbens modulation in reward and aversion. Cold spring harbor symposia on quantitative biology, 83, 119129. doi: 10.1101/sqb.2018.83.037457CrossRefGoogle ScholarPubMed
Knutson, B., Adams, C. M., Fong, G. W., & Hommer, D. (2001). Anticipation of increasing monetary reward selectively recruits nucleus accumbens. Journal of Neuroscience, 21(16), RC159. doi: 10.1523/JNEUROSCI.21-16-j0002.2001CrossRefGoogle ScholarPubMed
Kollmann, B., Scholz, V., Linke, J., Kirsch, P., & Wessa, M. (2017). Reward anticipation revisited-evidence from an fMRI study in euthymic bipolar I patients and healthy first-degree relatives. Journal of Affective Disorders, 219, 178186. doi: 10.1016/j.jad.2017.04.044CrossRefGoogle Scholar
Kring, A. M., & Elis, O. (2013). Emotion deficits in people with schizophrenia. Annual Review of Clinical Psychology, 9, 409433. doi: 10.1146/annurev-clinpsy-050212-185538CrossRefGoogle ScholarPubMed
Leucht, S., Samara, M., Heres, S., & Davis, J. M. (2016). Dose equivalents for antipsychotic drugs: The DDD method. Schizophrenia Bulletin, 42(Suppl. 1), S90S94. doi: 10.1093/schbul/sbv167CrossRefGoogle ScholarPubMed
Li, A., Zalesky, A., Yue, W., Howes, O., Yan, H., Liu, Y., … Liu, B. (2020). A neuroimaging biomarker for striatal dysfunction in schizophrenia. Nature Medicine, 26(4), 558565. doi: 10.1038/s41591-020-0793-8CrossRefGoogle ScholarPubMed
Li, Z., Wang, Y., Yan, C., Cheung, E. F., Docherty, A. R., Sham, P. C., … Chan, R. C. (2019). Inheritance of neural substrates for motivation and pleasure. Psychological Science, 30(8), 12051217. doi: 10.1177/0956797619859340CrossRefGoogle ScholarPubMed
Li, Z., Yan, C., Lv, Q. Y., Yi, Z. H., Zhang, J. Y., Wang, J. H., … Chan, R. C. (2018). Striatal dysfunction in patients with schizophrenia and their unaffected first-degree relatives. Schizophrenia Research, 195, 215221. doi: 10.1016/j.schres.2017.08.043CrossRefGoogle ScholarPubMed
Liu, X., Hairston, J., Schrier, M., & Fan, J. (2011). Common and distinct networks underlying reward valence and processing stages: A meta-analysis of functional neuroimaging studies. Neuroscience and Biobehavioral Reviews, 35(5), 12191236. doi: 10.1016/j.neubiorev.2010.12.012CrossRefGoogle ScholarPubMed
Mäkinen, J., Miettunen, J., Isohanni, M., & Koponen, H. (2008). Negative symptoms in schizophrenia—a review. Nordic Journal of Psychiatry, 62(5), 334341. doi: 10.1080/08039480801959307CrossRefGoogle ScholarPubMed
Mazziotta, J., Toga, A., Evans, A., Fox, P., Lancaster, J., Zilles, K., … Mazoyer, B. (2001a). A probabilistic atlas and reference system for the human brain: International Consortium for Brain Mapping (ICBM). Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences, 356(1412), 12931322. doi: 10.1098/rstb.2001.0915CrossRefGoogle Scholar
Mazziotta, J., Toga, A., Evans, A., Fox, P., Lancaster, J., Zilles, K., … Mazoyer, B. (2001b). A four-dimensional probabilistic atlas of the human brain. Journal of the American Medical Informatics Association, 8(5), 401430. doi: 10.1136/jamia.2001.0080401CrossRefGoogle ScholarPubMed
Mohr, P. N., Biele, G., & Heekeren, H. R. (2010). Neural processing of risk. Journal of Neuroscience, 30(19), 66136619. doi: 10.1523/JNEUROSCI.0003-10.2010CrossRefGoogle ScholarPubMed
Moran, E. K., Culbreth, A. J., Kandala, S., & Barch, D. M. (2019). From neuroimaging to daily functioning: A multimethod analysis of reward anticipation in people with schizophrenia. Journal of Abnormal Psychology, 128(7), 723. doi: 10.1037/abn0000461CrossRefGoogle ScholarPubMed
Mucci, A., Dima, D., Soricelli, A., Volpe, U., Bucci, P., Frangou, S., … Maj, M. (2015). Is avolition in schizophrenia associated with a deficit of dorsal caudate activity? A functional magnetic resonance imaging study during reward anticipation and feedback. Psychological Medicine, 45(8), 17651778. doi: 10.1017/S0033291714002943CrossRefGoogle ScholarPubMed
Murray, G. K., Clark, L., Corlett, P. R., Blackwell, A. D., Cools, R., Jones, P. B., … Poustka, L. (2008). Incentive motivation in first-episode psychosis: A behavioural study. BMC Psychiatry, 8(1), 34. doi: 10.1186/1471-244X-8-34CrossRefGoogle ScholarPubMed
Nielsen, , Rostrup, E., Hilker, R., Legind, C., Anhøj, S., Robbins, T. W., … Glenthøj, B. (2023). Reward processing as an indicator of vulnerability or compensatory resilience in psychoses? Results from a twin study. Biological Psychiatry Global Open Science, 3(1), 4755. doi: 10.1016/j.bpsgos.2022.01.002CrossRefGoogle ScholarPubMed
Nusslock, R., & Alloy, L. B. (2017). Reward processing and mood-related symptoms: An RDoC and translational neuroscience perspective. Journal of Affective Disorders, 216, 316. doi: 10.1016/j.jad.2017.02.001CrossRefGoogle ScholarPubMed
Oldham, S., Murawski, C., Fornito, A., Youssef, G., Yücel, M., & Lorenzetti, V. (2018). The anticipation and outcome phases of reward and loss processing: A neuroimaging meta-analysis of the monetary incentive delay task. Human Brain Mapping, 39(8), 33983418. doi: 10.1002/hbm.24184.CrossRefGoogle ScholarPubMed
Palaniyappan, L., & Liddle, P. F. (2012). Does the salience network play a cardinal role in psychosis? An emerging hypothesis of insular dysfunction. Journal of Psychiatry and Neuroscience, 37(1), 1727. doi: 10.1503/jpn.100176CrossRefGoogle ScholarPubMed
Purcell, J. R., Brown, J. W., Tullar, R., Bloomer, B., Kim, D. J., Moussa-Tooks, A. B., … Hetrick, W. P. (2023). Insular and striatal correlates of uncertain risky reward pursuit in schizophrenia. Schizophrenia Bulletin, 49(3), 726737. doi: 10.1093/schbul/sbac206CrossRefGoogle ScholarPubMed
Radua, J., Schmidt, A., Borgwardt, S., Heinz, A., Schlagenhauf, F., McGuire, P., & Fusar-Poli, P. (2015). Ventral striatal activation during reward processing in psychosis: A neurofunctional meta-analysis. JAMA Psychiatry, 72(12), 12431251. doi: 10.1001/jamapsychiatry.2015.2196CrossRefGoogle ScholarPubMed
Rissman, J., Gazzaley, A., & D'Esposito, M. (2004). Measuring functional connectivity during distinct stages of a cognitive task. Neuroimage, 23(2), 752763. doi: 10.1016/j.neuroimage.2004.06.035CrossRefGoogle ScholarPubMed
Rose, E. J., Ross, T. J., Salmeron, B. J., Lee, M., Shakleya, D. M., Huestis, M., & Stein, E. A. (2012). Chronic exposure to nicotine is associated with reduced reward-related activity in the striatum but not the midbrain. Biological Psychiatry, 71(3), 206213. doi: 10.1016/j.biopsych.2011.09.013CrossRefGoogle Scholar
Schmidt, A., Palaniyappan, L., Smieskova, R., Simon, A., Riecher-Rössler, A., Lang, U. E., … Borgwardt, S. J. (2016). Dysfunctional insular connectivity during reward prediction in patients with first-episode psychosis. Journal of Psychiatry and Neuroscience, 41(6), 367376. doi: 10.1503/jpn.150234CrossRefGoogle ScholarPubMed
Schwarz, K., Moessnang, C., Schweiger, J. I., Baumeister, S., Plichta, M. M., Brandeis, D., … Meyer-Lindenberg, A. (2020). Transdiagnostic prediction of affective, cognitive, and social function through brain reward anticipation in schizophrenia, bipolar disorder, major depression, and autism spectrum diagnoses. Schizophrenia Bulletin, 46(3), 592602. doi: 10.1093/schbul/sbz075CrossRefGoogle ScholarPubMed
Schwarz, K., Moessnang, C., Schweiger, J. I., Harneit, A., Schneider, M., Chen, J., … Meyer-Lindenberg, A. (2022). Ventral striatal–hippocampus coupling during reward processing as a stratification biomarker for psychotic disorders. Biological Psychiatry, 91(2), 216225. doi: 10.1016/j.biopsych.2021.07.016CrossRefGoogle ScholarPubMed
Simon, J. J., Cordeiro, S. A., Weber, M. A., Friederich, H. C., Wolf, R. C., Weisbrod, M., & Kaiser, S. (2015). Reward system dysfunction as a neural substrate of symptom expression across the general population and patients with schizophrenia. Schizophrenia Bulletin, 41(6), 13701378. doi: 10.1093/schbul/sbv067CrossRefGoogle ScholarPubMed
Smucny, J., Tully, L. M., Howell, A. M., Lesh, T. A., Johnson, S. L., O'Reilly, R. C., … Carter, C. S. (2021). Schizophrenia and bipolar disorder are associated with opposite brain reward anticipation-associated response. Neuropsychopharmacology, 46(6), 11521160. doi: 10.1038/s41386-020-00940-0CrossRefGoogle ScholarPubMed
Srirangarajan, T., Mortazavi, L., Bortolini, T., Moll, J., & Knutson, B. (2021). Multi-band FMRI compromises detection of mesolimbic reward responses. Neuroimage, 244, 118617. doi: 10.1016/j.neuroimage.2021.118617CrossRefGoogle ScholarPubMed
Stepien, M., Manoliu, A., Kubli, R., Schneider, K., Tobler, P. N., Seifritz, E., … Kirschner, M. (2018). Investigating the association of ventral and dorsal striatal dysfunction during reward anticipation with negative symptoms in patients with schizophrenia and healthy individuals. PLoS One, 13(6), e0198215. doi: 10.1371/journal.pone.0198215CrossRefGoogle ScholarPubMed
Strauss, G. P., Nuñez, A., Ahmed, A. O., Barchard, K. A., Granholm, E., Kirkpatrick, B., … Allen, D. N. (2018). The latent structure of negative symptoms in schizophrenia. JAMA Psychiatry, 75(12), 12711279. doi: 10.1001/jamapsychiatry.2018.2475CrossRefGoogle ScholarPubMed
Tricomi, E. M., Delgado, M. R., & Fiez, J. A. (2004). Modulation of caudate activity by action contingency. Neuron, 41(2), 281292. doi: 10.1016/s0896-6273(03)00848-1CrossRefGoogle ScholarPubMed
Vink, M., Ramsey, N. F., Raemaekers, M., & Kahn, R. S. (2006). Striatal dysfunction in schizophrenia and unaffected relatives. Biological Psychiatry, 60(1), 3239. doi: 10.1016/j.biopsych.2005.11.026CrossRefGoogle ScholarPubMed
Wang, X., Zhang, Y., Huang, J., Wang, Y., Niu, Y., Lui, S. S., … Chan, R. C. (2023). Revisiting reward impairments in schizophrenia spectrum disorders: A systematic review and meta-analysis for neuroimaging findings. Psychological Medicine, 53(15), 71897202. doi: 10.1017/S0033291723000703CrossRefGoogle ScholarPubMed
Whitton, A. E., Treadway, M. T., & Pizzagalli, D. A. (2015). Reward processing dysfunction in major depression, bipolar disorder and schizophrenia. Current Opinion in Psychiatry, 28, 712. doi: 10.1097/YCO.0000000000000122CrossRefGoogle Scholar
Wilson, R. P., Colizzi, M., Bossong, M. G., Allen, P., Kempton, M., & Bhattacharyya, S. (2018). The neural substrate of reward anticipation in health: A meta-analysis of fMRI findings in the monetary incentive delay task. Neuropsychology Review, 28(4), 496506. doi: 10.1007/s11065-018-9385-5CrossRefGoogle ScholarPubMed
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