Psychosis risk is associated with decreased resting-state functional connectivity between the striatum and the default mode network

  • Jessica P. Y. Hua
  • Nicole R. Karcher
  • Anne M. Merrill
  • Kathleen J. O’Brien
  • Kelsey T. Straub
  • Timothy J. Trull
  • John G. KernsEmail author


Psychosis is linked to aberrant salience or to viewing neutral stimuli as self-relevant, suggesting a possible impairment in self-relevance processing. Psychosis is also associated with increased dopamine in the dorsal striatum, especially the anterior caudate (Kegeles et al., 2010). Critically, the anterior caudate is especially connected to (a) the cortical default mode network (DMN), centrally involved in self-relevance processing, and (b) to a lesser extent, the cortical frontoparietal network (FPN; Choi, Yeo, & Buckner, 2012). However, no previous study has directly examined striatal–cortical DMN connectivity in psychosis risk. In Study 1, we examined resting-state functional connectivity in psychosis risk (n = 18) and control (n = 19) groups between (a) striatal DMN and FPN subregions and (b) cortical DMN and FPN. The psychosis risk group exhibited decreased connectivity between the striatal subregions and the cortical DMN. In contrast, the psychosis risk group exhibited intact connectivity between the striatal subregions and the cortical FPN. Additionally, recent distress was also associated with decreased striatal–cortical DMN connectivity. In Study 2, to determine whether the decreased striatal–cortical DMN connectivity was specific to psychosis risk or was related to recent distress more generally, we examined the relationship between connectivity and distress in individuals diagnosed with nonpsychotic emotional distress disorders (N = 25). In contrast to Study 1, here we found that distress was associated with evidence of increased striatal–cortical DMN connectivity. Overall, the present results suggest that decreased striatal–cortical DMN connectivity is associated with psychosis risk and could contribute to aberrant salience.


Dorsal caudate Corticostriatal loops Attenuated psychotic symptoms Positive schizotypy Temporal lobe 


Author note

We thank Mason H. Price, Jeffrey D. Johnson, and Shawn E. Christ for their coding and technical expertise regarding the neuroimaging analyses. This research was supported by National Institute of Mental Health (NIMH) Grants T32 MH014677 (N.R.K.) and R21 MH100359 (J.G.K. and T.J.T.), and by University of Missouri research funds (J.G.K.).

Supplementary material

13415_2019_698_MOESM1_ESM.docx (148 kb)
ESM 1 (DOCX 147 kb)


  1. Alderson-Day, B., Dierderen, K, Fernyhough, C., Ford, J. M., Horga, G., Marguiles, D. S., … Jardri, R. (2016). Auditory hallucinations and the brain’s resting-state networks: Findings and methodological obsevations. Schizophenia Bulletin, 42, 1110–1123. CrossRefGoogle Scholar
  2. Alexander, W. H., & Brown, J. W. (2010). Competition between learned reward and error outcome predictions in anterior cingulate cortex. NeuroImage, 49, 3210–3218. CrossRefGoogle Scholar
  3. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th). Washington DC.Google Scholar
  4. Baker, J. T., Holmes, A. J., Masters, G. A., Yeo, B. T. T., Krienen, F., Buckner, R. L., & Öngür, D. (2014). Disruption of cortical association networks in schizophrenia and psychotic bipolar disorder. JAMA Psychiatry, 71, 109–118. CrossRefGoogle Scholar
  5. Barbey, A. K., Koenigs, M., & Grafman, J. (2013). Dorsolateral prefrontal contributions to human working memory. Cortex, 49, 1195–1205.,cortex.2012.05.022 CrossRefGoogle Scholar
  6. Barch, D. M., & Ceaser, A. (2012). Cognition in schizophrenia: Core psychological and neural mechanisms. Trends in Cognitive Sciences, 16, 27–P34. CrossRefGoogle Scholar
  7. Bluhm, R., Williamson, P., Lanius, R., Tháberge, J., Densmore, M., Bartha, R., … Osuch, E. (2009). Resting state default-mode network connectivity in early depression using a seed region-of-interest analysis: Decreased connectivity with caudate nucleus. Psychiatry and Clinical Neurosciences, 63, 754–761. CrossRefGoogle Scholar
  8. Buckner, R. L., Andrews-Hanna, J. R., & Schacter, D. L. (2008). The brain’s default network. Annals of the New York Academy of Sciences, 1124, 1–38. CrossRefGoogle Scholar
  9. Buhle, J. T., Silvers, J. A., Wager, T. D., Lopez, R., Onyemekwu, C., Kober, H., … Oshsner, K. N. (2014). Cognitive reappriasal of emotion: A meta-analysis of human neuorimaging studies. Cerebral Cortex, 24, 2981–2990. CrossRefGoogle Scholar
  10. Burghy, C. A., Stodola, D. E., Ruttle, P. L., Molloy, E. K., Armstrong, J. M., Oler, J. A., … Birn, R. M., (2012). Developmental pathways to amygdala–prefrontal function and internalizing symptoms in adolescence. Nature Neuroscience, 15, 1736–1741. CrossRefGoogle Scholar
  11. Cannon, T. D., Yu, C., Addington, J., Bearden, C. E., Cadenhead, K. S., Cornblatt, B. A., … Kattan, M. W. (2016). An individualized risk calculator for research in prodromal psychosis. American Journal of Psychiatry, 173, 980–988. CrossRefGoogle Scholar
  12. Chapman, L. J., Chapman, J. P., Kwapil, T. R., Eckblad, M., & Zinser, M. (1994). Putatively psychosis-prone subjects 10 years later. Journal of Abnormal Psychology, 103, 171–183. CrossRefGoogle Scholar
  13. Chapman, L. J., Chapman, J. P., & Raulin, M. L. (1978). Body-image aberration in schizophrenia. Journal of Abnormal Psychology, 87, 399–407. CrossRefGoogle Scholar
  14. Chatham, C. H., & Badre, D. (2015). Multiple gates on working memory. Current Opinion in Behavioral Sciences, 1, 23–31. CrossRefGoogle Scholar
  15. Choi, E. Y., Yeo, B. T. T., & Buckner, R. L. (2012). The organization of the human striatum estimated by intrinsic functional connectivity. Journal of Neurophysiology, 108, 2242–2263. CrossRefGoogle Scholar
  16. Cicero, D. C., Becker, T. M., Martin, E. A., Docherty, A. R., & Kerns, J. G. (2013). The role of aberrant salience and self-concept clarity in psychotic-like experiences. Personality Disorders, 4, 33–42. CrossRefGoogle Scholar
  17. Clark, S. V, Mittal, V. A., Bernard, J. A., Ahmadi, A., King, T. Z., & Turner, J. A. (2018). Stronger default mode network connectivity is associated with poorer clinical insight in youth at ultra high-risk for psychotic disorders. Schizophrenia Research, 193, 244–250. CrossRefGoogle Scholar
  18. Cools, R., & D’Esposito, M. (2011). Inverted-U-shaped dopamine actions on human working memory and cognitive control. Biological Psychiatry, 69, e113–e125. CrossRefGoogle Scholar
  19. Dandash, O., Fornito, A., Lee, J., Keefe, R. S. E., Chee, M. W. L., Adcock, R. A., … Harrison, B. J. (2014). Altered striatal functional connectivity in subjects with an at-risk mental state for psychosis. Schizophrenia Bulletin, 40, 904–913. CrossRefGoogle Scholar
  20. Deichmann, R., Gottfried, J. A., Hutton, C., & Turner, R. (2003). Optimized EPI for fMRI studies of the orbitofrontal cortex. NeuroImage, 19, 430–441. CrossRefGoogle Scholar
  21. Duncan, J. (2013). The structure of cognition: Attentional episodes in mind and brain. Neuron, 80, 35–50. CrossRefGoogle Scholar
  22. Eckblad, M., & Chapman, L. J. (1983). Magical ideation as an indicator of schizotypy. Journal of Consulting and Clinical Psychology, 51, 215–225. CrossRefGoogle Scholar
  23. Egerton, A., Valmaggia, L. R., Howes, O. D., Day, F., Chaddock, C. A., Allen, P., … McGuire, P. (2016). Adversity in childhood linked to elevated striatal dopamine function in adulthood. Schizophrenia Research, 176, 171–176. CrossRefGoogle Scholar
  24. Faridi, K., Pawliuk, N., King, S., Joober, R., & Malla, A. K. (2009). Prevalence of psychotic and non-psychotic disorders in relatives of patients with a first episode psychosis. Schizophrenia Research, 114, 57–63. CrossRefGoogle Scholar
  25. Faul, F., Erdfelder, E., Buchner, A., & Lang, A. G. (2009). Statistical power analyses using G*Power 3.1: Tests for correlatoin and regression analyses. Behavior Research Methods, 41, 1149–1160. CrossRefGoogle Scholar
  26. Fornito, A., Harrison, B. J., Goodby, E., Dean, A., Ooi, C., Nathan, P. J., … Bullmore, E. T. (2013). Functional dysconnectivity of corticostriatal circuitry as a risk phenotype for psychosis. JAMA Psychiatry, 70, 1143–1151. CrossRefGoogle Scholar
  27. Frank, M. J., Loughry, B, & O’Reilly, R. C. (2001). Interactions between frontal cortex and basal ganglia in working memory: A computational model. Cognitive, Affective, & Behavioral Neuroscience, 2, 137–160. CrossRefGoogle Scholar
  28. Furman, D. J., Hamilton, J. P., & Gotlib, I. H. (2011). Frontostriatal functional connectivity in major depressive disorder. Biology of Mood & Anxiety Disorders, 1, 11.
  29. Fusar-Poli, P., Cappucciati, M., Borgwardt, S., Woods, S. W., Addington, J., Nelson, B., … McGuire, P. K. (2016). Heterogeneity of psychosis risk within individuals at clinical high risk: A meta-analytical stratification. JAMA Psychiatry, 73, 113–120. CrossRefGoogle Scholar
  30. Fusar-Poli, P., Howes, O. D., Allen, P., Broome, M., Valli, I., Asselin, M.-C., … McGuire, P. (2011). Abnormal prefrontal activation directly related to pre-synaptic striatal dopamine dysfunction in people at clinical high risk for psychosis. Molecular Psychiatry, 16, 67–75. CrossRefGoogle Scholar
  31. Goldberg, L. R. (1999). A broad-bandwidth, public domain, personality inventory measuring the lower-level facets of several five-factor models. In I. I. Mervielde, F. Deary, D. Fruyt, & F. Ostendorf (Eds.), Personality psychology in Europe (pp. 7–28). Tilburg: Tilburg University Press.Google Scholar
  32. Haber, S. N. (2014). The place of dopamine in the cortico-basal ganglia circuit. Neuroscience, 282, 248–257. CrossRefGoogle Scholar
  33. Haber, S. N. (2016). Corticostriatal circuitry. Dialogues in Clinical Neuroscience, 18, 7–21. Google Scholar
  34. Henry, J. D., & Crawford, J. R. (2005). The short-form version of the Depression Anxiety Stress Scales (DASS-21): Construct validity and normative data in a large non-clinical sample. British Journal of Clinical Psychology, 44, 227–239. CrossRefGoogle Scholar
  35. Horga, G., Cassidy, C. M., Xu, X., Moore, H., Slifstein, M., Van Snellenberg, J. X., & Abi-Dargham, A. (2016). Dopamine-related disruption of functional topography of striatal connections in unmedicated patients with schizophrenia. JAMA Psychiatry, 73, 862–870. CrossRefGoogle Scholar
  36. Howes, O. D., Kambeitz, J., Kim, E., Stahl, D., Slifstein, M., Abi-Dargham, A., & Kapur, S. (2012). The nature of dopamine dysfunction in schizophrenia and what this means for treatment. Archives of General Psychiatry, 69, 776–786. CrossRefGoogle Scholar
  37. Howes, O. D., & Nour, M. M. (2016). Dopamine and the aberrant salience hypothesis of schizophrenia. World Psychiatry, 15, 3–4. CrossRefGoogle Scholar
  38. Hua, J. P. Y., Karcher, N. R., Merrill, A. M., O’Brien, K. J., Straub, K. T., Trull, T. J., & Kerns, J. G. (2018). Data for: Psychosis risk is associated with decreased resting-state functional connectivity between the striatum and the default mode network. Retrieved from
  39. Hwang, J. W., Xin, S. C., Ou, Y. M., Zhang, W. Y., Liang, Y. L., Chen, J., … Kong, J. (2016). Enhanced default mode network connectivity with ventral striatum in subthreshold depression individuals. Journal of Psychiatric Research, 76, 111–120. CrossRefGoogle Scholar
  40. Jauhar, S., Nour, M. M., Veronese, M., Rogdaki, M., Bonoldi, I., Azis, M., … Howes, O. D. (2017). A test of the transdiagnostic dopamine hypothesis of psychosis using positron emission tomographic imaging in bipolar affective disorder and schizophrenia. JAMA Psychiatry, 74, 1206–1213. CrossRefGoogle Scholar
  41. Kapur, S. (2003). Psychosis as a state of aberrant salience: A framework linking biology, phenomenology, and pharmacology in schizophrenia. American Journal of Psychiatry, 160, 13–23. CrossRefGoogle Scholar
  42. Karcher, N. R., Bartholow, B. D., Martin, E. A., & Kerns, J. G. (2017). Associations between electrophysiological evidence of reward and punishment based-learning and psychotic experiences and social anhedonia in at-risk groups. Neuropsychpharmacology, 42, 925–932. CrossRefGoogle Scholar
  43. Karcher, N. R., Hua, J. P. Y., & Kerns, J. G. (2019). Probabilistic category learning and striatal functional activation in psychosis risk. Schizophrenia Bulletin.
  44. Karcher, N. R., Martin, E. A., & Kerns, J. G. (2015). Examining associations between psychosis risk, social anhedonia, and performance of striatum-related behavioral tasks. Journal of Abnormal Psychology, 124, 507–518. CrossRefGoogle Scholar
  45. Kegeles, L. S., Abi-Dargham, A., Frankle, W. G., Gil, R., Cooper, T. B., Slifstein, M., … Laruelle, M. (2010). Increased synaptic dopamine function in associative regions of the striatum in schizophrenia. Archives of General Psychiatry, 67, 231–239. CrossRefGoogle Scholar
  46. Kerestes, R., Harrison, B. J., Dandash, O., Stephanou, K., Whittle, S., Pujol, J., & Davey, C. G. (2015). Specific functional connectivity alteraions of the dorsal striatum in young people with depression. NeuroImage: Clinical, 7, 266–272. CrossRefGoogle Scholar
  47. Kerns, J. G. (2006). Schizotpy facets, cognitive control, and emotion. Journal of Abnormal Psychology, 115, 418–427. CrossRefGoogle Scholar
  48. Kerns, J. G., Nuechterlein, K. H., Braver, T. S., & Barch, D. M. (2008). Executive functioning component mechanisms and schizophrenia. Biological Psychiatry, 64, 26–33. CrossRefGoogle Scholar
  49. Kwapil, T. R., & Barrantes-Vidal, N. (2015). Schizotypy: Looking back and moving forward. Schizophrenia Bulletin, 41(Suppl. 2), S366–S373. CrossRefGoogle Scholar
  50. Lenzenweger, M. F. (2010). Schizotypy and schizophrenia: The view from experimental psychopathology. New York: Guilford Press.Google Scholar
  51. Lesh, T. A., Niendam, T. A., Minzenberg, M. J., & Carter, C. S. (2011). Cognitive control deficits in schizophrenia: Mechanisms and meaning. Neuropsychopharmacology, 36, 316–338. CrossRefGoogle Scholar
  52. MathWorks, Inc (2010). MATLAB (Software). Natick, MA: Author.Google Scholar
  53. Menon, V. (2011). Large-scale brain networks and psychopathology: A unifying triple network model. Trends in Cognitive Sciences, 15, 483–506. CrossRefGoogle Scholar
  54. Miller, T. J., McGlashan, T. H., Rosen, J. L., Cadenhead, K., Ventura, J., McFarlane, W., … Woods, S. W. (2003). Prodromal assessment with the Structured Interview for Prodromal Syndromes and the Scale of Prodromal Symptoms: Predictive validity, interrater reliability, and training to reliability. Schizophrenia Bulletin, 29, 703–715. CrossRefGoogle Scholar
  55. Nelson, A. B., & Kreitzer, A. C. (2014). Reassessing models of basal ganglia function and dysfunction. Annual Review of Neuroscience, 37, 117–135. CrossRefGoogle Scholar
  56. Nelson, B., Fornito, A., Harrison, B. J., Yücel, M., Sass, L. A., Yung, A. R., … McGorry, P. D. (2009). A disturbed sense of self in the psychosis prodrome: Linking phenomenology and neurobiology. Schizophrenia Bulletin, 33, 807–817. Google Scholar
  57. Northoff, G., & Duncan, N. W. (2016). How do abnormalitis in the brain’s spontaneous activity translate into symptoms in schizophrenia? From an overview of resting state activity findings to a proposed spatiotemporal psychopathology. Progress in Neurobiology, 145–146, 26–45. CrossRefGoogle Scholar
  58. Patriat, R., Molloy, E. K., Meier, T. B., Kirk, G. R., Nair, V. A., Meyerand, M. E., … Birn, R. M. (2013). The effect of resting condition on resting-state fMRI reliability and consistency: A comparison between resting with eyes open, closed, and fixated. NeuroImage, 78, 463–473. CrossRefGoogle Scholar
  59. Pedersen, C. B., Mors, O., Bertelsen, A., Waltoft, B. L., Agerbo, E., McGrath, J. J., … Eaton, W. W. (2014). A comprehensive nationwide study of the incidence rate and lifetime risk for treated mental disorders. JAMA Psychiatry, 71, 573–581. CrossRefGoogle Scholar
  60. Pfohl, B., Blum, N. S., & Zimmerman, M. (1997). Structured Interview for DSM-IV Personality: SIDP-IV. Washington, DC: American Psychiatric Press.Google Scholar
  61. Power, J. D., Barnes, K. A., Snyder, A. Z., Schlaggar, B. L., & Petersen, S. E. (2012). Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion. NeuroImage, 59, 2142–2154. CrossRefGoogle Scholar
  62. Psychology Software Tools Inc. (2012). E-Prime 2.0 (Software). Sharpsburg, PA: Author.Google Scholar
  63. Raichle, M. E. (2015). The brain’s default mode network. Annual Review of Neuroscience, 38, 433–447. CrossRefGoogle Scholar
  64. Roiser, J. P., Stephan, K. E., den Ouden, H. E. M., Barnes, T. R. E., Friston, K. J., & Joyce, E. M. (2009). Do patients with schizophrenia exhibit aberrant salience? Psychological Medicine, 39, 199–209. CrossRefGoogle Scholar
  65. Sarpal, D. K., Robinson, D. G., Lencz, T., Argyelan, M., Ikuta, T., Karlsgodt, K., … Malhotra, A. K. (2015). Antipsychotic treatment and functional connectivity of the striatum: A prospective controlled study in first-episode schizophrenia. JAMA Psychiatry, 72, 5–13. CrossRefGoogle Scholar
  66. Sass, L. A., & Parnas, J. (2003). Schizophrenia, consciousness, and the self. Schizophrenia Bulletin, 29, 427–444. CrossRefGoogle Scholar
  67. Satterthwaite, T. D., Ciric, R., Roalf, D. R., Davatzikos, C., Bassett, D. S., & Wolf, D. H. (2019). Motion artifact in studies of functional connectivity: Characteristics and mitigation strategies. Human Brain Mapping.
  68. Sheehan, D. V, Lecrubier, Y., Sheehan, K. H., Amorim, P., Janavs, J., Weiller, E., … Dunbar, G. C. (1998). The Mini-International Neuropsychiatric Interview (M.I.N.I.): The development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. Journal of Clinical Psychiatry, 59, 22–33.Google Scholar
  69. Sheffield, J. M., & Barch, D. M. (2016). Cognition and resting-state functional connectivity in schizophrenia. Neuroscience and Biobehavioral Reviews, 61, 108–120. CrossRefGoogle Scholar
  70. Shim, G., Oh, J. S., Jung, W. H., Jang, J. H., Choi, C.-H., Kim, E., … Kwon, J. S. (2010). Altered resting-state connectivity in subjects at ultra-high risk for psychosis: An fMRI study. Behavioral and Brain Functions, 6, 58. CrossRefGoogle Scholar
  71. Smith, S. M., Beckman, C. F., Andersson, J., Auerbach, E. J., Bijsterbosch, J., Douaud, G., … WU-Minn HCP Consortium. (2013). Resting-state fMRI in the Human Connectome Project. NeuroImage, 80, 144–168. CrossRefGoogle Scholar
  72. Spreng, R. N., Sepulcre, J., Turner, G. R., Stevens, W. D., & Schacter, D. L. (2013). Intrinsic architecture underlying the relations among the default, dorsal attention, and frontoparietal control networks of the human brain. Journal of Cognitive Neuroscience, 25, 74–86. CrossRefGoogle Scholar
  73. Tandon, R., Keshavan, M. S., & Nasrallah, H. A. (2008). Schizophrenia, “just the facts”: What we know in 2008 Part 1: Overview. Schizophrenia Research, 100, 4–19. CrossRefGoogle Scholar
  74. Van Dijk, K. R., Hedden, T., Venkataraman, A., Evans, K. C., Lazar, S. W., & Buckner, R. L. (2010). Intrinsice functional connectivity as a tool for human connectomics: Theory, properties, and optimization. Neurophysiology, 103, 297–321. CrossRefGoogle Scholar
  75. Van Dijk, K. R. A., Sabuncu, M. R., & Buckner, R. L. (2012). The influence of head motion on intrinsic functional connectivity MRI. NeuroImage, 59, 431–438. CrossRefGoogle Scholar
  76. Vincent, J. L., Kahn, I., Snyder, A. Z., Raichle, M. E., & Buckner, R. L. (2008). Evidence for a frontoparietal control system revealed by intrinsic functional connectivity. Journal of Neurophysiology, 100, 3328–3342. CrossRefGoogle Scholar
  77. Walker, E., Mittal, V., & Tessner, K. (2008). Stress and the hypothalamic pituitary adrenal axis in the developmental course of schizophrenia. Annual Review of Clinical Psychology, 4, 189–216. CrossRefGoogle Scholar
  78. Wang, Y., Ettinger, U., Meindl, T., & Chan, R. C. K. (2018). Association of schizotypy with striatocortical functional connectivity and its asymmetry in healthy adults. Human Brain Mapping, 39, 288–299. CrossRefGoogle Scholar
  79. Wellcome Trust Centre for Neuroimaging. (2009). SPM8 (Software). London. UK: Wellcome Trust Centre for Neuroimaging at UCL. Retrieved from
  80. Whitfield-Gabrieli, S., & Ford, J. M. (2012). Default mode network activity and connectivity in psychopathology. Annual Review of Clinical Psychology, 8, 49–76. CrossRefGoogle Scholar
  81. Yeo, B. T. T., Krienen, F. M., Sepulcre, J., Sabuncu, M. R., Lashkari, D., Hollinshead, M., … Buckner, R. L. (2011). The organization of the human cerebral cortex estimated by intrinsic functional connectivity. Journal of Neurophysiology, 106, 1125–1165. CrossRefGoogle Scholar

Copyright information

© The Psychonomic Society, Inc. 2019

Authors and Affiliations

  • Jessica P. Y. Hua
    • 1
  • Nicole R. Karcher
    • 1
    • 2
  • Anne M. Merrill
    • 1
  • Kathleen J. O’Brien
    • 1
    • 2
  • Kelsey T. Straub
    • 1
  • Timothy J. Trull
    • 1
  • John G. Kerns
    • 1
    Email author
  1. 1.Department of Psychological SciencesUniversity of MissouriColumbiaUSA
  2. 2.Department of PsychiatryWashington University School of MedicineSt. LouisUSA

Personalised recommendations