Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Opposite effects of dopamine and serotonin on resting-state networks: review and implications for psychiatric disorders

Molecular Psychiatry volume 25, pages 82–93 (2020)Cite this article

Subjects

Abstract

Alterations in brain intrinsic activity—as organized in resting-state networks (RSNs) such as sensorimotor network (SMN), salience network (SN), and default-mode network (DMN)—and in neurotransmitters signaling—such as dopamine (DA) and serotonin (5-HT)—have been independently detected in psychiatric disorders like bipolar disorder and schizophrenia. Thus, the aim of this work was to investigate the relationship between such neurotransmitters and RSNs in healthy, by reviewing the relevant work on this topic and performing complementary analyses, in order to better understand their physiological link, as well as their alterations in psychiatric disorders. According to the reviewed data, neurotransmitters nuclei diffusively project to subcortical and cortical regions of RSNs. In particular, the dopaminergic substantia nigra (SNc)-related nigrostriatal pathway is structurally and functionally connected with core regions of the SMN, whereas the ventral tegmental area (VTA)-related mesocorticolimbic pathway with core regions of the SN. The serotonergic raphe nuclei (RNi) connections involve regions of the SMN and DMN. Coherently, changes in neurotransmitters activity impact the functional configuration and level of activity of RSNs, as measured by functional connectivity (FC) and amplitude of low-frequency fluctuations/temporal variability of BOLD signal. Specifically, DA signaling is associated with increase in FC and activity in the SMN (hypothetically via the SNc-related nigrostriatal pathway) and SN (hypothetically via the VTA-related mesocorticolimbic pathway), as well as concurrent decrease in FC and activity in the DMN. By contrast, 5-HT signaling (via the RNi-related pathways) is associated with decrease in SMN activity along with increase in DMN activity. Complementally, our empirical data showed a positive correlation between SNc-related FC and SMN activity, whereas a negative correlation between RNi-related FC and SMN activity (along with tilting of networks balance toward the DMN). According to these data, we hypothesize that the activity of neurotransmitter-related neurons synchronize the low-frequency oscillations within different RSNs regions, thus affecting the baseline level of RSNs activity and their balancing. In our model, DA signaling favors the predominance of SMN-SN activity, whereas 5-HT signaling favors the predominance of DMN activity, manifesting in distinct behavioral patterns. In turn, alterations in neurotransmitters signaling (or its disconnection) may favor a correspondent functional reorganization of RSNs, manifesting in distinct psychopathological states. The here suggested model carries important implications for psychiatric disorders, providing novel and well testable hypotheses especially on bipolar disorder and schizophrenia.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it

$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2
Fig. 3
Fig. 4

References

  1. Frangou S. A systems neuroscience perspective of schizophrenia and bipolar disorder. Schizophr Bull. 2014;40:523–31.

    PubMed  PubMed Central  Google Scholar 

  2. Savitz JB, Rauch SL, Drevets WC. Clinical application of brain imaging for the diagnosis of mood disorders: the current state of play. Mol Psychiatry. 2013;18:528–39.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Maudoux A, Lefebvre P, Cabay JE, Demertzi A, Vanhaudenhuyse A, Laureys S, et al. Auditory resting-state network connectivity in tinnitus: a functional MRI study. PLoS ONE. 2012;7:e36222.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Biswal B, Yetkin FZ, Haughton VM, Hyde JS. Functional connectivity in the motor cortex of resting human brain using echo-planar MRI. Magn Reson Med. 1995;34:537–41.

    CAS  PubMed  Google Scholar 

  5. Fox MD, Raichle ME. Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging. Nat Rev Neurosci. 2007;8:700–11.

    CAS  PubMed  Google Scholar 

  6. Buckner RL, Andrews-Hanna JR, Schacter DL. The brain’s default network: anatomy, function, and relevance to disease. Ann N Y Acad Sci. 2008;1124:1–38.

    PubMed  Google Scholar 

  7. Seeley WW, Menon V, Schatzberg AF, Keller J, Glover GH, Kenna H, et al. Dissociable intrinsic connectivity networks for salience processing and executive control. J Neurosci. 2007;27:2349–56.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Huang S, Li Y, Zhang W, Zhang B, Liu X, Mo L, et al. Multisensory competition is modulated by sensory pathway interactions with fronto-sensorimotor and default-mode network regions. J Neurosci. 2015;35:9064–77.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. De Luca M, Beckmann CF, De Stefano N, Matthews PM, Smith SM. fMRI resting state networks define distinct modes of long-distance interactions in the human brain. Neuroimage. 2006;29:1359–67.

    PubMed  Google Scholar 

  10. Damoiseaux JS, Rombouts SA, Barkhof F, Scheltens P, Stam CJ, Smith SM, et al. Consistent resting-state networks across healthy subjects. Proc Natl Acad Sci USA. 2006;103:13848–53.

    CAS  PubMed  Google Scholar 

  11. Dosenbach NU, Fair DA, Miezin FM, Cohen AL, Wenger KK, Dosenbach RA, et al. Distinct brain networks for adaptive and stable task control in humans. Proc Natl Acad Sci USA. 2007;104:11073–8.

    CAS  PubMed  Google Scholar 

  12. Goulden N, Khusnulina A, Davis NJ, Bracewell RM, Bokde AL, McNulty JP, et al. The salience network is responsible for switching between the default mode network and the central executive network: replication from DCM. Neuroimage. 2014;99:180–90.

    PubMed  Google Scholar 

  13. Fox MD, Snyder AZ, Vincent JL, Corbetta M, Van Essen DC, Raichle ME. The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proc Natl Acad Sci USA. 2005;102:9673–8.

    CAS  PubMed  Google Scholar 

  14. van den Heuvel MP, Hulshoff Pol HE. Exploring the brain network: a review on resting-state fMRI functional connectivity. Eur Neuropsychopharmacol. 2010;20:519–34.

    PubMed  Google Scholar 

  15. Beckmann CF, DeLuca M, Devlin JT, Smith SM. Investigations into resting-state connectivity using independent component analysis. Philos Trans R Soc Lond B Biol Sci. 2005;360:1001–13.

    PubMed  PubMed Central  Google Scholar 

  16. Martino M, Magioncalda P, Huang Z, Conio B, Piaggio N, Duncan NW, et al. Contrasting variability patterns in the default mode and sensorimotor networks balance in bipolar depression and mania. Proc Natl Acad Sci USA. 2016;113:4824–9.

    CAS  PubMed  Google Scholar 

  17. Northoff G. Is schizophrenia a spatiotemporal disorder of the brain’s resting state? World Psychiatry. 2015;14:34–35.

    PubMed  PubMed Central  Google Scholar 

  18. Northoff G, Duncan NW. How do abnormalities in the brain’s spontaneous activity translate into symptoms in schizophrenia? From an overview of resting state activity findings to a proposed spatiotemporal psychopathology. Prog Neurobiol. 2016;145–6:26–45.

    Google Scholar 

  19. Looijestijn J, Blom JD, Aleman A, Hoek HW, Goekoop R. An integrated network model of psychotic symptoms. Neurosci Biobehav Rev. 2015;59:238–50.

    PubMed  Google Scholar 

  20. Palaniyappan L, Liddle PF. Does the salience network play a cardinal role in psychosis? An emerging hypothesis of insular dysfunction. J Psychiatry Neurosci. 2012;37:17–27.

    PubMed  PubMed Central  Google Scholar 

  21. Northoff G, Qin P. How can the brain’s resting state activity generate hallucinations? A ‘resting state hypothesis’ of auditory verbal hallucinations. Schizophr Res. 2011;127:202–14.

    PubMed  Google Scholar 

  22. Baldessarini RJ. Chemotherapy in psychiatry: the pharmacologic basis of treatments for major mental illness. 3rd ed. New York (NY). Springer Press. 2013.

    Google Scholar 

  23. Tost H, Alam T, Meyer-Lindenberg A. Dopamine and psychosis: theory, pathomechanisms and intermediate phenotypes. Neurosci Biobehav Rev. 2010;34:689–700.

    CAS  PubMed  Google Scholar 

  24. Howes OD, Kapur S. The dopamine hypothesis of schizophrenia: version III–the final common pathway. Schizophr Bull. 2009;35:549–62.

    PubMed  PubMed Central  Google Scholar 

  25. Wainwright SR, Galea LA. The neural plasticity theory of depression: assessing the roles of adult neurogenesis and PSA-NCAM within the hippocampus. Neural Plast. 2013;2013:805497.

    PubMed  PubMed Central  Google Scholar 

  26. Mulinari S. Monoamine theories of depression: historical impact on biomedical research. J Hist Neurosci. 2012;21:366–92.

    PubMed  Google Scholar 

  27. Pralong E, Magistretti P, Stoop R. Cellular perspectives on the glutamate-monoamine interactions in limbic lobe structures and their relevance for some psychiatric disorders. Prog Neurobiol. 2002;67:173–202.

    CAS  PubMed  Google Scholar 

  28. Grace AA. Phasic versus tonic dopamine release and the modulation of dopamine system responsivity: a hypothesis for the etiology of schizophrenia. Neuroscience. 1991;41:1–24.

    CAS  PubMed  Google Scholar 

  29. Dalley JW, Roiser JP. Dopamine, serotonin and impulsivity. Neuroscience. 2012;215:42–58.

    CAS  PubMed  Google Scholar 

  30. Andrews PW, Bharwani A, Lee KR, Fox M, Thomson JA Jr. Is serotonin an upper or a downer? The evolution of the serotonergic system and its role in depression and the antidepressant response. Neurosci Biobehav Rev. 2015;51:164–88.

    CAS  PubMed  Google Scholar 

  31. Howes OD, Kambeitz J, Kim E, Stahl D, Slifstein M, Abi-Dargham A, et al. The nature of dopamine dysfunction in schizophrenia and what this means for treatment. Arch Gen Psychiatry. 2012;69:776–86.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Buzsaki G, Draguhn A. Neuronal oscillations in cortical networks. Science. 2004;304:1926–9.

    CAS  PubMed  Google Scholar 

  33. Zuo XN, Di Martino A, Kelly C, Shehzad ZE, Gee DG, Klein DF, et al. The oscillating brain: complex and reliable. Neuroimage. 2010;49:1432–45.

    PubMed  Google Scholar 

  34. Yeo BT, Krienen FM, Chee MW, Buckner RL. Estimates of segregation and overlap of functional connectivity networks in the human cerebral cortex. Neuroimage. 2014;88:212–27.

    PubMed  Google Scholar 

  35. Engel AK, Fries P, Singer W. Dynamic predictions: oscillations and synchrony in top-down processing. Nat Rev Neurosci. 2001;2:704–16.

    CAS  PubMed  Google Scholar 

  36. Gottlich M, Munte TF, Heldmann M, Kasten M, Hagenah J, Kramer UM. Altered resting state brain networks in Parkinson’s disease. PLoS ONE. 2013;8:e77336.

    PubMed  PubMed Central  Google Scholar 

  37. Christoff K, Gordon AM, Smallwood J, Smith R, Schooler JW. Experience sampling during fMRI reveals default network and executive system contributions to mind wandering. Proc Natl Acad Sci USA. 2009;106:8719–24.

    CAS  PubMed  Google Scholar 

  38. Mason MF, Norton MI, Van Horn JD, Wegner DM, Grafton ST, Macrae CN. Wandering minds: the default network and stimulus-independent thought. Science. 2007;315:393–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Davidson RJ. Affective style, psychopathology, and resilience: brain mechanisms and plasticity. Am Psychol. 2000;55:1196–214.

    CAS  PubMed  Google Scholar 

  40. Menon V. Large-scale brain networks and psychopathology: a unifying triple network model. Trends Cogn Sci. 2011;15:483–506.

    Google Scholar 

  41. Geng H, Li X, Chen J, Gu R. Decreased intra- and inter-salience network functional connectivity is related to trait anxiety in adolescents. Front Behav Neurosci. 2015;9:350.

    PubMed  Google Scholar 

  42. Yang GJ, Murray JD, Repovs G, Cole MW, Savic A, Glasser MF, et al. Altered global brain signal in schizophrenia. Proc Natl Acad Sci USA. 2014;111:7438–43.

    CAS  PubMed  Google Scholar 

  43. Bentivoglio M, Morelli M. The organization and circuits of mesencephalic dopaminergic neurons and the distribution of dopamine receptors in the brain. In: Dunnett SB, editor. Handbook of chemical neuroanatomy. 21. Amsterdam: Elsevier; 2005.

    Google Scholar 

  44. Haber SN, Fudge JL, McFarland NR. Striatonigrostriatal pathways in primates form an ascending spiral from the shell to the dorsolateral striatum. J Neurosci. 2000;20:2369–82.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Bartholomew RA, Li H, Gaidis EJ, Stackmann M, Shoemaker CT, Rossi MA, et al. Striatonigral control of movement velocity in mice. Eur J Neurosci. 2016;43:1097–110.

    PubMed  Google Scholar 

  46. Dunnett SB. Motor function(s) of the nigrostriatal dopamine system: studies of lesions and behavior. In: Dunnett SB, editor. Handbook of chemical neuroanatomy. 21. Amsterdam: Elsevier; 2005.

    Google Scholar 

  47. Ikemoto S. Dopamine reward circuitry: two projection systems from the ventral midbrain to the nucleus accumbens-olfactory tubercle complex. Brain Res Rev. 2007;56:27–78.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Di Chiara G. Dopamine, motivation and reward. In: Dunnett SB, editor. Handbook of chemical neuroanatomy. 21. Amsterdam: Elsevier; 2005.

    Google Scholar 

  49. Robbins TW. Role of cortical and striatal dopamine in cognitive function. In: Dunnett SB, editor. Handbook of Chemical Neuroanatomy. 21. Amsterdam: Elsevier; 2005.

    Google Scholar 

  50. Carr GV, Lucki I. The role of serotonin receptor subtypes in treating depression: a review of animal studies. Psychopharmacology (Berl). 2011;213:265–87.

    CAS  Google Scholar 

  51. Jacobs BL, Azmitia EC. Structure and function of the brain serotonin system. Physiol Rev. 1992;72:165–229.

    CAS  PubMed  Google Scholar 

  52. Carrasco GA, Van de Kar LD. Neuroendocrine pharmacology of stress. Eur J Pharmacol. 2003;463:235–72.

    CAS  PubMed  Google Scholar 

  53. Bobillier P, Seguin S, Petitjean F, Salvert D, Touret M, Jouvet M. The raphe nuclei of the cat brain stem: a topographical atlas of their efferent projections as revealed by autoradiography. Brain Res. 1976;113:449–86.

    CAS  PubMed  Google Scholar 

  54. Azmitia EC, Segal M. An autoradiographic analysis of the differential ascending projections of the dorsal and median raphe nuclei in the rat. J Comp Neurol. 1978;179:641–67.

    CAS  PubMed  Google Scholar 

  55. Zilles K, Palomero-Gallagher N, Grefkes C, Scheperjans F, Boy C, Amunts K, et al. Architectonics of the human cerebral cortex and transmitter receptor fingerprints: reconciling functional neuroanatomy and neurochemistry. Eur Neuropsychopharmacol. 2002;12:587–99.

    CAS  PubMed  Google Scholar 

  56. Palomero-Gallagher N, Vogt BA, Schleicher A, Mayberg HS, Zilles K. Receptor architecture of human cingulate cortex: evaluation of the four-region neurobiological model. Hum Brain Mapp. 2009;30:2336–55.

    PubMed  Google Scholar 

  57. Saulin A, Savli M, Lanzenberger R. Serotonin and molecular neuroimaging in humans using PET. Amino Acids. 2012;42:2039–57.

    CAS  PubMed  Google Scholar 

  58. Dugue GP, Lorincz ML, Lottem E, Audero E, Matias S, Correia PA, et al. Optogenetic recruitment of dorsal raphe serotonergic neurons acutely decreases mechanosensory responsivity in behaving mice. PLoS ONE. 2014;9:e105941.

    PubMed  PubMed Central  Google Scholar 

  59. Correia PA, Lottem E, Banerjee D, Machado AS, Carey MR, Mainen ZF. Transient inhibition and long-term facilitation of locomotion by phasic optogenetic activation of serotonin neurons. Elife. 2017;6:e20975.

  60. Miyazaki KW, Miyazaki K, Tanaka KF, Yamanaka A, Takahashi A, Tabuchi S, et al. Optogenetic activation of dorsal raphe serotonin neurons enhances patience for future rewards. Curr Biol. 2014;24:2033–40.

    CAS  PubMed  Google Scholar 

  61. Uchida N, Cohen JY. Slow motion. Elife. 2017;6:e24792.

  62. McDannald MA. Serotonin: waiting but not rewarding. Curr Biol. 2015;25:R103–4.

    CAS  PubMed  Google Scholar 

  63. Ranade S, Pi HJ, Kepecs A. Neuroscience: waiting for serotonin. Curr Biol. 2014;24:R803–5.

    CAS  PubMed  Google Scholar 

  64. Mosienko V, Beis D, Pasqualetti M, Waider J, Matthes S, Qadri F, et al. Life without brain serotonin: reevaluation of serotonin function with mice deficient in brain serotonin synthesis. Behav Brain Res. 2015;277:78–88.

    CAS  PubMed  Google Scholar 

  65. Bar KJ, de la Cruz F, Schumann A, Koehler S, Sauer H, Critchley H, et al. Functional connectivity and network analysis of midbrain and brainstem nuclei. Neuroimage. 2016;134:53–63.

    PubMed  Google Scholar 

  66. Murty VP, Shermohammed M, Smith DV, Carter RM, Huettel SA, Adcock RA. Resting state networks distinguish human ventral tegmental area from substantia nigra. Neuroimage. 2014;100:580–9.

    PubMed  PubMed Central  Google Scholar 

  67. Tomasi D, Volkow ND. Functional connectivity of substantia nigra and ventral tegmental area: maturation during adolescence and effects of ADHD. Cereb Cortex. 2014;24:935–44.

    PubMed  Google Scholar 

  68. Nagano-Saito A, Lissemore JI, Gravel P, Leyton M, Carbonell F, Benkelfat C. Posterior dopamine D2/3 receptors and brain network functional connectivity. Synapse. 2017;71(11).

    Google Scholar 

  69. McCutcheon RA, Nour MM, Dahoun T, Jauhar S, Pepper F, Expert P, et al. Mesolimbic dopamine function is related to salience network connectivity: an integrative positron emission tomography and magnetic resonance study. Biol Psychiatry. 2018;85:368–78.

    PubMed  Google Scholar 

  70. Beliveau V, Svarer C, Frokjaer VG, Knudsen GM, Greve DN, Fisher PM. Functional connectivity of the dorsal and median raphe nuclei at rest. Neuroimage. 2015;116:187–95.

    PubMed  PubMed Central  Google Scholar 

  71. Hahn A, Wadsak W, Windischberger C, Baldinger P, Hoflich AS, Losak J, et al. Differential modulation of the default mode network via serotonin-1A receptors. Proc Natl Acad Sci USA. 2012;109:2619–24.

    CAS  PubMed  Google Scholar 

  72. Cole DM, Beckmann CF, Oei NY, Both S, van Gerven JM, Rombouts SA. Differential and distributed effects of dopamine neuromodulations on resting-state network connectivity. Neuroimage. 2013;78:59–67.

    CAS  PubMed  Google Scholar 

  73. Kelly C, de Zubicaray G, Di Martino A, Copland DA, Reiss PT, Klein DF, et al. L-dopa modulates functional connectivity in striatal cognitive and motor networks: a double-blind placebo-controlled study. J Neurosci. 2009;29:7364–78.

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Ye Z, Hammer A, Munte TF. Pramipexole modulates interregional connectivity within the sensorimotor network. Brain Connect. 2017;7:258–63.

    PubMed  Google Scholar 

  75. Alavash M, Lim S, Thiel C, Sehm B, Deserno L, Obseler J. Dopaminergic modulation of brain signal variability and functional connectome during cognitive performance. bioRxiv. 2017;172:341–56.

    Google Scholar 

  76. Shafiei G, Zeighami Y, Clark CA, Coull JT, Nagano-Saito A, Leyton M, et al. Dopamine signaling modulates the stability and integration of intrinsic brain networks. Cereb Cortex. 2018;29:397–409.

    PubMed Central  Google Scholar 

  77. Cole DM, Oei NY, Soeter RP, Both S, van Gerven JM, Rombouts SA, et al. Dopamine-dependent architecture of cortico-subcortical network connectivity. Cereb Cortex. 2013;23:1509–16.

    PubMed  Google Scholar 

  78. Nagano-Saito A, Leyton M, Monchi O, Goldberg YK, He Y, Dagher A. Dopamine depletion impairs frontostriatal functional connectivity during a set-shifting task. J Neurosci. 2008;28:3697–706.

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Carbonell F, Nagano-Saito A, Leyton M, Cisek P, Benkelfat C, He Y, et al. Dopamine precursor depletion impairs structure and efficiency of resting state brain functional networks. Neuropharmacology. 2014;84:90–100.

    CAS  PubMed  Google Scholar 

  80. Kunisato Y, Okamoto Y, Okada G, Aoyama S, Demoto Y, Munakata A, et al. Modulation of default-mode network activity by acute tryptophan depletion is associated with mood change: a resting state functional magnetic resonance imaging study. Neurosci Res. 2011;69:129–34.

    CAS  PubMed  Google Scholar 

  81. Scharinger C, Rabl U, Kasess CH, Meyer BM, Hofmaier T, Diers K, et al. Platelet serotonin transporter function predicts default-mode network activity. PLoS ONE. 2014;9:e92543.

    PubMed  PubMed Central  Google Scholar 

  82. Helmbold K, Zvyagintsev M, Dahmen B, Biskup CS, Bubenzer-Busch S, Gaber TJ, et al. Serotonergic modulation of resting state default mode network connectivity in healthy women. Amino Acids. 2016;48:1109–20.

    CAS  PubMed  Google Scholar 

  83. Lu H, Stein EA. Resting state functional connectivity: its physiological basis and application in neuropharmacology. Neuropharmacology. 2014;84:79–89.

    CAS  PubMed  Google Scholar 

  84. Shmuel A, Leopold DA. Neuronal correlates of spontaneous fluctuations in fMRI signals in monkey visual cortex: implications for functional connectivity at rest. Hum Brain Mapp. 2008;29:751–61.

    PubMed  Google Scholar 

  85. Balduzzi D, Riedner BA, Tononi G. A BOLD window into brain waves. Proc Natl Acad Sci USA. 2008;105:15641–2.

    CAS  PubMed  Google Scholar 

  86. Mitra A, Snyder AZ, Blazey T, Raichle ME. Lag threads organize the brain’s intrinsic activity. Proc Natl Acad Sci USA. 2015;112:E2235–44.

    CAS  PubMed  Google Scholar 

  87. Huang Z, Zhang J, Longtin A, Dumont G, Duncan NW, Pokorny J, et al. Is there a nonadditive interaction between spontaneous and evoked activity? Phase-dependence and its relation to the temporal structure of scale-free brain activity. Cereb Cortex. 2017;27:1037–59.

    PubMed  Google Scholar 

  88. Garrett DD, Kovacevic N, McIntosh AR, Grady CL. Blood oxygen level-dependent signal variability is more than just noise. J Neurosci. 2010;30:4914–21.

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Garrett DD, Kovacevic N, McIntosh AR, Grady CL. The importance of being variable. J Neurosci. 2011;31:4496–503.

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Garrett DD, McIntosh AR, Grady CL. Brain signal variability is parametrically modifiable. Cereb Cortex. 2013;24:2931–40.

    PubMed  PubMed Central  Google Scholar 

  91. Garrett DD, Samanez-Larkin GR, MacDonald SW, Lindenberger U, McIntosh AR, Grady CL. Moment-to-moment brain signal variability: a next frontier in human brain mapping? Neurosci Biobehav Rev. 2013;37:610–24.

    PubMed  PubMed Central  Google Scholar 

  92. Basalyga G, Salinas E. When response variability increases neural network robustness to synaptic noise. Neural Comput. 2006;18:1349–79.

    PubMed  Google Scholar 

  93. Faisal AA, Selen LP, Wolpert DM. Noise in the nervous system. Nat Rev Neurosci. 2008;9:292–303.

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Lugo E, Doti R, Faubert J. Ubiquitous crossmodal stochastic resonance in humans: auditory noise facilitates tactile, visual and proprioceptive sensations. PLoS ONE. 2008;3:e2860.

    PubMed  PubMed Central  Google Scholar 

  95. Ward LM. Synchronous neural oscillations and cognitive processes. Trends Cogn Sci. 2003;7:553–9.

    PubMed  Google Scholar 

  96. Magioncalda P, Martino M, Conio B, Escelsior A, Piaggio N, Presta A, et al. Functional connectivity and neuronal variability of resting state activity in bipolar disorder–reduction and decoupling in anterior cortical midline structures. Hum Brain Mapp. 2015;36:666–82.

    PubMed  Google Scholar 

  97. Yu Q, Sui J, Liu J, Plis SM, Kiehl KA, Pearlson G, et al. Disrupted correlation between low frequency power and connectivity strength of resting state brain networks in schizophrenia. Schizophr Res. 2013;143:165–71.

    PubMed  Google Scholar 

  98. A.P.A. Diagnostic and statistical manual for mental disorders. 5th ed. (DSM-5). Washington: American Psychiatrich Association; 2013.

  99. Kraepelin E. Clinical psychiatry. London. Macmillan. 1902.

  100. Martino M, Magioncalda P, Saiote C, Conio B, Escelsior A, Rocchi G, et al. Abnormal functional-structural cingulum connectivity in mania: combined functional magnetic resonance imaging-diffusion tensor imaging investigation in different phases of bipolar disorder. Acta Psychiatr Scand. 2016;134:339–49.

    CAS  PubMed  Google Scholar 

  101. Zhang J, Magioncalda P, Huang Z, Tan Z, Hu X, Hu Z, et al. Altered global signal topography and its different regional localization in motor cortex and hippocampus in mania and depression. Schizophr Bull. 2018. [Epub ahead of print].

  102. He Z, Deng W, Li M, Chen Z, Jiang L, Wang Q, et al. Aberrant intrinsic brain activity and cognitive deficit in first-episode treatment-naive patients with schizophrenia. Psychol Med. 2013;43:769–80.

    CAS  PubMed  Google Scholar 

  103. Giraldo-Chica M, Woodward ND. Review of thalamocortical resting-state fMRI studies in schizophrenia. Schizophr Res. 2017;180:58–63.

    PubMed  Google Scholar 

  104. Kraguljac NV, White DM, Hadley JA, Visscher K, Knight D, ver Hoef L, et al. Abnormalities in large scale functional networks in unmedicated patients with schizophrenia and effects of risperidone. Neuroimage Clin. 2016;10:146–58.

    PubMed  Google Scholar 

  105. Yang GJ, Murray JD, Glasser M, Pearlson GD, Krystal JH, Schleifer C, et al. Altered global signal topography in schizophrenia. Cereb Cortex. 2017;27:5156–69.

    PubMed  Google Scholar 

  106. Hoptman MJ, Zuo XN, Butler PD, Javitt DC, D’Angelo D, Mauro CJ, et al. Amplitude of low-frequency oscillations in schizophrenia: a resting state fMRI study. Schizophr Res. 2010;117:13–20.

    PubMed  Google Scholar 

  107. Guo W, Liu F, Chen J, Wu R, Li L, Zhang Z, et al. Hyperactivity of the default-mode network in first-episode, drug-naive schizophrenia at rest revealed by family-based case-control and traditional case-control designs. Medicine (Baltimore). 2017;96:e6223.

    Google Scholar 

  108. Davis KL, Kahn RS, Ko G, Davidson M. Dopamine in schizophrenia: a review and reconceptualization. Am J Psychiatry. 1991;148:1474–86.

    CAS  PubMed  Google Scholar 

  109. Martino M, Magioncalda P, Yu H, Li X, Wang Q, Meng Y, et al. Abnormal resting-state connectivity in a substantia nigra-related striato-thalamo-cortical network in a large sample of first-episode drug-naive patients wwith schizophrenia. Schizophr Bull. 2017;44:419–31.

    PubMed Central  Google Scholar 

  110. Nikolaus S, Antke C, Muller HW. In vivo imaging of synaptic function in the central nervous system: II. Mental and affective disorders. Behav Brain Res. 2009;204:32–66.

    PubMed  Google Scholar 

  111. Ashok AH, Marques TR, Jauhar S, Nour MM, Goodwin GM, Young AH, et al. The dopamine hypothesis of bipolar affective disorder: the state of the art and implications for treatment. Mol Psychiatry. 2017;22:666–79.

    CAS  PubMed  PubMed Central  Google Scholar 

  112. Kambeitz J, Abi-Dargham A, Kapur S, Howes OD. Alterations in cortical and extrastriatal subcortical dopamine function in schizophrenia: systematic review and meta-analysis of imaging studies. Br J Psychiatry. 2014;204:420–9.

    PubMed  Google Scholar 

  113. Sarter M, Bruno JP. Cortical acetylcholine, reality distortion, schizophrenia, and Lewy Body Dementia: too much or too little cortical acetylcholine? Brain Cogn. 1998;38:297–316.

    CAS  PubMed  Google Scholar 

  114. Schmauss C, Emrich HM. Dopamine and the action of opiates: a reevaluation of the dopamine hypothesis of schizophrenia. With special consideration of the role of endogenous opioids in the pathogenesis of schizophrenia. Biol Psychiatry. 1985;20:1211–31.

    CAS  PubMed  Google Scholar 

  115. Northoff G. Spatiotemporal psychopathology I: no rest for the brain’s resting state activity in depression? Spatiotemporal psychopathology of depressive symptoms. J Affect Disord. 2016;190:854–66.

    PubMed  Google Scholar 

  116. Northoff G. Spatiotemporal psychopathology II: how does a psychopathology of the brain’s resting state look like? Spatiotemporal approach and the history of psychopathology. J Affect Disord. 2016;190:867–79.

    PubMed  Google Scholar 

  117. Northoff G. The brain’s spontaneous activity and its psychopathological symptoms - “Spatiotemporal binding and integration”. Prog Neuropsychopharmacol Biol Psychiatry. 2018;80(Pt B):81–90.

    PubMed  Google Scholar 

Download references

Author information

Author notes

  1. These authors contributed equally: Benedetta Conio, Matteo Martino, Paola Magioncalda

Authors and Affiliations

  1. Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Psychiatry, University of Genoa, Genoa, Italy

    Benedetta Conio, Paola Magioncalda, Andrea Escelsior & Mario Amore

  2. IRCCS Ospedale Policlinico San Martino, Genoa, Italy

    Benedetta Conio, Paola Magioncalda, Andrea Escelsior, Matilde Inglese & Mario Amore

  3. Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Matteo Martino

  4. Brain and Consciousness Research Center, Taipei Medical University - Shuang Ho Hospital, New Taipei City, Taiwan

    Paola Magioncalda

  5. Graduate Institute of Mind Brain and Consciousness, Taipei Medical University, Taipei, Taiwan

    Paola Magioncalda

  6. Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Neurology, University of Genoa, Genoa, Italy

    Matilde Inglese

  7. Department of Neurology, Radiology and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Matilde Inglese

  8. University of Ottawa Brain and Mind Research Institute, and Mind Brain Imaging and Neuroethics Royal’s Institute of Mental Health Research, University of Ottawa, Ottawa, ON, Canada

    Georg Northoff

  9. Centre for Cognition and Brain Disorders, Hangzhou Normal University, Hangzhou, China

    Georg Northoff

  10. Mental Health Centre, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China

    Georg Northoff

Authors
  1. Benedetta Conio
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Matteo Martino
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paola Magioncalda
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Andrea Escelsior
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Matilde Inglese
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mario Amore
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Georg Northoff
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Matteo Martino, Paola Magioncalda or Georg Northoff.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Conio, B., Martino, M., Magioncalda, P. et al. Opposite effects of dopamine and serotonin on resting-state networks: review and implications for psychiatric disorders. Mol Psychiatry 25, 82–93 (2020). https://doi.org/10.1038/s41380-019-0406-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41380-019-0406-4

This article is cited by

Search

Advanced search

Quick links