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Prefrontal cortex and the dysconnectivity hypothesis of schizophrenia

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Abstract

Schizophrenia is hypothesized to arise from disrupted brain connectivity. This “dysconnectivity hypothesis” has generated interest in discovering whether there is anatomical and functional dysconnectivity between the prefrontal cortex (PFC) and other brain regions, and how this dysconnectivity is linked to the impaired cognitive functions and aberrant behaviors of schizophrenia. Critical advances in neuroimaging technologies, including diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI), make it possible to explore these issues. DTI affords the possibility to explore anatomical connectivity in the human brain in vivo and fMRI can be used to make inferences about functional connections between brain regions. In this review, we present major advances in the understanding of PFC anatomical and functional dysconnectivity and their implications in schizophrenia. We then briefly discuss future prospects that need to be explored in order to move beyond simple mapping of connectivity changes to elucidate the neuronal mechanisms underlying schizophrenia.

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References

  1. Stephan KE, Baldeweg T, Friston KJ. Synaptic plasticity and dysconnection in schizophrenia. Biol Psychiatry 2006, 59: 929–939.

    CAS  PubMed  Google Scholar 

  2. Pettersson-Yeo W, Allen P, Benetti S, McGuire P, Mechelli A. Dysconnectivity in schizophrenia: where are we now? Neurosci Biobehav Rev 2011, 35: 1110–1124.

    PubMed  Google Scholar 

  3. Friston KJ, Frith CD. Schizophrenia: a disconnection syndrome? Clin Neurosci 1995, 3: 89–97.

    CAS  PubMed  Google Scholar 

  4. Friston KJ. The disconnection hypothesis. Schizophr Res 1998, 30: 115–125.

    CAS  PubMed  Google Scholar 

  5. Andreasen NC, Paradiso S, O’Leary DS. “Cognitive dysmetria” as an integrative theory of schizophrenia: a dysfunction in cortical-subcortical-cerebellar circuitry? Schizophr Bull 1998, 24: 203–218.

    CAS  PubMed  Google Scholar 

  6. Liang M, Zhou Y, Jiang T, Liu Z, Tian L, Liu H, et al. Widespread functional disconnectivity in schizophrenia with resting-state functional magnetic resonance imaging. Neuroreport 2006, 17: 209–213.

    PubMed  Google Scholar 

  7. Liu Y, Liang M, Zhou Y, He Y, Hao Y, Song M, et al. Disrupted small-world networks in schizophrenia. Brain 2008, 131: 945–961.

    PubMed  Google Scholar 

  8. Wang Q, Su TP, Zhou Y, Chou KH, Chen I, Jiang T, et al. Anatomical insights into disrupted small-world networks in schizophrenia. NeuroImage 2012, 59: 1085–1093.

    PubMed  Google Scholar 

  9. Fallon JH, Opole IO, Potkin SG. The neuroanatomy of schizophrenia: circuitry and neurotransmitter systems. Clin Neurosci Res 2003, 3: 77–107.

    CAS  Google Scholar 

  10. Zhou Y, Liang M, Jiang T, Tian L, Liu Y, Liu Z, et al. Functional dysconnectivity of the dorsolateral prefrontal cortex in first-episode schizophrenia using resting-state fMRI. Neurosci Lett 2007, 417: 297–302.

    CAS  PubMed  Google Scholar 

  11. van den Heuvel MP, Fornito A. Brain networks in schizophrenia. Neuropsychol Rev 2014, 24: 32–48.

    PubMed  Google Scholar 

  12. Szczepanski SM, Knight RT. Insights into human behavior from lesions to the prefrontal cortex. Neuron 2014, 83: 1002–1018.

    CAS  PubMed  Google Scholar 

  13. Brodmann K. Vergleichende lokalisationslehre der grosshirnrinde: in ihren principien dargestellt auf grund des zellenbaues. Leipzig, Germany: Johann Ambrosius Barth Verlag, 1909.

    Google Scholar 

  14. Ongur D, Ferry AT, Price JL. Architectonic subdivision of the human orbital and medial prefrontal cortex. J Comp Neurol 2003, 460: 425–449.

    PubMed  Google Scholar 

  15. Arnsten AF. The neurobiology of thought: the groundbreaking discoveries of Patricia Goldman-Rakic 1937–2003. Cereb Cortex 2013, 23: 2269–2281.

    PubMed Central  PubMed  Google Scholar 

  16. Konrad A, Winterer G. Disturbed structural connectivity in schizophrenia primary factor in pathology or epiphenomenon? Schizophr Bull 2008, 34: 72–92.

    PubMed Central  PubMed  Google Scholar 

  17. Zuo N, Cheng J, Jiang T. Diffusion magnetic resonance imaging for Brainnetome: a critical review. Neurosci Bull 2012, 28: 375–388.

    PubMed  Google Scholar 

  18. Peters BD, Blaas J, de Haan L. Diffusion tensor imaging in the early phase of schizophrenia: what have we learned? J Psychiatr Res 2010, 44: 993–1004.

    PubMed  Google Scholar 

  19. Buchsbaum M S, Tang CY, Peled S, Gudbjartsson H, Lu D, Hazlett EA, et al. MRI white matter diffusion anisotropy and PET metabolic rate in schizophrenia. Neuroreport 1998, 9: 425–430.

    CAS  PubMed  Google Scholar 

  20. Shenton ME, Whitford TJ, Kubicki M. Structural neuroimaging in schizophrenia: from methods to insights to treatments. Dialogues Clin Neurosci 2010, 12: 317–332.

    PubMed Central  PubMed  Google Scholar 

  21. Ellison-Wright I, Bullmore E. Meta-analysis of diffusion tensor imaging studies in schizophrenia. Schizophr Res 2009, 108: 3–10.

    PubMed  Google Scholar 

  22. Yao L, Lui S, Liao Y, Du MY, Hu N, Thomas JA, et al. White matter deficits in first episode schizophrenia: an activation likelihood estimation meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry 2013, 45: 100–106.

    PubMed  Google Scholar 

  23. Kubicki M, Westin CF, Nestor PG, Wible CG, Frumin M, Maier SE, et al. Cingulate fasciculus integrity disruption in schizophrenia: a magnetic resonance diffusion tensor imaging study. Biol Psychiatry 2003, 54: 1171–1180.

    PubMed Central  PubMed  Google Scholar 

  24. Fujiwara H, Namiki C, Hirao K, Miyata J, Shimizu M, Fukuyama H, et al. Anterior and posterior cingulum abnormalities and their association with psychopathology in schizophrenia: a diffusion tensor imaging study. Schizophr Res 2007, 95: 215–222.

    PubMed  Google Scholar 

  25. Abdul-Rahman MF, Qiu A, Sim K. Regionally specific white matter disruptions of fornix and cingulum in schizophrenia. PLoS One 2011, 6: e18652.

    PubMed Central  CAS  PubMed  Google Scholar 

  26. Qiu A, Tuan TA, Woon PS, Abdul-Rahman MF, Graham S, Sim K. Hippocampal-cortical structural connectivity disruptions in schizophrenia: an integrated perspective from hippocampal shape, cortical thickness, and integrity of white matter bundles. Neuroimage 2010, 52: 1181–1189.

    PubMed  Google Scholar 

  27. Voineskos AN, Lobaugh NJ, Bouix S, Rajji TK, Miranda D, Kennedy JL, et al. Diffusion tensor tractography findings in schizophrenia across the adult lifespan. Brain 2010, 133: 1494–1504.

    PubMed Central  PubMed  Google Scholar 

  28. Segal D, Haznedar MM, Hazlett EA, Entis JJ, Newmark RE, Torosjan Y, et al. Diffusion tensor anisotropy in the cingulate gyrus in schizophrenia. Neuroimage 2010, 50: 357–365.

    PubMed  Google Scholar 

  29. Wang F, Jiang T, Sun Z, Teng SL, Luo X, Zhu Z, et al. Neuregulin 1 genetic variation and anterior cingulum integrity in patients with schizophrenia and healthy controls. J Psychiatry Neurosci 2009, 34: 181–186.

    PubMed Central  PubMed  Google Scholar 

  30. Nestor PG, Kubicki M, Nakamura M, Niznikiewicz M, McCarley RW, Shenton ME. Comparing prefrontal gray and white matter contributions to intelligence and decision making in schizophrenia and healthy controls. Neuropsychology 2010, 24: 121–129.

    PubMed Central  PubMed  Google Scholar 

  31. Takei K, Yamasue H, Abe O, Yamada H, Inoue H, Suga M, et al. Structural disruption of the dorsal cingulum bundle is associated with impaired Stroop performance in patients with schizophrenia. Schizophr Res 2009, 114: 119–127.

    PubMed  Google Scholar 

  32. Manoach DS, Ketwaroo GA, Polli FE, Thakkar KN, Barton JJ, Goff DC, et al. Reduced microstructural integrity of the white matter underlying anterior cingulate cortex is associated with increased saccadic latency in schizophrenia. Neuroimage 2007, 37: 599–610.

    PubMed  Google Scholar 

  33. Roalf DR, Ruparel K, Verma R, Elliott MA, Gur RE, Gur RC. White matter organization and neurocognitive performance variability in schizophrenia. Schizophr Res 2013, 143: 172–178.

    PubMed Central  PubMed  Google Scholar 

  34. Von Der Heide RJ, Skipper LM, Klobusicky E, Olson IR. Dissecting the uncinate fasciculus: disorders, controversies and a hypothesis. Brain 2013, 136: 1692–1707.

    Google Scholar 

  35. Kitis O, Ozalay O, Zengin EB, Haznedaroglu D, Eker MC, Yalvac D, et al. Reduced left uncinate fasciculus fractional anisotropy in deficit schizophrenia but not in non-deficit schizophrenia. Psychiatry Clin Neurosci 2012, 66: 34–43.

    PubMed  Google Scholar 

  36. Voineskos AN, Foussias G, Lerch J, Felsky D, Remington G, Rajji TK, et al. Neuroimaging evidence for the deficit subtype of schizophrenia. JAMA Psychiatry 2013, 70: 472–480.

    PubMed  Google Scholar 

  37. Kubicki M, Westin CF, McCarley RW, Shenton ME. The application of DTI to investigate white matter abnormalities in schizophrenia. Ann N Y Acad Sci 2005, 1064: 134–148.

    PubMed Central  PubMed  Google Scholar 

  38. Melonakos ED, Shenton ME, Rathi Y, Terry DP, Bouix S, Kubicki M. Voxel-based morphometry (VBM) studies in schizophrenia-can white matter changes be reliably detected with VBM? Psychiatry Res 2011, 193: 65–70.

    PubMed Central  PubMed  Google Scholar 

  39. de Weijer AD, Neggers SF, Diederen KM, Mandl RC, Kahn RS, Hulshoff Pol HE, et al. Aberrations in the arcuate fasciculus are associated with auditory verbal hallucinations in psychotic and in non-psychotic individuals. Hum Brain Mapp 2013, 34: 626–634.

    PubMed  Google Scholar 

  40. Catani M, Craig MC, Forkel SJ, Kanaan R, Picchioni M, Toulopoulou T, et al. Altered integrity of perisylvian language pathways in schizophrenia: relationship to auditory hallucinations. Biol Psychiatry 2011, 70: 1143–1150.

    PubMed  Google Scholar 

  41. Hubl D, Koenig T, Strik W, Federspiel A, Kreis R, Boesch C, et al. Pathways that make voices: white matter changes in auditory hallucinations. Arch Gen Psychiatry 2004, 61: 658–668.

    PubMed  Google Scholar 

  42. Kubicki M, Shenton ME, Maciejewski PK, Pelavin PE, Hawley KJ, Ballinger T, et al. Decreased axial diffusivity within language connections: a possible biomarker of schizophrenia risk. Schizophr Res 2013, 148: 67–73.

    PubMed Central  CAS  PubMed  Google Scholar 

  43. Boos HB, Mandl RC, van Haren NE, Cahn W, van Baal GC, Kahn RS, et al. Tract-based diffusion tensor imaging in patients with schizophrenia and their non-psychotic siblings. Eur Neuropsychopharmacol 2013, 23: 295–304.

    CAS  PubMed  Google Scholar 

  44. Zhou Y, Shu N, Liu Y, Song M, Hao Y, Liu H, et al. Altered resting-state functional connectivity and anatomical connectivity of hippocampus in schizophrenia. Schizophr Res 2008, 100: 120–132.

    PubMed  Google Scholar 

  45. Liu X, Lai Y, Wang X, Hao C, Chen L, Zhou Z, et al. A combined DTI and structural MRI study in medicated-naive chronic schizophrenia. Magn Reson Imaging 2014, 32: 1–8.

    CAS  PubMed  Google Scholar 

  46. Liu X, Lai Y, Wang X, Hao C, Chen L, Zhou Z, et al. Reduced white matter integrity and cognitive deficit in never-medicated chronic schizophrenia: a diffusion tensor study using TBSS. Behav Brain Res 2013, 252: 157–163.

    PubMed  Google Scholar 

  47. Epstein KA, Cullen KR, Mueller BA, Robinson P, Lee S, Kumra S. White matter abnormalities and cognitive impairment in early-onset schizophrenia-spectrum disorders. J Am Acad Child Adolesc Psychiatry 2014, 53: 362–372 e362.

    PubMed Central  PubMed  Google Scholar 

  48. Fujino J, Takahashi H, Miyata J, Sugihara G, Kubota M, Sasamoto A, et al. Impaired empathic abilities and reduced white matter integrity in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2014, 48: 117–123.

    PubMed  Google Scholar 

  49. Levitt JJ, Alvarado JL, Nestor PG, Rosow L, Pelavin PE, McCarley RW, et al. Fractional anisotropy and radial diffusivity: diffusion measures of white matter abnormalities in the anterior limb of the internal capsule in schizophrenia. Schizophr Res 2012, 136: 55–62.

    PubMed  Google Scholar 

  50. Mamah D, Conturo TE, Harms MP, Akbudak E, Wang L, McMichael AR, et al. Anterior thalamic radiation integrity in schizophrenia: a diffusion-tensor imaging study. Psychiatry Res 2010, 183: 144–150.

    PubMed  Google Scholar 

  51. Penades R, Pujol N, Catalan R, Massana G, Rametti G, Garcia-Rizo C, et al. Brain effects of cognitive remediation therapy in schizophrenia: a structural and functional neuroimaging study. Biol Psychiatry 2013, 73: 1015–1023.

    PubMed  Google Scholar 

  52. Shergill SS, Kanaan RA, Chitnis XA, O’Daly O, Jones DK, Frangou S, et al. A diffusion tensor imaging study of fasciculi in schizophrenia. Am J Psychiatry 2007, 164: 467–473.

    PubMed  Google Scholar 

  53. Kubicki M, McCarley R, Westin CF, Park HJ, Maier S, Kikinis R, et al. A review of diffusion tensor imaging studies in schizophrenia. J Psychiatr Res 2007, 41: 15–30.

    PubMed Central  PubMed  Google Scholar 

  54. Song M, Jiang T. A review of functional magne tic resonance imaging for Brainnetome. Neurosci Bull 2012, 28: 389–398.

    CAS  PubMed  Google Scholar 

  55. Cox SR, Ferguson KJ, Royle NA, Shenkin SD, Mac Pherson SE, MacLullich AM, et al. A systematic review of brain frontal lobe parcellation techniques in magnetic resonance imaging. Brain Struct Funct 2014, 219: 1–22.

    PubMed  Google Scholar 

  56. Howes OD, Kapur S. The dopamine hypothesis of s chizophrenia: version III—the final common pathway. Schizophr Bull 2009, 35: 549–562.

    PubMed Central  PubMed  Google Scholar 

  57. Salvador R, Martinez A, Pomarol-Clotet E, Sarro S, Suckling J, Bullmore E. Frequency based mutual information measures between clusters of brain regions in functional magnetic resonance imaging. Neuroimage 2007, 35: 83–88.

    CAS  PubMed  Google Scholar 

  58. Yoon JH, Minzenberg MJ, Raouf S, D’Esposito M, Carter CS. Impaired prefrontal-basal ganglia functional connectivity and substantia nigra hyperactivity in schizophrenia. Biol Psychiatry 2013, 74: 122–129.

    PubMed Central  PubMed  Google Scholar 

  59. Quide Y, Morris RW, Shepherd AM, Rowland JE, Green MJ. Task-related fronto-striatal functional connectivity during working memory performance in schizophrenia. Schizophr Res 2013, 150: 468–475.

    PubMed  Google Scholar 

  60. Lawrie SM, Buechel C, Whalley HC, Frith CD, Friston KJ, Johnstone EC. Reduced frontotemporal functional connectivity in schizophrenia associated with auditory hallucinations. Biol Psychiatry 2002, 51: 1008–1011.

    PubMed  Google Scholar 

  61. Hoffman RE, Hampson M. Functional connectivity studies of patients with auditory verbal hallucinations. Front Hum Neurosci 2011, 6: 6.

    PubMed  Google Scholar 

  62. Raij TT, Valkonen-Korhonen M, Holi M, Therman S, Lehtonen J, Hari R. Reality of auditory verbal hallucinations. Brain 2009, 132: 2994–3001.

    PubMed Central  PubMed  Google Scholar 

  63. 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 U S A 2007, 104: 11073–11078.

    PubMed Central  CAS  PubMed  Google Scholar 

  64. Dosenbach NU, Fair DA, Cohen AL, Schlaggar BL, Petersen SE. A dual-networks architecture of top-down control. Trends Cogn Sci 2008, 12: 99–105.

    PubMed Central  PubMed  Google Scholar 

  65. Jiang T, Zhou Y. Brainnetome of schizophrenia: focus on impaired cognitive function. Shanghai Archives of Psychiatry 2012, 24: 3–10.

    PubMed Central  CAS  PubMed  Google Scholar 

  66. MacDonald AW, 3rd, Carter CS, Kerns JG, Ursu S, Barch DM, Holmes AJ, et al. Specificity of prefrontal dysfunction and context processing deficits to schizophrenia in nevermedicated patients with first-episode psychosis. Am J Psychiatry 2005, 162: 475–484.

    PubMed  Google Scholar 

  67. Rotarska-Jagiela A, van de Ven V, Oertel-Knochel V, Uhlhaas PJ, Vogeley K, Linden DE. Resting-state functional network correlates of psychotic symptoms in schizophrenia. Schizophr Res 2010, 117: 21–30.

    PubMed  Google Scholar 

  68. Weinberger DR, Berman KF, Suddath R, Torrey EF. Evidence of dysfunction of a prefrontal-limbic network in schizophrenia: a magnetic resonance imaging and regional cerebral blood flow study of discordant monozygotic twins. Am J Psychiatry 1992, 149: 890–897.

    CAS  PubMed  Google Scholar 

  69. Meyer-Lindenberg AS, Olsen RK, Kohn PD, Brown T, Egan MF, Weinberger DR, et al. Regionally specific disturbance of dorsolateral prefrontal-hippocampal functional connectivity in schizophrenia. Arch Gen Psychiatry 2005, 62: 379–386.

    PubMed  Google Scholar 

  70. Benetti S, Mechelli A, Picchioni M, Broome M, Williams S, Mc Guire P. Functional integration between the posterior hippocampus and prefrontal cortex is impaired in both first episode schizophrenia and the at risk mental state. Brain 2009, 132: 2426–2436.

    PubMed  Google Scholar 

  71. Gusnard DA, Akbudak E, Shulman GL, Raichle ME. Medial prefrontal cortex and self-referential mental activity: relation to a default mode of brain function. Proc Natl Acad Sci U S A 2001, 98: 4259–4264.

    PubMed Central  CAS  PubMed  Google Scholar 

  72. Whitfield-Gabrieli S, Thermenos HW, Milanovic S, Tsuang MT, Faraone SV, McCarley RW, et al. Hyperactivity and hyperconnectivity of the default network in schizophrenia and in first-degree relatives of persons with schizophrenia. Proc Natl Acad Sci U S A 2009, 106: 1279–1284.

    PubMed Central  CAS  PubMed  Google Scholar 

  73. Wang L, Metzak PD, Woodward TS. Aberrant connectivity during se lf-other source monitoring in schizophrenia. Schizophr Res 2011, 125: 136–142.

    PubMed  Google Scholar 

  74. Eack SM, Wojtalik JA, Newhill CE, Keshavan MS, Phillips ML. Prefrontal cortical dysfunction during visual perspective-taking in schizophrenia. Schizophr Res 2013, 150: 491–497.

    PubMed  Google Scholar 

  75. Fan FM, Tan SP, Yang FD, Tan YL, Zhao YL, Chen N, et al. Ventral medial prefrontal functional connectivity and emotion regulation in chronic schizophrenia: a pilot study. Neurosci Bull 2013, 29: 59–74.

    PubMed  Google Scholar 

  76. Amunts K, Lenzen M, Friederici AD, Schleicher A, Morosan P, Palomero-Gallagher N, et al. Broca’s region: novel organizational principles and multiple receptor mapping. PLoS Biol 2010, 8.

  77. Clos M, Amunts K, Laird AR, Fox PT, Eickhoff SB. Tackling the multifunctional nature of Broca’s region meta-analytically: co-activation-based parcellation of area 44. Neuroimage 2013, 83: 174–188.

    PubMed  Google Scholar 

  78. Liu H, Qin W, Li W, Fan L, Wang J, Jiang T, et al. Connectivity-based parcellation of the human frontal pole with diffusion tensor imaging. J Neurosci 2013, 33: 6782–6790.

    CAS  PubMed  Google Scholar 

  79. Sallet J, Mars RB, Noonan MP, Neubert FX, Jbabdi S, O’Reilly JX, et al. The organization of dorsal frontal cortex in humans and macaques. J Neurosci 2013, 33: 12255–12274.

    PubMed Central  CAS  PubMed  Google Scholar 

  80. Neubert FX, Mars RB, Thomas AG, Sallet J, Rushworth MF. Comparison of human ventral frontal cortex areas for cognitive control and language with areas in monkey frontal cortex. Neuron 2014, 81: 700–713.

    CAS  PubMed  Google Scholar 

  81. Kahnt T, Chang LJ, Park SQ, Heinzle J, Haynes JD. Connectivity-based parcellation of the human orbitofrontal cortex. J Neurosci 2012, 32: 6240–6250.

    CAS  PubMed  Google Scholar 

  82. Moayedi M, Salomons TV, Dunlop KA, Downar J, Davis KD. Connectivity-bas ed parcellation of the human frontal polar cortex. Brain Struct Funct 2014. doi: 10.1007/s00429-014-0809-6.

    Google Scholar 

  83. Jiang T. Brainnetome: A new -ome to understand the brain and its disorders. Neuroimage 2013, 80: 263–272.

    PubMed  Google Scholar 

  84. Fan L, Wang J, Zhang Y, Han W, Yu C, Jiang T. Connectivity-based parcellation of the human temporal pole using diffusion tensor imaging. Cereb Cortex 2014, 24: 3365–3378.

    PubMed  Google Scholar 

  85. Wang J, Fan L, Zhang Y, Liu Y, Jiang D, Zhang Y, et al. Tractography-based parcellation of the human left inferior parietal lobule. Neuroimage 2012, 63: 641–652.

    PubMed  Google Scholar 

  86. Wang J, Yang Y, Fan L, Xu J, Li C, Liu Y, et al. Convergent functional architecture of the superior parietal lobule unraveled with multimodal neuroimaging approaches. Hum Brain Mapp 2015, 36: 238–257

    PubMed  Google Scholar 

  87. Zhang Y, Fan L, Zhang Y, Wang J, Zhu M, Zhang Y, et al. Connectivity-based parcellation of the human posteromedial cortex. Cereb Cortex 2014, 24: 719–727.

    PubMed  Google Scholar 

  88. Goulas A, Uylings HB, Stiers P. Unravelling the intrinsic functional organization of the human lateral frontal cortex: a parcellation scheme based on resting state fMRI. J Neurosci 2012, 32: 10238–10252.

    CAS  PubMed  Google Scholar 

  89. van den Heuvel MP, Sporns O. An anatomical substrate for integration among functional networks in human cortex. J Neurosci 2013, 33: 14489–14500.

    PubMed  Google Scholar 

  90. Honey CJ, Sporns O, Cammoun L, Gigandet X, Thiran JP, Meuli R, et al. Predicti ng human resting-state functional connectivity from structural connectivity. Proc Natl Acad Sci U S A 2009, 106: 2035–2040.

    PubMed Central  CAS  PubMed  Google Scholar 

  91. Greicius MD, Supekar K, Menon V, Dougherty RF. Restingstate functional connectivity reflects structural connectivity in the default mode network. Cereb Cortex 2009, 19: 72–78..

    PubMed Central  PubMed  Google Scholar 

  92. van den Heuvel MP, Fornito A. Brain networks in schizophrenia. Neuropsychol Rev 2014, 24: 32–48.

    PubMed  Google Scholar 

  93. Fitzsimmons J, Kubicki M, Shenton ME. Review of functional and anatomical brain connectivity findings in schizophrenia. Curr Opin Psychiatry 2013, 26: 172–187.

    PubMed  Google Scholar 

  94. Zhou Y, Wang K, Liu Y, Song M, Song SW, Jiang T. Spontaneous brain activity observed with functional magnetic resonance imaging as a potential biomarker in neuropsychiatric disorders. Cognitive Neurodynamics 2010, 4: 275–294.

    PubMed Central  PubMed  Google Scholar 

  95. van den Heuvel MP, Sporns O, Collin G, Scheewe T, Mandl RC, Cahn W, et al. Abnormal rich club organization and functional brain dynamics in schizophrenia. JAMA Psychiatry 2013, 70: 783–792.

    PubMed  Google Scholar 

  96. Tan HY, Callicott JH, Weinberger DR. Prefrontal cognitive systems in schizophrenia: towards human genetic brain mechanisms. Cogn Neuropsychiatry 2009, 14: 277–298.

    PubMed  Google Scholar 

  97. Karlsgodt KH, Bachman P, Winkler AM, Bearden CE, Glahn DC. Genetic influence on the working memory circuitry: behavior, structure, function and extensions to illness. Behav Brain Res 2011, 225: 610–622.

    PubMed Central  PubMed  Google Scholar 

  98. Glahn DC, Winkler AM, Kochunov P, Almasy L, Duggirala R, Carless MA, et al. Genetic control over the resting brain. Proc Natl Acad Sci U S A 2010, 107: 1223–1228.

    PubMed Central  CAS  PubMed  Google Scholar 

  99. Gottesman II, Gould TD. The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry 2003, 160: 636–645.

    PubMed  Google Scholar 

  100. Liu B, Song M, Li J, Liu Y, Li K, Yu C, et al. Prefrontal-related functional connectivi ties within the default network are modulated by COMT val158met in healthy young adults. J Neurosci 2010, 30: 64–69.

    PubMed  Google Scholar 

  101. Liu B, Fan L, Cui Y, Zhang X, Hou B, Li Y, et al. DISC1 Ser704Cys impacts thalamic-prefrontal connectivity. Brain Struct Funct 2015, 220: 91–100.

    PubMed Central  PubMed  Google Scholar 

  102. Buckner RL, Krienen FM, Yeo BT. Opportunities and limitations of intrinsic functional connectivity MRI. Nat Neurosci 2013, 16: 832–837.

    PubMed  Google Scholar 

  103. Sigurdsson T, Stark KL, Karayiorgou M, Gogos JA, Gordon JA. Impaired hippocampal-prefront al synchrony in a genetic mouse model of schizophrenia. Nature 2010, 464: 763–767.

    PubMed Central  CAS  PubMed  Google Scholar 

  104. Shen B, Zhang J, Wu H, Wang J, Ma K, Li Z, et al. Generation of gene-modified mice via Cas 9/RNA-mediated gene targeting. Cell Res 2013, 23: 720–723.

    PubMed Central  CAS  PubMed  Google Scholar 

  105. Wang H, Yang H, Shivalila CS, Dawlaty MM, Cheng AW, Zhang F, et al. One-step generation of mice carrying mutations in multiple genes by CRISPR/Cas-mediated genome engineering. Cell 2013, 153: 910–918.

    PubMed Central  CAS  PubMed  Google Scholar 

  106. McClintock SM, Freitas C, Oberman L, Lisanby SH, Pascual-Leone A. Transcranial magnetic stimulation: a neuroscientific probe of cortical function in schizophrenia. Biol Psychiatry 2011, 70: 19–27.

    PubMed Central  PubMed  Google Scholar 

  107. Sandrini M, Umilta C, Rusconi E. The use of transcranial magnetic stimulation in cognitive neuroscience: a new synthesis of methodological issues. Neurosci Biobehav Rev 2011, 35: 516–536.

    PubMed  Google Scholar 

  108. Reithler J, Peters JC, Sack AT. Multimodal transcranial magnetic stimulation: using concurrent neuroimaging to reveal the neural network dynamics of noninvasive brain stimulation. Prog Neurobiol 2011, 94: 149–165.

    CAS  PubMed  Google Scholar 

  109. Friston KJ, Harrison L, Penny W. Dynamic causal modelling. Neuroimage 2003, 19: 1273–1302.

    CAS  PubMed  Google Scholar 

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Zhou, Y., Fan, L., Qiu, C. et al. Prefrontal cortex and the dysconnectivity hypothesis of schizophrenia. Neurosci. Bull. 31, 207–219 (2015). https://doi.org/10.1007/s12264-014-1502-8

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