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.
Keywords: prefrontal cortex, schizophrenia, anatomical connectivity, functional connectivity
References
- [1].Stephan KE, Baldeweg T, Friston KJ. Synaptic plasticity and dysconnection in schizophrenia. Biol Psychiatry. 2006;59:929–939. doi: 10.1016/j.biopsych.2005.10.005. [DOI] [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. doi: 10.1016/j.neubiorev.2010.11.004. [DOI] [PubMed] [Google Scholar]
- [3].Friston KJ, Frith CD. Schizophrenia: a disconnection syndrome? Clin Neurosci. 1995;3:89–97. [PubMed] [Google Scholar]
- [4].Friston KJ. The disconnection hypothesis. Schizophr Res. 1998;30:115–125. doi: 10.1016/s0920-9964(97)00140-0. [DOI] [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. doi: 10.1093/oxfordjournals.schbul.a033321. [DOI] [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. doi: 10.1097/01.wnr.0000198434.06518.b8. [DOI] [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. doi: 10.1093/brain/awn018. [DOI] [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. doi: 10.1016/j.neuroimage.2011.09.035. [DOI] [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. [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. doi: 10.1016/j.neulet.2007.02.081. [DOI] [PubMed] [Google Scholar]
- [11].van den Heuvel MP, Fornito A. Brain networks in schizophrenia. Neuropsychol Rev. 2014;24:32–48. doi: 10.1007/s11065-014-9248-7. [DOI] [PubMed] [Google Scholar]
- [12].Szczepanski SM, Knight RT. Insights into human behavior from lesions to the prefrontal cortex. Neuron. 2014;83:1002–1018. doi: 10.1016/j.neuron.2014.08.011. [DOI] [PMC free article] [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. doi: 10.1002/cne.10609. [DOI] [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. doi: 10.1093/cercor/bht195. [DOI] [PMC free article] [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. doi: 10.1093/schbul/sbm034. [DOI] [PMC free article] [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. doi: 10.1007/s12264-012-1245-3. [DOI] [PMC free article] [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. doi: 10.1016/j.jpsychires.2010.05.003. [DOI] [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. doi: 10.1097/00001756-199802160-00013. [DOI] [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. doi: 10.31887/DCNS.2010.12.3/mshenton. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [21].Ellison-Wright I, Bullmore E. Meta-analysis of diffusion tensor imaging studies in schizophrenia. Schizophr Res. 2009;108:3–10. doi: 10.1016/j.schres.2008.11.021. [DOI] [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. doi: 10.1016/j.pnpbp.2013.04.019. [DOI] [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. doi: 10.1016/s0006-3223(03)00419-0. [DOI] [PMC free article] [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. doi: 10.1016/j.schres.2007.05.044. [DOI] [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. doi: 10.1371/journal.pone.0018652. [DOI] [PMC free article] [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. doi: 10.1016/j.neuroimage.2010.05.046. [DOI] [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. doi: 10.1093/brain/awq040. [DOI] [PMC free article] [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. doi: 10.1016/j.neuroimage.2009.12.071. [DOI] [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. [PMC free article] [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. doi: 10.1037/a0016981. [DOI] [PMC free article] [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. doi: 10.1016/j.schres.2009.05.012. [DOI] [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. doi: 10.1016/j.neuroimage.2007.04.062. [DOI] [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. doi: 10.1016/j.schres.2012.10.014. [DOI] [PMC free article] [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. doi: 10.1093/brain/awt094. [DOI] [PMC free article] [PubMed] [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. doi: 10.1111/j.1440-1819.2011.02293.x. [DOI] [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. doi: 10.1001/jamapsychiatry.2013.786. [DOI] [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. doi: 10.1196/annals.1340.024. [DOI] [PMC free article] [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. doi: 10.1016/j.pscychresns.2011.01.009. [DOI] [PMC free article] [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. doi: 10.1002/hbm.21463. [DOI] [PMC free article] [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. doi: 10.1016/j.biopsych.2011.06.013. [DOI] [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. doi: 10.1001/archpsyc.61.7.658. [DOI] [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. doi: 10.1016/j.schres.2013.06.014. [DOI] [PMC free article] [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. doi: 10.1016/j.euroneuro.2012.05.015. [DOI] [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. doi: 10.1016/j.schres.2007.11.039. [DOI] [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. doi: 10.1016/j.mri.2013.08.004. [DOI] [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. doi: 10.1016/j.bbr.2013.05.061. [DOI] [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. doi: 10.1016/j.jaac.2013.12.007. [DOI] [PMC free article] [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. doi: 10.1016/j.pnpbp.2013.09.018. [DOI] [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. doi: 10.1016/j.schres.2011.09.009. [DOI] [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. doi: 10.1016/j.pscychresns.2010.04.013. [DOI] [PMC free article] [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. doi: 10.1016/j.biopsych.2013.01.017. [DOI] [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. doi: 10.1176/ajp.2007.164.3.467. [DOI] [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. doi: 10.1016/j.jpsychires.2005.05.005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [54].Song M, Jiang T. A review of functional magne tic resonance imaging for Brainnetome. Neurosci Bull. 2012;28:389–398. doi: 10.1007/s12264-012-1244-4. [DOI] [PMC free article] [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. doi: 10.1007/s00429-013-0527-5. [DOI] [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. doi: 10.1093/schbul/sbp006. [DOI] [PMC free article] [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. doi: 10.1016/j.neuroimage.2006.12.001. [DOI] [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. doi: 10.1016/j.biopsych.2012.11.018. [DOI] [PMC free article] [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. doi: 10.1016/j.schres.2013.08.009. [DOI] [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. doi: 10.1016/s0006-3223(02)01316-1. [DOI] [PubMed] [Google Scholar]
- [61].Hoffman RE, Hampson M. Functional connectivity studies of patients with auditory verbal hallucinations. Front Hum Neurosci. 2011;6:6. doi: 10.3389/fnhum.2012.00006. [DOI] [PMC free article] [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. doi: 10.1093/brain/awp186. [DOI] [PMC free article] [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. doi: 10.1073/pnas.0704320104. [DOI] [PMC free article] [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. doi: 10.1016/j.tics.2008.01.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [65].Jiang T, Zhou Y. Brainnetome of schizophrenia: focus on impaired cognitive function. Shanghai Archives of Psychiatry. 2012;24:3–10. doi: 10.3969/j.issn.1002-0829.2012.01.001. [DOI] [PMC free article] [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. doi: 10.1176/appi.ajp.162.3.475. [DOI] [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. doi: 10.1016/j.schres.2010.01.001. [DOI] [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. doi: 10.1176/ajp.149.7.890. [DOI] [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. doi: 10.1001/archpsyc.62.4.379. [DOI] [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. doi: 10.1093/brain/awp098. [DOI] [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. doi: 10.1073/pnas.071043098. [DOI] [PMC free article] [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. doi: 10.1073/pnas.0809141106. [DOI] [PMC free article] [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. doi: 10.1016/j.schres.2010.11.012. [DOI] [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. doi: 10.1016/j.schres.2013.08.022. [DOI] [PMC free article] [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. doi: 10.1007/s12264-013-1300-8. [DOI] [PMC free article] [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. [DOI] [PMC free article] [PubMed]
- [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. doi: 10.1016/j.neuroimage.2013.06.041. [DOI] [PMC free article] [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. doi: 10.1523/JNEUROSCI.4882-12.2013. [DOI] [PMC free article] [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. doi: 10.1523/JNEUROSCI.5108-12.2013. [DOI] [PMC free article] [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. doi: 10.1016/j.neuron.2013.11.012. [DOI] [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. doi: 10.1523/JNEUROSCI.0257-12.2012. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [82].Moayedi M, Salomons TV, Dunlop KA, Downar J, Davis KD. Brain Struct Funct. 2014. Connectivity-bas ed parcellation of the human frontal polar cortex. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [83].Jiang T. Brainnetome: A new -ome to understand the brain and its disorders. Neuroimage. 2013;80:263–272. doi: 10.1016/j.neuroimage.2013.04.002. [DOI] [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. doi: 10.1093/cercor/bht196. [DOI] [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. doi: 10.1016/j.neuroimage.2012.07.045. [DOI] [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. doi: 10.1002/hbm.22626. [DOI] [PMC free article] [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. doi: 10.1093/cercor/bhs353. [DOI] [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. doi: 10.1523/JNEUROSCI.5852-11.2012. [DOI] [PMC free article] [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. doi: 10.1523/JNEUROSCI.2128-13.2013. [DOI] [PMC free article] [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. doi: 10.1073/pnas.0811168106. [DOI] [PMC free article] [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.. doi: 10.1093/cercor/bhn059. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [92].van den Heuvel MP, Fornito A. Brain networks in schizophrenia. Neuropsychol Rev. 2014;24:32–48. doi: 10.1007/s11065-014-9248-7. [DOI] [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. doi: 10.1097/YCO.0b013e32835d9e6a. [DOI] [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. doi: 10.1007/s11571-010-9126-9. [DOI] [PMC free article] [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. doi: 10.1001/jamapsychiatry.2013.1328. [DOI] [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. doi: 10.1080/13546800903091665. [DOI] [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. doi: 10.1016/j.bbr.2011.08.016. [DOI] [PMC free article] [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. doi: 10.1073/pnas.0909969107. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [99].Gottesman II, Gould TD. The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry. 2003;160:636–645. doi: 10.1176/appi.ajp.160.4.636. [DOI] [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. doi: 10.1523/JNEUROSCI.3941-09.2010. [DOI] [PMC free article] [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. doi: 10.1007/s00429-013-0640-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [102].Buckner RL, Krienen FM, Yeo BT. Opportunities and limitations of intrinsic functional connectivity MRI. Nat Neurosci. 2013;16:832–837. doi: 10.1038/nn.3423. [DOI] [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. doi: 10.1038/nature08855. [DOI] [PMC free article] [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. doi: 10.1038/cr.2013.46. [DOI] [PMC free article] [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. doi: 10.1016/j.cell.2013.04.025. [DOI] [PMC free article] [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. doi: 10.1016/j.biopsych.2011.02.031. [DOI] [PMC free article] [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. doi: 10.1016/j.neubiorev.2010.06.005. [DOI] [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. doi: 10.1016/j.pneurobio.2011.04.004. [DOI] [PubMed] [Google Scholar]
- [109].Friston KJ, Harrison L, Penny W. Dynamic causal modelling. Neuroimage. 2003;19:1273–1302. doi: 10.1016/s1053-8119(03)00202-7. [DOI] [PubMed] [Google Scholar]