The dysconnection hypothesis (2016)
Open accessAbstract
Twenty years have passed since the dysconnection hypothesis was first proposed (Friston and Frith, 1995; Weinberger, 1993). In that time, neuroscience has witnessed tremendous advances: we now live in a world of non-invasive neuroanatomy, computational neuroimaging and the Bayesian brain. The genomics era has come and gone. Connectomics and large-scale neuroinformatics initiatives are emerging everywhere. So where is the dysconnection hypothesis now? This article considers how the notion of schizophrenia as a dysconnection syndrome has developed - and how it has been enriched by recent advances in clinical neuroscience. In particular, we examine the dysconnection hypothesis in the context of (i) theoretical neurobiology and computational psychiatry; (ii) the empirical insights afforded by neuroimaging and associated connectomics - and (iii) how bottom-up (molecular biology and genetics) and top-down (systems biology) perspectives are converging on the mechanisms and nature of dysconnections in schizophrenia.
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Broadly, these findings are consistent with reports in neuropsychiatric disorders of brain network dysconnectivity and failures of neural integration.
“Broadly, these findings are consistent with reports in neuropsychiatric disorders of brain network dysconnectivity and failures of neural integration [57–59]”
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Cites
Biological insights from 108 schizophrenia-associated genetic loci
Schizophrenia Working Group of the Psychiatric Genomics Consortium (2014) · Nature · doi:10.1038/nature13595 · Cited by 7,577 · see citing works
The International HapMap Project
†The International HapMap Consortium, Genotyping centres: Baylor College of Medicine and ParAllele BioScience, Gibbs, R. A., Belmont, J. W., Hardenbol, P., Willis, T. D., Yu, F., Chinese HapMap Consortium, Yang, H., Ch'ang, L.-Y., et al. (2003) · Nature · doi:10.1038/nature02168 · Cited by 6,057 · see citing works
Whatever next? Predictive brains, situated agents, and the future of cognitive science
Clark, A. (2013) · Behavioral and Brain Sciences · doi:10.1017/s0140525x12000477 · Cited by 5,924 · cited 4× · see citing works
“This represents a subtle but generic problem that the brain must solve, where the solution may rest on modulating the gain or excitability of neuronal populations reporting prediction error (Clark, 2013a; Feldman and Friston, 2010; Friston, 2008).”
BackgroundInfluentialRao, R. P. N., & Ballard, D. H. (1999) · Nature Neuroscience · doi:10.1038/4580 · Cited by 5,483 · cited 1× · see citing works
“Modern formulations of Helmholtz's ideas usually appeal to theories such as predictive coding (Clark, 2013b; Friston, 2008; Rao and Ballard, 1999; Srinivasan et al., 1982).”
BackgroundKrystal, J. H. (1994) · Archives of General Psychiatry · doi:10.1001/archpsyc.1994.03950030035004 · Cited by 3,330 · see citing works
Kapur, S. (2003) · American Journal of Psychiatry · doi:10.1176/appi.ajp.160.1.13 · Cited by 2,813 · see citing works
Canonical Microcircuits for Predictive Coding
Bastos, A. M., Usrey, W. M., Adams, R. A., Mangun, G. R., Fries, P., & Friston, K. J. (2012) · Neuron · doi:10.1016/j.neuron.2012.10.038 · Cited by 2,421 · cited 5× · see citing works
“Predictive coding describes how the brain processes sensory information by optimizing explanations for its sensations: see (Bastos et al., 2012) for a review of canonical microcircuits and hierarchical predictive coding in perception and (Adams et al., 2013a; Shipp et al., 2013) for corresponding…”
BackgroundInfluentialSelf-citationAbnormal neural oscillations and synchrony in schizophrenia
Uhlhaas, P. J., & Singer, W. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2774 · Cited by 2,120 · see citing works
Uncertainty, Neuromodulation, and Attention
Yu, A. J., & Dayan, P. (2005) · Neuron · doi:10.1016/j.neuron.2005.04.026 · Cited by 1,774 · see citing works
Genome-wide association analysis identifies 13 new risk loci for schizophrenia
Multicenter Genetic Studies of Schizophrenia Consortium, Ripke, S., Psychosis Endophenotypes International Consortium, Wellcome Trust Case Control Consortium 2, O'Dushlaine, C., Chambert, K., Moran, J. L., Kähler, A. K., Akterin, S., Bergen, S. E., et al. (2013) · Nature Genetics · doi:10.1038/ng.2742 · Cited by 1,496 · see citing works
Hierarchical Bayesian inference in the visual cortex
Lee, T. S., & Mumford, D. (2003) · Journal of the Optical Society of America A · doi:10.1364/josaa.20.001434 · Cited by 1,473 · cited 1× · see citing works
“In the past decades this approach has been formalized to cover deep or hierarchical Bayesian inference – about the causes of our sensations – and how these inferences induce beliefs and behavior (Clark, 2013b; Dayan et al., 1995; Friston et al., 2006; Hohwy, 2013; Lee and Mumford, 2003).”
BackgroundThe mismatch negativity: a review of underlying mechanisms
Garrido, M. I., Kilner, J. M., Stephan, K. E., & Friston, K. J. (2009) · Clinical Neurophysiology · doi:10.1016/j.clinph.2008.11.029 · Cited by 1,441 · cited 1× · see citing works
“Importantly, the MMN is sensitive to manipulations of NMDA and cholinergic receptors (Garrido et al., 2009; Gil-da-Costa et al., 2013).”
BackgroundSelf-citationDysconnection in schizophrenia: from abnormal synaptic plasticity to failures of self-monitoring
Stephan, K. E., Friston, K. J., & Frith, C. D. (2009) · Schizophrenia Bulletin · doi:10.1093/schbul/sbn176 · Cited by 1,134 · see citing works
Self-citationPredictive coding: a fresh view of inhibition in the retina
Srinivasan, M. V., Laughlin, S. B., & Dubs, A. (1982) · Proceedings of the Royal Society of London. Series B. Biological Sciences · doi:10.1098/rspb.1982.0085 · Cited by 1,042 · see citing works
NMDA receptor hypofunction model of schizophrenia
Olney, J. W., Newcomer, J. W., & Farber, N. B. (1999) · Journal of Psychiatric Research · doi:10.1016/s0022-3956(99)00029-1 · Cited by 1,020 · see citing works
Hierarchical Models in the Brain
Friston, K. (2008) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000211 · Cited by 952 · cited 2× · see citing works
“This represents a subtle but generic problem that the brain must solve, where the solution may rest on modulating the gain or excitability of neuronal populations reporting prediction error (Clark, 2013a; Feldman and Friston, 2010; Friston, 2008).”
BackgroundSelf-citationPrecise minds in uncertain worlds: Predictive coding in autism.
Van de Cruys, S., Evers, K., Van der Hallen, R., Van Eylen, L., Boets, B., de-Wit, L., & Wagemans, J. (2014) · Psychological Review · doi:10.1037/a0037665 · Cited by 885 · see citing works
The Computational Anatomy of Psychosis
Adams, R. A., Stephan, K. E., Brown, H. R., Frith, C. D., & Friston, K. J. (2013) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2013.00047 · Cited by 850 · cited 8× · see citing works
“…for example, howdo dopamine and other neuromodulators interact with NMDA receptors and GABAergic interneurons to adjust postsynaptic gain – and is this the key pathophysiological dimension which explains heterogeneity within patients with schizophrenia (Adams et al., 2013b; Stephan et al., 2009).”
BackgroundInfluentialSelf-citationDysconnectivity in schizophrenia: where are we now?
Pettersson-Yeo, W., Allen, P., Benetti, S., McGuire, P., & Mechelli, A. (2011) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2010.11.004 · Cited by 712 · see citing works
An aberrant precision account of autism
Lawson, R. P., Rees, G., & Friston, K. J. (2014) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2014.00302 · Cited by 641 · see citing works
Self-citationLawrie, S. M., Buechel, C., Whalley, H. C., Frith, C. D., Friston, K. J., & Johnstone, E. C. (2002) · Biological Psychiatry · doi:10.1016/s0006-3223(02)01316-1 · Cited by 529 · see citing works
De novo gene mutations highlight patterns of genetic and neural complexity in schizophrenia
Xu, B., Ionita-Laza, I., Roos, J. L., Boone, B., Woodrick, S., Sun, Y., Levy, S., Gogos, J. A., & Karayiorgou, M. (2012) · Nature Genetics · doi:10.1038/ng.2446 · Cited by 442 · cited 2× · see citing works
“…patients carry a higher burden of non-synonymous and deleterious de novo SNPs (variants that result from a new mutational event and are unique to the child) than normal controls (Girard et al., 2011; Xu et al., 2011), some of which have been replicated in unrelated patients (Xu et al., 2012).”
BackgroundIncreased exonic de novo mutation rate in individuals with schizophrenia
Girard, S. L., Gauthier, J., Noreau, A., Xiong, L., Zhou, S., Jouan, L., Dionne-Laporte, A., Spiegelman, D., Henrion, E., Diallo, O., et al. (2011) · Nature Genetics · doi:10.1038/ng.886 · Cited by 438 · see citing works
Evidence for sensory prediction deficits in schizophrenia
Shergill, S. S., Samson, G., Bays, P. M., Frith, C. D., & Wolpert, D. M. (2005) · American Journal of Psychiatry · doi:10.1176/appi.ajp.162.12.2384 · Cited by 432 · see citing works
The Penetrance of Copy Number Variations for Schizophrenia and Developmental Delay
Kirov, G., Rees, E., Walters, J. T. R., Escott-Price, V., Georgieva, L., Richards, A. L., Chambert, K. D., Davies, G., Legge, S. E., Moran, J. L., et al. (2014) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.07.022 · Cited by 368 · see citing works
Free Energy, Precision and Learning: The Role of Cholinergic Neuromodulation
Moran, R. J., Campo, P., Symmonds, M., Stephan, K. E., Dolan, R. J., & Friston, K. J. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.4255-12.2013 · Cited by 312 · see citing works
Self-citationTeufel, C., Subramaniam, N., Dobler, V., Perez, J., Finnemann, J., Mehta, P. R., Goodyer, I. M., & Fletcher, P. C. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1503916112 · Cited by 308 · see citing works
Glutamatergic model psychoses: prediction error, learning, and inference
Corlett, P. R., Honey, G. D., Krystal, J. H., & Fletcher, P. C. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2010.163 · Cited by 229 · see citing works
Circular inferences in schizophrenia
Jardri, R., & Denève, S. (2013) · Brain · doi:10.1093/brain/awt257 · Cited by 201 · see citing works
Seeing other minds: Attributed mental states influence perception
Teufel, C., Fletcher, P. C., & Davis, G. (2010) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2010.05.005 · Cited by 199 · see citing works
What visual illusions teach us about schizophrenia
Notredame, C.-E., Pins, D., Deneve, S., & Jardri, R. (2014) · Frontiers in Integrative Neuroscience · doi:10.3389/fnint.2014.00063 · Cited by 177 · see citing works
Keifer Jr, O. P., Hurt, R. C., Gutman, D. A., Keilholz, S. D., Gourley, S. L., & Ressler, K. J. (2015) · Nature Communications · doi:10.1038/ncomms8582 · Cited by 132 · see citing works
Dopamine-modulated dynamic cell assemblies generated by the GABAergic striatal microcircuit
Humphries, M. D., Wood, R., & Gurney, K. (2009) · Neural Networks · doi:10.1016/j.neunet.2009.07.018 · Cited by 129 · see citing works
The functional anatomy of schizophrenia: A dynamic causal modeling study of predictive coding
Fogelson, N., Litvak, V., Peled, A., Fernandez-del-Olmo, M., & Friston, K. (2014) · Schizophrenia Research · doi:10.1016/j.schres.2014.06.011 · Cited by 85 · cited 3× · see citing works
“…of disconnection are consistent with a failure of top-downmodulation (from prefrontal and parietal cortex) of postsynaptic gain or precision in DCM studies of electrophysiological data; especially studies of the mismatch negativity and related paradigms (Dima et al., 2012; Fogelson et al., 2014).”
BackgroundResultSelf-citationAtypical scanpaths in schizophrenia: Evidence of a trait- or state-dependent phenomenon?
Beedie, S. A., St. Clair, D. M., & Benson, P. J. (2011) · Journal of Psychiatry and Neuroscience · doi:10.1503/jpn.090169 · Cited by 78 · see citing works
Dima, D., Frangou, S., Burge, L., Braeutigam, S., & James, A. C. (2012) · Schizophrenia Research · doi:10.1016/j.schres.2011.12.024 · Cited by 65 · see citing works
Flagged first, then by citations
Research works printed but not linked: 107
- Adams R.A. Shipp S. Friston K.J. Predictions not commands: active inference in the motor system Brain Struct. Funct. 218 2013 611 643 23129312 PMC3637647
- Adams R.A. Perrinet L.U. Friston K. Smooth pursuit and visual occlusion: active inference and oculomotor control in schizophrenia PLoS One 7 2012 e47502 PMC3482214 23110076
- Ahn K. Gotay N. Andersen T.M. Anvari A.A. Gochman P. Lee Y. Sanders S. Guha S. Darvasi A. Glessner J.T. High rate of disease-related copy number variations in childhood onset schizophrenia Mol. Psychiatry 19 2014 568 572 23689535 PMC5157161
- Allen P. Stephan K.E. Mechelli A. Day F. Ward N. Dalton J. Williams S.C. McGuire P. Cingulate activity and fronto-temporal connectivity in people with prodromal signs of psychosis NeuroImage 49 2010 947 955 19703570 PMC3221036
- Anticevic A. Hu X. Xiao Y. Hu J. Li F. Bi F. Cole M.W. Savic A. Yang G.J. Repovs G. Early-course unmedicated schizophrenia patients exhibit elevated prefrontal connectivity associated with longitudinal change J. Neurosci. 35 2015 267 286 25568120 PMC4287147
- Averbeck B.B. Evans S. Chouhan V. Bristow E. Shergill S.S. Probabilistic learning and inference in schizophrenia Schizophr. Res. 127 2011 115 122 20810252 PMC3008301
- Barch D.M. Carter C.S. Dakin S.C. Gold J. Luck S.J. Macdonald A. 3rd Ragland J.D. Silverstein S. Strauss M.E. The clinical translation of a measure of gain control: the contrast-contrast effect task Schizophr. Bull. 38 2012 135 143 22101963 PMC3245599
- Bastos-Leite A.J. Ridgway G.R. Silveira C. Norton A. Reis S. Friston K.J. Dysconnectivity within the default mode in first-episode schizophrenia: a stochastic dynamic causal modeling study with functional magnetic resonance imaging Schizophr. Bull. 41 2015 144 153 24939881 PMC4266292
- Belousov A.B. van den Pol A.N. Dopamine inhibition: enhancement of GABA activity and potassium channel activation in hypothalamic and arcuate nucleus neurons J. Neurophysiol. 78 1997 674 688 9307104
- Benetti S. Mechelli A. Picchioni M. Broome M. Williams S. McGuire P. Functional integration between the posterior hippocampus and prefrontal cortex is impaired in both first episode schizophrenia and the at risk mental state Brain 132 2009 2426 2436 19420091
- Bob P. Mashour G.A. Schizophrenia, dissociation, and consciousness Conscious. Cogn. 20 2011 1042 1049 21602061
- Bonci A. Malenka R.C. Properties and plasticity of excitatory synapses on dopaminergic and GABAergic cells in the ventral tegmental area J. Neurosci. 19 1999 3723 3730 10234004 PMC6782740
- Braff D.L. Geyer M.A. Swerdlow N.R. Human studies of prepulse inhibition of startle: normal subjects, patient groups, and pharmacological studies Psychopharmacology 156 2001 234 258 11549226
- Braver T.S. Barch D.M. Cohen J.D. Cognition and control in schizophrenia: a computational model of dopamine and prefrontal function Biol. Psychiatry 46 1999 312 328 10435197
- Brodersen K.H. Deserno L. Schlagenhauf F. Lin Z. Penny W.D. Buhmann J.M. Stephan K.E. Dissecting psychiatric spectrum disorders by generative embedding NeuroImage Clinical 4 2014 98 111 24363992 PMC3863808
- Brown H. Adams R.A. Parees I. Edwards M. Friston K. Active inference, sensory attenuation and illusions Cogn. Process. 14 2013 411 427 23744445 PMC3824582
- Butler P.D. Silverstein S.M. Dakin S.C. Visual perception and its impairment in schizophrenia Biol. Psychiatry 64 2008 40 47 18549875 PMC2435292
- Catts V.S. Fung S.J. Long L.E. Joshi D. Vercammen A. Allen K.M. Fillman S.G. Rothmond D.A. Sinclair D. Tiwari Y. Rethinking schizophrenia in the context of normal neurodevelopment Front. Cell. Neurosci. 7 2013 60 23720610 PMC3654207
- Chawla D. Lumer E.D. Friston K.J. The relationship between synchronization among neuronal populations and their mean activity levels Neural Comput. 11 1999 1389 1411 10423500
- Cisek P. Cortical mechanisms of action selection: the affordance competition hypothesis Philos. Trans. R. Soc. Lond. Ser. B Biol. Sci. 362 2007 1585 1599 17428779 PMC2440773
- Clark A. The many faces of precision Front. Psychol. 4 2013 270 23734133 PMC3659294
- Cohen J.D. Servan-Schreiber D. Context, cortex, and dopamine: a connectionist approach to behavior and biology in schizophrenia Psychol. Rev. 99 1992 45 77 1546118
- Cull-Candy S. Brickley S. Farrant M. NMDA receptor subunits: diversity, development and disease Curr. Opin. Neurobiol. 11 2001 327 335 11399431
- Curcic-Blake B. van der Meer L. Pijnenborg G.H. David A.S. Aleman A. Insight and psychosis: functional and anatomical brain connectivity and self-reflection in schizophrenia Hum. Brain Mapp. 36 2015 4859 4868 26467308 PMC6869637
- Dauvermann M.R. Whalley H.C. Romaniuk L. Valton V. Owens D.G. Johnstone E.C. Lawrie S.M. Moorhead T.W. The application of nonlinear dynamic causal modelling for fMRI in subjects at high genetic risk of schizophrenia NeuroImage 73 2013 16 29 23384525
- Dayan P. Hinton G.E. Neal R. The Helmholtz machine Neural Comput. 7 1995 889 904 7584891
- Doya K. Modulators of decision making Nat. Neurosci. 11 2008 410 416 18368048
- Ehrlichman R.S. Luminais S.N. White S.L. Rudnick N.D. Ma N. Dow H.C. Kreibich A.S. Abel T. Brodkin E.S. Hahn C.G. Neuregulin 1 transgenic mice display reduced mismatch negativity, contextual fear conditioning and social interactions Brain Res. 1294 2009 116 127 19643092 PMC2771287
- Ellison-Wright I. Bullmore E.T. Meta-analysis of diffusion tensor imaging studies in schizophrenia Schizophr. Res. 108 2009 3 10 19128945
- Feldman H. Friston K.J. Attention, uncertainty, and free-energy Front. Hum. Neurosci. 4 2010 215 21160551 PMC3001758
- Ferrarelli F. Tononi G. The thalamic reticular nucleus and schizophrenia Schizophr. Bull. 37 2011 306 315 21131368 PMC3044616
- Fields R.D. A new mechanism of nervous system plasticity: activity-dependent myelination Nat. Rev. Neurosci. 16 2015 756 767 26585800 PMC6310485
- Fletcher P.C. Frith C.D. Perceiving is believing: a Bayesian approach to explaining the positive symptoms of schizophrenia Nat. Rev. Neurosci. 10 2009 48 58 19050712
- Fornito A. Bullmore E.T. Reconciling abnormalities of brain network structure and function in schizophrenia Curr. Opin. Neurobiol. 30 2015 44 50 25238608
- Frank M.J. Scheres A. Sherman S.J. Understanding decision-making deficits in neurological conditions: insights from models of natural action selection Philos. Trans. R. Soc. Lond. Ser. B Biol. Sci. 362 2007 1641 1654 17428775 PMC2440777
- Fries P. Womelsdorf T. Oostenveld R. Desimone R. The effects of visual stimulation and selective visual attention on rhythmic neuronal synchronization in macaque area V4 J. Neurosci. 28 2008 4823 4835 18448659 PMC3844818
- Friston K.J. Frith C.D. Schizophrenia - a disconnection syndrome Clin. Neurosci. 3 1995 89 97 7583624
- Friston K. Kilner J. Harrison L. A free energy principle for the brain J. Physiol. Paris 100 2006 70 87 17097864
- Friston K. Mattout J. Kilner J. Action understanding and active inference Biol. Cybern. 104 2011 137 160 21327826 PMC3491875
- Friston K.J. Shiner T. Fitzgerald T. Galea J.M. Adams R. Brown H. Dolan R.J. Moran R. Stephan K.E. Bestmann S. Dopamine, affordance and active inference PLoS Comput. Biol. 8 2012 e1002327 PMC3252266 22241972
- Frith C.D. Blakemore S.J. Wolpert D.M. Abnormalities in the awareness and control of action Philos. Trans. R. Soc. Lond. Ser. B Biol. Sci. 355 2000 1771 1788 11205340 PMC1692910
- Fromer M. Pocklington A.J. Kavanagh D.H. Williams H.J. Dwyer S. Gormley P. Georgieva L. Rees E. Palta P. Ruderfer D.M. De novo mutations in schizophrenia implicate synaptic networks Nature 506 2014 179 184 24463507 PMC4237002
- Garrido M.I. Kilner J.M. Kiebel S.J. Friston K.J. Evoked brain responses are generated by feedback loops Proc. Natl. Acad. Sci. U. S. A. 104 2007 20961 20966 18087046 PMC2409249
- Geyer M.A. Krebs-Thomson K. Braff D.L. Swerdlow N.R. Pharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenia: a decade in review Psychopharmacology 156 2001 117 154 11549216
- Gil-da-Costa R. Stoner G.R. Fung R. Albright T.D. Nonhuman primate model of schizophrenia using a noninvasive EEG method Proc. Natl. Acad. Sci. U. S. A. 110 2013 15425 15430 23959894 PMC3780912
- Goldman-Rakic P.S. Lidow M.S. Smiley J.F. Williams M.S.T.a.o.d.i.m.a.h.p.c.J.N.T.S. The anatomy of dopamine in monkey and human prefrontal cortex J. Neural Transm. Suppl. 36 1992 163 177 1527516
- Gonzalez-Burgos G. Lewis D.A. NMDA receptor hypofunction, parvalbumin-positive neurons, and cortical gamma oscillations in schizophrenia Schizophr. Bull. 38 2012 950 957 22355184 PMC3446219
- Gothelf D. Law A.J. Frisch A. Chen J. Zarchi O. Michaelovsky E. Ren-Patterson R. Lipska B.K. Carmel M. Kolachana B. Biological effects of COMT haplotypes and psychosis risk in 22q11.2 deletion syndrome Biol. Psychiatry 75 2014 406 413 23992923 PMC3872263
- Hohwy J. The Predictive Mind 2013 Oxford University Press Oxford
- Iglesias S. Mathys C. Brodersen K.H. Kasper L. Piccirelli M. den Ouden H.E.M. Stephan K.E. Hierarchical prediction errors in midbrain and basal forebrain during sensory learning Neuron 80 2013 519 530 24139048
- Jardri R. Denève S. Circular inferences in schizophrenia Brain 136 2013 3227 3241 24065721
- Javitt D.C. Zukin S.R. Recent advances in the phencyclidine model of schizophrenia Am. J. Psychiatr. 148 1991 1301 1308 1654746
- Jentsch J.D. Roth R.H. The neuropsychopharmacology of phencyclidine: from NMDA receptor hypofunction to the dopamine hypothesis of schizophrenia Neuropsychopharmacology 20 1999 201 225 10063482
- Jiang J. Summerfield C. Egner T. Attention sharpens the distinction between expected and unexpected percepts in the visual brain J. Neurosci. 33 2013 18438 18447 24259568 PMC3834051
- Joyce D.W. Averbeck B.B. Frith C.D. Shergill S.S. Examining belief and confidence in schizophrenia Psychol. Med. 43 2013 2327 2338 23521846 PMC5873321
- Kaplan C.M. Saha D. Molina J.L. Hockeimer W.D. Postell E.M. Apud J.A. Weinberger D.R. Tan H.Y. Estimating changing contexts in schizophrenia Brain 139 2016 2082 2095 27217338 PMC4939701
- Kenny E.M. Cormican P. Furlong S. Heron E. Kenny G. Fahey C. Kelleher E. Ennis S. Tropea D. Anney R. Excess of rare novel loss-of-function variants in synaptic genes in schizophrenia and autism spectrum disorders Mol. Psychiatry 19 2014 872 879 24126926
- Khadka S. Meda S.A. Stevens M.C. Glahn D.C. Calhoun V.D. Sweeney J.A. Tamminga C.A. Keshavan M.S. O'Neil K. Schretlen D. Is aberrant functional connectivity a psychosis endophenotype? A resting state functional magnetic resonance imaging study Biol. Psychiatry 74 2013 458 466 23746539 PMC3752322
- Kong A. Frigge M.L. Masson G. Besenbacher S. Sulem P. Magnusson G. Gudjonsson S.A. Sigurdsson A. Jonasdottir A. Jonasdottir A. Rate of de novo mutations and the importance of father/’s age to disease risk Nature 488 2012 471 475 22914163 PMC3548427
- Laruelle M. Schizophrenia: from dopaminergic to glutamatergic interventions Curr. Opin. Pharmacol. 14C 2014 97 102 24524997
- Lee S.H. DeCandia T.R. Ripke S. Yang J. Sullivan P.F. Goddard M.E. Keller M.C. Visscher P.M. Wray N.R. Estimating the proportion of variation in susceptibility to schizophrenia captured by common SNPs Nat. Genet. 44 2012 247 250 22344220 PMC3327879
- Liang M. Zhou Y. Jiang T.Z. Liu Z.N. Tian L.X. Liu H.H. Hao Y.H. Widespread functional disconnectivity in schizophrenia with resting-state functional magnetic resonance imaging Neuroreport 17 2006 209 213 16407773
- Lidow M.S. Goldman-Rakic P.S. Gallager D.W. Rakic P. Distribution of dopaminergic receptors in the primate cerebral cortex: quantitative autoradiographic analysis using [3H]raclopride, [3H]spiperone and [3H]SCH23390 Neuroscience 40 1991 657 671 2062437
- Light G.A. Swerdlow N.R. Thomas M.L. Calkins M.E. Green M.F. Greenwood T.A. Gur R.E. Gur R.C. Lazzeroni L.C. Nuechterlein K.H. Validation of mismatch negativity and P3a for use in multi-site studies of schizophrenia: characterization of demographic, clinical, cognitive, and functional correlates in COGS-2 Schizophr. Res. 163 2015 63 72 25449710 PMC4382452
- Lisman J. Excitation, inhibition, local oscillations, or large-scale loops: what causes the symptoms of schizophrenia? Curr. Opin. Neurobiol. 22 2012 537 544 22079494 PMC3302967
- Lisman J.E. Coyle J.T. Green R.W. Javitt D.C. Benes F.M. Heckers S. Grace A.A. Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophrenia Trends Neurosci. 31 2008 234 242 18395805 PMC2680493
- Lundgaard I. Luzhynskaya A. Stockley J.H. Wang Z. Evans K.A. Swire M. Volbracht K. Gautier H.O. Franklin R.J. Attwell D. Neuregulin and BDNF induce a switch to NMDA receptor-dependent myelination by oligodendrocytes PLoS Biol. 11 2013 e1001743 PMC3876980 24391468
- Lynall M.E. Bassett D.S. Kerwin R. McKenna P.J. Kitzbichler M. Muller U. Bullmore E.T. Functional connectivity and brain networks in schizophrenia J. Neurosci. 30 2010 9477 9487 20631176 PMC2914251
- Marenco S. Steele S.U. Egan M.F. Goldberg T.E. Straub R.E. Sharrief A.Z. Weinberger D.R. Effect of metabotropic glutamate receptor 3 genotype on N-acetylaspartate measures in the dorsolateral prefrontal cortex Am. J. Psychiatry 163 2006 740 742 16585454 PMC1855226
- Meyer-Lindenberg A. Poline J.B. Kohn P.D. Holt J.L. Egan M.F. Weinberger D.R. Berman K.F. Evidence for abnormal cortical functional connectivity during working memory in schizophrenia Am. J. Psychiatr. 158 2001 1809 1817 11691686
- Monfils M.H. Teskey G.C. Induction of long-term depression is associated with decreased dendritic length and spine density in layers III and V of sensorimotor neocortex Synapse 53 2004 114 121 15170823
- Mothersill O. Kelly S. Rose E.J. Donohoe G. The effects of psychosis risk variants on brain connectivity: a review Front Psychiatry 3 2012 18 22416237 PMC3299399
- Mukai J. Tamura M. Fenelon K. Rosen A.M. Spellman T.J. Kang R. MacDermott A.B. Karayiorgou M. Gordon J.A. Gogos J.A. Molecular substrates of altered axonal growth and brain connectivity in a mouse model of schizophrenia Neuron 86 2015 680 695 25913858 PMC4603834
- Murphy K.C. Jones L.A. Owen M.J. High rates of schizophrenia in adults with velo-cardio-facial syndrome Arch. Gen. Psychiatry 56 1999 940 945 10530637
- O'Donovan M.C. Craddock N. Norton N. Williams H. Peirce T. Moskvina V. Nikolov I. Hamshere M. Carroll L. Georgieva L. Identification of loci associated with schizophrenia by genome-wide association and follow-up Nat. Genet. 40 2008 1053 1055 18677311
- Oestreich L.K. Mifsud N.G. Ford J.M. Roach B.J. Mathalon D.H. Whitford T.J. Subnormal sensory attenuation to self-generated speech in schizotypy: electrophysiological evidence for a ‘continuum of psychosis’ Int. J. Psychophysiol. 97 2015 131 138 26027781 PMC4607510
- Olney J.W. Labruyere J. Price M.T. Pathological-changes induced in cerebrocortical neurons by phencyclidine and related drugs Science 244 1989 1360 1362 2660263
- Paton B. Hohwy J. Enticott P.G. The rubber hand illusion reveals proprioceptive and sensorimotor differences in autism spectrum disorders J. Autism Dev. Disord. 42 2012 1870 1883 22189963
- Pellicano E. Burr D. When the world becomes ‘too real’: a Bayesian explanation of autistic perception Trends Cogn. Sci. 16 2012 504 510 22959875
- Powers Iii A.R. Gancsos M.G. Finn E.S. Morgan P.T. Corlett P.R. Ketamine-induced hallucinations Psychopathology 48 2015 376 385 26361209 PMC4684980
- Radua J. Surguladze S.A. Marshall N. Walshe M. Bramon E. Collier D.A. Prata D.P. Murray R.M. McDonald C. The impact of CACNA1C allelic variation on effective connectivity during emotional processing in bipolar disorder Mol. Psychiatry 18 2013 526 527 22614292
- Rubinov M. Knock S.A. Stam C.J. Micheloyannis S. Harris A.W.F. Williams L.M. Breakspear M. Small-world properties of nonlinear brain activity in schizophrenia Hum. Brain Mapp. 30 2009 403 416 18072237 PMC6871165
- Rujescu D. Ingason A. Cichon S. Pietiläinen O.P.H. Barnes M.R. Toulopoulou T. Picchioni M. Vassos E. Ettinger U. Bramon E. Disruption of the neurexin 1 gene is associated with schizophrenia Hum. Mol. Genet. 18 2009 988 996 18945720 PMC2695245
- Schmidt A. Diaconescu A.O. Kometer M. Friston K.J. Stephan K.E. Vollenweider F.X. Modeling ketamine effects on synaptic plasticity during the mismatch negativity Cereb. Cortex 23 2013 2394 2406 22875863 PMC3767962
- Schmidt A. Smieskova R. Simon A. Allen P. Fusar-Poli P. McGuire P.K. Bendfeldt K. Aston J. Lang U.E. Walter M. Abnormal effective connectivity and psychopathological symptoms in the psychosis high-risk state J. Psychiatry Neurosci. 39 2014 239 248 24506946 PMC4074235
- Sesack S.R. Carr D.B. Selective prefrontal cortex inputs to dopamine cells: implications for schizophrenia Physiol. Behav. 77 2002 513 517 12526992
- Shipp S. Adams R.A. Friston K.J. Reflections on agranular architecture: predictive coding in the motor cortex Trends Neurosci. 36 2013 706 716 24157198 PMC3858810
- Sigurdsson T. Stark K.L. Karayiorgou M. Gogos J.A. Gordon J.A. Impaired hippocampal-prefrontal synchrony in a genetic mouse model of schizophrenia Nature 464 2010 (763-U139) PMC2864584 20360742
- Sin W.C. Haas K. Ruthazer E.S. Cline H.T. Dendrite growth increased by visual activity requires NMDA receptor and Rho GTPases Nature 419 2002 475 480 12368855
- Skewes J.C. Jegindo E.M. Gebauer L. Perceptual inference and autistic traits Autism 2014 (Epub ahead of print) 24523412
- Sohal V.S. Zhang F. Yizhar O. Deisseroth K. Parvalbumin neurons and gamma rhythms enhance cortical circuit performance Nature 459 2009 698 702 19396159 PMC3969859
- Spencer K.M. Nestor P.G. Niznikiewicz M.A. Salisbury D.F. Shenton M.E. McCarley R.W. Abnormal neural synchrony in schizophrenia J. Neurosci. 23 2003 7407 7411 12917376 PMC2848257
- St Clair D. Blackwood D. Muir W. Carothers A. Walker M. Spowart G. Gosden C. Evans H.J. Association within a family of a balanced autosomal translocation with major mental illness Lancet 336 1990 13 16 (London, England) 1973210
- Sun Y. Chen Y. Lee R. Bezerianos A. Collinson S.L. Sim K. Disruption of brain anatomical networks in schizophrenia: a longitudinal, diffusion tensor imaging based study Schizophr. Res. 171 2016 149 157 26811255
- Tamura M. Mukai J. Gordon J.A. Gogos J.A. Developmental inhibition of Gsk3 rescues behavioral and neurophysiological deficits in a mouse model of schizophrenia predisposition Neuron 89 2016 1100 1109 26898776 PMC4783174
- Tan H.Y. Chen A.G. Kolachana B. Apud J.A. Mattay V.S. Callicott J.H. Chen Q. Weinberger D.R. Effective connectivity of AKT1-mediated dopaminergic working memory networks and pharmacogenetics of anti-dopaminergic treatment Brain 135 2012 1436 1445 22525159 PMC3338927
- Timms A.E. Dorschner M.O. Wechsler J. Choi K.Y. Kirkwood R. Girirajan S. Baker C. Eichler E.E. Korvatska O. Roche K.W. Support for the N-methyl-d-aspartate receptor hypofunction hypothesis of schizophrenia from exome sequencing in multiplex families JAMA Psychiatry 70 2013 582 590 23553203
- Trepanier C. Lei G. Xie Y.F. MacDonald J.F. Group II metabotropic glutamate receptors modify N-methyl-d-aspartate receptors via Src kinase Sci. Rep. 3 2013 926 23378895 PMC3558700
- Umbricht D. Krljes S. Mismatch negativity in schizophrenia: a meta-analysis Schizophr. Res. 76 2005 1 23 15927795
- Ungvari G.S. The Wernicke-Kleist-Leonhard School of psychiatry Biol. Psychiatry 34 1993 749 752 8292677
- van Haren N.E. Schnack H.G. Cahn W. van den Heuvel M.P. Lepage C. Collins L. Evans A.C. Hulshoff Pol H.E. Kahn R.S. Changes in cortical thickness during the course of illness in schizophrenia Arch. Gen. Psychiatry 68 2011 871 880 21893656
- Weinberger D.R. A connectionist approach to the prefrontal cortex J. Neuropsychiatr. Clin. Neurosci. 5 1993 241 253 8369632
- Winterer G. Weinberger D.R. Genes, dopamine and cortical signal-to-noise ratio in schizophrenia Trends Neurosci. 27 2004 683 690 15474169
- Wynn J.K. Sugar C. Horan W.P. Kern R. Green M.F. Mismatch negativity, social cognition, and functioning in schizophrenia patients Biol. Psychiatry 67 2010 940 947 20074704 PMC2862843
- Xu B. Roos J.L. Dexheimer P. Boone B. Plummer B. Levy S. Gogos J.A. Karayiorgou M. Exome sequencing supports a de novo mutational paradigm for schizophrenia Nat. Genet. 43 2011 864 868 21822266 PMC3196550
- Zarchi O. Carmel M. Avni C. Attias J. Frisch A. Michaelovsky E. Patya M. Green T. Weinberger R. Weizman A. Schizophrenia-like neurophysiological abnormalities in 22q11.2 deletion syndrome and their association to COMT and PRODH genotypes J. Psychiatr. Res. 47 2013 1623 1629 23910792
- Zhang Z. Zheng F. You Y. Ma Y. Lu T. Yue W. Zhang D. Growth arrest specific gene 7 is associated with schizophrenia and regulates neuronal migration and morphogenesis Molecular brain 9 2016 54 27189492 PMC4870797
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Self-citation
- Authors
- Friston, K., Brown, H. R., Siemerkus, J., & Stephan, K. E.
- Affiliations
- Wellcome Centre for Human Neuroimaging (GB)
- University of Zurich (CH)
- Corresponding author
- Friston, Karl
- Venue
- Schizophrenia Research
- Publisher
- Elsevier BV
- Published
- 2016-10
- Volume
- 176
- Issue
- 2-3
- Pages
- 83-94
- ISSN
- 0920-9964 (ISSN-L)
- PMC
- PMC5147460
- OpenAlex
- W2498492890
- Cited by
- 561
- References
- 36
- Citations by year
- 2026: 42 · 2025: 62 · 2024: 72 · 2023: 48 · 2022: 65 · 2021: 77 · 2020: 63 · 2019: 50 · 2018: 51 · 2017: 30 · 2016: 1
- FWCI
- 6.30
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Schizophrenia Research (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Repository for Publications and Research Data (ETH Zurich) (submittedVersion, cc-by)
- ETH Zürich Research Collection (cc-by)
- Funders
- Wellcome Trust (088130/Z/09/Z)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Social Sciences › Arts and Humanities › Philosophy › Mental Health and Psychiatry
- Keywords
- schizophrenia
- MeSH terms
- Animals, Brain, Humans, Models, Neurological, Schizophrenia
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