When Doors of Perception Close: Bottom-up Models of Disrupted Cognition in Schizophrenia
Open accessAbstract
Schizophrenia is a major mental disorder that affects approximately 1% of the population worldwide. Cognitive deficits are a key feature of schizophrenia and a primary cause of long-term disability. Current neurophysiological models of schizophrenia focus on distributed brain dysfunction with bottom-up as well as top-down components. Bottom-up deficits in cognitive processing are driven by impairments in basic perceptual processes that localize to primary sensory brain regions. Within the auditory system, deficits are apparent in elemental sensory processing, such as tone matching following brief delay. Such deficits lead to impairments in higher-order processes such as phonological processing and auditory emotion recognition. Within the visual system, deficits are apparent in functioning of the magnocellular visual pathway, leading to higher-order deficits in processes such as perceptual closure, object recognition, and reading. In both auditory and visual systems, patterns of deficit are consistent with underlying impairment of brain N-methyl-d-aspartate receptor systems.
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MMN has been tied to impaired neurotransmission at NMDARs based upon both intracranial and surface recordings in non-human primates and ketamine challenge studies in healthy human volunteers.
“MMN has been tied to impaired neurotransmission at NMDARs based upon both intracranial (54) and surface (55) recordings in non-human primates and ketamine challenge studies in healthy human volunteers (rev. in 3).”
From Sensory Processing Dysfunction in the Personal Experience and Neuronal Machinery of Schizophrenia (2015) · cites this paper as [3]
Deficits in MMN generation are associated with impairments of basic auditory discrimination, such as tone matching and auditory spatial discrimination.
“On a behavioral level, deficits in MMN generation are associated with impairments of basic auditory discrimination, such as tone matching (3) and auditory spatial discrimination (49)”
From Sensory Processing Dysfunction in the Personal Experience and Neuronal Machinery of Schizophrenia (2015) · cites this paper as [3]
Deficits in MMN generation were first reported in the early 1990s and have since been a widely replicated neurophysiological finding in schizophrenia.
“Deficits in MMN generation were first reported in the early 1990’s, and this finding has since been a widely replicated neurophysiological finding in schizophrenia (rev. in 3, 61, 62, 63)”
From Sensory Processing Dysfunction in the Personal Experience and Neuronal Machinery of Schizophrenia (2015) · cites this paper as [3]
Low level visual deficits cascade up the system to undermine higher order cognitive impairments, as in the auditory system.
“supporting recent suggestions that low level visual deficits cascade up the system to undermine higher order cognitive impairments, as in the auditory system (3).”
From Sensory Processing Dysfunction in the Personal Experience and Neuronal Machinery of Schizophrenia (2015) · cites this paper as [3]
Deficits in MMN are tied to impairments in both orientation to critical environmental events and detection of the sensory modulations that are used to communicate social information such as emotion or attitude by tone of voice.
“Deficits in MMN are tied to impairments in both orientation to critical environmental events and detection of the sensory modulations that are used to communicate social information such as emotion or attitude by tone of voice (3).”
From Sensory Processing Dysfunction in the Personal Experience and Neuronal Machinery of Schizophrenia (2015) · cites this paper as [3]
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Martı́nez, A., Ramanathan, D., Foxe, J. J., Javitt, D. C., & Hillyard, S. A. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.0031-07.2007 · Cited by 83 · see citing works
Self-citationDysfunction of early-stage visual processing in schizophrenia: Harmonic analysis
Kim, D., Zemon, V., Saperstein, A., Butler, P. D., & Javitt, D. C. (2005) · Schizophrenia Research · doi:10.1016/j.schres.2004.10.011 · Cited by 79 · see citing works
Self-citationJavitt, D. C., Jayachandra, M., Lindsley, R. W., Specht, C. M., & Schroeder, C. E. (2000) · Clinical Neurophysiology · doi:10.1016/s1388-2457(99)00313-2 · Cited by 79 · see citing works
Self-citationKwon, Y. H., Esguerra, M., & Sur, M. (1991) · Journal of Neurophysiology · doi:10.1152/jn.1991.66.2.414 · Cited by 79 · see citing works
Optimized mismatch negativity paradigm reflects deficits in schizophrenia patients
Thönneßen, H., Zvyagintsev, M., Harke, K. C., Boers, F., Dammers, J., Norra, C., & Mathiak, K. (2007) · Biological Psychology · doi:10.1016/j.biopsycho.2007.10.009 · Cited by 71 · see citing works
Selemon, L. D., & Begović, A. (2007) · Psychiatry Research · doi:10.1016/j.psychres.2006.11.003 · Cited by 65 · see citing works
Early Visual Processing Deficits in Dysbindin-Associated Schizophrenia
Donohoe, G. J., Morris, D. W., Sanctis, P. D., Magno, E., Montesi, J. L., Garavan, H., Robertson, I. H., Javitt, D. C., Gill, M., Corvin, A. P., et al. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.07.022 · Cited by 64 · see citing works
Self-citationStoet, G., & Snyder, L. H. (2005) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300930 · Cited by 61 · see citing works
What's in a face? Effects of stimulus duration and inversion on face processing in schizophrenia
Butler, P. D., Tambini, A., Yovel, G., Jalbrzikowski, M., Ziwich, R., Silipo, G. S., Kanwisher, N., & Javitt, D. C. (2008) · Schizophrenia Research · doi:10.1016/j.schres.2008.03.007 · Cited by 61 · see citing works
Self-citationTask set switching in schizophrenia.
Meiran, N., Levine, J. S., Meiran, N., et al. (2000) · Neuropsychology · doi:10.1037/0894-4105.14.3.471 · Cited by 60 · see citing works
An fMRI study of language processing in people at high genetic risk for schizophrenia
Li, X., Branch, C. A., Bertisch, H. C., Brown, K., Szulc, K. U., Ardekani, B. A., & DeLisi, L. E. (2007) · Schizophrenia Research · doi:10.1016/j.schres.2006.12.016 · Cited by 59 · see citing works
Preserved function of the fusiform face area in schizophrenia as revealed by fMRI
Yoon, J. H., D’Esposito, M., & Carter, C. S. (2006) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2006.06.002 · Cited by 58 · see citing works
Kasai, K., Yamada, H., Kamio, S., Nakagome, K., Iwanami, A., Fukuda, M., Yumoto, M., Itoh, K., Koshida, I., Abe, O., et al. (2002) · Schizophrenia Research · doi:10.1016/s0920-9964(01)00382-6 · Cited by 57 · see citing works
Rivadulla, C., Sharma, J., & Sur, M. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-05-01710.2001 · Cited by 55 · see citing works
Stoodley, C. J., Hill-Feltham, P., Stein, J. F., & Bishop, D. (2006) · Brain Research · doi:10.1016/j.brainres.2006.08.095 · Cited by 51 · see citing works
Impaired Temporal Lobe Processing of Preattentive Auditory Discrimination in Schizophrenia
Pekkonen, E., Katila, H., Ahveninen, J., et al. (2002) · Schizophrenia Bulletin · doi:10.1093/oxfordjournals.schbul.a006954 · Cited by 50 · see citing works
Perceptual organization by proximity and similarity in schizophrenia
Kurylo, D. D., Pasternak, R., Silipo, G., Javitt, D. C., & Butler, P. D. (2007) · Schizophrenia Research · doi:10.1016/j.schres.2007.07.001 · Cited by 46 · see citing works
Bruder, G. E., Kayser, J., Tenke, C. E., et al. (2001) · Biological Psychiatry · doi:10.1016/s0006-3223(01)01168-4 · Cited by 45 · see citing works
Impaired categorical perception of synthetic speech sounds in schizophrenia
Cienfuegos, A., March, L., Shelley, A. M., & Javitt, D. C. (1999) · Biological Psychiatry · doi:10.1016/s0006-3223(98)00064-x · Cited by 45 · see citing works
Self-citationBipolar and schizophrenic patients differ in patterns of visual motion discrimination
Chen, Y., Levy, D. L., Sheremata, S., & Holzman, P. S. (2006) · Schizophrenia Research · doi:10.1016/j.schres.2006.06.004 · Cited by 42 · see citing works
March, L., Cienfuegos, A., Goldbloom, L. M., Ritter, W., Cowan, N., & Javitt, D. C. (1999) · Journal of Abnormal Psychology · doi:10.1037//0021-843x.108.1.69 · Cited by 41 · see citing works
Self-citationUhlhaas, P. J., Millard, I., Muetzelfeldt, L., Curran, H. V., & Morgan, C. J. A. (2007) · Journal of Psychopharmacology · doi:10.1177/0269881107077739 · Cited by 36 · see citing works
March, L., Cienfuegos, A., Goldbloom, L. M., et al. (1999) · Journal of Abnormal Psychology · doi:10.1037/0021-843x.108.1.69 · Cited by 34 · see citing works
AUDITORY PERCEPTION IN SCHIZOPHRENIA: A SECOND STUDY OF THE INTONATION TEST
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Wylie, G. R., Clark, E., Butler, P. D., & Javitt, D. C. (2008) · Schizophrenia Bulletin · doi:10.1093/schbul/sbn119 · Cited by 30 · see citing works
Self-citationEvent related brain potential evidence for preserved attentional set switching in schizophrenia
Kieffaber, P. D., O’Donnell, B. F., Shekhar, A., et al. (2007) · Schizophrenia Research · doi:10.1016/j.schres.2007.03.018 · Cited by 30 · see citing works
Phoneme Discrimination in Schizophrenia
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Perceptual Closure in Acute Paranoid Schizophrenics
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Effects of Ketamine on perceptual grouping in rats
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Neuromagnetic evidence of broader auditory cortical tuning in schizophrenia
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Assessment of perceptual functioning in schizophrenia
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The Prophetic Books of William Blake: Jerusalem
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- Bleuler E 1950 Dementia Praecox of the Group of the Schizophrenias New York Intl. Univ. Press
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Moghaddam, B., & Javitt, D. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2011.181 · Cited by 1,035 · see citing works
Self-citationNonsocial and social cognition in schizophrenia: current evidence and future directions
Green, M. F., Horan, W. P., & Lee, J. (2019) · World Psychiatry · doi:10.1002/wps.20624 · Cited by 612 · see citing works
Sensory Processing Dysfunction in the Personal Experience and Neuronal Machinery of Schizophrenia
Javitt, D. C., & Freedman, R. (2015) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2014.13121691 · Cited by 403 · see citing works
Self-citationJavitt, D. C., Zukin, S. R., Heresco-Levy, U., & Umbricht, D. (2012) · Schizophrenia Bulletin · doi:10.1093/schbul/sbs069 · Cited by 322 · 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
Thomas, M. L., Green, M. F., Hellemann, G., Sugar, C. A., Tarasenko, M., Calkins, M. E., Greenwood, T. A., Gur, R. E., Gur, R. C., Lazzeroni, L. C., et al. (2017) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2016.2980 · Cited by 206 · see citing works
Altered Cortical Ensembles in Mouse Models of Schizophrenia
Hamm, J. P., Peterka, D. S., Gogos, J. A., & Yuste, R. (2017) · Neuron · doi:10.1016/j.neuron.2017.03.019 · Cited by 175 · see citing works
Autism As a Disorder of High Intelligence
Crespi, B. J. (2016) · Frontiers in Neuroscience · doi:10.3389/fnins.2016.00300 · Cited by 156 · see citing works
Rotaru, D. C., Yoshino, H., Lewis, D. A., Ermentrout, G. B., & Gonzalez-Burgos, G. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.1970-10.2011 · Cited by 151 · see citing works
Deficits in high- (>60 Hz) gamma-band oscillations during visual processing in schizophrenia
Grützner, C., Wibral, M., Sun, L., Rivolta, D., Singer, W., Maurer, K., & Uhlhaas, P. J. (2013) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2013.00088 · Cited by 140 · see citing works
RETRACTED: Impaired Visual Cortical Plasticity in Schizophrenia
Çavuş, I., Reinhart, R. M. G., Roach, B. J., Gueorguieva, R., Teyler, T. J., Clapp, W. C., Ford, J. M., Krystal, J. H., & Mathalon, D. H. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.01.013 · Cited by 130 · see citing works
RetractedFriedman, T., Sehatpour, P., Dias, E., Perrin, M., & Javitt, D. C. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.10.037 · Cited by 102 · see citing works
Self-citationConsequences of Magnocellular Dysfunction on Processing Attended Information in Schizophrenia
Martinez, A., Hillyard, S. A., Bickel, S., Dias, E. C., Butler, P. D., & Javitt, D. C. (2012) · Cerebral Cortex · doi:10.1093/cercor/bhr195 · Cited by 94 · see citing works
Self-citationDavies, D. J., Teufel, C., & Fletcher, P. C. (2018) · Schizophrenia Bulletin · doi:10.1093/schbul/sbx177 · Cited by 69 · see citing works
Electrophysiological assessment of auditory stimulus-specific plasticity in schizophrenia
Mears, R. P., & Spencer, K. M. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.12.016 · Cited by 64 · see citing works
Disruption of Conscious Access in Schizophrenia
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Impaired magnocellular/dorsal stream activation predicts impaired reading ability in schizophrenia
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Self-citationSauer, A., Zeev‐Wolf, M., Grent‐'t‐Jong, T., Recasens, M., Wacongne, C., Wibral, M., Helbling, S., Peled, A., Grinshpoon, A., Singer, W., et al. (2017) · Human Brain Mapping · doi:10.1002/hbm.23716 · Cited by 31 · see citing works
Nasiriavanaki, Z., Barbour, T., Farabaugh, A. H., Fava, M., Holmes, A. J., Tootell, R. B. H., & Holt, D. J. (2021) · NeuroImage: Clinical · doi:10.1016/j.nicl.2021.102585 · Cited by 24 · see citing works
Hallucinations, neuroplasticity, and prediction errors in schizophrenia
McCleery, A., Wynn, J. K., & Green, M. F. (2018) · Scandinavian Journal of Psychology · doi:10.1111/sjop.12413 · Cited by 25 · see citing works
Simultaneous fMRI-EEG-DTI recording of MMN in patients with schizophrenia
Kirino, E., Hayakawa, Y., Inami, R., Inoue, R., & Aoki, S. (2019) · PLoS ONE · doi:10.1371/journal.pone.0215023 · Cited by 22 · see citing works
Damiani, S., Fusar-Poli, L., Brondino, N., Provenzani, U., Baldwin, H., Fusar-Poli, P., & Politi, P. (2020) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2020.111068 · Cited by 18 · see citing works
- Authors
- Javitt, D. C.
- Affiliations
- Nathan Kline Institute for Psychiatric Research (US)
- Corresponding author
- Javitt, Daniel C.
- ORCID
- Javitt, Daniel C.
- Venue
- Annual Review of Clinical Psychology
- Publisher
- Annual Reviews
- Published
- 2009-04-01
- Volume
- 5
- Issue
- 1
- Pages
- 249-275
- ISSN
- 1548-5943 (ISSN-L)
- 1548-5951
- PMC
- PMC4501390
- OpenAlex
- W2149954813
- Cited by
- 503
- References
- 125
- Citations by year
- 2026: 16 · 2025: 15 · 2024: 18 · 2023: 31 · 2022: 22 · 2021: 32 · 2020: 28 · 2019: 49 · 2018: 22 · 2017: 26 · 2016: 33 · 2015: 36 · 2014: 34 · 2013: 43 · 2012: 28
- FWCI
- 4.04
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annual Review of Clinical Psychology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R37MH049334, R37MH49334, R24MH082790, R24 MH82790, R01MH049334)
- National Institute on Drug Abuse (R01DA03383, R01DA003383)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Social Sciences › Arts and Humanities › Philosophy › Mental Health and Psychiatry
- Life Sciences › Neuroscience › Cognitive Neuroscience › Hallucinations in medical conditions
- Keywords
- schizophrenia, cognitive impairment, bottom-up processing, top-down processing, auditory processing, visual processing, NMDA receptor dysfunction, perceptual closure, phonological processing, auditory emotion recognition, object recognition, reading deficits
- MeSH terms
- Brain, Cognition Disorders, Evoked Potentials, Visual, Humans, Magnetic Resonance Imaging, Memory, Short-Term, Perceptual Disorders, Schizophrenia, Verbal Behavior, Receptors, N-Methyl-D-Aspartate, Glutamic Acid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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