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A Dynamical Systems Hypothesis of Schizophrenia
Open accessAbstract
We propose a top-down approach to the symptoms of schizophrenia based on a statistical dynamical framework. We show that a reduced depth in the basins of attraction of cortical attractor states destabilizes the activity at the network level due to the constant statistical fluctuations caused by the stochastic spiking of neurons. In integrate-and-fire network simulations, a decrease in the NMDA receptor conductances, which reduces the depth of the attractor basins, decreases the stability of short-term memory states and increases distractibility. The cognitive symptoms of schizophrenia such as distractibility, working memory deficits, or poor attention could be caused by this instability of attractor states in prefrontal cortical networks. Lower firing rates are also produced, and in the orbitofrontal and anterior cingulate cortex could account for the negative symptoms, including a reduction of emotions. Decreasing the GABA as well as the NMDA conductances produces not only switches between the attractor states, but also jumps from spontaneous activity into one of the attractors. We relate this to the positive symptoms of schizophrenia, including delusions, paranoia, and hallucinations, which may arise because the basins of attraction are shallow and there is instability in temporal lobe semantic memory networks, leading thoughts to move too freely round the attractor energy landscape.
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“In addition, the discrete-pool model used in Loh et al. (2007) cannot capture features that emerge naturally from a continuous model described here: Broadening of WM representations, smooth random drift of memory, and sensitivity to target-distractor similarity.”
From Linking microcircuit dysfunction to cognitive impairment: Effects of disinhibition associated with schizophrenia in a cortical working memory model (2014) · cites this paper as Loh et al. 2007
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“Increased miss rate would be expected if the persistent activity pattern was completely lost in the target cells (Loh et al. 2007), or a bump spontaneously appeared in nontarget cells, interfering with target encoding (Cano-Colino and Compte 2012).”
From Linking microcircuit dysfunction to cognitive impairment: Effects of disinhibition associated with schizophrenia in a cortical working memory model (2014) · cites this paper as Loh et al. 2007
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Metadata
- Authors
- Loh, M., Rolls, E. T., & Deco, G.
- Affiliations
- Universitat Pompeu Fabra (ES)
- University of Oxford (GB)
- Institució Catalana de Recerca i Estudis Avançats (ES)
- Corresponding author
- Rolls, Edmund T
- Venue
- PLoS Computational Biology
- Publisher
- Public Library of Science (PLoS)
- Published
- 2007-11-09
- Volume
- 3
- Issue
- 11
- Pages
- e228
- ISSN
- 1553-734X (ISSN-L)
- 1553-7358
- PMC
- PMC2065887
- OpenAlex
- W2113693127
- Cited by
- 164
- References
- 84
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 6 · 2023: 9 · 2022: 5 · 2021: 7 · 2020: 3 · 2019: 8 · 2018: 11 · 2017: 13 · 2016: 5 · 2015: 12 · 2014: 7 · 2013: 12 · 2012: 11
- FWCI
- 5.68
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Computational Biology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Repositori digital de la UPF (Universitat Pompeu Fabra) (submittedVersion, other-oa)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- Boehringer Ingelheim Fonds
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- schizophrenia, dynamical systems, basins of attraction, short-term memory, distractibility, working memory deficits, negative symptoms, positive symptoms, orbitofrontal cortex, anterior cingulate cortex, statistical fluctuations, network stability
- MeSH terms
- Action Potentials, Animals, Brain, Computer Simulation, Humans, Models, Neurological, Nerve Net, Synaptic Transmission, Schizophrenia, Receptors, N-Methyl-D-Aspartate, Receptors, GABA
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