NMDA receptor function in large-scale anticorrelated neural systems with implications for cognition and schizophrenia
| Autor: | Naomi Driesen, Peter T. Morgan, Mark A. Smith, Xiao Jing Wang, John D. Murray, Toral Surti, Philip R. Corlett, Ramachandran Ramani, Michael H. Bloch, Debra J. Ennis, Mark J. Niciu, John H. Krystal, Alan Anticevic, Grega Repovs, Mark Gancsos |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Adult
Male Models Neurological Receptors N-Methyl-D-Aspartate Synaptic Transmission Glutamatergic Young Adult Cognition Double-Blind Method Memory medicine Humans Infusions Intravenous Default mode network Multidisciplinary Working memory Brain Human brain Biological Sciences medicine.disease Magnetic Resonance Imaging medicine.anatomical_structure Pattern Recognition Visual Schizophrenia Disinhibition NMDA receptor Female Ketamine medicine.symptom Psychology Neuroscience Excitatory Amino Acid Antagonists Algorithms Psychomotor Performance |
| Popis: | Glutamatergic neurotransmission mediated by N -methyl- d -aspartate (NMDA) receptors is vital for the cortical computations underlying cognition and might be disrupted in severe neuropsychiatric illnesses such as schizophrenia. Studies on this topic have been limited to processes in local circuits; however, cognition involves large-scale brain systems with multiple interacting regions. A prominent feature of the human brain’s global architecture is the anticorrelation of default-mode vs. task-positive systems. Here, we show that administration of an NMDA glutamate receptor antagonist, ketamine, disrupted the reciprocal relationship between these systems in terms of task-dependent activation and connectivity during performance of delayed working memory. Furthermore, the degree of this disruption predicted task performance and transiently evoked symptoms characteristic of schizophrenia. We offer a parsimonious hypothesis for this disruption via biophysically realistic computational modeling, namely cortical disinhibition. Together, the present findings establish links between glutamate’s role in the organization of large-scale anticorrelated neural systems, cognition, and symptoms associated with schizophrenia in humans. |
| Databáze: | OpenAIRE |
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