Impaired theta phase coupling underlies frontotemporal dysconnectivity in schizophrenia
| Autor: | Oliver D. Howes, Neil Burgess, Rick A. Adams, Raphael Kaplan, Fanfan Zheng, Stelios Orfanos, Sofie S. Meyer, Daniel Bush, Tiago Reis Marques |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male hippocampus Hippocampus Hippocampal formation behavioral disciplines and activities Temporal lobe 03 medical and health sciences Phase coupling 0302 clinical medicine mental disorders Neural Pathways medicine Humans Theta Rhythm Prefrontal cortex 030304 developmental biology 0303 health sciences prefrontal cortex medicine.diagnostic_test Matched control Magnetoencephalography Original Articles spatial memory medicine.disease Receptors GABA-A Temporal Lobe schizophrenia Schizophrenia theta Positron-Emission Tomography Female Neurology (clinical) Psychology Neuroscience psychological phenomena and processes 030217 neurology & neurosurgery |
| Zdroj: | Brain |
| ISSN: | 1460-2156 |
| Popis: | Communication between the frontal and medial temporal lobes is impaired in schizophrenia. Adams et al. find that when retrieving memories, subjects with schizophrenia have lower theta phase oscillatory coupling between these areas, and lower α-GABAA receptor availability in the hippocampal area where coupling is lost. Frontotemporal dysconnectivity is a key pathology in schizophrenia. The specific nature of this dysconnectivity is unknown, but animal models imply dysfunctional theta phase coupling between hippocampus and medial prefrontal cortex (mPFC). We tested this hypothesis by examining neural dynamics in 18 participants with a schizophrenia diagnosis, both medicated and unmedicated; and 26 age, sex and IQ matched control subjects. All participants completed two tasks known to elicit hippocampal-prefrontal theta coupling: a spatial memory task (during magnetoencephalography) and a memory integration task. In addition, an overlapping group of 33 schizophrenia and 29 control subjects underwent PET to measure the availability of GABAARs expressing the α5 subunit (concentrated on hippocampal somatostatin interneurons). We demonstrate—in the spatial memory task, during memory recall—that theta power increases in left medial temporal lobe (mTL) are impaired in schizophrenia, as is theta phase coupling between mPFC and mTL. Importantly, the latter cannot be explained by theta power changes, head movement, antipsychotics, cannabis use, or IQ, and is not found in other frequency bands. Moreover, mPFC-mTL theta coupling correlated strongly with performance in controls, but not in subjects with schizophrenia, who were mildly impaired at the spatial memory task and no better than chance on the memory integration task. Finally, mTL regions showing reduced phase coupling in schizophrenia magnetoencephalography participants overlapped substantially with areas of diminished α5-GABAAR availability in the wider schizophrenia PET sample. These results indicate that mPFC-mTL dysconnectivity in schizophrenia is due to a loss of theta phase coupling, and imply α5-GABAARs (and the cells that express them) have a role in this process. |
| Databáze: | OpenAIRE |
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