Modulation of hippocampal theta and hippocampal-prefrontal cortex function by a schizophrenia risk gene
Hippocampal theta-band oscillations are thought to facilitate the co-ordination of brain activity across distributed networks, including between the hippocampus and prefrontal cortex (PFC). Impairments in hippocampus-PFC functional connectivity are implicated in schizophrenia and are associated with...
| Main Authors: | , , , , , , , |
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| Formato: | Journal article |
| Idioma: | English |
| Publicado em: |
Wiley
2015
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| _version_ | 1826308899551051776 |
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| author | Cousijn, H Tunbridge, EM Rolinski, M Wallis, G Colclough, GL Woolrich, MW Nobre, AC Harrison, PJ |
| author_facet | Cousijn, H Tunbridge, EM Rolinski, M Wallis, G Colclough, GL Woolrich, MW Nobre, AC Harrison, PJ |
| author_sort | Cousijn, H |
| collection | OXFORD |
| description | Hippocampal theta-band oscillations are thought to facilitate the co-ordination of brain activity across distributed networks, including between the hippocampus and prefrontal cortex (PFC). Impairments in hippocampus-PFC functional connectivity are implicated in schizophrenia and are associated with a polymorphism within the ZNF804A gene that shows a genome-wide significant association with schizophrenia. However, the mechanisms by which ZNF804A affects hippocampus-PFC connectivity are unknown. We used a multimodal imaging approach to investigate the impact of the ZNF804A polymorphism on hippocampal theta and hippocampal network coactivity. Healthy volunteers homozygous for the ZNF804A rs1344706 (A[risk]/C[nonrisk]) polymorphism were imaged at rest using both magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI). A dual-regression approach was used to investigate coactivations between the hippocampal network and other brain regions for both modalities, focusing on the theta band in the case of MEG. We found a significant decrease in intrahippocampal theta (using MEG) and greater coactivation of the superior frontal gyrus with the hippocampal network (using fMRI) in risk versus nonrisk homozygotes. Furthermore, these measures showed a significant negative correlation. Our demonstration of an inverse relationship between hippocampal theta and hippocampus-PFC coactivation supports a role for hippocampal theta in coordinating hippocampal-prefrontal activity. The ZNF804A-related differences that we find in hippocampus-PFC coactivation are consistent with previously reported associations with functional connectivity and with these changes lying downstream of altered hippocampal theta. Changes in hippocampal-PFC co-ordination, driven by differences in oscillatory activity, may be one mechanism by which ZNF804A impacts on brain function and risk for psychosis. |
| first_indexed | 2024-03-07T07:26:06Z |
| format | Journal article |
| id | oxford-uuid:bb1b0ccb-6c0e-4b05-aaeb-99a7c9fb0e7f |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:26:06Z |
| publishDate | 2015 |
| publisher | Wiley |
| record_format | dspace |
| spelling | oxford-uuid:bb1b0ccb-6c0e-4b05-aaeb-99a7c9fb0e7f2022-11-11T17:40:07ZModulation of hippocampal theta and hippocampal-prefrontal cortex function by a schizophrenia risk geneJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:bb1b0ccb-6c0e-4b05-aaeb-99a7c9fb0e7fEnglishSymplectic ElementsWiley2015Cousijn, HTunbridge, EMRolinski, MWallis, GColclough, GLWoolrich, MWNobre, ACHarrison, PJHippocampal theta-band oscillations are thought to facilitate the co-ordination of brain activity across distributed networks, including between the hippocampus and prefrontal cortex (PFC). Impairments in hippocampus-PFC functional connectivity are implicated in schizophrenia and are associated with a polymorphism within the ZNF804A gene that shows a genome-wide significant association with schizophrenia. However, the mechanisms by which ZNF804A affects hippocampus-PFC connectivity are unknown. We used a multimodal imaging approach to investigate the impact of the ZNF804A polymorphism on hippocampal theta and hippocampal network coactivity. Healthy volunteers homozygous for the ZNF804A rs1344706 (A[risk]/C[nonrisk]) polymorphism were imaged at rest using both magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI). A dual-regression approach was used to investigate coactivations between the hippocampal network and other brain regions for both modalities, focusing on the theta band in the case of MEG. We found a significant decrease in intrahippocampal theta (using MEG) and greater coactivation of the superior frontal gyrus with the hippocampal network (using fMRI) in risk versus nonrisk homozygotes. Furthermore, these measures showed a significant negative correlation. Our demonstration of an inverse relationship between hippocampal theta and hippocampus-PFC coactivation supports a role for hippocampal theta in coordinating hippocampal-prefrontal activity. The ZNF804A-related differences that we find in hippocampus-PFC coactivation are consistent with previously reported associations with functional connectivity and with these changes lying downstream of altered hippocampal theta. Changes in hippocampal-PFC co-ordination, driven by differences in oscillatory activity, may be one mechanism by which ZNF804A impacts on brain function and risk for psychosis. |
| spellingShingle | Cousijn, H Tunbridge, EM Rolinski, M Wallis, G Colclough, GL Woolrich, MW Nobre, AC Harrison, PJ Modulation of hippocampal theta and hippocampal-prefrontal cortex function by a schizophrenia risk gene |
| title | Modulation of hippocampal theta and hippocampal-prefrontal cortex function by a schizophrenia risk gene |
| title_full | Modulation of hippocampal theta and hippocampal-prefrontal cortex function by a schizophrenia risk gene |
| title_fullStr | Modulation of hippocampal theta and hippocampal-prefrontal cortex function by a schizophrenia risk gene |
| title_full_unstemmed | Modulation of hippocampal theta and hippocampal-prefrontal cortex function by a schizophrenia risk gene |
| title_short | Modulation of hippocampal theta and hippocampal-prefrontal cortex function by a schizophrenia risk gene |
| title_sort | modulation of hippocampal theta and hippocampal prefrontal cortex function by a schizophrenia risk gene |
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