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Impaired theta phase coupling underlies frontotemporal dysconnectivity in schizophrenia

文献类型：期刊论文

作者Adams, Rick A.1,9,10,11,12; Bush, Daniel1,8; Zheng, Fanfan1,7; Meyer, Sofie S.1,8; Kaplan, Raphael6,9; Orfanos, Stelios4,5; Marques, Tiago Reis2,3; Howes, Oliver D.2,3; Burgess, Neil1,8,9
刊名BRAIN
出版日期2020-04-01
卷号143页码:1261-1277
ISSN号0006-8950
关键词schizophrenia hippocampus prefrontal cortex theta spatial memory
DOI10.1093/brain/awaa035
通讯作者Adams, Rick A.(rick.adams@ucl.ac.uk)
英文摘要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 GABA(A)Rs expressing the alpha 5 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 alpha 5-GABA(A)R 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 alpha 5-GABA(A)Rs (and the cells that express them) have a role in this process.
WOS关键词SPATIAL WORKING-MEMORY ; MEDIAL TEMPORAL-LOBE ; PREFRONTAL CORTEX ; HIPPOCAMPAL THETA ; RELATIONAL MEMORY ; FUNCTIONAL CONNECTIVITY ; TRANSITIVE INFERENCE ; SUSTAINED ATTENTION ; EPISODIC MEMORY ; ANIMAL-MODEL
资助项目Academy of Medical Sciences[AMS-SGCL13-Adams] ; National Institute of Health Research[CL-2013-18-003] ; NIHR UCLH Biomedical Research Centre ; Sir Henry Wellcome Fellowship[101261/Z/13/Z] ; Medical Research Council UK[MC-A656-5QD30] ; Maudsley Charity[666] ; Brain and Behavior Research Foundation ; Wellcome Trust[094849/Z/10/Z] ; ERC advanced grant (NEUROMEM)
WOS研究方向Neurosciences & Neurology
语种英语
出版者OXFORD UNIV PRESS
WOS记录号WOS:000541770600031
资助机构Academy of Medical Sciences ; National Institute of Health Research ; NIHR UCLH Biomedical Research Centre ; Sir Henry Wellcome Fellowship ; Medical Research Council UK ; Maudsley Charity ; Brain and Behavior Research Foundation ; Wellcome Trust ; ERC advanced grant (NEUROMEM)
源URL[http://ir.ia.ac.cn/handle/173211/39924]  
专题自动化研究所_脑网络组研究中心
通讯作者Adams, Rick A.
作者单位1.UCL, Inst Cognit Neurosci, 17 Queen Sq, London WC1N 3AZ, England
2.Kings Coll London, Dept Psychosis Studies, Inst Psychiat Psychol & Neurosci IoPPN, London SE5 8AF, England
3.Imperial Coll London, Hammersmith Hosp, Fac Med, Inst Clin Sci, London W12 0NN, England
4.Kings Coll London, Dept Forens & Neurodev Sci, Inst Psychiat Psychol & Neurosci, De Crespigny Pk,Denmark Hill, London SE5 8AF, England
5.Springfield Univ Hosp, South West London & St Georges Mental Hlth NHS Tr, 61 Glenburnie Rd, London SW17 7DJ, England
6.Norwegian Univ Sci & Technol, Kavli Inst Syst Neurosci, Trondheim, Norway
7.Chinese Acad Sci, Brainnetome Ctr, Inst Automat, 95 Zhongguancun East Rd, Beijing 100190, Peoples R China
8.UCL, Queen Sq Inst Neurol, London WC1N 3BG, England
9.UCL, Welcome Ctr Human Neuroimaging, 12 Queen Sq, London WC1N 3BG, England
10.UCL, Ctr Med Image Comp, Dept Comp Sci, Malet Pl, London WC1E 7JE, England
推荐引用方式
GB/T 7714		 Adams, Rick A.,Bush, Daniel,Zheng, Fanfan,et al. Impaired theta phase coupling underlies frontotemporal dysconnectivity in schizophrenia[J]. BRAIN,2020,143:1261-1277.
APA Adams, Rick A..,Bush, Daniel.,Zheng, Fanfan.,Meyer, Sofie S..,Kaplan, Raphael.,...&Burgess, Neil.(2020).Impaired theta phase coupling underlies frontotemporal dysconnectivity in schizophrenia.BRAIN,143,1261-1277.
MLA Adams, Rick A.,et al."Impaired theta phase coupling underlies frontotemporal dysconnectivity in schizophrenia".BRAIN 143(2020):1261-1277.

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