Cousijn Helena, Tunbridge Elizabeth M, Rolinski Michal, Wallis George, Colclough Giles L, Woolrich Mark W, Nobre Anna C, Harrison Paul J
Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford,, United Kingdom; Oxford Centre for Human Brain Activity, University of Oxford, Warneford Hospital, Oxford, United Kingdom.
Hum Brain Mapp. 2015 Jun;36(6):2387-95. doi: 10.1002/hbm.22778. Epub 2015 Mar 10.
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.
海马体θ波段振荡被认为有助于协调分布式网络中的大脑活动，包括海马体与前额叶皮质（PFC）之间的活动。海马体与PFC的功能连接受损与精神分裂症有关，并且与ZNF804A基因内的一种多态性相关，该多态性在全基因组范围内与精神分裂症存在显著关联。然而，ZNF804A影响海马体与PFC连接的机制尚不清楚。我们采用多模态成像方法来研究ZNF804A多态性对海马体θ波和海马体网络共同活动的影响。对ZNF804A rs1344706（A[风险]/C[非风险]）多态性的纯合健康志愿者在静息状态下使用脑磁图（MEG）和功能磁共振成像（fMRI）进行成像。采用双回归方法研究两种模态下海马体网络与其他脑区之间的共同激活情况，在MEG的情况下重点关注θ波段。我们发现，与非风险纯合子相比，风险纯合子的海马体内θ波（使用MEG）显著降低，且额上回与海马体网络的共同激活程度更高（使用fMRI）。此外，这些测量结果显示出显著的负相关。我们证明海马体θ波与海马体 - PFC共同激活之间存在反比关系，这支持了海马体θ波在协调海马体 - 前额叶活动中发挥作用。我们在海马体 - PFC共同激活中发现的与ZNF804A相关的差异与先前报道的功能连接关联一致，并且这些变化位于海马体θ波改变的下游。由振荡活动差异驱动的海马体 - PFC协调变化可能是ZNF804A影响脑功能和精神病风险的一种机制。
