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Neuroimage. 2015 Oct 15;120:362-70. doi: 10.1016/j.neuroimage.2015.07.016. Epub 2015 Jul 14.

Ventromedial prefrontal cortex drives hippocampal theta oscillations induced by mismatch computations.

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Queensland Brain Institute, The University of Queensland, St Lucia 4072, Brisbane, Australia; Centre for Advanced Imaging, The University of Queensland, St Lucia 4072, Brisbane, Australia; Australian Research Council Centre of Excellence for Integrative Brain Function Centre of Excellence for Integrative Brain Function, The University of Queensland, St Lucia 4072, Brisbane, Australia. Electronic address:
Wellcome Trust Centre for Neuroimaging, Institute of Neurology, University College London, 12 Queen Square, London WC1N 3BG, UK.
Institute of Cognitive Neuroscience, University College London, 17 Queen Square, London WC1N 3AR, UK.


Detecting environmental change is fundamental for adaptive behavior in an uncertain world. Previous work indicates the hippocampus supports the generation of novelty signals via implementation of a match-mismatch detector that signals when an incoming sensory input violates expectations based on past experience. While existing work has emphasized the particular contribution of the hippocampus, here we ask which other brain structures also contribute to match-mismatch detection. Furthermore, we leverage the fine-grained temporal resolution of magnetoencephalography (MEG) to investigate whether mismatch computations are spectrally confined to the theta range, based on the prominence of this range of oscillations in models of hippocampal function. By recording MEG activity while human subjects perform a task that incorporates conditions of match-mismatch novelty we show that mismatch signals are confined to the theta band and are expressed in both the hippocampus and ventromedial prefrontal cortex (vmPFC). Effective connectivity analyses (dynamic causal modeling) show that the hippocampus and vmPFC work as a functional circuit during mismatch detection. Surprisingly, our results suggest that the vmPFC drives the hippocampus during the generation and processing of mismatch signals. Our findings provide new evidence that the hippocampal-vmPFC circuit is engaged during novelty processing, which has implications for emerging theories regarding the role of vmPFC in memory.


Connectivity; Hippocampus; MEG; Mismatch; Novelty; Prediction; Theta entrainment; Uncertainty; Ventromedial prefrontal cortex

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