title: Unmasking Latent Inhibitory Connections in Human Cortex to Reveal Dormant Cortical Memories.
abstract: Balance of cortical excitation and inhibition (EI) is thought to be disrupted in several neuropsychiatric conditions, yet it is not clear how it is maintained in the healthy human brain. When EI balance is disturbed during learning and memory in animal models, it can be restabilized via formation of inhibitory replicas of newly formed excitatory connections. Here we assess evidence for such selective inhibitory rebalancing in humans. Using fMRI repetition suppression we measure newly formed cortical associations in the human brain. We show that expression of these associations reduces over time despite persistence in behavior, consistent with inhibitory rebalancing. To test this, we modulated excitation/inhibition balance with transcranial direct current stimulation (tDCS). Using ultra-high-field (7T) MRI and spectroscopy, we show that reducing GABA allows cortical associations to be re-expressed. This suggests that in humans associative memories are stored in balanced excitatory-inhibitory ensembles that lie dormant unless latent inhibitory connections are unmasked.
authors.affiliation: The Wellcome Trust Centre for Neuroimaging, Institute of Neurology, University College London, London WC1N 3BG, UK; The Oxford Centre for Functional Magnetic Resonance Imaging of the Brain, University of Oxford, Oxford OX3 9DU, UK. Electronic address: helen.barron@merton.ox.ac.uk.
authors.forename: H C
authors.initials: HC
authors.lastname: Barron
authors.affiliation: Centre for Neural Circuits and Behaviour, University of Oxford, Oxford OX1 3SR, UK.
authors.forename: T P
authors.initials: TP
authors.lastname: Vogels
authors.affiliation: The Oxford Centre for Functional Magnetic Resonance Imaging of the Brain, University of Oxford, Oxford OX3 9DU, UK.
authors.forename: U E
authors.initials: UE
authors.lastname: Emir
authors.affiliation: The Oxford Centre for Functional Magnetic Resonance Imaging of the Brain, University of Oxford, Oxford OX3 9DU, UK.
authors.forename: T R
authors.initials: TR
authors.lastname: Makin
authors.affiliation: The Oxford Centre for Functional Magnetic Resonance Imaging of the Brain, University of Oxford, Oxford OX3 9DU, UK.
authors.forename: J
authors.initials: J
authors.lastname: O'Shea
authors.affiliation: The Oxford Centre for Functional Magnetic Resonance Imaging of the Brain, University of Oxford, Oxford OX3 9DU, UK.
authors.forename: S
authors.initials: S
authors.lastname: Clare
authors.affiliation: The Oxford Centre for Functional Magnetic Resonance Imaging of the Brain, University of Oxford, Oxford OX3 9DU, UK.
authors.forename: S
authors.initials: S
authors.lastname: Jbabdi
authors.affiliation: The Wellcome Trust Centre for Neuroimaging, Institute of Neurology, University College London, London WC1N 3BG, UK.
authors.forename: R J
authors.initials: RJ
authors.lastname: Dolan
authors.affiliation: The Wellcome Trust Centre for Neuroimaging, Institute of Neurology, University College London, London WC1N 3BG, UK; The Oxford Centre for Functional Magnetic Resonance Imaging of the Brain, University of Oxford, Oxford OX3 9DU, UK. Electronic address: behrens@fmrib.ox.ac.uk.
authors.forename: T E J
authors.initials: TE
authors.lastname: Behrens
mesh_terms: D001244:Association; D002540:Cerebral Cortex / Q000378:metabolism / Q000502:physiology*; D005260:Female; D059907:Functional Neuroimaging; D006801:Humans; D007858:Learning / Q000502:physiology; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008568:Memory / Q000502:physiology*; D009433:Neural Inhibition / Q000502:physiology*; D009434:Neural Pathways; D065908:Transcranial Direct Current Stimulation; D055815:Young Adult; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D005680:gamma-Aminobutyric Acid