Unmasking Latent Inhibitory Connections in Human Cortex to Reveal Dormant Cortical Memories

Summary 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. Video Abstract
Highlights • Associative memories can be measured in human cortex following learning • Over time the expression of these memories becomes silenced • By reducing cortical GABA with brain stimulation these memories are re-expressed • Cortical memories appear to be stored in balanced excitatory-inhibitory ensembles
Barron et al. show that otherwise silent cortical memories are unmasked in the human brain when the concentration of cortical GABA is reduced using brain stimulation. This suggests that memories are stored in cortex in balanced excitatory and inhibitory ensembles.