Cell-specific mechanisms of medial frontal theta during error monitoring

Theta oscillations in dorsomedial frontal cortex (DMFC) are prominent signatures of cognitive control and error monitoring (Cavanagh and Frank, Trends Cogn. Sci., 2014; Cohen, Trends Neurosci., 2014). Yet, the neuronal mechanisms generating these signals remain uncertain. Here, we study whether neocortical pyramidal neurons alone can induce frontal theta during error monitoring by combining electrophysiological data and biophysical modeling. We recorded neuronal spiking and local field potentials (LFPs) across all layers of DMFC from two macaque monkeys performing a saccade countermanding stop-signal task. In this task, subjects were required to generate a saccade to a peripheral target, but to inhibit this planned saccade when a stop-signal appeared. Errors occurred when monkeys generated a saccade despite the appearance of a stop-signal. We utilized the recorded error-related spiking activity of putative L3 and L5 pyramidal neurons to estimate the pre-synaptic inputs of these neurons in realistic biophysical neuronal models around the saccade onset time (L3 model: Eyal et al., Front. Cell. Neurosci., 2018; L5 model: Hay et al., PLoS Comput. Biol., 2011). We focused on reproducing the spiking activity of correct and error trials and considered only excitatory synaptic inputs (AMPA and NMDA synapses). After estimating the pre-synaptic inputs onto these neurons, we simulated the LFPs produced by the activity of a population of L3 and L5 error neurons at 16 equally spaced (150 μm) vertically aligned points located at the center of the cortical column. Recorded LFPs showed an increase in theta power across cortical layers around saccade onset, which was more pronounced in L3 and L5, and significantly larger in error versus correct trials. Simulated LFPs showed a similar increase in the laminar time-varying theta power around saccade onset, which was also significantly larger in error versus correct trials. Simulations indicate that L5 error pyramidal neurons, but not L3 contributed to the increase in the laminar theta power around saccade onset.