(B-63) Error neurons in supplementary eye field drive low-frequency cortical rhythmicity with a negligible contribution to current sources

Introduction:: Human and macaque electrophysiological studies have characterized the scalp potentials associated with error monitoring, notably an error-related negativity (ERN) and increased theta power over medial frontal cortex (Gehring et al., 2012; Cavanagh and Frank, 2014). While the ERN is thought to originate from midfrontal areas such as the supplementary eye field (SEF), the cellular-level mechanisms originating these signals and their involvement in midfrontal theta generation remain uncertain. Previously, we have characterized the relationship between the spiking activity of neurons in SEF and the ERN (Sajad et al., 2019). We identified a population of error neurons that showed a higher discharge rate on error versus correct trials and proposed their role in the microcircuit for error processing. Yet, a direct evaluation of the contribution of error putative pyramidal neurons to these signatures observed in scalp EEG is still missing. Here, we address this question by combining detailed biophysical modeling with neural data recorded in SEF from a macaque monkey performing the saccade stop-signal task.

Materials and Methods:: We recorded neuronal spiking and local field potentials (LFPs) across all layers of SEF 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. The power spectrum density was calculated to identify the presence of slow oscillations on the simulated LFPs. The laminar time-varying power maps were calculated using the Hilbert Transform.

Results, Conclusions, and Discussions:: Results and Discussion: 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 (Figure – top). 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 (Figure – bottom). Simulations indicate that L5 error pyramidal neurons drive this increase in laminar theta-power but that error neurons have little to no contribution to the laminar current sources observed in SEF.
Conclusions: 1) Biophysical models of L3 and L5 pyramidal error neurons fit the spike-rate modulation and inter-spike interval profiles. 2) L5 but not L3 error pyramidal cells intrinsically produce theta rhythm, which phase-resets with saccades. 3) Contribution from L3 and L5 pyramidal cells signaling errors to the total current source power in SEF was negligible.

Acknowledgements (Optional): : This work was supported by the NEI [grant numbers: P30EY008126, R01EY019882], NIMH [grant number: R01-MH55806], Canadian Institutes of Health Research Postdoctoral Fellowship, and FIU SEED Grant Wallace Coulter Foundation. Beatriz Herrera was supported by a fellowship from NIMH [award number: F31MH129101].

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