CNS*2026 Halifax

Introduction
Electroencephalography (EEG) and Magnetoencephalography (MEG) are widely used non-invasive techniques to record electric brain activity from the human brain. While it has long been known that synchronous intracellular currents in dendrites of neocortical pyramidal neurons underlie E/MEG signals, only few theories on the computational role of E/MEG dynamics consider dendritic computations. For instance, high-amplitude transient ~20Hz oscillations known as cortical beta-events, dominate human E/MEG signals and have been repeatedly argued to support perception and motor action by orchestrating spiking activity [1,2]. Yet, the neural generators of lower frequency oscillations and their effect on dendritic activity are underexplored.


Methods
Here, we present a biophysically detailed neocortical circuit model that is optimized to study how dendritic processes manifest in human E/MEG signals. Somatic conductances were tuned to reproduce dynamics observed in in vitro experiments from human donors. The active conductances in the pyramidal neuron dendrites were tuned to reproduce non-linear processes associated with intracellular calcium. The layer 5 neurons exhibit calcium plateau potentials in response to high-frequency somatic spiking, coincident somatic and dendritic inputs, and strong feedback inputs, as repeatedly shown in the literature [3,4]. The layer 2/3 pyramidal neurons generate shorter dendritic spikes that have recently been reported in human neurons [5,6].


Results
Expanding prior theories on the generation of beta events [7,8], we demonstrate how dendritic calcium spikes, in combination with somatic and dendritic inhibition by GABAergic interneurons, can produce the characteristic waveform shapes at 15-25 Hz observed in human E/MEG data. These findings complement previous reports of dendritic calcium spikes being detectable at the cortical surface in rodents [9], by demonstrating that these spikes are associated with large currents that dominate the E/MEG signal. To test and constrain model predictions, we show preliminary evidence comparing simulated extracellular fields to laminar recordings during homologous beta events in rodents.


Discussion
Our modeling work makes important contributions to understanding the role of dendritic calcium dynamics in the multiscale neural generators of functionally relevant human brain oscillations. Across species translation of our results provides a powerful framework to examine the causal influence of dendritic processes and other beta event generating mechanisms in sensory perception and motor action.  The circuit is packaged and distributed within the user-friendly Human Neocortical Neurosolver (HNN) software (https://hnn.brown.edu) designed for multiscale interpretation of human E/MEG signals, making our tools and results available to a broad neuroscience community.


References
[1] Shin, H. et al. (2017). elife, 6, e29086.
[2] Bonaiuto, J. J. et al. (2021). NeuroImage, 242, 118479.
[3] Larkum, M. E. et al. (1999). Proceedings of the National Academy of Sciences, 96(25), 14600-14604.
[4] Larkum, M. et al. (1999). Nature, 398(6725), 338-341.
[5] Gidon, A. et al. (2020). Science, 367(6473), 83-87.
[6] Gooch, H. M. et al. (2022). Cell reports, 41(3).
[7] Sherman, M. A. et al. (2016). Proceedings of the National Academy of Sciences, 113(33), E4885-E4894.
[8] Law, R. G. et al. (2022). Cerebral Cortex, 32(4), 668-688.
[9] Suzuki, M., & Larkum, M. E. (2017). Nature communications, 8(1), 276.