Beta oscillations in neocortex: A multiscale modeling study

Beta oscillations (15-30 Hz) are prevalent in the firing patterns of neocortical neurons and the microcircuits they are embedded in. Beta oscillations are hypothesized to enable effective communication between neurons, setting fluctuating windows of excitability when neurons are most likely to respond to or send information. Beta oscillations are expected to emerge from interactions across multiple spatial scales, arising from a diverse set of biophysical mechanisms. Key contributors to Beta oscillations are the Layer 5 (L5) pyramidal neurons, with their large dendrites which span multiple cortical layers. To explore the origins of neocortical Beta oscillations, we developed a 6-layer 1715 compartmental cell multiscale model of neocortex with multiple classes of excitatory (E) and inhibitory (I) neurons wired based on mouse neocortex circuit mapping experiments. We optimized models of L5 pyramidal cells using whole-cell somatic voltage recordings. Neurons contained membrane calcium, sodium, potassium, and hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. In L5 pyramidal cells, increasing HCN channel density in apical dendrites with distance from soma promoted synaptic resonance in the Beta frequency range, with increasing resonant frequency with distance from soma. The network model displayed coherent Beta oscillations produced through interactions between E and I neurons. We applied independent random variations in ion channel densities to cells in the network model to identify parameter sets that contributed to Beta oscillations. These variations produced simulations with distinct physiological (phys) and pathological (path) hyperexcitable states, each with different expressions of Beta oscillations, neuronal synchrony, and firing patterns. The simulation categories demonstrated degeneracy: there were many parameter combinations that produced each simulation type with weak intra-class similarity of parameter vectors (phys/phys r=0.06; path/path r=0.07; n=65 for each class) and weak inter-class dis-similarity (path/phys r=-0.05). Some of the model predictions were verified through analyzing Beta oscillations in laminar neocortex recordings of nonhuman primates. Our results suggest the neocortex contains a robust set of mechanisms that contribute to Beta oscillations at multiple spatial scales.