Rhythmic modulation of thalamic oscillations depends on intrinsic cellular dynamics.

objectiveRhythmic brain stimulation has emerged as a powerful tool to modulate cognition and to target pathological oscillations related to neurological and psychiatric disorders. However, we lack a systematic understanding of how periodic stimulation interacts with endogenous neural activity as a function of the brain state and target. APPROACH: To address this critical issue, we applied periodic stimulation to a unified biophysical thalamic network model that generates multiple distinct oscillations, and examined thoroughly the impact of rhythmic stimulation on different oscillatory states. MAIN

resultsWe found that rhythmic perturbation induces four basic response mechanisms: entrainment, acceleration, resonance and suppression. Importantly, the appearance and expression of these mechanisms depend highly on the intrinsic cellular dynamics in each state. Specifically, the low-threshold bursting of thalamocortical cells (TCs) in delta (δ) oscillation renders the network relatively insensitive to entrainment; the high-threshold bursting of TCs in alpha (α) oscillation leads to widespread oscillation suppression while the tonic spiking of TC cells in gamma (γ) oscillation results in prominent entrainment and resonance. In addition, we observed entrainment discontinuity during α oscillation that is mediated by firing pattern switching of high-threshold bursting TC cells. Furthermore, we demonstrate that direct excitatory stimulation of the lateral geniculate nucleus (LGN) entrains thalamic oscillations via an asymmetric Arnold tongue that favors higher frequency entrainment and resonance, while stimulation of the inhibitory circuit, the reticular nucleus, induces much weaker and more symmetric entrainment and resonance. These results support the notion that rhythmic stimulation engages brain oscillations in a state- and target-dependent manner. SIGNIFICANCE: Overall, our study provides, for the first time, insights into how the biophysics of thalamic oscillations guide the emergence of complex, state-dependent mechanisms of target engagement, which can be leveraged for the future rational design of novel therapeutic stimulation modalities.