Modulation of Spontaneous Cortical Network Dynamics by Weak Global Perturbations

Transcranial current stimulation (TCS) represents a non-invasive brain stimulation paradigm that manipulates cortical networks by application of weak electric fields. Such stimulation causes very small changes in the membrane voltage of individual neurons (<1 mV) yet has pronounced effects on the overall rhythmic activity structure in cortex. For example, weak sine-wave electric fields enhanced slow oscillations during deep sleep in human EEGs [1] and modulated the rhythmic structure of network activity at the spiking level in vitro [2,3]. However, the underlying mechanisms that mediate this network effect remain poorly understood.

We used large-scale computer simulations of cortical networks to probe how weak yet global perturbations shape macroscopic dynamics in network models with different topologies. Our computational model was comprised of 1 million pyramidal neurons and 250’000 fast spiking inhibitory interneurons that were connected with excitatory and inhibitory synapses. The model neurons were based on the Izhikevich model, which combines biological plausibility of spike initiation dynamics with high computational efficiency. We found that the stimulation waveform crucially determines the effect of TCS on network dynamics. Constant stimulation (tDCS, transcranial direct current stimulation) had a very limited effect on overall oscillation structure in comparison to sine-wave perturbations. For such periodic stimulation, we found that the presence of network level resonance depended on the underlying mechanisms that generated the spontaneous oscillations. We further found that both (1) network topology and (2) intrinsic excitability profiles crucially determined the effect magnitude of global weak perturbations applied to cortical networks.

Together, our results indicate that weak global perturbations can represent effective network modulators and that they act through amplification at the level of individual neurons at spiking threshold and at the level of the entire network through propagation by synaptic connectivity. Our results provide mechanistic insights into how TCS can modulate spontaneous cortical network dynamics and therefore provide the starting point for pre-clinical trials of optimized, more dynamic stimulation waveforms.

[1] Marshall, L., et al.,Nature, 2006. 444(7119)
[2] Fröhlich, F. and D. McCormick, Neuron, 2010. 67(1)
[3] Reato, D., et al., J Neurosci, 2010. 30(45)