Uncovering network mechanism underlying thalamic Deep Brain Stimulation using a novel firing rate model

Thalamic ventral intermediate nucleus (Vim) is the primary surgical target of deep brain stimulation (DBS) for reducing symptoms of essential tremor. High-frequency Vim-DBS ([&ge;]100Hz) has been clinically effective, generating two experimentally-observed features in Vim spiking activity: 1) a large transient excitatory response (lasting <1s), followed by 2) a suppressed steady-state consisting of oscillations. Yet, mechanisms underlying these observations have not been fully understood by previous studies. In this work, we developed a network rate model and a novel parameter optimization method that accurately fit in-vivo single-unit recordings of Vim in human patients with essential tremor receiving a wide range of DBS frequencies (5[~]200Hz). Our model incorporates both the DBS-induced synaptic plasticity of Vim neurons, and the recurrent connections among excitatory and inhibitory neurons in Vim-network. We hypothesized that besides inducing synaptic depression, the therapeutic mechanism of high-frequency Vim-DBS could be to engage more inhibitory neurons in stabilizing the underlying circuits. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=86 SRC="FIGDIR/small/570924v2_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@1e78cbcorg.highwire.dtl.DTLVardef@c8bde1org.highwire.dtl.DTLVardef@12a3bb3org.highwire.dtl.DTLVardef@1b5a0dd_HPS_FORMAT_FIGEXP M_FIG C_FIG