Differential modulation of subcortical target and cortex during deep brain stimulation.

The combination of electrical deep brain stimulation (DBS) with functional imaging offers a unique model for tracing brain circuitry and for testing the modulatory potential of electrical stimulation on a neuronal network in vivo. We therefore applied parametric positron emission tomography (PET) analyses that allow characterization of rCBF responses as linear and nonlinear functions of the experimentally modulated stimulus (variable stimulator setting). In patients with electrodes in the thalamic ventrointermediate nucleus (VIM) for the treatment of essential tremor (ET) here we show that variations in voltage and frequency of thalamic stimulation have differential effects in a thalamo-cortical circuitry. Increasing stimulation amplitude was associated with a linear raise in rCBF at the thalamic stimulation site, but with a nonlinear rCBF response in the primary sensorimotor cortex (M1/S1). The reverse pattern in rCBF changes was observed with increasing stimulation frequency. These results indicate close connectivity between the stimulated nucleus (VIM) and primary sensorimotor cortex. Likewise, stimulation parameter-specific modulation occurs at this simple interface between an electrical and a cerebral system and suggests that the scope of DBS extends beyond an ablation-like on-off effect: DBS could rather allow a gradual tuning of activity within a neuronal circuit.