Closed-loop control of deep brain stimulation: a simulation study.

Deep brain stimulation (DBS) is an effective therapy to treat movement disorders including essential tremor, dystonia, and Parkinson's disease. Despite over a decade of clinical experience the mechanisms of DBS are still unclear, and this lack of understanding makes the selection of stimulation parameters quite challenging. The objective of this work was to develop a closed-loop control system that automatically adjusted the stimulation amplitude to reduce oscillatory neuronal activity, based on feedback of electrical signals recorded from the brain using the same electrode as implanted for stimulation. We simulated a population of 100 intrinsically active model neurons in the Vim thalamus, and the local field potentials (LFPs) generated by the population were used as the feedback (control) variable for closed loop control of DBS amplitude. Based on the correlation between the spectral content of the thalamic activity and tremor (Hua , 1998), (Lenz , 1988), we implemented an adaptive minimum variance controller to regulate the power spectrum of the simulated LFPs and restore the LFP power spectrum present under tremor conditions to a reference profile derived under tremor free conditions. The controller was based on a recursively identified autoregressive model (ARX) of the relationship between stimulation input and LFP output, and showed excellent performances in tracking the reference spectral features through selective changes in the theta (2-7 Hz), alpha (7-13 Hz), and beta (13-35 Hz) frequency ranges. Such changes reflected modifications in the firing patterns of the model neuronal population, and, differently from open-loop DBS, replaced the tremor-related pathological patterns with patterns similar to those simulated in tremor-free conditions. The closed-loop controller generated a LFP spectrum that approximated more closely the spectrum present in the tremor-free condition than did open loop fixed intensity stimulation and adapted to match the spectrum after a change in the neuronal oscillation frequency. This computational study suggests the feasibility of closed-loop control of DBS amplitude to regulate the spectrum of the local field potentials and thereby normalize the aberrant pattern of neuronal activity present in tremor.