Design of efficient and safe neural stimulators

Abstract

Neural stimulation is an established treatment methodology for an increasing number of diseases. Electrical Stimulation injects a stimulation signal through electrodes that are implanted in the target area of the central or peripheral nervous system in order to evoke a specific neuronal response that suppresses or treats pathological activity. This thesis discusses the design of neural stimulators: the device that is responsible for generating the stimulation signal in a safe, efficient and controlled manner. The design of such a device requires a highly multidisciplinary approach which involves disciplines such as neuroscience, electrophysiology, electrochemistry and electrical engineering. The first part of this thesis focuses on the processes associated with the neuronal recruitment. After describing the stimulation processes in detail at various levels, the discussion zooms in on the processes at the electrode-tissue interface and in particular the electrochemical behavior. Many neural stimulators include coupling capacitors between the stimulator and the electrodes to reduce the risk of potentially harmful electrochemical reactions. However, it is shown that coupling capacitors also have negative implications that need to be considered, such as a shift in the equilibrium potential of the electrode-tissue interface. Also, the reversibility of charge transfer processes at the electrode-tissue interface is analyzed. Most studies rely on monitoring the electrode-tissue interface potential to determine the maximum reversible charge injection limits. By measuring the reversible charge in a more direct way, it was found that under specific conditions the irreversible charge transfer processes already play a role for stimulation intensities that are well below the established charge injection limits. The extensive description of the stimulation process is furthermore used to introduce a fundamentally different stimulation paradigm. Instead of using a constant current or voltage to stimulate the electrodes, a high frequency, switched-mode stimulation signal is applied. The advantage of such a stimulation pattern is that it can be generated in a power efficient way by the neurostimulator circuit using switched-mode operation that is common in energy efficient amplifiers (class-D operation) or power management circuits. The efficacy of the proposed stimulation pattern is verified both using modeling as well as using in vitro measurements by analyzing the response of patch-clamped Purkinje cells. The second part of the thesis focuses on the electrical design of neural stimulators. The first system is designed to be used in a specific neuroscientific experiment and features arbitrary waveform stimulation. The user has full flexibility over the choice of stimulation waveform, while the stimulator circuit guarantees safety by ensuring charge balanced operation. The stimulator circuit is realized and included in a system implementation that is suitable for the specific in vivo experimental setup. The stimulation pulse (which uses a burst pattern) is synchronized with auditory stimulation in an attempt to recondition the neural pathways in a mouse that suffers from tinnitus. The second design implements the high-frequency switched-mode stimulation pattern that was introduced in the first part of the thesis. The system features an unfiltered forward buck-boost converter at its core to directly stimulate the target tissue. It is possible to operate the system with multiple independent channels that connect to an arbitrary electrode configuration, making the system well suited for current steering techniques. Furthermore, comprehensive control was implemented using a dual clock configuration that allows both autonomic tonic stimulation, as well as single shot stimulation. Each channel can be configured individually with tailored stimulation parameters and multiple channels can operate in a synchronized fashion. The system is power efficient, especially when compared with state-of-the-art constant current stimulators with an adaptive power supply that operate in multichannel mode. Efficiency improvements up to 200% compared with state of the art constant current stimulators are demonstrated. Furthermore, the number of external components required is reduced to a single inductor.