Evaluation of novel stimulus waveforms for deep brain stimulation

Abstract

Deep brain stimulation (DBS) is an established therapy for the treatment of a wide range of neurological disorders. Historically, DBS and other neurostimulation technologies have relied on rectangular stimulation waveforms to impose their effects on the nervous system. Recent work has suggested that non-rectangular waveforms may have advantages over the traditional rectangular pulse. Therefore, we used detailed computer models to compare a range of charge-balanced biphasic waveforms with rectangular, exponential, triangular, Gaussian, and sinusoidal stimulus pulse shapes. We explored the neural activation energy of these waveforms in both intracellular and extracellular stimulation. In the context of extracellular stimulation, we compared their effects on both axonal fibers of passage and projection neurons. Finally, we evaluated the impact of delivering the waveforms through a clinical DBS electrode, as opposed to a theoretical point source. Our results suggest that DBS with a 1 ms centered-triangular pulse can decrease energy consumption by 64 % when compared to the standard 100 μs rectangular pulse (energy cost of 48 nJ and 133 nJ, respectively, to stimulate 50 % of a distributed population of axons) and can decrease energy consumption by 10 % when compared to the most energy efficient rectangular pulse (1.25 ms duration). In turn, there may be measureable energy savings when using appropriately designed non-rectangular pulses in clinical DBS applications, thereby warranting further experimental investigation.

Computational Modeling of Deep Brain Stimulation

“…Computational modeling represents a useful technique to analyze current DBS practice, and to enable the creation of virtual testing grounds for the evaluation of future innovations. For example, new DBS technical developments in current-controlled stimulation , current steering between electrodes (Butson and McIntyre, 2008), stimulus waveform shape (Foutz and McIntyre, 2010), temporal patterning of stimuli (Birdno et al, 2012), and electrode contact design (Martens et al, 2011) have been vetted in computational models and are beginning to enter clinical testing. In turn, advances in scientific knowledge and technology are laying the groundwork for the re-engineering of DBS technology better to serve clinicians and patients.…”

Optimization of Stimulation Parameters for Targeted Activation of Multiple Neurons Using Closed-Loop Search Methods

“…In all five line searches, activation curves were constructed using the sigmoid model in Equation (1). Stimulus-evoked responses were collected at each stimulus point, and the sigmoid model was fit to all available data for each neuron according to the methods.…”

“…A priority in designing stimuli is to reduce side effects resulting from the activation of off-target populations. During DBS, stimuli must be designed to specifically target a baseline activity level such that the stimulus evokes sufficient activity to provide a therapeutic effect, while not excessively activating tissue leading to side effects [1][2][3][4]. There is a therapeutic subspace in the strength-duration waveform space, between which side effects are reduced and stimulus efficacy is increased, and stimulation algorithms must incorporate feedback of the evoked activity to enable neuronal targeting within this subspace.…”

Response of the Hodgkin-Huxley Neuron to a Periodic Sequence of Biphasic Pulses

“…This encompasses, but is not limited to, cochlear and retinal prostheses [13], deep brain stimulation (DBS) [4,5], as well as high-frequency conduction block of peripheral nerves [6]. Typically such devices should minimize charge and energy per pulse.…”

“…Selection of the most ecient waveform shape and duration, such that delivered charge, energy and power are simultaneously optimized is a dicult task [15,16]. Most studies indicate that non-rectangular pulses are more energy efcient than rectangular ones [11,13,14,16].…”