Abstract
Despite the current success of neuromodulation, standard biphasic, rectangular pulse shapes may not be optimal to achieve symptom alleviation. Here, we compared stimulation efficiency (in terms of charge) between complex and standard pulses in two areas of the rat brain. In motor cortex, Gaussian and interphase gap stimulation (IPG) increased stimulation efficiency in terms of charge per phase compared with a standard pulse. Moreover, IPG stimulation of the deep mesencephalic reticular formation in freely moving rats was more efficient compared to a standard pulse. We therefore conclude that complex pulses are superior to standard stimulation, as less charge is required to achieve the same behavioral effects in a motor paradigm. These results have important implications for the understanding of electrical stimulation of the nervous system and open new perspectives for the design of the next generation of safe and efficient neural implants.
Highlights
Electrical stimulation of the nervous system has a wide range of clinical applications, from sensory restoration delivered via retinal implants[1], to the treatment of neurological and psychiatric disorders with deep brain stimulation[2,3]
Pseudomonophasic pulses (PM), in which the first phase is followed by a longer and lower-amplitude charge-balancing phase (Fig. 1C), are more effective than biphasic pulses[10,11,12]. These findings can be partially attributed to the counteracting effects of the two opposite phases in a typical biphasic pulse: the first phase depolarizes the membrane and initiates an action potential, whereas the second phase counters this effect by rapidly hyperpolarizing the membrane
In Phase I, we used rat motor cortex to evaluate the effect of pulse-shape (BP, PM, interphase gap stimulation (IPG), GAUS and TRI) on limb displacement
Summary
Electrical stimulation of the nervous system has a wide range of clinical applications, from sensory restoration delivered via retinal implants[1], to the treatment of neurological and psychiatric disorders with deep brain stimulation[2,3]. At the most basic level, the pulse must inject enough charge to move the membrane from resting to threshold potential, thereby causing the neuron to fire an action potential. This very basic stimulation mechanism can lead to a cascade of more complex, often system-wide, effects[4]. We first designed pulses that were matched in terms of amplitude, pulse width and charge per phase, but differed in shape (Fig. 1) This allows us to evaluate each pulse shape in terms of its charge efficiency. Experiment 1 was conducted in anesthetized rats and used motor cortex stimulation to evoke limb movements allowing us to quickly evaluate a wide range of pulse-shapes. The pulse-shape that produced the largest limb displacement was selected for further testing in Experiment 2 where the outcome measure was immobility levels evoked by stimulating the mRT in awake rats
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