1 3 Med Biol Eng Comput DOI 10.1007/s11517-015-1442-0 REVIEW ARTICLE Implantable neurotechnologies: electrical stimulation and applications Sudip Nag 1 · Nitish V. Thakor 1 Received: 13 August 2015 / Accepted: 14 December 2015 © International Federation for Medical and Biological Engineering 2016 electric shock-induced pain relief in the 18th century [111], and soon after Luigi Galvani induced muscle contractions via electrical stimulation in the leg muscles of killed frogs [32]. Although the technique of electrical stimulation- mediated therapy originated centuries ago, routine test- ing only began in animals and humans in the 19th and 20th centuries, respectively [30, 85]. Functionally useful stimulation-induced movement of muscles with damaged nerves was reported by the middle of the 20th century [59]. Later, Brindley and Lewin [8] showed that stimulation of the visual cortex can produce the sensation of light flashes. Table 1 outlines the major breakthrough discoveries and therapeutic studies using electrical stimulation. The field of neural stimulation harbors promise for basic science discovery, clinical therapies and translation for the benefit of the society. Neural stimulation has been carried out to probe neurons, nerves and all regions of the nervous system. Major improvements and optimizations were the result of the fundamental discoveries and novel technolo- gies developed during the mid-20th century [85]. Hodgkin and Huxley [40] laid the foundation of the scientific under- standing of excitable biological tissues, notably in their dis- covery of the excitability of the nerve and axon by using a long duration voltage or current pulse. Later, a series of experimental methods and devices for cell and organ-level stimulation were developed for both bench-top investiga- tions and clinical translation [63, 72]. Experimental inves- tigations on nerves, both peripheral [97] and visceral [47], and on spinal cord [34] and brain [69, 101] have demon- strated potential clinical therapies to restore function or treat neurological disorders. An electrical stimulator injects Coulombic charge into biological tissue in a controlled manner to activate or inhibit excitable cells [38, 108]. Such stimulation is intended to induce a functional response in otherwise Abstract Neural stimulation using injected electrical charge is widely used both in functional therapies and as an experimental tool for neuroscience applications. Elec- trical pulses can induce excitation of targeted neural path- ways that aid in the treatment of neural disorders or dys- function of the central and peripheral nervous system. In this review, we summarize the recent trends in the field of electrical stimulation for therapeutic interventions of nerv- ous system disorders, such as for the restoration of brain, eye, ear, spinal cord, nerve and muscle function. Neural prosthetic applications are discussed, and functional elec- trical stimulation parameters for treating such disorders are reviewed. Important considerations for implantable pack- aging and enhancing device reliability are also discussed. Neural stimulators are expected to play a profound role in implantable neural devices that treat disorders and help restore functions in injured or disabled nervous system. Keywords Functional electrical stimulation · Charge injection · Neural prostheses · Biphasic constant current · Charge-balanced stimulator · Energy efficiency · Voltage compliance 1 Introduction Electrical stimulation is becoming increasingly popular in medical therapies and research studies to restore biological functions, such as vision, hearing, movement, tactile per- ception and proprioception. John Wesley first demonstrated * Sudip Nag sudipnag1@nus.edu.sg 1 National University of Singapore, Singapore, Singapore