Successful clinical application of closedloop TES has two fundamental requirements(9, 11, 26, 27)。 The first is the recording and identifying of causal pathophysiological network patterns。 In generalized SW and focal cortical epilepsies, subdural or epidural electrodes, or even electrodes inserted into the skull, may be sufficient。In complex partial seizures, which make up the largest fraction of drug-resistent epilepsies,deep-electrode recordings  are required for accurate detection of abnormal patterns (11, 13)。The second requirement is closed-loop feedback stimulation of the target circuits, whose activation can interfere with the emerging pathological pattern。 Intra-skull plate electrodes may ideally diffuse the applied currents to affect sufficiently large groups of neurons (28)。 Alternatively, multiple and appropriately placed plates may be used to achieve more focal concentration of current。In

contrast to transcranial magnetic stimulation,which requires large and heavy coils, TES electrodes implanted in the skull and powered by ultralight electrical circuits are a cosmetically acceptable solution for long-term clinical applications。Noninvasive, closed-loop TES stimulation may also prove useful for improving mental and mood  states。 Neurostimulation is  a  therapeutic  activation  of  part  of  the nervous  system using microelectrodes。   The

electrodes are used to interface with excitable tissue in order to either restore sensation, such as a cochlear implant for hearing, or control an organ, such as a heart pacemaker。[1]

Neurostimulation technology improves the life quality of those who are severely paralyzed or suffering from profound losses to various sense organs。 It serves as the key part of neural prosthetics for hearing aids, artificial vision,artificial limbs, and brain-machine interfaces。 In the case of neural stimulation, mostly an electrical stimulation is utilized and charge-balanced biphasic constant current waveforms or capacitively coupled charge injection approaches are adopted。 Alternatively, the transcranial magnetic stimulation has been proposed as a non-invasive method in which a magnetic field causes neurostimulation。[2]

一、History

The primary findings about neurostimulation originated from the idea to stimulate nerves for therapeutic purposes。 The 1st recorded use of electrical stimulation for pain relief goes back to 46 AD, when Scribonius Largus used torpedo fish (electric ray) for relieving headaches。[3] In the late 18th century,Luigi Galvani discovered that the muscles of dead frog legs twitched when struck by direct current on the nervous system。[4] The modulation of the brain activity by electrical stimulation of the motor cortex in dogs was shown in 1870 that resulted in limb movement。[5] From the late 18th century to today many milestones have been developed。 Nowadays, sensory prosthetic devices, such as visual implants, cochlear implants, auditory midbrain implants, and spinal cord stimulators and also motor prosthetic devices, such  as deep brain stimulators, Bion microstimulators, the brain control and sensing interface, and cardiac electro-stimulation devices are widely used。[6] Since the time of the Egyptians when a patie-nt received strong shocks from an electric fish, it has been known that electrical stimulation can produce physiological effects。The invention of the transistor at Bell Telephone Laboratories in Murray Hill, NJ, in the 1950s led to the development andimplantation of battery-powered implantable cardiac pacemakers in 1958, first by Elmquist and Sennings [1] in Sweden and two weeks later by Greatbatch and Chardack in the United States。 Elmquist’s first cardiac pacemaker used a rechargeable battery and transistor circuit cast in an epoxy

mold about 3/4 of an inch in thickness and about 2 1/2-in in diameter。 It required several hours to recharge every few days by an ac magnetic field。 The pacemaker was implanted under the skin with a catheter cable attached to the heart。Greatbatc’s first pacemaker was slightly larger but had primary batteries that were supposed to last about seven years。 However,they lasted only about 18 months。 It also had a catheter electrode hooked directly to the heart。