The difficulty in the surgical treatment of functional brain lesions is mainly focused on the difficulty of correctly localizing the functional brain areas intraoperatively. At present, the most accurate, reliable and minimally invasive method for locating functional brain areas is intraoperative direct electrical stimulation, but incorrect stimulation methods and parameter settings can lead to false-positive and false-negative stimulation results, which bring some trouble to functional area localization. This article reviews the literature on direct electrical stimulation and provides a review of the history, basic principles, basic parameters and precautions of direct electrical stimulation in the hope of providing a basis for clinical improvement of the efficacy of intraoperative electrical stimulation applications. In surgery for intracerebral lesions in functional areas, aggressive resection of the lesion without postoperative limb and speech impairment, thus safeguarding the quality of patient survival, has become a special concern in current neurosurgery. The difficulty in this type of surgery is the intraoperative difficulty in correctly localizing the functional brain area. Currently, the most accurate and reliable method for localizing functional brain areas is intraoperative direct electrical stimulation, which can be used to determine the necessary sites for motor, sensory, language and other brain functions in real time. However, if the stimulation method is incorrect, false-positive and false-negative results are prone to occur [1-2]. To this end, this paper reviews the history, basic principles, basic parameters and considerations of direct electrical stimulation by reviewing the relevant literature on direct electrical stimulation, in the hope of providing a basis for clinical improvement of the efficacy of intraoperative electrical stimulation applications. For benign lesions or low-grade gliomas with a long survival period, the quality of the patient’s postoperative survival is the key to the success or failure of the operation. (1) High incidence of postoperative neurological deficits. The incidence of permanent neurological deficits after surgery for functional lesions was as high as 15% to 27.5% before the adoption of functional area localization techniques [3], whereas the incidence was reduced to 6.5% after the adoption of intraoperative direct electrical stimulation to localize the functional areas of the brain [4]. (ii) The degree of lesion resection is low. Duffau et al [4] reported that the rates of subtotal and total resection of functional area lesions were 37.0% and 6.0%, respectively, before the use of direct electrical stimulation, whereas they increased to 50.8% and 25.4%, respectively, after the use of intraoperative electrical stimulation. Therefore, it is necessary to perform functional area localization, which can be influenced by many factors, such as: (1) the existence of functional area variation. Uematsu et al [5] concluded that the motor cortex is 2 cm beyond the central sulcus of the classical somatotopic localization, whereas Gilbert et al [6] found that tumor nudging could shift the functional area by (2 ± 1.3) cm. ii) Non-invasive localization methods are (ii) Non-invasive localization methods are limited. Recent imaging methods such as PET, functional MRI (fMRI), and magnetoencephalography have made it possible to localize sensory and motor cortices preoperatively. However, these methods are still not accurate enough to localize complex functional brain areas, for example, the sensitivity of fMRI to localize language areas is 81%, while the specificity is only 53% [7]. These methods cannot monitor the location of functional brain areas in real time intraoperatively, cannot localize white matter fibers, and can detect all cortical areas associated with a function, but cannot determine which areas are necessary to preserve. Diffusion tensor imaging (DTI) can be used to determine the patient’s white matter distribution preoperatively and noninvasively, but the visualized nerve fibers shown by DTI are not equivalent to the myelinated nerve fibers in the brain tissue; especially in the presence of pathological changes in the brain tissue, DTI tracing results should never be used directly as the sole basis for preoperative evaluation of nerve fiber bundle function and postoperative neurological prognosis. The DTI images fused with navigation can be used as a preliminary basis for determining the location of the nerve fiber bundles, and the surgical approach can be selected accordingly, but for intraoperative operations involving intra-white matter dissection and resection, subcortical electrical stimulation still needs to be applied for confirmation. In conclusion, although these noninvasive localization methods have improved the level of localization to a certain extent, they still cannot be the “golden method” of functional area localization. In 1874, Bartholow first used electrodes to stimulate the cortex intraoperatively and recorded the motor response when it appeared. In 1931, Foerster first applied direct electrical stimulation in neurosurgery to determine functional brain areas; subsequently, Penfield applied it to resection of epileptic (interictal) lesions and established the famous Brodmann model of cerebral cortical localization on this basis. ojemann improved the stimulator to bipolar stimulation, which greatly improved the accuracy of stimulation, and thereafter direct electrical stimulation techniques were In 2004, Wang Weimin et al [2] applied the direct cortical electrical stimulation technique to the surgery of lesions in functional brain areas in China, and then this technique was rapidly promoted in domestic neurosurgery [8-9]. 2. basic principles and main parameters of direct electrical stimulation 2.1 Basic principles The cell membrane of neurons has a resting potential, negative inside and positive outside, with a size of about -60 ~ -100 mA. When the cathodal stimulation reaches a certain threshold, it causes a rapid Na+ inward flow, producing an all-or-none action potential, after which the cell membrane potential is reset, and the reset process and the subsequent small period of time exist during the under- and hyperexcitation period. The principle of direct electrical stimulation is that depolarization of local neurons and their conduction tracts leads to local tissue excitation or inhibition, e.g. stimulation of sensory and motor structures causes abnormal sensory and motor responses (excitatory effect), while stimulation of speech and memory structures causes transient functional inhibition (inhibitory effect). The currently used bipolar stimulator is the most ideal method of localization because it avoids local diffusion of current and allows for more accurate localization, with an accuracy of about 5 mm. Direct electrical stimulation is safe, with no inflammation or other damage at the stimulation site on histological examination and no significant complications at patient follow-up. However, if the stimulation method is incorrect, there is a risk of causing epileptic (interictal) continuity [10]. Therefore, it is particularly important to use the correct stimulation method and stimulation parameters during intraoperative direct electrical stimulation. 2.2 Main stimulation parameters ① A bipolar electrical nerve stimulator (bipolar interval 5 mm) was used, stimulating all exposed areas of the cortex and suspected subcortical areas, with at least 3 stimulations per site. (ii) Biphasic square waves were used. This is because sinusoidal waves can cause adaptive modulation of the cell membrane during stimulation and increase the required stimulation current, resulting in false-positive results or inducing interictal seizures. The biphasic wave avoids superimposed currents around the cell membrane that could cause ionized hydrolysis and heat production of particles in the local cerebrospinal fluid, resulting in nerve cell damage. An effective stimulation depends on the intensity and frequency of the stimulation and the speed of the current change; too fast a stimulation frequency is prone to heat production, while too slow is prone to negative stimulation. ④Cortical stimulation current: the stimulation size is determined according to the EEG monitoring when post-emergence discharge occurs, starting with 1 mA and increasing by 1 mA, usually to 4-6 mA; subcortical stimulation is usually 2 mA higher than cortical stimulation current. ⑤Stimulation duration: about 1 s for motor and sensory tasks and about 4 s for language and cognitive tasks [1-2, 4]. 2.3 Precautions ① Preferably choose general anesthesia for intraoperative arousal anesthesia. Do not use sedative-hypnotic drugs such as sodium phenobarbital preoperatively to avoid intraoperative drowsiness of the patient. Pay attention to the use of thermal blankets during arousal to avoid chills and inability to cooperate after arousal. ②Avoid 2 consecutive positive stimuli to avoid inducing intraoperative epilepsy (interictal) persistence in the patient or persistent false-negative stimulation results. ③The stimulation area should be kept dry and should not have cerebrospinal fluid or saline, as its resistance is less than the cortical resistance, which can easily lead to a short circuit between the bipoles and cause false-negative stimulation results. ④The patient’s neurological function must be closely monitored during stimulation to determine positive stimulation results and early detection of seizures (sickness). The motor area is the contralateral limb or face evoked movements (EMG should be recorded at the same time); the sensory area is the contralateral limb or face evoked abnormal sensations in the pulse type; the language area is the patient’s interruptions in counting or reading slides, confusion in speech and other types of language disorders. If the patient shows weakness in limb movement, abnormal speech or presence of sensory abnormalities, subcortical electrical stimulation should be performed immediately to confirm the presence of important conduction bundles. ⑤ Prevention and control of intraoperative epilepsy (interictal) continuity: first, we should try to prevent it, such as stimulation frequency should not be too fast, stimulation duration should not be too long, stimulation current should not be too large, and avoid 2 consecutive positive stimulations. Once a seizure (interictal) persistent state seizure is induced during surgery, ice saline can be used to flush the cerebral cortex, which can usually terminate the seizure (interictal). (6) Determine the extent of functional area preservation: the functional areas determined by direct cortical or subcortical electrical stimulation are the areas that cannot be damaged by surgery. Usually, motor and sensory areas can be preserved as long as the localized area is preserved, while speech areas need to be preserved 1 cm outside the localized area. (7) Management after obtaining negative stimulation results: Taylor et al [10] reported that patients are prone to permanent postoperative dysfunction after intraoperative negative stimulation results. duffau [11] recommended a large bone flap craniotomy to ensure that negative results are avoided. In our practice, we found that the main reasons for negative stimulation results are that the bone flap is small and the functional area is outside the exposure range; in addition, due to the remodeling of the cortex in the functional area of the brain, etc., causing no positive stimulation results before resection of the tumor, and after tumor removal, a positive response can often occur with re-stimulation during the preparation for extended resection. Therefore, we suggest that negative stimulation can be avoided by the following methods: the central sulcus cannot be localized purely according to the somatic anatomical method, and should be combined with the preoperative fMRI results to initially determine the location of the functional area cortices, and perform large bone flap craniotomy to expose the functional area cortices as much as possible to ensure the emergence of positive stimulation; the use of arousal anesthesia method, and the emergence of negative stimulation when the patient completes a series of motor and speech during the resection of the lesion After the task, if slight neurological deficits occur, electrical stimulation can be performed again to confirm the presence of functional areas, when positive results may occur due to the rapid remodeling of the cortices in functional brain areas. 9 Transient dysfunction often occurs after direct electrical cortical stimulation because the surgical area is already close to the functional area, which may be related to postoperative edema, disturbances in blood circulation and damage to the supplementary motor area [1], and is mostly recoverable. In conclusion, direct electrical stimulation technique is a reliable and noninvasive method for localization of functional brain areas, which provides a new surgical concept for functional brain area surgery. The correct and rational use of this method will improve the quality of surgery for lesions in the functional brain area and may also help the field of neuroscience to explore the function of the human brain.