Elicit Motor Responses Research Articles

Ultrasound Neurostimulation in Mice: Impact of Ultrasound Settings and Beam Properties.

Ultrasound neurostimulation (USNS) is being investigated as a treatment approach for neuropsychiatric and neurodegenerative disorders. Indeed, unlike the existing methods that use electric or magnetic stimulation, it offers the possibility to modulate brain activity in a noninvasive way, with good spatial specificity and a high penetration capacity. However, there is no consensus yet on ultrasound parameters and beam properties required for efficient neurostimulation. In this context, this preclinical study aimed to elucidate the effect of frequency, peak negative pressure (PNP), pulse duration (PD), and focal spot diameter, on the USNS efficiency. This was done by targeting the motor cortex (M1) of 70 healthy mice and analyzing the elicited motor responses (visually and with electromyography). Also, a further investigation was performed by assessing the corresponding neuronal activity, using c-Fos immunostaining. The results showed that the success rate, a metric that depicts USNS efficacy, increased with PNP in a sigmoidal way, reaching up to 100%. This was verified at different frequencies (0.5, 1, 1.5, and 2.25 MHz) and PDs (53.3, 160, and 320 ms, at 1.5 MHz fixed frequency). Moreover, it was shown that higher PNP values were required to achieve a constant USNS efficacy not only when frequency increased, but also when the focal spot diameter decreased, emphasizing a close link between these acoustic parameters and USNS efficacy. These findings were confirmed with immunohistochemistry (IHC), which showed a strong relationship between neural activation, the applied PNP, and the focal spot diameter.

Olfactory-induced locomotion in lampreys.

The olfactory system allows animals to navigate in their environment to feed, mate, and escape predators. It is well established that odorant exposure or electrical stimulation of the olfactory system induces stereotyped motor responses in fishes. However, the neural circuitry responsible for the olfactomotor transformations is only beginning to be unraveled. A neural substrate eliciting motor responses to olfactory inputs was identified in the lamprey, a basal vertebrate used extensively to examine the neural mechanisms underlying sensorimotor transformations. Two pathways were discovered from the olfactory organ in the periphery to the brainstem motor nuclei responsible for controlling swimming. The first pathway originates from sensory neurons located in the accessory olfactory organ and reaches a single population of projection neurons in the medial olfactory bulb, which, in turn, transmit the olfactory signals to the posterior tuberculum and then to downstream brainstem locomotor centers. A second pathway originates from the main olfactory epithelium and reaches the main olfactory bulb, the neurons of which project to the pallium/cortex. The olfactory signals are then conveyed to the posterior tuberculum and then to brainstem locomotor centers. Olfactomotor behavior can adapt, and studies were aimed at defining the underlying neural mechanisms. Modulation of bulbar neural activity by GABAergic, dopaminergic, and serotoninergic inputs is likely to provide strong control over the hardwired circuits to produce appropriate motor behavior in response to olfactory cues. This review summarizes current knowledge relative to the neural circuitry producing olfactomotor behavior in lampreys and their modulatory mechanisms.

How to Identify Responders and Nonresponders to Dorsal Root Ganglion-Stimulation Aimed at Eliciting Motor Responses in Chronic Spinal Cord Injury: Post Hoc Clinical and Neurophysiological Tests in a Case Series of Five Patients

ObjectiveWhile integrity of spinal pathways below injury is generally thought to be an important factor in the success‐rate of neuromodulation strategies for spinal cord injury (SCI), it is still unclear how the integrity of these pathways conveying the effects of stimulation should be assessed. In one of our institutional case series of five patients receiving dorsal root ganglion (DRG)‐stimulation for elicitation of immediate motor response in motor complete SCI, only two out of five patients presented as responders, showing immediate muscle activation upon DRG‐stimulation. The current study focuses on post hoc clinical‐neurophysiological tests performed within this patient series to illustrate their use for prediction of spinal pathway integrity, and presumably, responder‐status.Materials and MethodsIn a series of three nonresponders and two responders (all male, American Spinal Injury Association [ASIA] impairment scale [AIS] A/B), a test‐battery consisting of questionnaires, clinical measurements, as well as a series of neurophysiological measurements was performed less than eight months after participation in the initial study.ResultsNonresponders presented with a complete absence of spasticity and absence of leg reflexes. Additionally, nonresponders presented with close to no compound muscle action potentials (CMAPs) or Hofmann(H)‐reflexes. In contrast, both responders presented with clear spasticity, elicitable leg reflexes, CMAPs, H‐reflexes, and sensory nerve action potentials, although not always consistent for all tested muscles.ConclusionsPost hoc neurophysiological measurements were limited in clearly separating responders from nonresponders. Clinically, complete absence of spasticity‐related complaints in the nonresponders was a distinguishing factor between responders and nonresponders in this case series, which mimics prior reports of epidural electrical stimulation, potentially illustrating similarities in mechanisms of action between the two techniques. However, the problem remains that explicit use and report of preinclusion clinical‐neurophysiological measurements is missing in SCI literature. Identifying proper ways to assess these criteria might therefore be unnecessarily difficult, especially for nonestablished neuromodulation techniques.

High-Resolution Focused Ultrasound Neuromodulation Induces Limb-Specific Motor Responses in Mice in Vivo

Ultrasound can modulate activity in the central nervous system, including the induction of motor responses in rodents. Recent studies investigating ultrasound-induced motor movements have described mostly bilateral limb responses, but quantitative evaluations have failed to reveal lateralization or differences in response characteristics between separate limbs or how specific brain targets dictate distinct limb responses. This study uses high-resolution focused ultrasound (FUS) to elicit motor responses in anesthetized mice in vivo and four-limb electromyography (EMG) to evaluate the latency, duration and power of paired motor responses (n = 1768). The results indicate that FUS generates target-specific differences in electromyographic characteristics and that brain targets separated by as little as 1 mm can modulate the responses in individual limbs differentially. Exploiting these differences may provide a tool for quantifying the susceptibility of underlying neural volumes to FUS, understanding the functioning of the targeted neuroanatomy and aiding in mechanistic studies of this non-invasive neuromodulation technique.

Altered physiology of gastrointestinal vagal afferents following neurotrauma.

The adaptability of the central nervous system has been revealed in several model systems. Of particular interest to central nervous system-injured individuals is the ability for neural components to be modified for regain of function. In both types of neurotrauma, traumatic brain injury and spinal cord injury, the primary parasympathetic control to the gastrointestinal tract, the vagus nerve, remains anatomically intact. However, individuals with traumatic brain injury or spinal cord injury are highly susceptible to gastrointestinal dysfunctions. Such gastrointestinal dysfunctions attribute to higher morbidity and mortality following traumatic brain injury and spinal cord injury. While the vagal efferent output remains capable of eliciting motor responses following injury, evidence suggests impairment of the vagal afferents. Since sensory input drives motor output, this review will discuss the normal and altered anatomy and physiology of the gastrointestinal vagal afferents to better understand the contributions of vagal afferent plasticity following neurotrauma.

Automated search of stimulation targets with closed-loop transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS) protocols often include a manual search of an optimal location and orientation of the coil or peak stimulating electric field to elicit motor responses in a target muscle. This target search is laborious, and the result is user-dependent. Here, we present a closed-loop search method that utilizes automatic electronic adjustment of the stimulation based on the previous responses. The electronic adjustment is achieved by multi-locus TMS, and the adaptive guiding of the stimulation is based on the principles of Bayesian optimization to minimize the number of stimuli (and time) needed in the search. We compared our target-search method with other methods, such as systematic sampling in a predefined cortical grid. Validation experiments on five healthy volunteers and further offline simulations showed that our adaptively guided search method needs only a relatively small number of stimuli to provide outcomes with good accuracy and precision. The automated method enables fast and user-independent optimization of stimulation parameters in research and clinical applications of TMS.

Elimination of peripheral auditory pathway activation does not affect motor responses from ultrasound neuromodulation

BackgroundRecent studies in a variety of animal models including rodents, monkeys, and humans suggest that transcranial focused ultrasound (tFUS) has considerable promise for non-invasively modulating neural activity with the ability to target deep brain structures. However, concerns have been raised that motor responses evoked by tFUS may be due to indirect activation of the auditory pathway rather than direct activation of motor circuits. ObjectiveIn this study, we sought to examine the involvement of peripheral auditory system activation from tFUS stimulation applied to elicit motor responses. The purpose was to determine to what extent ultrasound induced auditory artifact could be a factor in ultrasound motor neuromodulation. MethodsIn this study, tFUS-induced electromyography (EMG) signals were recorded and analyzed in wild-type (WT) normal hearing mice and two strains of genetically deaf mice to examine the involvement of the peripheral auditory system in tFUS-stimulated motor responses. In addition, auditory brainstem responses (ABRs) were measured to elucidate the effect of the tFUS stimulus envelope on auditory and motor responses. We also varied the tFUS stimulation duration to measure its effect on motor response duration. ResultsWe show, first, that the sharp edges in a tFUS rectangular envelope stimulus activate the peripheral afferent auditory pathway and, second, that smoothing these edges eliminates the auditory responses without affecting the motor responses in normal hearing WT mice. We further show that by eliminating peripheral auditory activity using two different strains of deaf knockout mice, motor responses are the same as in normal hearing WT mice. Finally, we demonstrate a high correlation between tFUS pulse duration and EMG response duration. ConclusionThese results support the concept that tFUS-evoked motor responses are not a result of stimulation of the peripheral auditory system.

Ultrasonic Neuromodulation Causes Widespread Cortical Activation via an Indirect Auditory Mechanism

Ultrasound has received widespread attention as anemerging technology for targeted, non-invasive neuromodulation based on its ability to evoke electrophysiological and motor responses in animals. However, little is known about the spatiotemporal pattern of ultrasound-induced brain activity that could drive these responses. Here, we address this question by combining focused ultrasound with wide-field optical imaging of calcium signals in transgenic mice. Surprisingly, we find cortical activity patterns consistent with indirect activation of auditory pathways rather than direct neuromodulation at the ultrasound focus. Ultrasound-induced activity is similar to that evoked by audible sound. Furthermore, both ultrasound and audible sound elicit motor responses consistent with a startle reflex, with both responses reduced by chemical deafening. These findings reveal an indirect auditory mechanism for ultrasound-induced cortical activity and movement requiring careful consideration in future development of ultrasonic neuromodulation as a tool in neuroscience research.

Noninvasive extraction of microsecond-scale dynamics from human motor cortex.

State-of-the-art noninvasive electromagnetic recording techniques allow observing neuronal dynamics down to the millisecond scale. Direct measurement of faster events has been limited to in vitro or invasive recordings. To overcome this limitation, we introduce a new paradigm for transcranial magnetic stimulation. We adjusted the stimulation waveform on the microsecond scale, by varying the duration between the positive and negative phase of the induced electric field, and studied corresponding changes in the elicited motor responses. The magnitude of the electric field needed for given motor-evoked potential amplitude decreased exponentially as a function of this duration with a time constant of 17 µs. Our indirect noninvasive measurement paradigm allows studying neuronal kinetics on the microsecond scale in vivo.

Focused ultrasound for modulation of the central and peripheral nervous system

Noninvasive neuromodulation has been the preferred option of neurological treatment but noninvasive approaches fall short when it comes to depth penetration. Ultrasound modulation has been shown feasible in several species including humans both in vitro and in vivo. In this paper, an overview of our group’s ultrasound neuromodulation in both the central (CNS) and the peripheral (PNS) nervous systems will be provided. In CNS, both motor- and sensory-related responses have been elicited in mice in vivo both in ipsilateral and contralateral limbs and pupils, respectively. The success are was highly correlated with the applied intensity and pressure in both the limb movement and ocular changes. The brain regions targeted were the somatosensory and visual cortex for the limb movement and the superior colliculus and locus coeruleus for the pupil dilation. In PNS, stimulation and inhibition of the sciatic nerve with FUS was elicited at different ultrasound parameters in vivo. Displacement of the nerve highly correlated with the elicited motor response. The success rate also correlated with higher intensities. Histology confirmed safety while temperature elevation was more correlated with inhibitory responses.

Eliciting motor responses through pavlovian conditioning

Classical conditioning theory involves learning a new behaviour through the process of association. In simple terms, two stimuli are linked together to produce a newly learned response in a person or animal. It is the process of associating, and consequently, providing meaning to a neutral stimulus with another meaningful stimulus, in order to elicit similar response and the basic processes that occur in classical conditioning include acquisition, stimulus generalisation, stimulus discrimination, and extinction. It is, in fact, no doubt that Pavlovian theory is also known as the theory of classical conditioning has an impeccable illustration of associative learning, this paper attempts to depict its application to learning motor skills as well as to critically evaluate its influence in sports.

Factors affecting localization and dispersion of alcohol in peripheral nerve block.

To explore the relationship between electrical current and nerve-needle distance for localization of target nerves in peripheral nerve block, and the effects of injection speed, concentration, and injectate volume on alcohol dispersion using an animal model. Rabbit tibial nerves were selected for localization. Nerve-needle distance was ascertained using a manipulator. The minimum current eliciting motor responses was recorded at nerve-needle distances of 0, 1, 2, 3, 4 and 5 mm. Rabbit tibial nerves were assigned into 3 groups: speed group, concentration group, and volume group. Nerves were localized by a stimulator and neurolysed with alcohol/contrast medium. Helical computed tomography (CT) was performed to measure volume/dispersion patterns of injectate. A linear relationship was observed between nerve-needle distance (X) and minimal current (Y) (Y = 0.13X + 0.22; r2 = 0.974; p<0.05) for the localization of the target nerve. CT scan revealed that the injection speed and volume significantly influenced the dispersion of alcohol (p<0.01), but concentration had no effect (p<0.05). This study found a positive linear relationship between nerve-needle distance and minimum electrical stimulation in tibial nerve blockade. In addition, the results suggest that a low volume of alcohol with a low injection speed can help to improve nerve block in clinical practice.

Ultrasonic neuromodulation of the mouse cortex increases cardiorespiratory activity

Focused ultrasound (FUS) has demonstrated its ability to modulate neuronal activity in both cortical and subcortical brain regions in a noninvasive and safe fashion in mice, non-human primates, and humans. Rodent studies have shown that ultrasonic neuromodulation (UNMOD) can elicit motor responses in limbs and trigger pupil dilation. Little is known about the effect of ultrasonic neuromodulation of the CNS on the autonomic activity in mice, primarily due to the cardiorespiratory depression caused by the anesthesia used. However, urethane has limited effects on autonomic activity and brain hemodynamics. In this paper, we demonstrate that UNMOD of the cortex increases cardiorespiratory activity in mice. A 1.9-MHz single-element focused ultrasound transducer was used to apply pulsed ultrasound to the mouse cortex. Each animal was injected intraperitoneally with urethane (1500 mg/kg), allowing for a stable plane of anesthesia and experimental efficacy window often exceeding 4 hours with minimal effects on autonomic activity. Sonications were performed in a grid spanning the cortex centered at the Bregma skull suture and heart and breathing rates were acquired using a pulse oximeter. FUS resulted in significant increases in both breathing and heart rates immediately following sonication. This study demonstrated that FUS can have an autonomous excitatory effect invivo.

Ipsi- and Contralateral Motor Response Using Ultrasound-induced Neurostimulation in Deeply Anesthetized Mice

Ultrasound neurostimulation has been proven capable of eliciting motor responses. However, the studies in sedated rodents presented problems with target specificity due to the use of low ultrasound frequencies (<700kHz). Here, we show that focused ultrasound (FUS) in mega-Hz range was able to evoke motor responses in mice under deep anesthesia. Contralateral movements of the hind limbs were observed when sonications were carried out at +2mm of Lambda and ±2mm lateral of midline in three mice. Moreover, stimulating other regions of the somatosensory and cerebellum induced trunk and ipsilateral limb movements in all six mice.

Inhibiting reactions to emotional versus non-emotional response cues in schizophrenia: Insights from a motor-process paradigm.

Recent models of schizophrenia suggest deficient use of contextual response cues when confronted with countermanding emotional cues. It is important to clinically validate these models by testing patients diagnosed with schizophrenia on tasks with competing emotional and contextual response determinants. Control and schizophrenia groups completed a novel task that elicited motor responses consistent with, or in opposition to, pre-potent emotional actions (i.e., approach vs. avoidance). An analogous non-emotional task was also used to examine cue-conflict impairment more generally. The groups demonstrated statistically equivalent performance decrements on incongruent versus congruent trials on both tasks. However, within the schizophrenia group, the incongruency effect was significantly greater in the emotional versus non-emotional task. These data suggest that, while patients with schizophrenia were able to employ contextual response cues to override competing emotional responses, they were slower to resolve emotional versus non-emotional response conflict. When patients were subdivided according to the presence or absence of disorganized symptoms, this effect was confined to patients with disorganized symptoms.

Deep brain stimulation of the inferior colliculus: A possible animal model to study paradoxical kinesia observed in some parkinsonian patients?

The inferior colliculus (IC) plays an important role in the normal processing of the acoustic message and is also involved in the filtering of acoustic stimuli of aversive nature. The neural substrate of the IC can also influence haloperidol-induced catalepsy. Considering that (i) paradoxical kinesia, observed in some parkinsonian patients, seems to be dependent of their emotional state and (ii) deep brain stimulation (DBS) represents an alternative therapeutic route for the relief of parkinsonian symptoms, the present study investigated the consequence of DBS at the IC on the catalepsy induced by haloperidol in rats. Additionally, we investigated if DBS of the IC can elicit motor responses in anesthetized rats and whether DBS elicits distinct neural firing patterns of activity at the dorsal cortex (DCIC) or central nucleus (CNIC) of the IC. A significant reduction of the catalepsy response was seen in rats previously given haloperidol and receiving DBS at the IC. In addition, electrical stimulation to the ventral part of the CNIC induced immediate motor responses in anesthetized rats. The neuronal spontaneous activity was higher at the ventral part of the CNIC than the dorsal part. DBS to the ventral part but not to the dorsal part of the CNIC increased the spike rate at neurons a few hundred microns away from the stimulation site. It is possible that the IC plays a role in the sensorimotor gating activated by emotional stimuli, and that DBS at the IC can be a promising new animal model to study paradoxical kinesia in rats.

Focused ultrasound-mediated non-invasive brain stimulation: examination of sonication parameters.

Transcranial focused ultrasound (FUS) has emerged as a new brain stimulation modality. The range of sonication parameters for successful brain stimulation warrants further investigation. The objective of this study was to examine the range of FUS sonication parameters that minimize the acoustic intensity/energy deposition while successfully stimulating the motor brain area in Sprague-Dawley rats. We transcranially administered FUS to the somatomotor area of the rat brain and measured the acoustic intensity that caused excitatory effects with respect to different pulsing parameters (tone-burst duration, pulse-repetition frequency, duty cycle, and sonication duration) at 350 and 650kHz of fundamental frequency. We observed that motor responses were elicited at minimum threshold acoustic intensities (4.9-5.6W/cm(2) in spatial-peak pulse-average intensity; 2.5-2.8W/cm(2) in spatial-peak temporal-average intensity) in a limited range of sonication parameters, i.e. 1-5ms of tone-burst duration, 50% of duty cycle, and 300ms of sonication duration, at 350kHz fundamental frequency. We also found that the pulsed sonication elicited motor responses at lower acoustic intensities than its equivalent continuous sonication. Our results suggest that the pulsed application of FUS selectively stimulates specific brain areas-of-interest at an acoustic intensity that is compatible with regulatory safety limits on biological tissue, thus allowing for potential applications in neurotherapeutics.

22. Implementation of multimodal intraoperative neuromonitoring into an established setting of awake craniotomy

Bipolar 60 Hz-stimulation-mapping and clinical evaluation are commonly used for patient assessment in awake neurosurgical procedures. Stimulation related seizures, afterdischarges, delayed wake-up or malcompliance interfere with successful testing. Somatosensory (SEPs) and motor evoked potentials (MEPs) are objective tools for mapping and monitoring independent of patients’ compliance. Their introduction into an established ‘awake setting’ were prospectively analysed for feasibility, reliability and effect on surgical strategy. Multimodal intraoperative neuromonitoring consisting of contralateral SEPs, transcranially (TES) and direct cortically (DCS) elicited MEPs (monopolar, train-of-five-technique with 250 Hz) were implemented in a 13 month period. 105 patients (53 ± 14 years, 60 male) with frontal/precentral (48), postcentral/parietal (33), temporal (16) and trigonal (8) located lesions (glioma (81), metastasis (18), others (6)) were analysed. SEPs and TES-MEPs were present in all 105 patients, as well as DCS for cortical and subcortical motor mapping. There were no serious side effects despite the description of tingling pain during direct cortical stimulation. After 5 months, a bias towards motor mapping with the monopolar stimulation was seen, such monopolar vs. bipolar stimulation was only compared in the first 70 patients: DCS-MEPs were elicited in all 70 patients, whereas the 60 Hz-stimulation elicited motor responses in 60/70 patients (p = 0.0016; Fisher’̃s-test). 90/105 patients (86%) were cooperative for the awake setting. In 4 of the 15 remaining patients (4%) language testing was considered essential and surgery was prematurely terminated. In the other 11 patients (10%), surgery was continued asleep with monopolar cortical and subcortical mapping and continuous monitoring of SEPs and MEPs. Multimodal monitoring is feasible in awake craniotomies and was well tolerated. Despite malcompliance and clinical deterioration it allows for objective assessment of somatosensory and motor pathways and proceeding with the surgical tumour resection. In conclusion, the inclusion of multimodal monitoring might be essential for pericentral surgery.

The epidural electric stimulation test does not predict local anesthetic spread or consumption in labour epidural analgesia

The epidural electrical stimulation test (EEST) is a highly specific and sensitive test for confirming placement of the epidural catheter in the epidural space. The purpose of this study was to investigate if the EEST could predict the spread and consumption of local anesthetic solutions during labour epidural analgesia. This observational study was conducted in labouring parturients requesting epidural analgesia. The EEST was performed after the epidural catheter placement (T0) and repeated five minutes after a test dose with 2% lidocaine 3 mL (T1). The minimum current required to elicit the motor response at each time point was recorded. A loading dose of 0.125% bupivacaine 10 mL and fentanyl 50 μg was administered and followed by patient-controlled epidural analgesia with 0.0625% bupivacaine and fentanyl 2 μg·mL(-1) (baseline infusion 10 mL·hr(-1), bolus dose 5 mL, lockout interval ten minutes, maximum dose 20 mL·hr(-1)). The primary outcome was the correlation between the current required to elicit motor responses at T0 and T1 and the consumption of bupivacaine in the first two hours of epidural administration. The secondary outcomes included the muscle contraction patterns determined by the EEST and the incidence of failed, inadequate, or asymmetric blocks. The study was conducted in 102 parturients. The mean electric current required to elicit muscle response was 4.43 mA (range 1-10 mA) at T0, 5.97 mA (range 1-14 mA) at T1, and the mean Δ (T1-T0) current was 1.54 mA (range 0-8 mA). There was no correlation between either the mean baseline current required or the Δ (T1-T0) current and the total bupivacaine consumption at two hours. The incidence of inadequate blocks at two hours was 18%; however, none of the catheters required replacement. Unilateral left (34%) or right (31%) leg contraction was the most frequent pattern elicited by the EEST. The EEST shows a wide range of electrical current requirements and elicits a variety of muscle twitch patterns on the lower limbs. Although it confirms the epidural placement of the catheter, the EEST cannot be used to predict the spread or consumption of the local anesthetic solution during labour epidural analgesia.

Strategic placement of epidural catheter

Epidural catheter insertion is useful for long term postoperative pain control or prolonged regional anesthesia for an operation, moreover, pain therapy for back pain or radiating pain [1,2]. For expected effect of epidural block, correct placement of epidural catheter is most important. However, the primary failure rate of epidural space catheterization can exceed 10% [3]. There is no objective, reliable, real time method to determine the correct catheter placement in the epidural space. Epidural test dose injection technique (2-3 ml lidocaine 1.5%) is usually used for verification of epidural catheter. But there is false positive and negative associated with the standard test dose injection [4]. Epidurography is also a useful modality for confirming location of the catheter. However, it is not a simple method because c-arm fluoroscope and contrast media are needed. Asato et al. [5] showed that the most frequent cause of unilateral epidural blockade was the misplacement of the catheter into the anterior epidural space. Tsui et al. [6] mentioned the use of low current epidural stimulation to confirm the epidural catheter placement for the first time. Epidural stimulation test (EST) is more accurate than standard test dose technique, and is deemed to be simpler than epidurography. The EST criteria define correct localization of the catheter tip in the epidural space by elicited motor response with a current between 1-10 mA at a frequency of 1 Hz with a pulse width of 0.2 ms [6,7]. There are truncal or limb movements when epidural catheter is correctly located. Appropriate muscle contractions consist of rhythmic hip adductors, iliopsoas, gluteus muscles and hamstring group movement on lumbar EST. If bilateral motor response was exhibited at an unusually low current, subarachnoid or epiradicular placement of catheter is considered. In this issue of the Korean Journal of Anesthesiology, Jung et al. [8] report on confirming the localization of an epiradicular catheter placement with different electrical pulse width. In the current study, instead of the threshold current, they compared the threshold charge. The number of charges (in nanocoulombs; nC) delivered is equal to the product of the current (in milliAmperes) and the pulse width (in milliseconds) [9]. Tsui et al. applied electric current between 1-10 mA with a pulse width of 0.2 ms for EST [6]. Pulse width of 0.2 ms is better than higher pulse width for EST because 0.2 ms is closer to the motor fiber's chronaxie. However, some nerve stimulator can't serve wide ranges of pulse width and current of electricity. Threshold charge might be a good parameter for determining correct catheter placement with variable kind of nerve stimulators. They used a single port, metal coil-reinforced, 19-gauge epidural catheter, instead of the conventional epidural catheter, which was usually used. It has an advantage that does not need normal saline for electrical conduction during EST. As the effective conduction of electricity is essential for the success of EST, the type of catheter is important. TheraCath, which they chose, provided an effective electrostimulation of the epidural space and offered an alternative to the traditional method of using a catheter primed with normal saline [10]. In this study, the electrical stimulation test performance results must be interpreted cautiously due to the specific patients group enrolled. They evaluated the threshold current of the patients group with spinal pathology. Tsui et al. [6] mentioned motor response at a current < 1 mA revealed an intrathecal, subdural or epiradicular placement of epidural catheter. The lower cutoff < 1 mA should not be considered an absolute limit but always a warning sign for possible epiradicular, subdural or subarachnoid position [11]. Epiradicular catheters were inserted for patients complaining of low extremity radiating pain due to spinal pathology. It is just a changing Tsui's way of thinking. They hypothesized that epiradicular current threshold of patients who have the degenerated nerve root or pathologic condition of spinal cord might be increased, compared with normal patients. Epiradicular threshold current (or charges) overlapped the epidural threshold current (or charges). The overlapping of the threshold current might be explained by adjacency of the catheter tip to the nerve root and chronic compression resulting in microvascular injury. The threshold current of epiradicular catheter could be useful for verifying spinal pathology, such as inflammation for patients undergoing back pain or radiating pain if more data is accumulated. EST is more accurate and simple real time method for confirming the localization of an epiradicular catheter placement. Moreover, it would make diagnosis of spinal pathology possible. Nonetheless, further studies are required before implementing its routine use in clinical settings.