Laparoscopic Electromyography and Electrostimulation of the Gastrointestinal Tract Before Placement of Theranostic Devices.

NEED: Electrical stimulation (ES) is a promising therapy for multisegmental gastrointestinal (GI) motility disorders such as gastroparesis with slow-transit constipation or chronic intestinal pseudo-obstruction. Wireless communicating GI devices for smart sensing and ES-based motility modulation will soon be available. Before placement, a potential benefit for each GI segment must be intraoperatively assessed. TECHNICAL SOLUTION: A minimally invasive multisegmental electromyography (EMG) analysis with ES of the GI tract is required. PROOF OF CONCEPT: Two porcine experiments were performed with a laparoscopic setup. Multiple hook-needle electrodes were subserosally applied in the stomach, duodenum, jejunum, ileum, and colon. EMG signals were acquired for computer-assisted motility analysis. Gastric ES, duodenal ES, jejunal ES, ileal ES, and colonic ES were applied. NEXT STEPS: Further technological and rapid regulatory solutions are desired to initialize a clinical trial of the next generation devices in the near future. CONCLUSION: We demonstrate a laparoscopic strategy with EMG analysis and ES of multiple GI segments. Thus, GI function may be evaluated before theranostic devices are placed. Extended GI resection or organ transplantation may be delayed or even avoided in affected patients.

A multi-Kalman filter-based approach for decoding arm kinematics from EMG recordings.

BACKGROUND: Remarkable work has been recently introduced to enhance the usage of Electromyography (EMG) signals in operating prosthetic arms. Despite the rapid advancements in this field, providing a reliable, naturalistic myoelectric prosthesis remains a significant challenge. Other challenges include the limited number of allowed movements, lack of simultaneous, continuous control and the high computational power that could be needed for accurate decoding. In this study, we propose an EMG-based multi-Kalman filter approach to decode arm kinematics; specifically, the elbow angle (θ), wrist joint horizontal (X) and vertical (Y) positions in a continuous and simultaneous manner. RESULTS: Ten subjects were examined from which we recorded arm kinematics and EMG signals of the biceps, triceps, lateral and anterior deltoid muscles corresponding to a randomized set of movements. The performance of the proposed decoder is assessed using the correlation coefficient (CC) and the normalized root-mean-square error (NRMSE) computed between the actual and the decoded kinematic. Results demonstrate that when training and testing the decoder using same-subject data, an average CC of 0.68 ± 0.1, 0.67 ± 0.12 and 0.64 ± 0.11, and average NRMSE of 0.21 ± 0.06, 0.18 ± 0.03 and 0.24 ± 0.07 were achieved for θ, X, and Y, respectively. When training the decoder using the data of one subject and decoding the data of other subjects, an average CC of 0.61 ± 0.19, 0.61 ± 0.16 and 0.48 ± 0.17, and an average NRMSE of 0.23 ± 0.07, 0.2 ± 0.05 and 0.38 ± 0.15 were achieved for θ, X, and Y, respectively. CONCLUSIONS: These results suggest the efficacy of the proposed approach and indicates the possibility of obtaining a subject-independent decoder.

Robotic Setup Promises Consistent Effects of Multilocular Gastrointestinal Electrical Stimulation: First Results of a Porcine Study.

BACKGROUND: Electrical stimulation (ES) of several gastrointestinal (GI) segments is a promising therapeutic option for multilocular GI dysmotility, but conventional surgical access by laparotomy involves a high degree of tissue trauma. We evaluated a minimally invasive surgical approach using a robotic surgical system to perform electromyographic (EMG) recordings and ES of several porcine GI segments, comparing these data to an open surgical approach by laparotomy. MATERIALS AND METHODS: In 5 acute porcine experiments, we placed multiple electrodes on the stomach, duodenum, jejunum, ileum, and colon. Three experiments were performed with a median laparotomy and 2 others using a robotic platform. Multichannel EMGs were recorded, and ES was sequentially delivered with 4 ES parameters to the 5 target segments. We calculated pre- and poststimulatory spikes per minute (Spm) and performed a statistical Poisson analysis. RESULTS: Electrode placement was achieved in all cases without complications. Increased technical and implantation time were required to achieve the robotic electrode placement, but invasiveness was markedly reduced in comparison to the conventional approach. The highest calculated (c)Spm values were found in the poststimulatory period of the small bowel with both the conventional and robotic approaches. Six of the 20 Poisson test results in the open setup reached statistical significance and 12 were significant in the robotic experiments. CONCLUSIONS: The robotic setup was less invasive, revealed more consistent effects of multilocular ES in several GI segments, and is a promising option for future preclinical and clinical studies of GI motility disorders.

Primate superior colliculus neurons activated by unexpected sensation.

Midbrain superior colliculus (SC) contains a variety of neuronal types, influencing a rich spectrum of functions beyond gaze orienting. Here, we report on a novel class of SC neurons in the rhesus monkey (Macaca mulatta) that are activated by an unexpected perturbation in a goal-directed arm-movement task. One monkey subject reached for and pressed an illuminated target on a working panel upon a visual go-signal, while maintaining visual fixation elsewhere. On 50 % of trials, a task perturbation occurred-the working panel abruptly and unexpectedly moved against the subject's hand after he pressed the target. During the performance, we recorded single SC neurons and found neurons activated exclusively for the task perturbation. These perturbation neurons were localized in the deep lateral zone of the SC, were silent during non-perturbed trials, did not appear to respond to task-irrelevant stimuli, and they had intriguingly long neuronal latencies. If the perturbation neurons' activity relates to the hand-target contact, it may reflect the saliency of an unexpected sensation, i.e. a sensation that is not self-induced and thus cannot be predicted on a basis of the monkey's motor program.

Surface Electromyography Reliably Records Electrophysiologically Evoked Internal Anal Sphincter Activity: A More Minimally Invasive Approach for Monitoring Extrinsic Innervation.

BACKGROUND: Even in the case of minimally invasive pelvic surgery, sparing of the autonomic nerve supply is a prerequisite for maintaining anal sphincter function. Internal anal sphincter (IAS) innervation could be electrophysiologically identified based on processed electromyographic (EMG) recordings with conventional bipolar needle electrodes (NE). This experimental study aimed for the development of a minimally invasive approach via intra-anal surface EMG for recordings of evoked IAS activity. METHODS: Six male pigs underwent nerve-sparing low anterior rectal resection. Electric autonomic nerve stimulations were performed under online-processed EMG of the IAS. EMG recordings were simultaneously carried out with conventional bipolar NE as the reference method and newly developed intra-anal surface electrodes (SE) in different designs. RESULTS: In all experiments, the IAS activity could be continuously visualized via EMG recordings based on NE and SE. The median number of bipolar electric stimulations per animal was 27 (range 5-52). The neurostimulations resulted in significant EMG amplitude increases for both recording types [NE: median 3.0 µV (interquartile range, IQR 2.8-3.5) before stimulation vs. 7.1 µV (IQR 3.9-13.8) during stimulation, p < 0.001; SE: median 3.6 µV (IQR 3.1-4.3) before stimulation vs. 6.8 µV (IQR 4.8-10.3) during stimulation, p < 0.001]. CONCLUSIONS: Intra-anal SE enabled reliable EMG of electrophysiologically evoked IAS activity similar to the conventional recording via NE. The transfer of the method to access platforms for transanal total mesorectal excision or robotics may offer a practical more minimally invasive approach for monitoring extrinsic innervation.

Arm movements induced by electrical microstimulation in the superior colliculus of the macaque monkey.

Neuronal activity in the deep layers of the macaque (Macaca mulatta) superior colliculus (SC) and the underlying reticular formation is correlated with the initiation and execution of arm movements (Werner, 1993). Although the correlation of this activity with EMGs of proximal arm muscles is as strong as in motor cortex (Werner et al., 1997a; Stuphorn et al., 1999), little is known about the influence of electrical microstimulation in the SC on the initiation and trajectories of arm movements. Our experiments on three macaque monkeys clearly show that arm movements can be elicited by electrical microstimulation in the deep layers of the lateral SC and underlying reticular formation. The most extensively trained monkey, M1, extended his arm toward the screen in front of him more or less stereotypically upon electrical SC stimulation. In two other monkeys, M2 and M3, a larger repertoire of arm movements were elicited, categorized into three movement types, and compared before (M3) and after (M2 and M3) training: twitch (56% vs. 62%), lift (6% vs. 5%), and extend (37% vs. 32%), respectively. Therefore, arm movements induced by electrical stimulation in the monkey SC represent a further component of the functional repertoire of the SC using its impact on motoneurons in the spinal cord, probably via premotor neurons in the brainstem, as well as on structures involved in executing more complex movements such as target-directed reaching. Therefore, the macaque SC could be involved directly in the initiation, execution, and amendment of arm and hand movements.

Visual selectivity for heading in the macaque ventral intraparietal area.

The patterns of optic flow seen during self-motion can be used to determine the direction of one's own heading. Tracking eye movements which typically occur during everyday life alter this task since they add further retinal image motion and (predictably) distort the retinal flow pattern. Humans employ both visual and nonvisual (extraretinal) information to solve a heading task in such case. Likewise, it has been shown that neurons in the monkey medial superior temporal area (area MST) use both signals during the processing of self-motion information. In this article we report that neurons in the macaque ventral intraparietal area (area VIP) use visual information derived from the distorted flow patterns to encode heading during (simulated) eye movements. We recorded responses of VIP neurons to simple radial flow fields and to distorted flow fields that simulated self-motion plus eye movements. In 59% of the cases, cell responses compensated for the distortion and kept the same heading selectivity irrespective of different simulated eye movements. In addition, response modulations during real compared with simulated eye movements were smaller, being consistent with reafferent signaling involved in the processing of the visual consequences of eye movements in area VIP. We conclude that the motion selectivities found in area VIP, like those in area MST, provide a way to successfully analyze and use flow fields during self-motion and simultaneous tracking movements.

Retinal ganglion cells projecting to the accessory optic system in optokinetic blind albinotic rats are direction-selective.

The optokinetic deficits in albinotic rats and ferrets are caused by the loss of direction selectivity in the accessory optic system (AOS). However, the underlying mechanisms for this loss are still not clear. Here we tested the hypothesis that, in albino rats, the retinal input to the AOS lacks direction selectivity and, as a consequence, neurons in the AOS are direction non-selective. We investigated ON-center direction-selective retinal ganglion cells, the major input to the AOS, in pigmented Long Evans and albino Wistar rats using extracellular in vitro patch-clamp techniques. To visualise putative AOS-projecting direction-selective ganglion cells, we retrogradely labeled them by injection of the infrared-sensitive dye indocyanine green into the medial terminal nucleus of the AOS. The present study is the first to present physiological evidence for retinal ON-center direction-selective ganglion cells in rat. Our results show that, in albinotic and pigmented rats, ON-center retinal ganglion cells projecting to the AOS are similarly direction-selective, suggesting that the optokinetic deficit must be caused by the abolition of direction selectivity in the AOS itself.

Development, manufacturing and application of double-sided flexible implantable microelectrodes.

Many neuroprosthetic applications require the use of very small, flexible multi-channel microelectrodes (e.g. polyimide-based film-like electrodes) to fit anatomical constraints. By arranging the electrode contacts on both sides of the polyimide film, selectivity can be further increased without increasing size. In this work, two approaches to create such double-sided electrodes are described and compared: sandwich electrodes prepared by precisely gluing two single-sided structures together, and monolithic electrodes created using a new double-sided photolithography process. Both methods were successfully applied to manufacture double-sided electrodes for stimulation of the vestibular system. In a case study, the electrodes were implanted in the semicircular canals of three guinea pigs and proven to provide electrical stimulation of the vestibular nerve. For both the monolithic electrodes and the sandwich electrodes, long-term stability and functionality was observed over a period of more than 12 months. Comparing the two types of electrodes with respect to the manufacturing process, it can be concluded that monolithic electrodes are the preferred solution for very thin electrodes (<20 µm), while sandwich electrode technology is especially suitable for thicker electrodes (40-50 µm).

Contribution of cholinergic and GABAergic mechanisms to direction tuning, discriminability, response reliability, and neuronal rate correlations in macaque middle temporal area.

Previous studies have investigated the effects of acetylcholine (ACh) on neuronal tuning, coding, and attention in primary visual cortex, but its contribution to coding in extrastriate cortex is unexplored. Here we investigate the effects of ACh on tuning properties of macaque middle temporal area MT neurons and contrast them with effects of gabazine, a GABA(A) receptor blocker. ACh increased neuronal activity, it had no effect on tuning width, but it significantly increased the direction discriminability of a neuron. Gabazine equally increased neuronal activity, but it widened tuning curves and decreased the direction discriminability of a neuron. Although gabazine significantly reduced response reliability, ACh application had little effect on response reliability. Finally, gabazine increased noise correlation of simultaneously recorded neurons, whereas ACh reduced it. Thus, both drugs increased firing rates, but only ACh application improved neuronal tuning and coding in line with effects seen in studies in which attention was selectively manipulated.

Cortical processing of saccade-related efference copy signals in patients with cerebellar lesion.

The updating of visual space across saccades is thought to rely on efference copies of motor commands. In humans, thalamic lesions impair performance on a saccadic double-step task, which requires the use of efference copy information, and the altering of saccade-related efference copy processing. This deficit is attributed to disruption of a pathway from the superior colliculus to the frontal eye field. However, the cerebellum is probably also involved in efference copy processing, due to its pivotal role for predictive motor control. The present study investigated the processing of efference copy information in eight patients with focal cerebellar lesions and 22 healthy controls by means of a saccadic double-step task with simultaneous event-related potential recording. Despite intact behavioural performance, a positive event-related potential component between 150 and 450 ms after first saccade onset in the updating condition, which has been interpreted in terms of the integration of efference copy signals with motor intentions for a subsequent saccade, was markedly reduced in the patients. These findings suggest that the cerebellum contributes to on-line saccade monitoring, and that cerebellar lesions alter saccade-related efference copy processing. However, given the intact behavioural performance, the reduced positivity in the patients may indicate that cerebellar damage is accounted for by either exploiting reduced saccade-related information, or making use of compensatory strategies to circumvent a deficit in using efference copy information procured by the cerebellum. The present study extends previous findings on the neural underpinnings of saccadic updating and further elucidates the mechanisms underlying cerebellar predictive motor control.

Updating of visual space across horizontal saccades in cerebellar and thalamic lesion patients.

Efference copies of motor commands are used to update visual space across saccades, ultimately ensuring transsaccadic constancy of space. Thalamic lesions have been shown to impair efference copy-based saccadic updating in an oculomotor context, i.e., when two successive saccades are required. Moreover, the cerebellum has also been discussed as one possible source of saccade-related efference copy signals. The present study aimed to investigate the effects of thalamic and cerebellar lesions on saccadic updating in a perceptual context. To this end, seven patients with focal cerebellar lesions, seven patients with focal thalamic lesions and 11 healthy controls completed a perceptual localisation task in which the position of a target had to be updated across a single horizontal saccade, while saccade-related event-related potentials (ERPs) were recorded. Contrary to the expectations, localisation precision in both patient groups did not differ from the respective controls. A positive ERP component with centroparietal distribution occurring from about 300 to 500 ms after saccade onset in the updating condition was observed equally pronounced in controls and thalamic lesion patients. In cerebellar lesion patients, there was evidence of a reduction of this relative positivity in the updating condition, particularly for leftward saccades. This finding suggests that cerebellar damage altered the neural processes underlying saccadic updating in a perceptual context without causing overt behavioural deficits.

Automated determination of peripheral nerve stimulation parameters to achieve desired effector response - a procedural routine, preliminary studies and proposal of improvements.

BACKGROUND: The feasibility of selectively stimulating fascicles and fibers within peripheral nerves has been demonstrated by a number of groups. Although various multi-contact electrodes have been developed for this purpose, the lack of procedures for fast determination of stimulation parameters to produce the desired effector activity hampers the clinical application of these techniques.In this paper, we propose an automated search routine that may facilitate the determination of stimulation parameters. To verify the routine's performance, we also developed an another routine that performs systematic stimulus-response mapping (the mapping routine). METHOD: The mapping routine performs systematic mapping of all possible combinations of the allowed stimulation parameters (i.e. combinations of electrode contacts used to provide the stimulus and sets of stimulus parameters values) and the observed displacements. The proposed automated search routine, similarly to the mapping routine, maps stimulation parameters to muscle responses, but it first investigates stimuli of the low charge and during the mapping process it compares the recorded responses with the desired one. Depending on the result of that comparison, it decides whether the use of a particular combination of electrode contacts should be further investigated or skipped.Both approaches were implemented on a custom-made closed-loop FES platform and preliminary experiments were performed on a rat model. The rat's sciatic nerve was stimulated with a 12-contact cuff electrode and the resulting displacement of the rat's paw was determined using a MEMS accelerometer. RESULTS: The automated search routine was faster than the mapping routine; however, it failed to find correct stimulation parameters in one out of three searches. This could be due to unexpectedly high variability in the responses to a constant stimulus. CONCLUSION: Our initial tests have proven that the proposed method determines the desired stimulation parameters much more quickly than systematic stimulus-response mapping. However, the factors influencing the variability of responses to constant stimuli should be identified, and their influence diminished; the remaining essential variability can then be identified. Thereafter, the criteria influencing the search process should be investigated and refined.Further improvements to the search routine are also proposed.

Visual Functions of the Primate Superior Colliculus.

The superior colliculus (SC) is a subcortical brain structure that is relevant for sensation, cognition, and action. In nonhuman primates, a rich history of studies has provided unprecedented detail about this structure's role in controlling orienting behaviors; as a result, the primate SC has become primarily regarded as a motor control structure. However, as in other species, the primate SC is also a highly visual structure: A fraction of its inputs is retinal and complemented by inputs from visual cortical areas, including the primary visual cortex. Motivated by this, recent investigations are revealing the rich visual pattern analysis capabilities of the primate SC, placing this structure in an ideal position to guide orienting movements. The anatomical proximity of the primate SC to both early visual inputs and final motor control apparatuses, as well as its ascending feedback projections to the cortex, affirms an important role for this structure in active perception.

Toward higher-performance bionic limbs for wider clinical use.

Most prosthetic limbs can autonomously move with dexterity, yet they are not perceived by the user as belonging to their own body. Robotic limbs can convey information about the environment with higher precision than biological limbs, but their actual performance is substantially limited by current technologies for the interfacing of the robotic devices with the body and for transferring motor and sensory information bidirectionally between the prosthesis and the user. In this Perspective, we argue that direct skeletal attachment of bionic devices via osseointegration, the amplification of neural signals by targeted muscle innervation, improved prosthesis control via implanted muscle sensors and advanced algorithms, and the provision of sensory feedback by means of electrodes implanted in peripheral nerves, should all be leveraged towards the creation of a new generation of high-performance bionic limbs. These technologies have been clinically tested in humans, and alongside mechanical redesigns and adequate rehabilitation training should facilitate the wider clinical use of bionic limbs.

Visual pathway for the optokinetic reflex in infant macaque monkeys.

The horizontal optokinetic nystagmus (hOKN) in primates is immature at birth. To elucidate the early functional state of the visual pathway for hOKN, retinal slip neurons were recorded in the nucleus of the optic tract and dorsal terminal nucleus (NOT-DTN) of 4 anesthetized infant macaques. These neurons were direction selective for ipsiversive stimulus movement shortly after birth [postnatal day 9 (P9)], although at a lower direction selectivity index (DSI). The DSI in the older infants (P12, P14, P60) was not different from adults. A total of 96% of NOT-DTN neurons in P9, P12, and P14 were binocular, however, significantly more often dominated by the contralateral eye than in adults. Already in the youngest animals, NOT-DTN neurons were well tuned to different stimulus velocities; however, tuning was truncated toward lower stimulus velocities when compared with adults. As early as at P12, electrical stimulation in V1 elicited orthodromic responses in the NOT-DTN. However, the incidence of activated neurons was much lower in infants (40-60% of the tested NOT-DTN neurons) than in adults (97%). Orthodromic latencies from V1 were significantly longer in P12-P14 (x = 12.2 ± 8.9 ms) than in adults (x = 3.51 ± 0.81 ms). At the same age, electrical stimulation in motion-sensitive area MT was more efficient in activating NOT-DTN neurons (80% of the tested cells) and yielded shorter latencies than in V1 (x = 7.8 ± 3.02 ms; adult x = 2.99 ± 0.85 ms). The differences in discharge rate between neurons in the NOT-DTN contra- and ipsilateral to the stimulated eye are equivalent to the gain asymmetry between monocularly elicited OKN in temporonasal and nasotemporal direction at the various ages.

Magnetic field perception in the rainbow trout Oncorynchus mykiss: magnetite mediated, light dependent or both?

In the present study, we demonstrate the role of the trigeminal system in the perception process of different magnetic field parameters by heartbeat conditioning, i.e. a significantly longer interval between two consecutive heartbeats after magnetic stimulus onset in the salmonid fish Oncorhynchus mykiss. The electrocardiogram was recorded with subcutaneous silver wire electrodes in freely swimming fish. Inactivation of the ophthalmic branch of the trigeminal nerve by local anaesthesia revealed its role in the perception of intensity/inclination of the magnetic field by abolishing the conditioned response (CR). In contrast, experiments with 90° direction shifts clearly showed the normal conditioning effect during trigeminal inactivation. In experiments under red light and in darkness, CR occurred in case of both the intensity/inclination stimulation and 90° direction shifts, respectively. With regard to the data obtained, we propose the trigeminal system to perceive the intensity/inclination of the magnetic field in rainbow trouts and suggest the existence of another light-independent sensory structure that enables fish to detect the magnetic field direction.

Neuronal activity in the superior colliculus related to saccade initiation during coordinated gaze-reach movements.

One must be quick and precise when foveating targets to be reached, because the eyes have to guide the hand trajectory by visual feedback, and we may miss a rapidly moving target if our grasping is not fast and accurate enough. To this end, our brains developed mechanisms coordinating gaze and hand movements to optimize the way in which we foveate and reach. One of these mechanisms is the facilitation of the primary saccade--proven in humans and confirmed here in monkeys--which allows the generation of short-latency gaze movements when reaching towards visual targets. Here we tested whether the neuronal activity in the superior colliculus (SC) accounts for this mechanism; alternatively, cortical saccade-related areas could play a major role in the fast initiation of saccades during such elaborated behaviours bypassing the SC. Upon presentation of a target, neurons located at the rostral pole of the SC started the saccade-related pause in their activity earlier in tasks involving coordinated gaze-reach movements than in tasks in which the saccades were made in isolation. In the same tasks neurons located at the caudal SC reached peak firing rates earlier in coordinated gaze-reach movements than with isolated saccades, confirming the tight coupling between their burst activity latencies and the saccadic reaction times. In sum, our results extend the role of the SC in saccade initiation to coordinated gaze-reach movements, identifying its activity as an important part of the distributed neural system for eye-hand coordination.

Decoding of grasping information from neural signals recorded using peripheral intrafascicular interfaces.

BACKGROUND: The restoration of complex hand functions by creating a novel bidirectional link between the nervous system and a dexterous hand prosthesis is currently pursued by several research groups. This connection must be fast, intuitive, with a high success rate and quite natural to allow an effective bidirectional flow of information between the user's nervous system and the smart artificial device. This goal can be achieved with several approaches and among them, the use of implantable interfaces connected with the peripheral nervous system, namely intrafascicular electrodes, is considered particularly interesting. METHODS: Thin-film longitudinal intra-fascicular electrodes were implanted in the median and ulnar nerves of an amputee's stump during a four-week trial. The possibility of decoding motor commands suitable to control a dexterous hand prosthesis was investigated for the first time in this research field by implementing a spike sorting and classification algorithm. RESULTS: The results showed that motor information (e.g., grip types and single finger movements) could be extracted with classification accuracy around 85% (for three classes plus rest) and that the user could improve his ability to govern motor commands over time as shown by the improved discrimination ability of our classification algorithm. CONCLUSIONS: These results open up new and promising possibilities for the development of a neuro-controlled hand prosthesis.

Intramuscular Stimulation of Muscle Afferents Attains Prolonged Tremor Reduction in Essential Tremor Patients.

This study proposes and clinically tests intramuscular electrical stimulation below motor threshold to achieve prolonged reduction of wrist flexion/extension tremor in Essential Tremor (ET) patients. The developed system consisted of an intramuscular thin-film electrode structure that included both stimulation and electromyography (EMG) recording electrodes, and a control algorithm for the timing of intramuscular stimulation based on EMG (closed-loop stimulation). Data were recorded from nine ET patients with wrist flexion/extension tremor recruited from the Gregorio Marañón Hospital (Madrid, Spain). Patients participated in two experimental sessions comprising: 1) sensory stimulation of wrist flexors/extensors via thin-film multichannel intramuscular electrodes; and 2) surface stimulation of the nerves innervating the same target muscles. For each session, four of these patients underwent random 60-s trials of two stimulation strategies for each target muscle: 1) selective and adaptive timely stimulation (SATS) - based on EMG of the antagonist muscle; and 2) continuous stimulation (CON) of target muscles. Two patients underwent SATS stimulation trials alone while the other three underwent CON stimulation trials alone in each session. Kinematics of wrist, elbow, and shoulder, together with clinical scales, were used to assess tremor before, right after, and 24 h after each session. Intramuscular SATS achieved, on average, 32% acute (during stimulation) tremor reduction on each trial, while continuous stimulation augmented tremorgenic activity. Furthermore, tremor reduction was significantly higher using intramuscular than surface stimulation. Prolonged reduction of tremor amplitude (24 h after the experiment) was observed in four patients. These results showed acute and prolonged (24 h) tremor reduction using a minimally invasive neurostimulation technology based on SATS of primary sensory afferents of wrist muscles. This strategy might open the possibility of an alternative therapeutic approach for ET patients.