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.

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.

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.

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.

Translational development and pre-clinical evaluation of prototype gastrointestinal mock-up devices: only robotic placement of plastic?

Background: The aim of this study was to address the vision of wireless theranostic devices distributed along the gastrointestinal (GI) tract by defining design requirements, developing prototype mock-ups, and establishing a minimally invasive surgical approach for the implantation process.Methods: Questionnaires for contextual analysis and use case scenarios addressing the technical issues of an implantable GI device, a possible scenario for implantation, preparation and calibration of a device, and therapeutic usage by professionals and patients were completed and discussed by an interdisciplinary team of surgeons, engineers, and product designers. Two acute porcine experiments were conducted with a robotic surgical system under general anaesthesia.Results: A variety of requirements for the design and implantation of implantable devices for modulating GI motility were defined. Five prototype implant mock-ups were three-dimensional (3D)-printed from black polymer material (width 22.32 mm, height 7.66 mm) and successfully implanted on the stomach, duodenum, jejunum, ileum, and colon using the robotic surgical system, without any complications.Conclusions: Our study shows the development and successful pre-clinical evaluation of a reliable device design with a minimally invasive implantation approach. Several stages of device development, including pre-clinical tests, characterisation of clinical requirements, regulatory affairs, and marketing issues should be managed side by side.

The Foveal Visual Representation of the Primate Superior Colliculus.

A defining feature of the primate visual system is its foveated nature. Processing of foveal retinal input is important not only for high-quality visual scene analysis but also for ensuring precise, albeit tiny, gaze shifts during high-acuity visual tasks. The representations of foveal retinal input in the primate lateral geniculate nucleus and early visual cortices have been characterized. However, how such representations translate into precise eye movements remains unclear. Here, we document functional and structural properties of the foveal visual representation of the midbrain superior colliculus. We show that the superior colliculus, classically associated with extra-foveal spatial representations needed for gaze shifts, is highly sensitive to visual input impinging on the fovea. The superior colliculus also represents such input in an orderly and very specific manner, and it magnifies the representation of foveal images in neural tissue as much as the primary visual cortex does. The primate superior colliculus contains a high-fidelity visual representation, with large foveal magnification, perfectly suited for active visuomotor control and perception.

Five-fold Gastrointestinal Electrical Stimulation With Electromyography-based Activity Analysis: Towards Multilocular Theranostic Intestinal Implants.

BACKGROUND/AIMS: Motility disorders are common and may affect the entire gastrointestinal (GI) tract but current treatment is limited. Multilocular sensing of GI electrical activity and variable electrical stimulation (ES) is a promising option. The aim of our study is to investigate the effects of adjustable ES on poststimulatory spike activities in 5 GI segments. METHODS: Six acute porcine experiments were performed with direct ES by 4 ES parameter sets (30 seconds, 25 mA, 500 microseconds or 1000 microseconds, 30 Hz or 130 Hz) applied through subserosal electrodes in the stomach, duodenum, ileum, jejunum, and colon. Multi-channel electromyography of baseline and post-stimulatory GI electrical activity were recorded for 3 minutes with hook needle and hook-wire electrodes. Spike activities were algorithmically calculated, visualized in a heat map, and tested for significance by Poisson analysis. RESULTS: Post-stimulatory spike activities were markedly increased in the stomach (7 of 24 test results), duodenum (8 of 24), jejunum (23 of 24), ileum (18 of 24), and colon (5 of 24). ES parameter analysis revealed that 80.0% of the GI parts (all but duodenum) required a pulse width of 1000 microseconds, and 60.0% (all but jejunum and colon) required 130 Hz frequency for maximum spike activity. Five reaction patterns were distinguished, with 30.0% earlier responses (type I), 42.5% later or mixed type responses (type II, III, and X), and 27.5% non-significant responses (type 0). CONCLUSIONS: Multilocular ES with variable ES parameters is feasible and may significantly modulate GI electrical activity. Automated electromyography analysis revealed complex reaction patterns in the 5 examined GI segments.

A thin-film multichannel electrode for muscle recording and stimulation in neuroprosthetics applications.

OBJECTIVE: We propose, design and test a novel thin-film multichannel electrode that can be used for both recording from and stimulating a muscle in acute implants. APPROACH: The system is built on a substrate of polyimide and contains 12 recording and three stimulation sites made of platinum. The structure is 420 µm wide, 20 µm thick and embeds the recording and stimulation contacts on the two sides of the polyimide over an approximate length of 2 cm. We show representative applications in healthy individuals as well as tremor patients. The designed system was tested by a psychometric characterization of the stimulation contacts in six tremor patients and three healthy individuals determining the perception threshold and current limit as well as the success rate in discriminating elicited sensations (electrotactile feedback). Also, we investigated the possibility of using the intramuscular electrode for reducing tremor in one patient by electrical stimulation delivered with timing based on the electromyographic activity recorded with the same electrode. MAIN RESULTS: In the tremor patients, the current corresponding to the perception threshold and the current limit were 0.7 ± 0.2 and 1.4 ± 0.7 mA for the wrist flexor muscles and 0.4 ± 0.2 and 1.5 ± 0.7 mA for the extensors. In one patient, closed-loop stimulation resulted in a decrease of the tremor power >50%. In healthy individuals the perception threshold and current limits were 0.9 ± 0.6 and 2.1 ± 0.6 mA for the extensor carpi radialis muscle. The subjects could distinguish four or six stimulation patterns (two or three stimulation sites × two stimulation current amplitudes) with true positive rate >80% (two subjects) and >60% (one subject), respectively. SIGNIFICANCE: The proposed electrode provides a compact multichannel interface for recording electromyogram and delivering electrical stimulation in applications such as neuroprostheses for tremor suppression and closed-loop myoelectric prostheses.

Research platform for medical device development to simplify translation to the market.

New regulations for medical products complicate research projects for new application fields and translation of innovative product ideas to refundable medical products becomes a high economic risk. All this demands for a CE-marked platform, which offers the possibility to access the recorded data online or even directly the hardware during research applications, to bridge the gap. This paper describes how a CE-marked medical product can be extended by different interfaces to enable basic research or simplify first proof-of-concept studies thus optimizing prototype development in research projects, simplifying the documentation process and reducing the risk for market access.

Technical, Medical and Ethical Challenges in Networks of Smart Active Implants.

Networks of distributed interactive micro-implants could enhance the treatment of otoneurological conditions such as tinnitus or restore impaired complex physiological/ motor functions such as gastrointestinal motility or grasping. For this, an electrical stimulation of neural and muscular tissue is a key prerequisite. Challenges in the development of such interactive micro-implants are the complex human-machine interface, the wireless power supply, and the long-term stability of implants as well as secure and safe signal transmission. This paper addresses all these topics as well as the ethical, legal and social implications of smart implant networks in general. First achievements of the German innovation cluster INTAKT will be presented.

Decoding motor neuron activity from epimysial thin-film electrode recordings following targeted muscle reinnervation.

OBJECTIVE: Surface electromyography (EMG) is currently used as a control signal for active prostheses in amputees who underwent targeted muscle reinnervation (TMR) surgery. Recent research has shown that it is possible to access the spiking activity of spinal motor neurons from multi-channel surface EMG. In this study, we propose the use of multi-channel epimysial EMG electrodes as an interface for decoding motor neurons activity following TMR. APPROACH: We tested multi-channel epimysial electrodes (48 detection sites) built with thin-film technology in an animal model of TMR. Eight animals were tested 12 weeks after reinnervation of the biceps brachii lateral head by the ulnar nerve. We identified the position of the innervation zone and the muscle fiber conduction velocity of motor units decoded from the multi-channel epimysial recordings. Moreover, we characterized the pick-up volume by the distribution of the motor unit action potential amplitude over the epimysium surface. MAIN RESULTS: The electrodes provided high quality signals with average signal-to-noise ratio >30 dB across 95 identified motor units. The motor unit action potential amplitude decreased with increasing distance of the electrode from the muscle fibers (P [Formula: see text] 0.001). The decrease was more pronounced for bipolar compared to monopolar derivations. The average muscle fiber conduction velocity was 2.46 ± 0.83 m s-1. Most of the neuromuscular junctions were close to the region where the nerve was neurotized, as observed from the EMG recordings and imaging data. SIGNIFICANCE: These results show that epimysial electrodes can be used for selective recordings of motor unit activities with a pick-up volume that included the entire muscle in the rat hindlimb. Epimysial electrodes can thus be used for detecting motor unit activity in muscles with specific fascicular territories associated to different functions following TMR surgery.

Extracorporeal Stimulation of Sacral Nerve Roots for Observation of Pelvic Autonomic Nerve Integrity: Description of a Novel Methodological Setup.

INTRODUCTION: Neurophysiologic monitoring can improve autonomic nerve sparing during critical phases of rectal cancer surgery. OBJECTIVES: To develop a system for extracorporeal stimulation of sacral nerve roots. METHODS: Dedicated software controlled a ten-electrode stimulation array by switching between different electrode configurations and current levels. A built-in impedance and current level measurement assessed the effectiveness of current injection. Intra-anal surface electromyography (sEMG) informed on targeting the sacral nerve roots. All tests were performed on five pig specimens. RESULTS: During switching between electrode configurations, the system delivered 100% of the set current (25 mA, 30 Hz, 200 µs cathodic pulses) in 93% of 250 stimulation trains across all specimens. The impedance measured between single stimulation array contacts and corresponding anodes across all electrode configurations and specimens equaled 3.7 ± 2.5 kΩ. The intra-anal sEMG recorded a signal amplitude increase as previously observed in the literature. When the stimulation amplitude was tested in the range from 1 to 21 mA using the interconnected contacts of the stimulation array and the intra-anal anode, the impedance remained below 250 Ω and the system delivered 100% of the set current in all cases. Intra-anal sEMG showed an amplitude increase for current levels exceeding 6 mA. CONCLUSION: The system delivered stable electric current, which was proved by built-in impedance and current level measurements. Intra-anal sEMG confirmed the ability to target the branches of the autonomous nervous system originating from the sacral nerve roots. SIGNIFICANCE: Stimulation outside of the operative field during rectal cancer surgery is feasible and may improve the practicality of pelvic intraoperative neuromonitoring.

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.

Long-term decoding of movement force and direction with a wireless myoelectric implant.

OBJECTIVE: The ease of use and number of degrees of freedom of current myoelectric hand prostheses is limited by the information content and reliability of the surface electromyography (sEMG) signals used to control them. For example, cross-talk limits the capacity to pick up signals from small or deep muscles, such as the forearm muscles for distal arm amputations, or sites of targeted muscle reinnervation (TMR) for proximal amputations. Here we test if signals recorded from the fully implanted, induction-powered wireless Myoplant system allow long-term decoding of continuous as well as discrete movement parameters with better reliability than equivalent sEMG recordings. The Myoplant system uses a centralized implant to transmit broadband EMG activity from four distributed bipolar epimysial electrodes. APPROACH: Two Rhesus macaques received implants in their backs, while electrodes were placed in their upper arm. One of the monkeys was trained to do a cursor task via a haptic robot, allowing us to control the forces exerted by the animal during arm movements. The second animal was trained to perform a center-out reaching task on a touchscreen. We compared the implanted system with concurrent sEMG recordings by evaluating our ability to decode time-varying force in one animal and discrete reach directions in the other from multiple features extracted from the raw EMG signals. MAIN RESULTS: In both cases, data from the implant allowed a decoder trained with data from a single day to maintain an accurate decoding performance during the following months, which was not the case for concurrent surface EMG recordings conducted simultaneously over the same muscles. SIGNIFICANCE: These results show that a fully implantable, centralized wireless EMG system is particularly suited for long-term stable decoding of dynamic movements in demanding applications such as advanced forelimb prosthetics in a wide range of configurations (distal amputations, TMR).

Direct projections from the dorsal premotor cortex to the superior colliculus in the macaque (macaca mulatta).

The dorsal premotor cortex (PMd) is part of the cortical network for arm movements during reach-related behavior. Here we investigate the neuronal projections from the PMd to the midbrain superior colliculus (SC), which also contains reach-related neurons, to investigate how the SC integrates into a cortico-subcortical network responsible for initiation and modulation of goal-directed arm movements. By using anterograde transport of neuronal tracers, we found that the PMd projects most strongly to the deep layers of the lateral part of the SC and the underlying reticular formation corresponding to locations where reach-related neurons have been recorded, and from where descending tectofugal projections arise. A somewhat weaker projection targets the intermediate layers of the SC. By contrast, terminals originating from prearcuate area 8 mainly project to the intermediate layers of the SC. Thus, this projection pattern strengthens the view that different compartments in the SC are involved in the control of gaze and in the control or modulation of reaching movements. The PMD-SC projection assists in the participation of the SC in the skeletomotor system and provides the PMd with a parallel path to elicit forelimb movements.

A new generation of double-sided intramuscular electrodes for multi-channel recording and stimulation.

In this work, a new generation of intramuscular multi-channel electrode for EMG recording and muscle stimulation is presented. The electrode is based on double-sided polyimide microtechnology, and features electrode contacts on both sides of a thin polyimide filament. The structure is attached to a cannula, allowing insertion and application of the electrode system similar to conventional intramuscular wire electrodes. In the presented design, the electrode has 12 small recording sites on one side of the structure, and 3 large stimulation sites on the other side. Applications of the system include diagnosis and treatment of tremor. To this end, the electrode has been successfully tested in tremor patients. In the future, the concept will be extended to other fields of application including intraneural electrodes.

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).