Multi-electrode Stimulation Research Articles

Assessment of Electrically Evoked Stapedius Reflex Threshold (eSRT) for Auditory Mapping in Pulse Width Modulation Cochlear Implants: The Effect of Multielectrode Stimulation.

This study assesses the electrically evoked stapedius reflex threshold (eSRT) as an objective method for generating auditory maps in individuals with pulse-width-modulation cochlear implants (CIs). It investigates the impact of both single- and multiple-electrode stimulations on eSRT detection rates and their association with patients' comfort loudness levels (C-levels). Despite eSRT exploration by several CI brands incorporating pulse-amplitude-modulation stimulation technology, there is a lack of information on systems using pulse-width modulation. The eSRT was measured in 19 ears ipsilaterally and contralaterally in response to stimulations in groups of 1, 3, and 5 electrodes across five distinct cochlear regions, spanning from apical to basal. For each group, the eSRT detection rate and its correlation with the C-levels were analyzed both regionally and overall. In both contralateral and ipsilateral sides, higher electrically evoked stapedius reflex (eSR) detection rates were obtained for multielectrode (67%, 47%) than for single-electrode (41%, 23%) stimulation. Invoking eSR in the apical and basal regions was easier than in the middle region. The multiple stimulation just increased slightly the correlation coefficients between eSRT and C-levels from 0.73 to 0.77 and from 0.77 to 0.85 (p < 0.05) for the contralateral and ipsilateral ears, respectively. Our research indicates that using a multielectrode stimulation approach enhances the detection rate of eSRT and slightly improves the correlation coefficient between eSRT and C-levels. It is found preferable to obtain measurements from the contralateral side due to its higher detection rate, although the ipsilateral side yields a marginally higher correlation coefficient. The findings suggest that eSRTs obtained from pulse width modulation implants could aid audiologists in programming the device.

Precise control of neural activity using dynamically optimized electrical stimulation.

Neural implants have the potential to restore lost sensory function by electrically evoking the complex naturalistic activity patterns of neural populations. However, it can be difficult to predict and control evoked neural responses to simultaneous multi-electrode stimulation due to nonlinearity of the responses. We present a solution to this problem and demonstrate its utility in the context of a bidirectional retinal implant for restoring vision. A dynamically optimized stimulation approach encodes incoming visual stimuli into a rapid, greedily chosen, temporally dithered and spatially multiplexed sequence of simple stimulation patterns. Stimuli are selected to optimize the reconstruction of the visual stimulus from the evoked responses. Temporal dithering exploits the slow time scales of downstream neural processing, and spatial multiplexing exploits the independence of responses generated by distant electrodes. The approach was evaluated using an experimental laboratory prototype of a retinal implant: large-scale, high-resolution multi-electrode stimulation and recording of macaque and rat retinal ganglion cells ex vivo. The dynamically optimized stimulation approach substantially enhanced performance compared to existing approaches based on static mapping between visual stimulus intensity and current amplitude. The modular framework enabled parallel extensions to naturalistic viewing conditions, incorporation of perceptual similarity measures, and efficient implementation for an implantable device. A direct closed-loop test of the approach supported its potential use in vision restoration.

Understanding responses to multi-electrode epiretinal stimulation using a biophysical model.

Neural interfaces are designed to evoke specific patterns of electrical activity in populations of neurons by stimulating with many electrodes. However, currents passed simultaneously through multiple electrodes often combine nonlinearly to drive neural responses, making evoked responses difficult to predict and control. This response nonlinearity could arise from the interaction of many excitable sites in each cell, any of which can produce a spike. However, this multi-site activation hypothesis is difficult to verify experimentally. We developed a biophysical model to study retinal ganglion cell (RGC) responses to multi-electrode stimulation and validated it using data collected from ex vivo preparations of the macaque retina using a microelectrode array (512 electrodes; 30µm pitch; 10µm diameter). First, the model was validated by using it to reproduce essential empirical findings from single-electrode recording and stimulation, including recorded spike voltage waveforms at multiple locations and sigmoidal responses to injected current. Then, stimulation with two electrodes was modeled to test how the positioning of the electrodes relative to the cell affected the degree of response nonlinearity. Currents passed through pairs of electrodes positioned near the cell body or far from the axon (>40 µm) exhibited approximately linear summation in evoking spikes. Currents passed through pairs of electrodes close to the axon summed linearly when their locations along the axon were similar, and nonlinearly otherwise. Over a range of electrode placements, several distinct, localized spike initiation sites were observed, and the number of these sites covaried with the degree of response nonlinearity. Similar trends were observed for three-electrode stimuli. All of these trends in the simulation were consistent with experimental observations. Significance . These findings support the multi-site activation hypothesis for nonlinear activation of neurons, providing a biophysical interpretation of previous experimental results and potentially enabling more efficient use of multi-electrode stimuli in future neural implants.

Effects of selective stimulation of apical electrodes on temporal pitch perception by cochlear implant recipients.

This study investigated whether selective apical stimulation improves temporal pitch perception in eight MED-EL cochlear implant recipients and whether any such improvement relates to auditory-nerve survival. Three stimulation conditions differing in the place and width of excitation were evaluated: single-electrode stimulation of (i) the most apical, (ii) a mid-array electrode, and (iii) multi-electrode stimulation of the four most apical electrodes. Stimulation-current-induced non-stimulating electrode voltages were recorded to identify extracochlear electrodes and gauge insertion depth. The pitches of the four most apical electrodes were compared using place-pitch ranking. Rate-pitch ranking was assessed between 80 and 981 pulses per second for the three stimulation conditions, to estimate the "upper limit" of temporal pitch. Single-electrode apical stimulation did not increase the upper limit relative to other conditions. The polarity effect (PE), defined as the difference between thresholds obtained for triphasic pulse trains with their central high-amplitude phase either anodic or cathodic, was obtained to evaluate peripheral neural health. The PE did not differ between apical and mid-array stimulation or correlate with the upper limit. In conclusion, we found no improvement of temporal pitch perception with single-electrode apical stimulation, and discuss possible explanations for this observation.

SAFE-OPT: a Bayesian optimization algorithm for learning optimal deep brain stimulation parameters with safety constraints

Objective.To treat neurological and psychiatric diseases with deep brain stimulation (DBS), a trained clinician must select parameters for each patient by monitoring their symptoms and side-effects in a months-long trial-and-error process, delaying optimal clinical outcomes. Bayesian optimization has been proposed as an efficient method to quickly and automatically search for optimal parameters. However, conventional Bayesian optimization does not account for patient safety and could trigger unwanted or dangerous side-effects.Approach.In this study we develop SAFE-OPT, a Bayesian optimization algorithm designed to learn subject-specific safety constraints to avoid potentially harmful stimulation settings during optimization. We prototype and validate SAFE-OPT using a rodent multielectrode stimulation paradigm which causes subject-specific performance deficits in a spatial memory task. We first use data from an initial cohort of subjects to build a simulation where we design the best SAFE-OPT configuration for safe and accurate searchingin silico. Main results.We then deploy both SAFE-OPT and conventional Bayesian optimization without safety constraints in new subjectsin vivo, showing that SAFE-OPT can find an optimally high stimulation amplitude that does not harm task performance with comparable sample efficiency to Bayesian optimization and without selecting amplitude values that exceed the subject's safety threshold.Significance.The incorporation of safety constraints will provide a key step for adopting Bayesian optimization in real-world applications of DBS.

Effects of acute hippocampal stimulation in the nonhuman primate penicillin model of temporal lobe seizures

Asynchronous distributed multielectrode stimulation (ADMES) is a novel approach to deep brain stimulation for medication resistant temporal lobe epilepsy that has shown promise in rodent and in vitro seizure models. To further evaluate its effects on a pre-clinical model, we characterized the effect of unilateral ADMES in an NHP model of temporal lobe seizures induced by intra-hippocampal injection of penicillin (PCN). Four non-human primates were used for this study in two contemporaneous cohorts. One cohort (n = 3 hemispheres) was implanted with the Medtronic RC + S stimulation (GIN cohort) and recording system connected to two 4-contact ring electrodes to evaluate three unilateral stimulation patterns: 7 Hz Ring ADMES, 20 Hz Dual Ring, and 125 Hz Dual Ring (analog of clinical stimulation). In an additional cohort (EPC cohort, n = 2), two 12-contact segmented electrodes were implanted in the right hippocampus and connected to an externalized recording and stimulation system to allow more flexibility in the stimulation pattern. In this second cohort, 4 variations of stimulation were evaluated (7 Hz Full ADMES, 7 Hz Ring ADMES, 31 Hz Wide Ring, and 31 Hz Dual Ring). In the GIN cohort, we found an increase in seizure frequency and time spent in seizure during the 7 Hz Ring ADMES stimulation compared to the respective post-stimulation. A similar post-stimulation effect was found in the EPC cohort. We also found an increase in seizure frequency during the 7Hz full ADMES compared to the respective post-stimulation. However, we did not find a difference between pre-stimulation and stimulation conditions suggesting a possible post stimulation effect of the 7Hz hippocampal stimulation. In conclusion, in the NHP PCN model of temporal lobe seizures, acute asynchronous hippocampal stimulation was not therapeutic, however, our findings related to the post-stimulation effect can support future studies using hippocampal stimulation for the treatment of temporal lobe epilepsy.

Effects of Monaural Temporal Electrode Asynchrony and Channel Interactions in Bilateral and Unilateral Cochlear-Implant Stimulation.

Timing cues such as interaural time differences (ITDs) and temporal pitch are pivotal for sound localization and source segregation, but their perception is degraded in cochlear-implant (CI) listeners as compared to normal-hearing listeners. In multi-electrode stimulation, intra-aural channel interactions between electrodes are assumed to be an important factor limiting access to those cues. The monaural asynchrony of stimulation timing across electrodes is assumed to mediate the amount of these interactions. This study investigated the effect of the monaural temporal electrode asynchrony (mTEA) between two electrodes, applied similarly in both ears, on ITD-based left/right discrimination sensitivity in five CI listeners, using pulse trains with 100 pulses per second and per electrode. Forward-masked spatial tuning curves were measured at both ears to find electrode separations evoking controlled degrees of across-electrode masking. For electrode separations smaller than 3 mm, results showed an effect of mTEA. Patterns were u/v-shaped, consistent with an explanation in terms of the effective pulse rate that appears to be subject to the well-known rate limitation in electric hearing. For separations larger than 7 mm, no mTEA effects were observed. A comparison to monaural rate-pitch discrimination in a separate set of listeners and in a matched setup showed no systematic differences between percepts. Overall, an important role of the mTEA in both binaural and monaural dual-electrode stimulation is consistent with a monaural pulse-rate limitation whose effect is mediated by channel interactions. Future CI stimulation strategies aiming at improved timing-cue encoding should minimize the stimulation delay between nearby electrodes that need to be stimulated successively.

Adaptive octree meshes for simulation of extracellular electrophysiology

Objective. The interaction between neural tissues and artificial electrodes is crucial for understanding and advancing neuroscientific research and therapeutic applications. However, accurately modeling this space around the neurons rapidly increases the computational complexity of neural simulations. Approach. This study demonstrates a dynamically adaptive simulation method that greatly accelerates computation by adjusting spatial resolution of the simulation as needed. Use of an octree structure for the mesh, in combination with the admittance method for discretizing conductivity, provides both accurate approximation and ease of modification on-the-fly. Main results. In tests of both local field potential estimation and multi-electrode stimulation, dynamically adapted meshes achieve accuracy comparable to high-resolution static meshes in an order of magnitude less time. Significance. The proposed simulation pipeline improves model scalability, allowing greater detail with fewer computational resources. The implementation is available as an open-source Python module, providing flexibility and ease of reuse for the broader research community.

Monopolar tDCS might affect brainstem reflexes: A computational and neurophysiological study

ObjectiveTo assess whether monopolar multi-electrode transcranial direct current stimulation (tDCS) montages might selectively affect deep brain structures through computational predictions and neurophysiological assessment. MethodsElectric field distribution in deep brain structures (i.e., thalamus and midbrain) were estimated through computational models simulating tDCS with two monopolar and two monopolar multi-electrode montages. Monopolar multi-electrode tDCS was then applied to healthy subject, and effects on pontine and medullary circuitries was evaluated studying changes in blink reflex (BR) and masseter inhibitory reflex (MIR). ResultsComputational results suggest that tDCS with monopolar multi-electrode montages might induce electric field intensities in deep brain structure comparable to those in grey matter, while neurophysiological results disclosed that BR and MIR were selectively modulated by tDCS only when cathode was placed over the right deltoid. ConclusionsMulti-electrode tDCS (anodes over motor cortices, cathode over right deltoid) could induce significant electric fields in the thalamus and midbrain, and selectively affect brainstem neural circuits. SignificanceMulti-electrode tDCS (anodes over motor cortices, cathode over right deltoid) might be further explored to affect brainstem activity, also in the context of non-invasive deep brain stimulation.

Inference of Electrical Stimulation Sensitivity from Recorded Activity of Primate Retinal Ganglion Cells.

High-fidelity electronic implants can in principle restore the function of neural circuits by precisely activating neurons via extracellular stimulation. However, direct characterization of the individual electrical sensitivity of a large population of target neurons, to precisely control their activity, can be difficult or impossible. A potential solution is to leverage biophysical principles to infer sensitivity to electrical stimulation from features of spontaneous electrical activity, which can be recorded relatively easily. Here, this approach is developed and its potential value for vision restoration is tested quantitatively using large-scale multielectrode stimulation and recording from retinal ganglion cells (RGCs) of male and female macaque monkeys ex vivo Electrodes recording larger spikes from a given cell exhibited lower stimulation thresholds across cell types, retinas, and eccentricities, with systematic and distinct trends for somas and axons. Thresholds for somatic stimulation increased with distance from the axon initial segment. The dependence of spike probability on injected current was inversely related to threshold, and was substantially steeper for axonal than somatic compartments, which could be identified by their recorded electrical signatures. Dendritic stimulation was largely ineffective for eliciting spikes. These trends were quantitatively reproduced with biophysical simulations. Results from human RGCs were broadly similar. The inference of stimulation sensitivity from recorded electrical features was tested in a data-driven simulation of visual reconstruction, revealing that the approach could significantly improve the function of future high-fidelity retinal implants.SIGNIFICANCE STATEMENT This study demonstrates that individual in situ primate retinal ganglion cells of different types respond to artificially generated, external electrical fields in a systematic manner, in accordance with theoretical predictions, that allows for prediction of electrical stimulus sensitivity from recorded spontaneous activity. It also provides evidence that such an approach could be immensely helpful in the calibration of clinical retinal implants.

Cortical layering disrupts multi-electrode current steering

Objective. Blindness affects approximately 40 million people worldwide and has inspired the development of cortical visual prostheses for restoring sight. Cortical visual prostheses electrically stimulate neurons of the visual cortex to artificially evoke visual percepts. Of the 6 layers of the visual cortex, layer 4 contains neurons that are likely to evoke a visual percept. Intracortical prostheses therefore aim to target layer 4; however, this can be difficult due to cortical curvature, inter-subject cortical variability, blindness-induced anatomical changes in cortex, and electrode placement variations. We investigated the feasibility of using current steering to stimulate specific cortical layers between electrodes in the laminar column. Approach. We explored whether the multiunit neural activity peak can be manipulated between two simultaneously stimulating electrodes in different layers of the cortical column. A 64-channel, 4-shank electrode array was implanted into the visual cortex of Sprague–Dawley rats (n = 7) orthogonal to the cortical surface. A remote return electrode was positioned over the frontal cortex in the same hemisphere. Charge was supplied to two stimulating electrodes along a single shank. Differing ratios of charge (100:0, 75:25, 50:50) and separation distances (300–500 μm) were tested. Results. Current steering across the cortical layers did not result in a consistent shift of the neural activity peak. Both single-electrode and dual-electrode stimulation induced activity throughout the cortical column. This contrasts observations that current steering evoked a controllable peak of neural activity between electrodes implanted at similar cortical depths. However, dual-electrode stimulation across the layers did reduce the stimulation threshold at each site compared to single-electrode stimulation. Significance. Multi-electrode stimulation is not suitable for targeted activation of layers using current steering. However, it can be used to reduce activation thresholds at adjacent electrodes within a given cortical layer. This may be applied to reduce the stimulation side effects of neural prostheses, such as seizures.

Astroglial Connexin 43 Regulates Synaptic Vesicle Release at Hippocampal Synapses.

Connexin 43, an astroglial gap junction protein, is enriched in perisynaptic astroglial processes and plays major roles in synaptic transmission. We have previously found that astroglial Cx43 controls synaptic glutamate levels and allows for activity-dependent glutamine release to sustain physiological synaptic transmissions and cognitiogns. However, whether Cx43 is important for the release of synaptic vesicles, which is a critical component of synaptic efficacy, remains unanswered. Here, using transgenic mice with a glial conditional knockout of Cx43 (Cx43-/-), we investigate whether and how astrocytes regulate the release of synaptic vesicles from hippocampal synapses. We report that CA1 pyramidal neurons and their synapses develop normally in the absence of astroglial Cx43. However, a significant impairment in synaptic vesicle distribution and release dynamics were observed. In particular, the FM1-43 assays performed using two-photon live imaging and combined with multi-electrode array stimulation in acute hippocampal slices, revealed a slower rate of synaptic vesicle release in Cx43-/- mice. Furthermore, paired-pulse recordings showed that synaptic vesicle release probability was also reduced and is dependent on glutamine supply via Cx43 hemichannel (HC). Taken together, we have uncovered a role for Cx43 in regulating presynaptic functions by controlling the rate and probability of synaptic vesicle release. Our findings further highlight the significance of astroglial Cx43 in synaptic transmission and efficacy.

NEUROMODULATION MODEL BASED ON MULTI-ELECTRODE COMBINED ELECTRICAL STIMULATION AND ANALYSIS OF SIGNAL CONDUCTION MECHANISM

This study aimed to analyze the diffusion of electrical stimulation signals in human tissue and provide a theoretical basis for multi-electrode combined stimulation. The standard single-layer human head model based on electromagnetic simulation was taken as the geometric structure model. The model filler was assumed to be muscle tissue, and a finite element model with muscle characteristics was established. A 20-mA DC electrical signal was input, and the propagation mechanism of the signal in the simplified brain model was calculated and analyzed through multi-physical field simulation software. The signal was mainly concentrated around the electrode; when multi-electrode combined stimulation was used, signal superposition existed at the geometric center of the model, and the signal was enhanced. Slice interception analysis demonstrated that the signal attenuation intensity was approximately 8 dB/cm in homogeneous muscle tissue. To compare the performance of the single-layer model and multi-layer model, a semi-refined digital brain model was established, and simulated signal diffusion of the two models was analyzed. Comparative analysis found that due to the uneven distribution of tissues and the high shielding property of bone, the signal was highly scattered at the bone contact, but the superposition of signals in the brain center still existed.

Multielectrode Cortical Stimulation Selectively Induces Unidirectional Wave Propagation of Excitatory Neuronal Activity in Biophysical Neural Model.

Cortical stimulation is emerging as an experimental tool in basic research and a promising therapy for a range of neuropsychiatric conditions. As multielectrode arrays enter clinical practice, the possibility of using spatiotemporal patterns of electrical stimulation to induce desired physiological patterns has become theoretically possible, but in practice can only be implemented by trial-and-error because of a lack of predictive models. Experimental evidence increasingly establishes traveling waves as fundamental to cortical information-processing, but we lack an understanding of how to control wave properties despite rapidly improving technologies. This study uses a hybrid biophysical-anatomical and neural-computational model to predict and understand how a simple pattern of cortical surface stimulation could induce directional traveling waves via asymmetric activation of inhibitory interneurons. We found that pyramidal cells and basket cells are highly activated by the anodal electrode and minimally activated by the cathodal electrodes, while Martinotti cells are moderately activated by both electrodes but exhibit a slight preference for cathodal stimulation. Network model simulations found that this asymmetrical activation results in a traveling wave in superficial excitatory cells that propagates unidirectionally away from the electrode array. Our study reveals how asymmetric electrical stimulation can easily facilitate traveling waves by relying on two distinct types of inhibitory interneuron activity to shape and sustain the spatiotemporal dynamics of endogenous local circuit mechanisms.SIGNIFICANCE STATEMENT Electrical brain stimulation is becoming increasingly useful to probe the workings of brain and to treat a variety of neuropsychiatric disorders. However, stimulation is currently performed in a trial-and-error fashion as there are no methods to predict how different electrode arrangements and stimulation paradigms will affect brain functioning. In this study, we demonstrate a hybrid modeling approach, which makes experimentally testable predictions that bridge the gap between the microscale effects of multielectrode stimulation and the resultant circuit dynamics at the mesoscale. Our results show how custom stimulation paradigms can induce predictable, persistent changes in brain activity, which has the potential to restore normal brain function and become a powerful therapy for neurological and psychiatric conditions.

Implantable AC-driven CMOS chip for distributed multichip retinal prosthesis capable of high-rate stimulation

Implantable retinal prostheses are stimulation devices used to compensate for the light sensitivity loss of retinal cells. In this study, we propose and demonstrate a novel method to significantly reduce the setting time for the stimulation conditions of a retinal prosthesis chip capable of multi-electrode stimulation. The efficiency of the control method is increased while using only two wires, as in our previous work. The chip comprises an 8 bit ID and 7 electrodes, and the stimulation current value can be set from 50 to 1550 μA. The fabricated chip requires only 32 pulses to set the stimulation conditions, which is approximately 1/65 of that of our previous chip. Furthermore, it is equipped with a complementary metal–oxide–semiconductor rectifier to enable it to be driven by a rectangular AC power supply. The effectiveness of the chip is demonstrated by setting the stimulation conditions at approximately 18 μs per electrode at a clock frequency of 2.3 MHz.

Multielectrode Array-Based Percutaneous Nerve Stimulation Strategy With Ultrasound Guidance for Ulnar Nerve Injury.

Studies have shown that percutaneous nerve stimulation can promote repair of ulnar neuropathy. However, this approach requires further optimization. We evaluated multielectrode array-based percutaneous nerve stimulation for treatment of ulnar nerve injury. The optimal stimulation protocol was determined using a multi-layer model of the human forearm using the finite element method. We optimized the number and distance between electrodes, and used ultrasound to aid in electrode placement. Six electrical needles in series along the injured nerve at alternating distances of five and seven centimeters. We validated the model in a clinical trial. Twenty-seven patients were randomly assigned to a control group (CN) and an electrical stimulation with finite element group (FES). The results showed that disability of arm shoulder and hand (DASH) scores decreased and grip strength increased to a greater extent in the FES group than those in the CN group following treatment (P<0.05). Furthermore, the amplitudes of compound motor action potentials (cMAPs) and sensory nerve action potentials (SNAPs) improved in the FES group to a greater extent than those in the CN group. The results showed that our intervention improved hand function and muscle strength, and aided in neurologic recovery, as shown using electromyography. Analysis of blood samples indicated that our intervention may have promoted conversion of the precursor form of brain-derived neurotrophic factor (pro-BDNF) to mature brain-derived neurotrophic factor (BDNF) to promote nerve regeneration. Our percutaneous nerve stimulation regimen for ulnar nerve injury has potential to become a standard treatment option.

Percepts evoked by multi-electrode stimulation of human visual cortex

BackgroundDirect electrical stimulation of early visual cortex evokes the perception of small spots of light known as phosphenes. Previous studies have examined the location, size, and brightness of phosphenes evoked by stimulation of single electrodes. While it has been envisioned that concurrent stimulation of many electrodes could be used as the basis for a visual cortical prosthesis, the percepts resulting from multi-electrode stimulation have not been fully characterized. ObjectiveTo understand the rules governing perception of phosphenes evoked by multi-electrode stimulation of visual cortex. MethodsMulti-electrode stimulation was conducted in human epilepsy patients. We examined the number and spatial arrangement of phosphenes evoked by stimulation of individual multi-electrode groups (n = 8), and the ability of subjects to discriminate between the pattern of phosphenes generated by stimulation of different multi-electrode groups (n = 7). ResultsSimultaneous stimulation of pairs of electrodes separated by greater than 4 mm tended to produce perception of two distinct phosphenes. Simultaneous stimulation of three electrodes gave rise to a consistent spatial pattern of phosphenes, but with significant variation in the absolute location, size, and orientation of that pattern perceived on each trial. Although multi-electrode stimulation did not produce perception of recognizable forms, subjects could use the pattern of phosphenes evoked by stimulation to perform simple discriminations. ConclusionsThe number of phosphenes produced by multi-electrode stimulation can be predicted using a model for spread of activity in early visual cortex, but there are additional subtle effects that must be accounted for.

Directionality of the injected current targeting the P20/N20 source determines the efficacy of 140 Hz transcranial alternating current stimulation (tACS)-induced aftereffects in the somatosensory cortex.

Interindividual anatomical differences in the human cortex can lead to suboptimal current directions and may result in response variability of transcranial electrical stimulation methods. These differences in brain anatomy require individualized electrode stimulation montages to induce an optimal current density in the targeted area of each individual subject. We aimed to explore the possible modulatory effects of 140 Hz transcranial alternating current stimulation (tACS) on the somatosensory cortex using personalized multi-electrode stimulation montages. In two randomized experiments using either tactile finger or median nerve stimulation, we measured by evoked potentials the plasticity aftereffects and oscillatory power changes after 140 Hz tACS at 1.0 mA as compared to sham stimulation (n = 17, male = 9). We found a decrease in the power of oscillatory mu-rhythms during and immediately after tactile discrimination tasks, indicating an engagement of the somatosensory system during stimulus encoding. On a group level both the oscillatory power and the evoked potential amplitudes were not modulated by tACS neither after tactile finger stimulation nor after median nerve stimulation as compared to sham stimulation. On an individual level we could however demonstrate that lower angular difference (i.e., differences between the injected current vector in the target region and the source orientation vector) is associated with significantly higher changes in both P20/N20 and N30/P30 source activities. Our findings suggest that the higher the directionality of the injected current correlates to the dipole orientation the greater the tACS-induced aftereffects are.

Randomized Clinical Study of Temporary Transvenous Phrenic Nerve Stimulation in Difficult-to-Wean Patients.

Rationale: Diaphragm dysfunction is frequently observed in critically ill patients with difficult weaning from mechanical ventilation. Objectives: To evaluate the effects of temporary transvenous diaphragm neurostimulation on weaning outcome and maximal inspiratory pressure. Methods: Multicenter, open-label, randomized, controlled study. Patients aged ⩾18 years on invasive mechanical ventilation for ⩾4 days and having failed at least two weaning attempts received temporary transvenous diaphragm neurostimulation using a multielectrode stimulating central venous catheter (bilateral phrenic stimulation) and standard of care (treatment) (n = 57) or standard of care (control) (n = 55). In seven patients, the catheter could not be inserted, and in seven others, pacing therapy could not be delivered; consequently, data were available for 43 patients. The primary outcome was the proportion of patients successfully weaned. Other endpoints were mechanical ventilation duration, 30-day survival, maximal inspiratory pressure, diaphragm-thickening fraction, adverse events, and stimulation-related pain. Measurements and Main Results: The incidences of successful weaning were 82% (treatment) and 74% (control) (absolute difference [95% confidence interval (CI)], 7% [-10 to 25]), P = 0.59. Mechanical ventilation duration (mean ± SD) was 12.7 ± 9.9 days and 14.1 ± 10.8 days, respectively, P = 0.50; maximal inspiratory pressure increased by 16.6 cm H2O and 4.8 cm H2O, respectively (difference [95% CI], 11.8 [5 to 19]), P = 0.001; and right hemidiaphragm thickening fraction during unassisted spontaneous breathing was +17% and -14%, respectively, P = 0.006, without correlation with changes in maximal inspiratory pressure. Serious adverse event frequency was similar in both groups. Median stimulation-related pain in the treatment group was 0 (no pain). Conclusions: Temporary transvenous diaphragm neurostimulation did not increase the proportion of successful weaning from mechanical ventilation. It was associated with a significant increase in maximal inspiratory pressure, suggesting reversal of the course of diaphragm dysfunction. Clinical trial registered with www.clinicaltrials.gov (NCT03096639) and the European Database on Medical Devices (CIV-17-06-020004).

Four-channel current switching device to enable multi-electrode magnetic resonance current density imaging.

Neurostimulation with multiple scalp electrodes has shown enhanced effects in recent studies. However, visualizations of stimulation-induced internal current distributions in brain is only possible through simulated current distributions obtained from computer model of human head. While magnetic resonance current density imaging (MRCDI) has a potential for direct in-vivo measurement of currents induced in brain with multi-electrode stimulation, existing MRCDI methods are only developed for two-electrode neurostimulation. A major bottleneck is the lack of a current switching device which is typically used to convert the DC current of neurostimulation devices into user-defined waveforms of positive and negative polarity with delays between them. In this work, we present a design of a four-electrode current switching device to enable simultaneous switching of current flowing through multiple scalp electrodes.