Wireless electrostimulation for cancer treatment: An integrated nanoparticle/coaxial fiber mesh platform.

Cancer, namely breast and prostate cancers, is the leading cause of death in many developed countries. Controlled drug delivery systems are key for the development of new cancer treatment strategies, to improve the effectiveness of chemotherapy and tackle off-target effects. In here, we developed a biomaterials-based wireless electrostimulation system with the potential for controlled and on-demand release of anti-cancer drugs. The system is composed of curcumin-loaded poly(3,4-ethylenedioxythiophene) nanoparticles (CUR/PEDOT NPs), encapsulated inside coaxial poly(glycerol sebacate)/poly(caprolactone) (PGS/PCL) electrospun fibers. First, we show that the PGS/PCL nanofibers are biodegradable, which allows the delivery of NPs closer to the tumoral region, and have good mechanical properties, allowing the prolonged storage of the PEDOT NPs before their gradual release. Next, we demonstrate PEDOT/CUR nanoparticles can release CUR on-demand (65 % of release after applying a potential of -1.5 V for 180 s). Finally, a wireless electrostimulation platform using this NP/fiber system was set up to promote in vitro human prostate cancer cell death. We found a decrease of 67 % decrease in cancer cell viability. Overall, our results show the developed NP/fiber system has the potential to effectively deliver CUR in a highly controlled way to breast and prostate cancer in vitro models. We also show the potential of using wireless electrostimulation of drug-loaded NPs for cancer treatment, while using safe voltages for the human body. We believe our work is a stepping stone for the design and development of biomaterial-based future smarter and more effective delivery systems for anti-cancer therapy.

Enhancing Visual-Guided Motor Imagery Performance via Sensory Threshold Somatosensory Electrical Stimulation Training.

OBJECTIVE: Motor imagery (MI) based brain- computer interface (BCI) has been widely studied as an effective way to enhance motor learning and promote motor recovery. However, the accuracy of MI-BCI heavily depends on whether subjects can perform MI tasks correctly, which largely limits the general application of MI-BCI. To overcome this limitation, a training strategy based on the combination of MI and sensory threshold somatosensory electrical stimulation (MI+st-SES) is proposed in this study. METHODS: Thirty healthy subjects were recruited and randomly divided into SES group and control group. Both groups performed left-hand and right-hand MI tasks in three consecutive blocks. The main difference between two groups lies in the second block, where subjects in SES group received the st-SES during MI tasks whereas the control group performed MI tasks only. RESULTS: The results showed that the SES group had a significant improvement in event-related desynchronization (ERD) of alpha rhythm after the training session of MI+st-SES (left-hand: F(2,27) = 9.98, p<0.01; right-hand: F(2, 27) = 10.43, p<0.01). The classification accuracy between left- and right-hand MI in the SES group was also significantly improved following MI+st-SES training (F(2,27) = 6.46, p<0.01). In contrary, there was no significant difference between the first and third blocks in the control group (F(2,27) = 0.18, p = 0.84). The functional connectivity based on weighted pairwise phase consistency (wPPC) over the sensorimotor area also showed an increase after the MI+st-SES training. CONCLUSION AND SIGNIFICANCE: Our findings indicate that training based on MI+st-SES is a promising way to foster MI performance and assist subjects in achieving efficient BCI control.

Accelerated complete human skin architecture restoration after wounding by nanogenerator-driven electrostimulation.

BACKGROUND: Electrostimulation (ES) therapy for wound healing is limited in clinical use due to barriers such as cumbersome equipment and intermittent delivery of therapy. METHODS: We adapted a human skin xenograft model that can be used to directly examine the nanogenerator-driven ES (NG-ES) effects on human skin in vivo-an essential translational step toward clinical application of the NG-ES technique for wound healing. RESULTS: We show that NG-ES leads to rapid wound closure with complete restoration of normal skin architecture within 7 days compared to more than 30 days in the literature. NG-ES accelerates the inflammatory phase of wound healing with more rapid resolution of neutrophils and macrophages and enhances wound bed perfusion with more robust neovascularization. CONCLUSION: Our results support the translational evaluation and optimization of the NG-ES technology to deliver convenient, efficient wound healing therapy for use in human wounds.

Evidence for Subcortical Plasticity after Paired Stimulation from a Wearable Device.

Existing non-invasive stimulation protocols can generate plasticity in the motor cortex and its corticospinal projections; techniques for inducing plasticity in subcortical circuits and alternative descending pathways such as the reticulospinal tract (RST) are less well developed. One possible approach developed by this laboratory pairs electrical muscle stimulation with auditory clicks, using a wearable device to deliver stimuli during normal daily activities. In this study, we applied a variety of electrophysiological assessments to male and female healthy human volunteers during a morning and evening laboratory visit. In the intervening time (∼6 h), subjects wore the stimulation device, receiving three different protocols, in which clicks and stimulation of the biceps muscle were paired at either low or high rate, or delivered at random. Paired stimulation: (1) increased the extent of reaction time shortening by a loud sound (the StartReact effect); (2) decreased the suppression of responses to transcranial magnetic brain stimulation (TMS) following a loud sound; (3) enhanced muscle responses elicited by a TMS coil oriented to induce anterior-posterior (AP) current, but not posterior-anterior (PA) current, in the brain. These measurements have all been suggested to be sensitive to subcortical, possibly reticulospinal, activity. Changes were similar for either of the two paired stimulus rates tested, but absent after unpaired (control) stimulation. Taken together, these results suggest that pairing clicks and muscle stimulation for long periods does indeed induce plasticity in subcortical systems such as the RST.SIGNIFICANCE STATEMENT Subcortical systems such as the reticulospinal tract (RST) are important motor pathways, which can make a significant contribution to functional recovery after cortical damage such as stroke. Here, we measure changes produced after a novel non-invasive stimulation protocol, which uses a wearable device to stimulate for extended periods. We observed changes in electrophysiological measurements consistent with the induction of subcortical plasticity. This protocol may prove an important tool for enhancing motor rehabilitation, in situations where insufficient cortical tissue survives to be a plausible substrate for recovery of function.

Electric acoustic stimulation (EAS) with the Naída CI Q90 sound processor in experienced cochlear implant users.

Objectives: The benefit of using the electroacoustic functionality was tested compared to electric stimulation alone. Two different cut-off frequencies between acoustic and electric stimulation were tried. Methods: Performance and subjective preference in 10 subjects was measured with electric only and electroacoustic stimulation with two settings: a cut-off for acoustic amplification at the frequency where thresholds exceeded 70 dB and 85 dB. An overlapping setting was also tried in five participants. Results: There was a non-significant trend with a median improvement in SRT of 1.3 dB (70 dB cut-off) and 0.8 dB (85 dB cut-off) compared to the electric only condition. From nine subjects who completed the study, one preferred the 85 dB cut-off frequency, with the others preferred either a 70 dB cut-off or an overlapping setting. Discussion: Nine subjects continued to use the EAS processor after study termination because of subjective benefits. The variability in speech outcomes and subjective preference is underlining the importance of being able to manually change acoustic and electric cut-off frequencies. Conclusion: There were non-significant median group benefits from use of the acoustic component for these existing CI users. A hearing loss of 70 dB HL is an appropriate default cut-off frequency in the fitting software.

Electro-haptic enhancement of speech-in-noise performance in cochlear implant users.

Cochlear implant (CI) users receive only limited sound information through their implant, which means that they struggle to understand speech in noisy environments. Recent work has suggested that combining the electrical signal from the CI with a haptic signal that provides crucial missing sound information ("electro-haptic stimulation"; EHS) could improve speech-in-noise performance. The aim of the current study was to test whether EHS could enhance speech-in-noise performance in CI users using: (1) a tactile signal derived using an algorithm that could be applied in real time, (2) a stimulation site appropriate for a real-world application, and (3) a tactile signal that could readily be produced by a compact, portable device. We measured speech intelligibility in multi-talker noise with and without vibro-tactile stimulation of the wrist in CI users, before and after a short training regime. No effect of EHS was found before training, but after training EHS was found to improve the number of words correctly identified by an average of 8.3%-points, with some users improving by more than 20%-points. Our approach could offer an inexpensive and non-invasive means of improving speech-in-noise performance in CI users.

Flexible, multichannel cuff electrode for selective electrical stimulation of the mouse trigeminal nerve.

The trigeminal nerve (cranial nerve V), along with other cranial nerves, has in recent years become a popular target for bioelectric medicine due to its direct access to neuromodulatory centers. Trigeminal nerve stimulation is currently being evaluated as an adjunctive treatment for various neurodegenerative and neuropsychiatric diseases despite the mechanism of action being in question. In this work, we describe the development and validation of a novel neural interface for the infraorbital branch of the trigeminal nerve utilizing a thin film (TF) nerve cuff containing multiple electrode sites allowing for more selective stimulation of the nerve. We characterized the properties of the device using electrochemical impedance spectroscopy, cyclic voltammetry, voltage excursions, and in vivo testing. Electrochemical measurements demonstrate that the platinum-based electrodes possess a capacitive charge carrying mechanism suitable for stimulation of biological tissue with a safe charge injection limit of 73.13 µC/cm2. In vivo stimulation experiments show that the TF cuff can reliably stimulate nerve targets eliciting cortical responses similar to a silicone cuff electrode. Furthermore, selecting different pairs of stimulation electrodes on the TF cuff modulated the magnitude and/or spatial pattern of cortical responses suggesting that the device may be able to selectively stimulate different parts of the nerve. These results suggest that the TF cuff is a viable neural interface for stimulation of the infraorbital branch of the trigeminal nerve that enables future research examining the therapeutic mechanisms of trigeminal nerve stimulation.

A simple electrical stimulation cell culture system on the myelination of dorsal root ganglia and Schwann cells.

A large number of animal experiments and clinical trials have confirmed that electrical stimulation can accelerate the growth of axons and recovery of motor function, all of which are inseparable from the formation of myelin. Therefore, establishment of a suitable electrical stimulation platform to study the effects of electrical stimulation on the myelin process of dorsal root ganglia and Schwann cells is of great significance for understanding the recovery of electrical stimulation. We designed a simple conductive glass cell culture system to overcome the shortcomings of direct contact of the electrode with the culture solution, and the number of culture chambers can be selected based on the purpose of the experiment in order to reduce experimental time and cost.

Brain Mesh: Technical Note.

BACKGROUND: Standard electrostimulation cortical mapping includes application of electrical current to the explored areas through an electrode and marking of functional zones by means of paper tags with different symbols. This approach has several disadvantages. First, the electrode is moved randomly. It leads to overlooking of some zones, which causes mapping deficiency, and restimulation of others, which can trigger epileptic seizures. Second, the tags easily shift and close the marked structures. We describe a new simple device that provides precise cortical mapping without indicated problems and the technique to apply it. METHODS: The device is a flexible polymer mesh with square pores of a certain size. The neurosurgeon applies the mesh onto the brain cortex and sequentially stimulates it through the pores. The functional areas are labeled. Pores corresponding to the lesion are cut out, and the lesion is removed through the cutout without removing the mesh. After operation, the mesh is removed. RESULTS: Using this technique, we operated on a patient with a glioma located near the primary motor cortex. The accessible cortical area was accurately mapped, and the tumor was resected without any complications. The mesh allowed us to significantly streamline the mapping process. CONCLUSIONS: Our case illustrates that the proposed invention can be successfully used in neurosurgical operations for precise electrostimulation mapping of the brain cortex.

Intracochlear near infrared stimulation: Feasibility of optoacoustic stimulation in vivo.

Intracochlear optical stimulation has been suggested as an alternative approach to hearing prosthetics in recent years. This study investigated the properties of a near infrared laser (NIR) induced optoacoustic effect. Pressure recordings were performed at the external meatus of anaesthetized guinea pigs during intracochlear NIR stimulation. The sound pressure and power spectra were determined. The results were compared to multi unit responses in the inferior colliculus (IC). Additionally, the responses to NIR stimulation were compared to IC responses induced by intracochlear electric stimulation at the same cochlear position to investigate a potentially confounding contribution of direct neural NIR stimulation. The power spectra of the sound recorded at the external meatus (n = 7) had most power at frequencies below 10 kHz and showed little variation for different stimulation sites. The mean spike rates of IC units responding to intracochlear NIR stimulation (n = 222) of 17 animals were significantly correlated with the power of the externally recorded signal at frequencies corresponding to the best frequencies of the IC units. The response strength as well as the sound pressure at the external meatus depended on the pulse peak power of the optical stimulus. The sound pressure recorded at the external meatus reached levels above 70 dB SPL peak equivalent. In hearing animals a cochlear activation apical to the location of the fiber was found. The absence of any NIR responses after pharmacologically deafening and the comparison to electric stimulation at the NIR stimulation site revealed no indication of a confounding direct neural NIR stimulation. Intracochlear optoacoustic stimulation might become useful in combined electro-acoustic stimulation devices in the future.

The peri-Sylvian cortical network underlying single word repetition revealed by electrocortical stimulation and direct neural recordings.

Verbal repetition requires the coordination of auditory, memory, linguistic, and motor systems. To date, the basic dynamics of neural information processing in this deceptively simple behavior are largely unknown. Here, we examined the neural processes underlying verbal repetition using focal interruption (electrocortical stimulation) in 58 patients undergoing awake craniotomies, and neurophysiological recordings (electrocorticography) in 8 patients while they performed a single word repetition task. Electrocortical stimulation revealed that sub-components of the left peri-Sylvian network involved in single word repetition could be differentially interrupted, producing transient perceptual deficits, paraphasic errors, or speech arrest. Electrocorticography revealed the detailed spatio-temporal dynamics of cortical activation, involving a highly-ordered, but overlapping temporal progression of cortical high gamma (75-150Hz) activity throughout the peri-Sylvian cortex. We observed functionally distinct serial and parallel cortical processing corresponding to successive stages of general auditory processing (posterior superior temporal gyrus), speech-specific auditory processing (middle and posterior superior temporal gyrus), working memory (inferior frontal cortex), and motor articulation (sensorimotor cortex). Together, these methods reveal the dynamics of coordinated activity across peri-Sylvian cortex during verbal repetition.

Impedance measures for a better understanding of the electrical stimulation of the inner ear.

The performance of cochlear implant (CI) listeners is limited by several factors among which the lack of spatial selectivity of the electrical stimulation. Recently, many studies have explored the use of multipolar strategies where several electrodes are stimulated simultaneously to focus the electrical field in a restricted region of the cochlea. OBJECTIVE: These strategies are based on several assumptions concerning the electrical properties of the inner ear that need validation. The first, often implicit, assumption is that the medium is purely resistive and that the current waveforms produced by several electrodes sum linearly. The second assumption relates to the estimation of the contribution of each electrode to the overall electrical field. These individual contributions are usually obtained by stimulating each electrode and measuring the resulting voltage with the other inactive electrodes (i.e. the impedance matrix). However, measuring the voltage on active electrodes (i.e. the diagonal of the matrix) is not straightforward because of the polarization of the electrode-fluid interface. In existing multipolar strategies, the diagonal terms of the matrix are therefore inferred using linear extrapolation from measurements made at neighboring electrodes. APPROACH: In experiment 1, several impedance measurements were carried out in vitro and in eight CI users using sinusoidal and pulsatile waveforms to test the resistivity and linearity hypotheses. In experiment 2, we used an equivalent electrical model including a constant phase element in order to isolate the polarization component of the contact impedance. MAIN RESULTS: In experiment 1, high-resolution voltage recordings (1.1 MHz sampling) showed the resistivity assumption to be valid at 46.4 kHz, the highest frequency tested. However, these measures also revealed the presence of parasitic capacitive effects at high frequency that could be deleterious to multipolar strategies. Experiment 2 showed that the electrical model provides a better account of the high-resolution impedance measurements than previous approaches in the CI field that used resistor-capacitance circuit models. SIGNIFICANCE: These results validate the main hypotheses underlying the use of multipolar stimulation but also suggest possible modifications to their implementation, including the use of an impedance model and the modification of the electrical pulse waveform.

Cytochrome P450 genes play central roles in transcriptional response by keratinocytes to a high-voltage alternating current electric field.

The endogenous electric field (EF) of skin wounds plays an important role in the biological processes that underlie wound healing. Treatments that modulate wound-EFs promote healing. However, the mechanism(s) that underlie this effect remain unclear. Agilent-based microarrays were used to determine the transcriptomes of the keratinocyte line HaCaT, normal human dermal fibroblasts, and the human dermal endothelial cell line HMEC-1 before and after high-voltage alternating current (AC)-EF (14,000 V, 90 Hz) treatment. The keratinocytes had the most genes whose transcription was altered by EF. They included the cytochrome P450 (CYP) genes CYP1A1 and CYP1B1, HMOX1, EREG, DUSP5, and SLC7A11 (all upregulated), and DOCK8, ABCC6, and CYP26A1 (all downregulated). As shown by transcriptional-network analysis, all three CYP genes played central roles in the EF-induced changes in keratinocyte transcriptome. To the best of our knowledge, this is the first study that demonstrates that CYP genes play a key role in the transcriptional responses of human keratinocytes to EF treatment. Further investigations into the effects of EF on wound healing, aging, and regenerative medicine are likely to yield promising results.

Custom edge-element FEM solver and its application to eddy-current simulation of realistic 2M-element human brain phantom.

Extensive research papers of three-dimensional computational techniques are widely used for the investigation of human brain pathophysiology. Eddy current analyzing could provide an indication of conductivity change within a biological body. A significant obstacle to current trend analyses is the development of a numerically stable and efficiency-finite element scheme that performs well at low frequency and does not require a large number of degrees of freedom. Here, a custom finite element method (FEM) solver based on edge elements is proposed using the weakly coupled theory, which separates the solution into two steps. First, the background field (the magnetic vector potential on each edge) is calculated and stored. Then, the electric scalar potential on each node is obtained by FEM based on Galerkin formulations. Consequently, the electric field and eddy current distribution in the object can be obtained. This solver is more efficient than typical commercial solvers since it reduces the vector eddy current equation to a scalar one, and reduces the meshing domain to just the eddy current region. It can therefore tackle complex eddy current calculations for models with much larger numbers of elements, such as those encountered in eddy current computation in biological tissues. An example is presented with a realistic human brain mesh of 2 million elements. In addition, with this solver, the equivalent magnetic field induced from the excitation coil is applied, and therefore there is no need to mesh the excitation coil. In combination, these significantly increase the efficiency of the solver. Bioelectromagnetics. 39:604-616, 2018. © 2018 Wiley Periodicals, Inc.

Effectiveness of percutaneous neuromuscular electrical stimulation for neck pain relief in patients with cervical spondylosis.

BACKGROUND: This study aimed to evaluate the effectiveness and safety of percutaneous neuromuscular electrical stimulation (PNMES) for treating neck pain in patients with cervical spondylosis (CS). METHODS: One hundred and twenty four patients with neck pain of CS were included, and then they were randomly divided into a PNMES group and a control group in a ratio of 1:1. All patients received PNMES or sham PNMES 30 minutes daily, 3 times weekly for 12 weeks. The primary outcome was assessed by the visual analog scale (VAS). The secondary outcomes were evaluated by the cervical range of motion (ROM), neck disability index (NDI) score, as well as the adverse events (AEs). All outcome measurements were measured at the end of 12-week treatment, and 4-week follow-up after treatment. RESULTS: At the end of the 12-week treatment, and 4-week follow-up, the patients receiving PNMES exhibited more decrease in the mean VAS (P < .01), and NDI (P < .01) respectively, compared with the patients receiving sham PNMES. Additionally, the increase in the mean ROM was also significantly higher in the PNMES group than that in the sham PNMES group at the end of the 12-week treatment, and 4-week follow-up, respectively (P < .01). No AEs were found in either group. CONCLUSIONS: The results of this study demonstrated that PNMES is more effective than Sham PNMES for neck pain relief in patients with CS.

Advantageous environment of micro-patterned, high-density complementary metal-oxide-semiconductor electrode array for spiral ganglion neurons cultured in vitro.

This study investigated micro-patterned, high-density complementary metal-oxide-semiconductor (CMOS) electrode array to be used as biologically permissive environment for organization, guidance and electrical stimulation of spiral ganglion neurons (SGN). SGNs extracted and isolated from cochleae of P5-P7 rat pups and adult guinea pigs were cultured 1, 4 and 7 days in vitro on glass coverslips (control) and CMOS electrode array. The cultures were analyzed visually and immunohistochemically for SGN presence, outgrowth, neurite alignment, neurite length, neurite asymmetry as well as the contact of a neuronal soma and neurites with the micro-electrodes. Our findings indicate that topographical environment of CMOS chip with micro-patterned pillars enhanced growth, survival, morphology, neural orientation and alignment of SGNs in vitro compared to control. Smaller spacing (0.8-1.6 µm) between protruding pillars on CMOS led SGNs to develop structured and guided neurites oriented along three topographical axes separated by 60°. We found morphological basis for positioning of the micro-electrodes on the chip that was appropriate for direct contact of SGNs with them. This configuration allowed CMOS electrode array to electrically stimulate the SGN whose responses were observed with live Fluo 4 calcium imaging.

Challenges associated with nerve conduction block using kilohertz electrical stimulation.

Neuromodulation therapies, which electrically stimulate parts of the nervous system, have traditionally attempted to activate neurons or axons to restore function or alleviate disease symptoms. In stark contrast to this approach is inhibiting neural activity to relieve disease symptoms and/or restore homeostasis. One potential approach is kilohertz electrical stimulation (KES) of peripheral nerves-which enables a rapid, reversible, and localized block of conduction. This review highlights the existing scientific and clinical utility of KES and discusses the technical and physiological challenges that must be addressed for successful translation of KES nerve conduction block therapies.

Selective recurrent laryngeal nerve stimulation using a penetrating electrode array in the feline model.

OBJECTIVES/HYPOTHESIS: Laryngeal muscles (LMs) are controlled by the recurrent laryngeal nerve (RLN), injury of which can result in vocal fold (VF) paralysis (VFP). We aimed to introduce a bioelectric approach to selective stimulation of LMs and graded muscle contraction responses. STUDY DESIGN: Acute experiments in cats. METHODS: The study included six anesthetized cats. In four cats, a multichannel penetrating microelectrode array (MEA) was placed into an uninjured RLN. For RLN injury experiments, one cat received a standardized hemostat-crush injury, and one cat received a transection-reapproximation injury 4 months prior to testing. In each experiment, three LMs (thyroarytenoid, posterior cricoarytenoid, and cricothyroid muscles) were monitored with an electromyographic (EMG) nerve integrity monitoring system. Electrical current pulses were delivered to each stimulating channel individually. Elicited EMG voltage outputs were recorded for each muscle. Direct videolaryngoscopy was performed for visualization of VF movement. RESULTS: Stimulation through individual channels led to selective activation of restricted nerve populations, resulting in selective contraction of individual LMs. Increasing current levels resulted in rising EMG voltage responses. Typically, activation of individual muscles was successfully achieved via single placement of the MEA by selection of appropriate stimulation channels. VF abduction was predominantly observed on videolaryngoscopy. Nerve histology confirmed injury in cases of RLN crush and transection experiments. CONCLUSIONS: We demonstrated the ability of a penetrating MEA to selectively stimulate restricted fiber populations within the feline RLN and selectively elicit contractions of discrete LMs in both acute and injury-model experiments, suggesting a potential role for intraneural MEA implantation in VFP management. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:1606-1614, 2018.

[The possibilities for the restoration of the laryngeal function: the current state-of-the-art]. / Vozmozhnosti vosstanovleniia funktsii gortani: sovremennyi podkhod.

The restoration of the functional competence of the larynx following bilateral laryngeal nerve damage and vocal fold paralysis is a serious challenge for the surgeon that has thus far no satisfactory solution. Physiological re-innervation that occurs naturally with time is non-selective and, in the majority of the cases, leads to synkinesis. Laryngeal pacing achieved with the application of the implantable microchips appears to be a promising approach. The animal experiments have demonstrated the possibility of successful restoration of all the functions of the larynx by means of laryngeal pacing but simultaneously revealed a number of technical issues that have to be addressed if the further progress in this field is to be achieved including the choice of the proper materials for implantation, solution of problems pertaining to the neuromuscular mapping during pacer implantation, etc.). The results of the first prospective clinical trial involving the human patients gave evidence suggesting that the laryngeal electrostimulation technology is both safe and efficient. Nevertheless, further investigations and modification of the method are needed before it can be recommended for the wider application in the routine clinical practice.

Integration of acoustic and electric hearing is better in the same ear than across ears.

Advances in cochlear implant (CI) technology allow for acoustic and electric hearing to be combined within the same ear (electric-acoustic stimulation, or EAS) and/or across ears (bimodal listening). Integration efficiency (IE; the ratio between observed and predicted performance for acoustic-electric hearing) can be used to estimate how well acoustic and electric hearing are combined. The goal of this study was to evaluate factors that affect IE in EAS and bimodal listening. Vowel recognition was measured in normal-hearing subjects listening to simulations of unimodal, EAS, and bimodal listening. The input/output frequency range for acoustic hearing was 0.1-0.6 kHz. For CI simulations, the output frequency range was 1.2-8.0 kHz to simulate a shallow insertion depth and the input frequency range was varied to provide increasing amounts of speech information and tonotopic mismatch. Performance was best when acoustic and electric hearing was combined in the same ear. IE was significantly better for EAS than for bimodal listening; IE was sensitive to tonotopic mismatch for EAS, but not for bimodal listening. These simulation results suggest acoustic and electric hearing may be more effectively and efficiently combined within rather than across ears, and that tonotopic mismatch should be minimized to maximize the benefit of acoustic-electric hearing, especially for EAS.