First evidence of a biomarker-based dose-response relationship in chronic pain using physiological closed-loop spinal cord stimulation.

BACKGROUND AND OBJECTIVES: In spinal cord stimulation (SCS) therapy, electricity is the medication delivered to the spinal cord for pain relief. In contrast to conventional medication where dose is determined by desired therapeutic plasma concentration, there is lack of equivalent means of determining dose delivery in SCS. In open-loop (OL) SCS, due to the dynamic nature of the epidural space, the activating electric field delivered is inconsistent at the level of the dorsal columns. Recent Food and Drug Administration guidance suggests accurate and consistent therapy delivered using physiologic closed-loop control (PCLC) devices can minimize underdosage or overdosage and enhance medical care. PCLC-based evoked compound action potential (ECAP)-controlled technology provides the ability to prescribe a precise stimulation dose unique to each patient, continuously measure neural activation, and objectively inform SCS therapy optimization. METHODS: Neurophysiological indicator metrics of therapy dose, usage above neural activation threshold, and accuracy of SCS therapy were assessed for relationship with pain reduction in over 600 SCS patients. RESULTS: Significant relationships between objective metrics and pain relief across the patient population are shown, including first evidence for a dose-response relationship in SCS. CONCLUSIONS: Higher dose, more time over ECAP threshold, and higher accuracy are associated with better outcomes across patients. There is potential to optimize individual patient outcomes based on unique objective measurable electrophysiological inputs.

Electrical Determinants of Tinnitus Extinction in a Cochlear Implant Patient.

HYPOTHESIS: Electrical tinnitus suppression by cochlear implants requires stimulation of a subset of neural elements in the cochlea. BACKGROUND: Tinnitus is the phantom perception of sound in the ears and is a known correlate of hearing loss. Cochlear implants restore hearing and are known to lessen or extinguish tinnitus. The amount of electrical charge required and the number and location of electrodes required to extinguish tinnitus with a cochlear implant are factors that remain poorly understood. METHODS: In a subject with single-sided deafness, with tinnitus in the deaf ear, we enabled single electrodes and groups of electrodes along the cochlea and increased the current until tinnitus was diminished or extinguished. We recorded the subject's perception of these changes using loudness scaling of both the electrical stimuli and the tinnitus. RESULTS: Tinnitus could be extinguished with individual electrodes and more effectively extinguished by activating a greater number of electrodes. Tinnitus suppression and loudness growth of the electrical stimuli were imperfectly correlated. CONCLUSION: Tinnitus suppression in this cochlear implant patient was achieved by electrically stimulating multiple distinct portions of the cochlea, and the cochlear neural substrate for tinnitus suppression may be distinct from that for auditory perception.

CompHEAR: A Customizable and Scalable Web-Enabled Auditory Performance Evaluation Platform for Cochlear Implant Sound Processing Research.

Objective: Cochlear implants (CIs) are auditory prostheses for individuals with severe to profound hearing loss, offering substantial but incomplete restoration of hearing function by stimulating the auditory nerve using electrodes. However, progress in CI performance and innovation has been constrained by the inability to rapidly test multiple sound processing strategies. Current research interfaces provided by major CI manufacturers have limitations in supporting a wide range of auditory experiments due to portability, programming difficulties, and the lack of direct comparison between sound processing algorithms. To address these limitations, we present the CompHEAR research platform, designed specifically for the Cochlear Implant Hackathon, enabling researchers to conduct diverse auditory experiments on a large scale. Study Design: Quasi-experimental. Setting: Virtual. Methods: CompHEAR is an open-source, user-friendly platform which offers flexibility and ease of customization, allowing researchers to set up a broad set of auditory experiments. CompHEAR employs a vocoder to simulate novel sound coding strategies for CIs. It facilitates even distribution of listening tasks among participants and delivers real-time metrics for evaluation. The software architecture underlies the platform's flexibility in experimental design and its wide range of applications in sound processing research. Results: Performance testing of the CompHEAR platform ensured that it could support at least 10,000 concurrent users. The CompHEAR platform was successfully implemented during the COVID-19 pandemic and enabled global collaboration for the CI Hackathon (www.cihackathon.com). Conclusion: The CompHEAR platform is a useful research tool that permits comparing diverse signal processing strategies across a variety of auditory tasks with crowdsourced judging. Its versatility, scalability, and ease of use can enable further research with the goal of promoting advancements in cochlear implant performance and improved patient outcomes.

Remote control catheter navigation: options for guidance under MRI.

BACKGROUND: Image-guided endovascular interventions have gained increasing popularity in clinical practice, and magnetic resonance imaging (MRI) is emerging as an attractive alternative to X-ray fluoroscopy for guiding such interventions. Steering catheters by remote control under MRI guidance offers unique challenges and opportunities. METHODS: In this review, the benefits and limitations of MRI-guided remote control intervention are addressed, and the tools for guiding such interventions in the magnetic environment are summarized. Designs for remote control catheter guidance include a catheter tip electromagnetic microcoil design, a ferromagnetic sphere-tipped catheter design, smart material-actuated catheters, and hydraulically actuated catheters. Remote control catheter guidance systems were compared and contrasted with respect to visualization, safety, and performance. Performance is characterized by bending angles achievable by the catheter, time to achieve bending, degree of rotation achievable, and miniaturization capacity of the design. Necessary improvements for furthering catheter design, especially for use in the MRI environment, are addressed, as are hurdles that must be overcome in order to make MRI guided endovascular procedures more accessible for regular use in clinical practice. CONCLUSIONS: MR-guided endovascular interventions under remote control steering are in their infancy due to issues regarding safety and reliability. Additional experimental studies are needed prior to their use in humans.

Direct electrical stimulation of human cortex evokes high gamma activity that predicts conscious somatosensory perception.

OBJECTIVE: Direct electrical stimulation (DES) is a clinical gold standard for human brain mapping and readily evokes conscious percepts, yet the neurophysiological changes underlying these percepts are not well understood. APPROACH: To determine the neural correlates of DES, we stimulated the somatosensory cortex of ten human participants at frequency-amplitude combinations that both elicited and failed to elicit conscious percepts, meanwhile recording neural activity directly surrounding the stimulation site. We then compared the neural activity of perceived trials to that of non-perceived trials. MAIN RESULTS: We found that stimulation evokes distributed high gamma activity, which correlates with conscious perception better than stimulation parameters themselves. SIGNIFICANCE: Our findings suggest that high gamma activity is a reliable biomarker for perception evoked by both natural and electrical stimuli.

Thin-film, high-density micro-electrocorticographic decoding of a human cortical gyrus.

High-density electrocorticography (ECoG) arrays are promising interfaces for high-resolution neural recording from the cortical surface. Commercial options for high-density arrays are limited, and historically tradeoffs must be made between spatial coverage and electrode density. However, thin-film technology is a promising alternative for generating electrode arrays capable of large area coverage and high channel count, with resolution on the order of cortical columns in the functional surface unit of a human gyrus. Here, we evaluate the sensing performance of a high-density thin-film 128-electrode array designed specifically for recording the distributed neural activity of a single human cortical gyrus. We found robust field potential responses throughout the superior temporal gyrus evoked by speech sounds, and clear phonetic feature selectivity at the resolution of 2 mm inter-electrode distance. Decoding accuracy improved with increasing density of electrodes over all three patients tested. Thin-film ECoG has significant potential for high-density neural interface applications at the scale of a human gyrus.

Spatial resolution dependence on spectral frequency in human speech cortex electrocorticography.

OBJECTIVE: Electrocorticography (ECoG) has become an important tool in human neuroscience and has tremendous potential for emerging applications in neural interface technology. Electrode array design parameters are outstanding issues for both research and clinical applications, and these parameters depend critically on the nature of the neural signals to be recorded. Here, we investigate the functional spatial resolution of neural signals recorded at the human cortical surface. We empirically derive spatial spread functions to quantify the shared neural activity for each frequency band of the electrocorticogram. APPROACH: Five subjects with high-density (4 mm center-to-center spacing) ECoG grid implants participated in speech perception and production tasks while neural activity was recorded from the speech cortex, including superior temporal gyrus, precentral gyrus, and postcentral gyrus. The cortical surface field potential was decomposed into traditional EEG frequency bands. Signal similarity between electrode pairs for each frequency band was quantified using a Pearson correlation coefficient. MAIN RESULTS: The correlation of neural activity between electrode pairs was inversely related to the distance between the electrodes; this relationship was used to quantify spatial falloff functions for cortical subdomains. As expected, lower frequencies remained correlated over larger distances than higher frequencies. However, both the envelope and phase of gamma and high gamma frequencies (30-150 Hz) are largely uncorrelated (<90%) at 4 mm, the smallest spacing of the high-density arrays. Thus, ECoG arrays smaller than 4 mm have significant promise for increasing signal resolution at high frequencies, whereas less additional gain is achieved for lower frequencies. SIGNIFICANCE: Our findings quantitatively demonstrate the dependence of ECoG spatial resolution on the neural frequency of interest. We demonstrate that this relationship is consistent across patients and across cortical areas during activity.