Long-Term Reductions in Opioid Medication Use After Spinal Stimulation: A Claims Analysis Among Commercially-Insured Population.

Purpose: Chronic, non-cancer pain significantly and negatively impacts patient quality of life. Neuromodulation is a major component of multi-modal interdisciplinary approaches to chronic pain management, which includes opioid and nonopioid medications. In randomized controlled trials, spinal cord stimulation (SCS) has been shown to reduce pain and decrease short-term opioid use for patients. This study sought to evaluate the effect of SCS on longer term opioid and non-opioid pain medication usage among patients over ≥3 years of follow-up. Patients and Methods: Claims analysis was conducted using the Merative™ MarketScan® Commercial Database. Patients aged ≥18 who initiated SCS between 1/1/2010 and 3/31/2021 with ≥1 year of baseline data and ≥3 years of follow-up data were included. Opioid discontinuation, daily dose (DD) reduction, proportion of days covered (PDC), concomitant co-medication with benzodiazepines and/or gabapentinoids, and polypharmacy were evaluated during the baseline and follow-up periods. Adjusted logistic regression was used to evaluate the impact of baseline dosages on discontinuation and dose reduction. Results: During follow-up, 60% of 2,669 SCS patients either discontinued opioid use or reduced opioid DD by at least 20% from baseline; another 15% reduced DD by 1-19%. Logistic regression showed patients with higher baseline dosages were less likely to discontinue opioids completely (odds ratio[OR] 95% confidence intervals[CI]: 0.31[0.18,0.54]) but more likely to reduce their daily dose (OR[CI]: 7.14[4.00,12.73], p<0.001). Mean PDC with opioids decreased from 0.58 (210 of 365 days) at baseline to 0.51 at year 3 (p<0.001). With SCS, co-medication with benzodiazepines decreased from 47.3% at baseline to 30.3% at year 3, co-medication with gabapentinoids reduced from 58.6% to 42.2%, and polypharmacy dropped from 15.6% to 9.6% (all p<0.001). Conclusion: Approximately three-quarters of patients who received SCS therapy either discontinued or reduced systemic opioid use over the study period. SCS could assist in reducing long-term reliance on opioids and other pain medications to treat chronic non-cancer pain.

Artificial neural network for brain-machine interface consistently produces more naturalistic finger movements than linear methods.

Brain-machine interfaces (BMI) aim to restore function to persons living with spinal cord injuries by 'decoding' neural signals into behavior. Recently, nonlinear BMI decoders have outperformed previous state-of-the-art linear decoders, but few studies have investigated what specific improvements these nonlinear approaches provide. In this study, we compare how temporally convolved feedforward neural networks (tcFNNs) and linear approaches predict individuated finger movements in open and closed-loop settings. We show that nonlinear decoders generate more naturalistic movements, producing distributions of velocities 85.3% closer to true hand control than linear decoders. Addressing concerns that neural networks may come to inconsistent solutions, we find that regularization techniques improve the consistency of tcFNN convergence by 194.6%, along with improving average performance, and training speed. Finally, we show that tcFNN can leverage training data from multiple task variations to improve generalization. The results of this study show that nonlinear methods produce more naturalistic movements and show potential for generalizing over less constrained tasks. Teaser: A neural network decoder produces consistent naturalistic movements and shows potential for real-world generalization through task variations.

Effect of Anisotropic Brain Conductivity on Patient-Specific Volume of Tissue Activation in Deep Brain Stimulation for Parkinson Disease.

OBJECTIVE: Deep brain stimulation (DBS) modeling can improve surgical targeting by quantifying the spatial extent of stimulation relative to subcortical structures of interest. A certain degree of model complexity is required to obtain accurate predictions, particularly complexity regarding electrical properties of the tissue around DBS electrodes. In this study, the effect of anisotropy on the volume of tissue activation (VTA) was evaluated in an individualized manner. METHODS: Tissue activation models incorporating patient-specific tissue conductivity were built for 40 Parkinson disease patients who had received bilateral subthalamic nucleus (STN) DBS. To assess the impact of local changes in tissue anisotropy, one VTA was computed at each electrode contact using identical stimulation parameters. For comparison, VTAs were also computed assuming isotropic tissue conductivity. Stimulation location was considered by classifying the anisotropic VTAs relative to the STN. VTAs were characterized based on volume, spread in three directions, sphericity, and Dice coefficient. RESULTS: Incorporating anisotropy generated significantly larger and less spherical VTAs overall. However, its effect on VTA size and shape was variable and more nuanced at the individual patient and implantation levels. Dorsal VTAs had significantly higher sphericity than ventral VTAs, suggesting more isotropic behavior. Contrastingly, lateral and posterior VTAs had significantly larger and smaller lateral-medial spreads, respectively. Volume and spread correlated negatively with sphericity. CONCLUSION: The influence of anisotropy on VTA predictions is important to consider, and varies across patients and stimulation location. SIGNIFICANCE: This study highlights the importance of considering individualized factors in DBS modeling to accurately characterize the VTA.

Impact of subthalamic nucleus stimulation on urinary dysfunction and constipation in Parkinson's disease.

OBJECTIVE: The effect of subthalamic nucleus (STN) deep brain stimulation (DBS) on urinary dysfunction and constipation in Parkinson's disease (PD) is variable. This study aimed to identify potential surgical and nonsurgical variables predictive of these outcomes. METHODS: The authors used the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part I to assess urinary dysfunction (item 10) and constipation (item 11) preoperatively and at 6-12 months postoperatively. A multiple linear regression model was used to investigate the impact of global cerebral atrophy (GCA) and active electrode contact location on the urinary dysfunction and constipation follow-up scores, controlling for age, disease duration, baseline score, motor improvement, and levodopa-equivalent dose changes. An electric field model was applied to localize the maximal-effect sites for constipation and urinary dysfunction compared with those for motor improvement. RESULTS: Among 74 patients, 23 improved, 28 deteriorated, and 23 remained unchanged for urinary dysfunction; 25 improved, 15 deteriorated, and 34 remained unchanged for constipation. GCA score and age significantly predicted urinary dysfunction follow-up score (R2 = 0.36, p < 0.001). Increased GCA and age were independently associated with worsening urinary symptoms. Disease duration, baseline constipation score, and anterior active electrode contacts in both hemispheres were significant predictors of constipation follow-up score (R2 = 0.31, p < 0.001). Higher baseline constipation score and disease duration were associated with worsening constipation; anterior active contact location was associated with improvement in constipation. CONCLUSIONS: Anterior active contact location was associated with improvement in constipation in PD patients after STN DBS. PD patients with greater GCA scores before surgery were more likely to experience urinary deterioration after DBS.

Electrical Stimulation of Regenerative Peripheral Nerve Interfaces (RPNIs) Induces Referred Sensations in People With Upper Limb Loss.

Individuals with upper limb loss lack sensation of the missing hand, which can negatively impact their daily function. Several groups have attempted to restore this sensation through electrical stimulation of residual nerves. The purpose of this study was to explore the utility of regenerative peripheral nerve interfaces (RPNIs) in eliciting referred sensation. In four participants with upper limb loss, we characterized the quality and location of sensation elicited through electrical stimulation of RPNIs over time. We also measured functional stimulation ranges (sensory perception and discomfort thresholds), sensitivity to changes in stimulation amplitude, and ability to differentiate objects of different stiffness and sizes. Over a period of up to 54 months, stimulation of RPNIs elicited sensations that were consistent in quality (e.g. tingling, kinesthesia) and were perceived in the missing hand and forearm. The location of elicited sensation was partially-stable to stable in 13 of 14 RPNIs. For 5 of 7 RPNIs tested, participants demonstrated a sensitivity to changes in stimulation amplitude, with an average just noticeable difference of 45 nC. In a case study, one participant was provided RPNI stimulation proportional to prosthetic grip force. She identified four objects of different sizes and stiffness with 56% accuracy with stimulation alone and 100% accuracy when stimulation was combined with visual feedback of hand position. Collectively, these experiments suggest that RPNIs have the potential to be used in future bi-directional prosthetic systems.

Dorsal subthalamic deep brain stimulation improves pain in Parkinson's disease.

Introduction: Inconsistent effects of subthalamic deep brain stimulation (STN DBS) on pain, a common non-motor symptom of Parkinson's disease (PD), may be due to variations in active contact location relative to some pain-reducing locus of stimulation. This study models and compares the loci of maximal effect for pain reduction and motor improvement in STN DBS. Methods: We measured Movement Disorder Society Unified PD Rating Scale (MDS-UPDRS) Part I pain score (item-9), and MDS-UPDRS Part III motor score, preoperatively and 6-12 months after STN DBS. An ordinary least-squares regression model was used to examine active contact location as a predictor of follow-up pain score while controlling for baseline pain, age, dopaminergic medication, and motor improvement. An atlas-independent isotropic electric field model was applied to distinguish sites of maximally effective stimulation for pain and motor improvement. Results: In 74 PD patients, mean pain score significantly improved after STN DBS (p = 0.01). In a regression model, more dorsal active contact location was the only significant predictor of pain improvement (R2 = 0.17, p = 0.03). The stimulation locus for maximal pain improvement was lateral, anterior, and dorsal to that for maximal motor improvement. Conclusion: STN stimulation, dorsal to the site of optimal motor improvement, improves pain. This region contains the zona incerta, which is known to modulate pain in humans, and may explain this observation.

Error detection and correction in intracortical brain-machine interfaces controlling two finger groups.

Objective.While brain-machine interfaces (BMIs) are promising technologies that could provide direct pathways for controlling the external world and thus regaining motor capabilities, their effectiveness is hampered by decoding errors. Previous research has demonstrated the detection and correction of BMI outcome errors, which occur at the end of trials. Here we focus on continuous detection and correction of BMI execution errors, which occur during real-time movements.Approach.Two adult male rhesus macaques were implanted with Utah arrays in the motor cortex. The monkeys performed single or two-finger group BMI tasks where a Kalman filter decoded binned spiking-band power into intended finger kinematics. Neural activity was analyzed to determine how it depends not only on the kinematics of the fingers, but also on the distance of each finger-group to its target. We developed a method to detect erroneous movements, i.e. consistent movements away from the target, from the same neural activity used by the Kalman filter. Detected errors were corrected by a simple stopping strategy, and the effect on performance was evaluated.Mainresults.First we show that including distance to target explains significantly more variance of the recorded neural activity. Then, for the first time, we demonstrate that neural activity in motor cortex can be used to detect execution errors during BMI controlled movements. Keeping false positive rate below5%, it was possible to achieve mean true positive rate of28.1%online. Despite requiring 200 ms to detect and react to suspected errors, we were able to achieve a significant improvement in task performance via reduced orbiting time of one finger group.Significance.Neural activity recorded in motor cortex for BMI control can be used to detect and correct BMI errors and thus to improve performance. Further improvements may be obtained by enhancing classification and correction strategies.

Balancing Memorization and Generalization in RNNs for High Performance Brain-Machine Interfaces.

Brain-machine interfaces (BMIs) can restore motor function to people with paralysis but are currently limited by the accuracy of real-time decoding algorithms. Recurrent neural networks (RNNs) using modern training techniques have shown promise in accurately predicting movements from neural signals but have yet to be rigorously evaluated against other decoding algorithms in a closed-loop setting. Here we compared RNNs to other neural network architectures in real-time, continuous decoding of finger movements using intracortical signals from nonhuman primates. Across one and two finger online tasks, LSTMs (a type of RNN) outperformed convolutional and transformer-based neural networks, averaging 18% higher throughput than the convolution network. On simplified tasks with a reduced movement set, RNN decoders were allowed to memorize movement patterns and matched able-bodied control. Performance gradually dropped as the number of distinct movements increased but did not go below fully continuous decoder performance. Finally, in a two-finger task where one degree-of-freedom had poor input signals, we recovered functional control using RNNs trained to act both like a movement classifier and continuous decoder. Our results suggest that RNNs can enable functional real-time BMI control by learning and generating accurate movement patterns.

Restoring continuous finger function with temporarily paralyzed nonhuman primates using brain-machine interfaces.

Objective.Brain-machine interfaces (BMIs) have shown promise in extracting upper extremity movement intention from the thoughts of nonhuman primates and people with tetraplegia. Attempts to restore a user's own hand and arm function have employed functional electrical stimulation (FES), but most work has restored discrete grasps. Little is known about how well FES can control continuous finger movements. Here, we use a low-power brain-controlled functional electrical stimulation (BCFES) system to restore continuous volitional control of finger positions to a monkey with a temporarily paralyzed hand.Approach.We delivered a nerve block to the median, radial, and ulnar nerves just proximal to the elbow to simulate finger paralysis, then used a closed-loop BMI to predict finger movements the monkey was attempting to make in two tasks. The BCFES task was one-dimensional in which all fingers moved together, and we used the BMI's predictions to control FES of the monkey's finger muscles. The virtual two-finger task was two-dimensional in which the index finger moved simultaneously and independently from the middle, ring, and small fingers, and we used the BMI's predictions to control movements of virtual fingers, with no FES.Main results.In the BCFES task, the monkey improved his success rate to 83% (1.5 s median acquisition time) when using the BCFES system during temporary paralysis from 8.8% (9.5 s median acquisition time, equal to the trial timeout) when attempting to use his temporarily paralyzed hand. In one monkey performing the virtual two-finger task with no FES, we found BMI performance (task success rate and completion time) could be completely recovered following temporary paralysis by executing recalibrated feedback-intention training one time.Significance.These results suggest that BCFES can restore continuous finger function during temporary paralysis using existing low-power technologies and brain-control may not be the limiting factor in a BCFES neuroprosthesis.

Localization of deep brain stimulation trajectories via automatic mapping of microelectrode recordings to MRI.

Objective. Suboptimal electrode placement during subthalamic nucleus deep brain stimulation (STN DBS) surgery may arise from several sources, including frame-based targeting errors and intraoperative brain shift. We present a computer algorithm that can accurately localize intraoperative microelectrode recording (MER) tracks on preoperative magnetic resonance imaging (MRI) in real-time, thereby predicting deviation between the surgical plan and the MER trajectories.Approach. Random forest (RF) modeling was used to derive a statistical relationship between electrophysiological features on intraoperative MER and voxel intensity on preoperative T2-weighted MR imaging. This model was integrated into a larger algorithm that can automatically localize intraoperative MER recording tracks on preoperative MRI in real-time. To verify accuracy, targeting error of both the planned intraoperative trajectory ('planned') and the algorithm-derived trajectory ('calculated') was estimated by measuring deviation from the final DBS lead location on postoperative high-resolution computed tomography ('actual').Main results. MR imaging and MERs were obtained from 24 STN DBS implant trajectories. The cross-validated RF model could accurately distinguish between gray and white matter regions along MER trajectories (AUC 0.84). When applying this model within the localization algorithm, thecalculatedMER trajectory estimate was found to be significantly closer to theactualDBS lead when compared to theplannedtrajectory recorded during surgery (1.04 mm vs 1.52 mm deviation,p< 0.002), with improvement shown in 19/24 cases (79%). When applying the algorithm to simulated DBS trajectory plans with randomized targeting error, up to 4 mm of error could be resolved to <2 mm on average (p< 0.0001).Significance. This work presents an automated system for intraoperative localization of electrodes during STN DBS surgery. This neuroengineering solution may enhance the accuracy of electrode position estimation, particularly in cases where high-resolution intraoperative imaging is not available.

Utah array characterization and histological analysis of a multi-year implant in non-human primate motor and sensory cortices.

Objective.The Utah array is widely used in both clinical studies and neuroscience. It has a strong track record of safety. However, it is also known that implanted electrodes promote the formation of scar tissue in the immediate vicinity of the electrodes, which may negatively impact the ability to record neural waveforms. This scarring response has been primarily studied in rodents, which may have a very different response than primate brain.Approach.Here, we present a rare nonhuman primate histological dataset (n= 1 rhesus macaque) obtained 848 and 590 d after implantation in two brain hemispheres. For 2 of 4 arrays that remained within the cortex, NeuN was used to stain for neuron somata at three different depths along the shanks. Images were filtered and denoised, with neurons then counted in the vicinity of the arrays as well as a nearby section of control tissue. Additionally, 3 of 4 arrays were imaged with a scanning electrode microscope to evaluate any materials damage that might be present.Main results.Overall, we found a 63% percent reduction in the number of neurons surrounding the electrode shanks compared to control areas. In terms of materials, the arrays remained largely intact with metal and Parylene C present, though tip breakage and cracks were observed on many electrodes.Significance.Overall, these results suggest that the tissue response in the nonhuman primate brain shows similar neuron loss to previous studies using rodents. Electrode improvements, for example using smaller or softer probes, may therefore substantially improve the tissue response and potentially improve the neuronal recording yield in primate cortex.

Thalamic Segmentation and Neural Activation Modeling Based on Individual Tissue Microstructure in Deep Brain Stimulation for Essential Tremor.

OBJECTIVE: Thalamic deep brain stimulation (DBS) is the primary surgical therapy for essential tremor (ET). Thalamic DBS traditionally uses an atlas-based targeting approach, which, although nominally accurate, may obscure individual anatomic differences from population norms. The objective of this study was to compare this traditional atlas-based approach with a novel quantitative modeling methodology grounded in individual tissue microstructure (N-of-1 approach). MATERIALS AND METHODS: The N-of-1 approach uses individual patient diffusion tensor imaging (DTI) data to perform thalamic segmentation and volume of tissue activation (VTA) modeling. For each patient, the thalamus was individually segmented into 13 nuclei using DTI-based k-means clustering. DBS-induced VTAs associated with tremor suppression and side effects were then computed for each patient with finite-element electric-field models incorporating DTI microstructural data. Results from N-of-1 and traditional atlas-based modeling were compared for a large cohort of patients with ET treated with thalamic DBS. RESULTS: The size and shape of individual N-of-1 thalamic nuclei and VTAs varied considerably across patients (N = 22). For both methods, tremor-improving therapeutic VTAs showed similar overlap with motor thalamic nuclei and greater motor than sensory nucleus overlap. For VTAs producing undesirable sustained paresthesia, 94% of VTAs overlapped with N-of-1 sensory thalamus estimates, whereas 74% of atlas-based segmentations overlapped. For VTAs producing dysarthria/motor contraction, the N-of-1 approach predicted greater spread beyond the thalamus into the internal capsule and adjacent structures than the atlas-based method. CONCLUSIONS: Thalamic segmentation and VTA modeling based on individual tissue microstructure explain therapeutic stimulation equally well and side effects better than a traditional atlas-based method in DBS for ET. The N-of-1 approach may be useful in DBS targeting and programming, particularly when patient neuroanatomy deviates from population norms.

Real-time brain-machine interface in non-human primates achieves high-velocity prosthetic finger movements using a shallow feedforward neural network decoder.

Despite the rapid progress and interest in brain-machine interfaces that restore motor function, the performance of prosthetic fingers and limbs has yet to mimic native function. The algorithm that converts brain signals to a control signal for the prosthetic device is one of the limitations in achieving rapid and realistic finger movements. To achieve more realistic finger movements, we developed a shallow feed-forward neural network to decode real-time two-degree-of-freedom finger movements in two adult male rhesus macaques. Using a two-step training method, a recalibrated feedback intention-trained (ReFIT) neural network is introduced to further improve performance. In 7 days of testing across two animals, neural network decoders, with higher-velocity and more natural appearing finger movements, achieved a 36% increase in throughput over the ReFIT Kalman filter, which represents the current standard. The neural network decoders introduced herein demonstrate real-time decoding of continuous movements at a level superior to the current state-of-the-art and could provide a starting point to using neural networks for the development of more naturalistic brain-controlled prostheses.

Perceived social support declines after deep brain stimulation surgery in patients with Parkinson's disease.

INTRODUCTION: The Social Provisions Scale (SPS) measures a person's perceived social support. We evaluated the perceived social support in Parkinson's disease (PD) patients before and after subthalamic nucleus (STN) deep brain stimulation (DBS) and its impact on clinical outcomes following DBS. METHODS: We analyzed 55 PD patients who underwent STN DBS surgery and completed the SPS, PDQ-39, and MDS-UPDRS Parts I-IV before and 6-12 months after surgery. Some patients also completed global cognitive, mood and apathy scales. Caregivers completed the CBI at each visit. Linear regression models and linear mixed models evaluated the association between the SPS baseline score, MDS-UPDRS and PDQ-39 scores, the association between MDS-UPDRS, CBI and the SPS follow-up score, and the association between SPS, global cognition and other psychological variables. RESULTS: DBS implantation improved MDS-UPDRS I-IV and PDQ-39 scores. Perceived social support declined after DBS (baseline SPS total 82.55 ± 7.52 vs. follow-up SPS total 78.83 ± 9.02, p = 0.0001). Baseline SPS total score was not significantly associated with the MDS-UPDRS or PDQ-39 scores at follow-up. MDS-UPDRS scores and the CBI at follow-up had no significant association with SPS total score at follow-up. Measures of global cognition, mood and apathy were associated with the SPS before and after DBS, and the association was independent of STN DBS. CONCLUSION: After STN DBS, PD patients experienced a decrease in perceived social support, but baseline perceived social support did not impact clinical outcomes. It is important to further identify factors that may contribute to this perception of worsened social support.

A Light-Tolerant Wireless Neural Recording IC for Motor Prediction With Near-Infrared-Based Power and Data Telemetry.

Miniaturized and wireless near-infrared (NIR) based neural recorders with optical powering and data telemetry have been introduced as a promising approach for safe long-term monitoring with the smallest physical dimension among state-of-the-art standalone recorders. However, a main challenge for the NIR based neural recording ICs is to maintain robust operation in the presence of light-induced parasitic short circuit current from junction diodes. This is especially true when the signal currents are kept small to reduce power consumption. In this work, we present a light-tolerant and low-power neural recording IC for motor prediction that can fully function in up to 300 µW/mm2 of light exposure. It achieves best-in-class power consumption of 0.57 µW at 38° C with a 4.1 NEF pseudo-resistorless amplifier, an on-chip neural feature extractor, and individual mote level gain control. Applying the 20-channel pre-recorded neural signals of a monkey, the IC predicts finger position and velocity with correlation coefficient up to 0.870 and 0.569, respectively, with individual mote level gain control enabled. In addition, wireless measurement is demonstrated through optical power and data telemetry using a custom PV/LED GaAs chip wire bonded to the proposed IC.

A low-power communication scheme for wireless, 1000 channel brain-machine interfaces.

Objective. Brain-machine interfaces (BMIs) have the potential to restore motor function but are currently limited by electrode count and long-term recording stability. These challenges may be solved through the use of free-floating 'motes' which wirelessly transmit recorded neural signals, if power consumption can be kept within safe levels when scaling to thousands of motes. Here, we evaluated a pulse-interval modulation (PIM) communication scheme for infrared (IR)-based motes that aims to reduce the wireless data rate and system power consumption.Approach. To test PIM's ability to efficiently communicate neural information, we simulated the communication scheme in a real-time closed-loop BMI with non-human primates. Additionally, we performed circuit simulations of an IR-based 1000-mote system to calculate communication accuracy and total power consumption.Main results. We found that PIM at 1 kb/s per channel maintained strong correlations with true firing rate and matched online BMI performance of a traditional wired system. Closed-loop BMI tests suggest that lags as small as 30 ms can have significant performance effects. Finally, unlike other IR communication schemes, PIM is feasible in terms of power, and neural data can accurately be recovered on a receiver using 3 mW for 1000 channels.Significance.These results suggest that PIM-based communication could significantly reduce power usage of wireless motes to enable higher channel-counts for high-performance BMIs.

A Power-Efficient Brain-Machine Interface System With a Sub-mw Feature Extraction and Decoding ASIC Demonstrated in Nonhuman Primates.

Intracortical brain-machine interfaces have shown promise for restoring function to people with paralysis, but their translation to portable and implantable devices is hindered by their high power consumption. Recent devices have drastically reduced power consumption compared to standard experimental brain-machine interfaces, but still require wired or wireless connections to computing hardware for feature extraction and inference. Here, we introduce a Neural Recording And Decoding (NeuRAD) application specific integrated circuit (ASIC) in 180 nm CMOS that can extract neural spiking features and predict two-dimensional behaviors in real-time. To reduce amplifier and feature extraction power consumption, the NeuRAD has a hardware accelerator for extracting spiking band power (SBP) from intracortical spiking signals and includes an M0 processor with a fixed-point Matrix Acceleration Unit (MAU) for efficient and flexible decoding. We validated device functionality by recording SBP from a nonhuman primate implanted with a Utah microelectrode array and predicting the one- and two-dimensional finger movements the monkey was attempting to execute in closed-loop using a steady-state Kalman filter (SSKF). Using the NeuRAD's real-time predictions, the monkey achieved 100% success rate and 0.82 s mean target acquisition time to control one-dimensional finger movements using just 581 µW. To predict two-dimensional finger movements, the NeuRAD consumed 588 µW to enable the monkey to achieve a 96% success rate and 2.4 s mean acquisition time. By employing SBP, ASIC brain-machine interfaces can close the gap to enable fully implantable therapies for people with paralysis.

Restoration of Proprioceptive and Cutaneous Sensation Using Regenerative Peripheral Nerve Interfaces in Humans with Upper Limb Amputations.

SUMMARY: Without meaningful and intuitive sensory feedback, even the most advanced prosthetic limbs remain insensate and impose an enormous cognitive burden during use. The regenerative peripheral nerve interface can serve as a novel bidirectional motor and sensory neuroprosthetic interface. In previous human studies, regenerative peripheral nerve interfaces demonstrated stable high-amplitude motor electromyography signals with excellent signal-to-noise ratio for prosthetic control. In addition, they can treat and prevent postamputation pain by mitigating neuroma formation. In this study, the authors investigated whether electrical stimulation applied to regenerative peripheral nerve interfaces could produce appreciable proprioceptive and/or tactile sensations in two participants with upper limb amputations. Stimulation of the interfaces resulted in both participants reporting proprioceptive sensations in the phantom hand. Specifically, stimulation of participant 1's median nerve regenerative peripheral nerve interface activated a flexion sensation in the thumb or index finger, whereas stimulation of the ulnar nerve interface evoked a flexion sensation of the ring or small finger. Likewise, stimulation of one of participant 2's ulnar nerve interfaces produced a sensation of flexion at the ring finger distal interphalangeal joint. In addition, stimulation of participant 2's other ulnar nerve interface and the median nerve interface resulted in perceived cutaneous sensations that corresponded to each nerve's respective dermatome. These results suggest that regenerative peripheral nerve interfaces have the potential to restore proprioceptive and cutaneous sensory feedback that could significantly improve prosthesis use and embodiment.

The Concept, Development, and Application of a Home-Based High-Definition tDCS for Bilateral Motor Cortex Modulation in Migraine and Pain.

Whereas, many debilitating chronic pain disorders are dominantly bilateral (e.g., fibromyalgia, chronic migraine), non-invasive and invasive cortical neuromodulation therapies predominantly apply unilateral stimulation. The development of excitatory stimulation targeting bilateral primary motor (M1) cortices could potentially expand its therapeutic effect to more global pain relief. However, this is hampered by increased procedural and technical complexity. For example, repetitive transcranial magnetic stimulation (rTMS) and 4 × 1/2 × 2 high-definition transcranial direct current stimulation (4 × 1/2 × 2 HD-tDCS) are largely center-based, with unilateral-target focus-bilateral excitation would require two rTMS/4 × 1 HD-tDCS systems. We developed a system that allows for focal, non-invasive, self-applied, and simultaneous bilateral excitatory M1 stimulation, supporting long-term home-based treatment with a well-tolerated wearable battery-powered device. Here, we overviewed the most employed M1 neuromodulation methods, from invasive techniques to non-invasive TMS and tDCS. The evaluation extended from non-invasive diffuse asymmetric bilateral (M1-supraorbital [SO] tDCS), non-invasive and invasive unilateral focal (4 × 1/2 × 2 HD-tDCS, rTMS, MCS), to non-invasive and invasive bilateral bipolar (M1-M1 tDCS, MCS), before outlining our proposal for a neuromodulatory system with unique features. Computational models were applied to compare brain current flow for current laboratory-based unilateral M11 and bilateral M12 HD-tDCS models with a functional home-based M11-2 HD-tDCS prototype. We concluded the study by discussing the promising concept of bilateral excitatory M1 stimulation for more global pain relief, which is also non-invasive, focal, and home-based.