Safety and efficacy of transcranial direct current stimulation in upper extremity rehabilitation after tetraplegia: protocol of a multicenter randomized, clinical trial.

STUDY DESIGN: A multisite, randomized, controlled, double-blinded phase I/II clinical trial. OBJECTIVE: The purpose of this clinical trial is to evaluate the safety, feasibility and efficacy of pairing noninvasive transcranial direct current stimulation (tDCS) with rehabilitation to promote paretic upper extremity recovery and functional independence in persons living with chronic cervical spinal cord injury (SCI). SETTING: Four-site trial conducted across Cleveland Clinic, Louis Stokes Veterans Affairs Medical Center of Cleveland and MetroHealth Rehabilitation Rehabilitation Institute of Ohio, and Kessler Foundation of New Jersey. METHODS: Forty-four adults (age ≥18 years) with tetraplegia following cervical SCI that occurred ≥1-year ago will participate. Participants will be randomly assigned to receive anodal tDCS or sham tDCS given in combination with upper extremity rehabilitation for 15 sessions each over 3-5 weeks. Assessments will be made twice at baseline separated by at least a 3-week interval, once at end-of-intervention, and once at 3-month follow-up. PRIMARY OUTCOME MEASURE(S): Primary outcome measure is upper extremity motor impairment assessed using the Graded Redefined Assessment of Strength, Sensibility and Prehension (GRASSP) scale. Functional abilities will be assessed using Capabilities of Upper Extremity-Test (CUE-T), while functional independence and participation restrictions will be evaluated using the self-care domain of Spinal Cord Independent Measure (SCIM), and Canadian Occupational Performance Measure (COPM). SECONDARY OUTCOME MEASURES: Treatment-associated change in corticospinal excitability and output will also be studied using transcranial magnetic stimulation (TMS) and safety (reports of adverse events) and feasibility (attrition, adherence etc.) will also be evaluated. TRIAL REGISTRATION: ClincalTrials.gov identifier NCT03892746. This clinical trial is being performed at four sites within the United States: Cleveland Clinic (lead site), Louis Stokes Cleveland Veterans Affairs Medical Center (VAMC) and MetroHealth Rehabilitation Institute in Ohio, and Kessler Foundation in New Jersey. The U.S. Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick MD 21702-5014 is the awarding and administering acquisition office.

Evaluation of Activated Carbon and Platinum Black as High-Capacitance Materials for Platinum Electrodes.

The application of direct current (DC) produces a rapid and reversible nerve conduction block. However, prolonged injection of charge through a smooth platinum electrode has been found to cause damage to nervous tissue. This damage can be mitigated by incorporating high-capacitance materials (HCM) (e.g., activated carbon or platinum black) into electrode designs. HCMs increase the storage charge capacity (i.e., "Q value") of capacitive devices. However, consecutive use of these HCM electrodes degrades their surface. This paper evaluates activated carbon and platinum black (PtB) electrode designs in vitro to determine the design parameters which improve surface stability of the HCMs. Electrode designs with activated carbon and PtB concentrations were stressed using soak, bend and vibration testing to simulate destructive in vivo environments. A Q value decrease represented the decreased stability of the electrode-HCM interface. Soak test results supported the long-term Q value stabilization (mean = 44.3 days) of HCM electrodes, and both HCMs displayed unique Q value changes in response to soaking. HCM material choices, Carbon Ink volume, and application of Nafion™ affected an electrode's ability to resist Q value degradation. These results will contribute to future developments of HCM electrodes designed for extended DC application for in vivo nerve conduction block.

Myoelectric signal from below the level of spinal cord injury as a command source for an implanted upper extremity neuroprosthesis - a case report.

Implanted motor neuroprostheses offer significant restoration of function for individuals with spinal cord injury. Providing adequate user control for these devices is a challenge but is crucial for successful performance. Electromyographic (EMG) signals can serve as effective control sources, but the number of above-injury muscles suitable to provide EMG-based control signals is very limited. Previous work has shown the presence of below-injury volitional myoelectric signals even in subjects diagnosed with motor complete spinal cord injury. In this case report, we present a demonstration of a hand grasp neuroprosthesis being controlled by a user with a C6 level, motor complete injury through EMG signals from their toe flexor. These signals were successfully translated into a functional grasp output, which performed similarly to the participant's usual shoulder position control in a grasp-release functional test. This proof-of-concept demonstrates the potential for below-injury myoelectric activity to serve as a novel form of neuroprosthesis control.

Upper Extremity Assessment in Tetraplegia: The Importance of Differentiating Between Upper and Lower Motor Neuron Paralysis.

Scientific advances are increasing the options for improved upper limb function in people with cervical level spinal cord injury (SCI). Some of these interventions rely on identifying an aspect of paralysis that is not uniformly assessed in SCI: the integrity of the lower motor neuron (LMN). SCI can damage both the upper motor neuron and LMN causing muscle paralysis. Differentiation between these causes of paralysis is not typically believed to be important during SCI rehabilitation because, regardless of the cause, the muscles are no longer under voluntary control by the patient. Emerging treatments designed to restore upper extremity function (eg, rescue microsurgical nerve transfers, motor learning-based interventions, functional electrical stimulation) all require knowledge of LMN status. The LMN is easily evaluated using surface electrical stimulation and does not add significant time to the standard clinical assessment of SCI. This noninvasive evaluation yields information that contributes to the development of a lifetime upper extremity care plan for maximizing function and quality of life. Given the relative simplicity of this assessment and the far-reaching implications for treatment and function, we propose that this assessment should be adopted as standard practice for acute cervical SCI.

Computational analysis of kilohertz frequency spinal cord stimulation for chronic pain management.

BACKGROUND: Kilohertz frequency spinal cord stimulation (KHFSCS) is an emerging therapy for treating refractory neuropathic pain. Although KHFSCS has the potential to improve the lives of patients experiencing debilitating pain, its mechanisms of action are unknown and thus it is difficult to optimize its development. Therefore, the goal of this study was to use a computer model to investigate the direct effects of KHFSCS on specific neural elements of the spinal cord. METHODS: This computer model consisted of two main components: (1) finite element models of the electric field generated by KHFSCS and (2) multicompartment cable models of axons in the spinal cord. Model analysis permitted systematic investigation into a number of variables (e.g., dorsal cerebrospinal fluid thickness, lead location, fiber collateralization, and fiber size) and their corresponding effects on excitation and conduction block thresholds during KHFSCS. RESULTS: The results of this study suggest that direct excitation of large-diameter dorsal column or dorsal root fibers require high stimulation amplitudes that are at the upper end or outside of the range used in clinical KHFSCS (i.e., 0.5 to 5 mA). Conduction block was only possible within the clinical range for a thin dorsal cerebrospinal fluid layer. CONCLUSIONS: These results suggest that clinical KHFSCS may not function through direct activation or conduction block of dorsal column or dorsal root fibers. Although these results should be validated with further studies, the authors propose that additional concepts and/or alternative hypotheses should be considered when examining the pain relief mechanisms of KHFSCS.

Implanted neuroprosthesis for restoring arm and hand function in people with high level tetraplegia.

OBJECTIVE: To develop and apply an implanted neuroprosthesis to restore arm and hand function to individuals with high level tetraplegia. DESIGN: Case study. SETTING: Clinical research laboratory. PARTICIPANTS: Individuals with spinal cord injuries (N=2) at or above the C4 motor level. INTERVENTIONS: The individuals were each implanted with 2 stimulators (24 stimulation channels and 4 myoelectric recording channels total). Stimulating electrodes were placed in the shoulder and arm, being, to our knowledge, the first long-term application of spiral nerve cuff electrodes to activate a human limb. Myoelectric recording electrodes were placed in the head and neck areas. MAIN OUTCOME MEASURES: Successful installation and operation of the neuroprosthesis and electrode performance, range of motion, grasp strength, joint moments, and performance in activities of daily living. RESULTS: The neuroprosthesis system was successfully implanted in both individuals. Spiral nerve cuff electrodes were placed around upper extremity nerves and activated the intended muscles. In both individuals, the neuroprosthesis has functioned properly for at least 2.5 years postimplant. Hand, wrist, forearm, elbow, and shoulder movements were achieved. A mobile arm support was needed to support the mass of the arm during functional activities. One individual was able to perform several activities of daily living with some limitations as a result of spasticity. The second individual was able to partially complete 2 activities of daily living. CONCLUSIONS: Functional electrical stimulation is a feasible intervention for restoring arm and hand functions to individuals with high tetraplegia. Forces and movements were generated at the hand, wrist, elbow, and shoulder that allowed the performance of activities of daily living, with some limitations requiring the use of a mobile arm support to assist the stimulated shoulder forces.

Reversible nerve conduction block using kilohertz frequency alternating current.

OBJECTIVES: The features and clinical applications of balanced-charge kilohertz frequency alternating currents (KHFAC) are reviewed. Preclinical studies of KHFAC block have demonstrated that it can produce an extremely rapid and reversible block of nerve conduction. Recent systematic analysis and experimentation utilizing KHFAC block have resulted in a significant increase in interest in KHFAC block, both scientifically and clinically. MATERIALS AND METHODS: We review the history and characteristics of KHFAC block, the methods used to investigate this type of block, the experimental evaluation of block, and the electrical parameters and electrode designs needed to achieve successful block. We then analyze the existing clinical applications of high-frequency currents, comparing the early results with the known features of KHFAC block. RESULTS: Although many features of KHFAC block have been characterized, there is still much that is unknown regarding the response of neural structures to rapidly fluctuating electrical fields. The clinical reports to date do not provide sufficient information to properly evaluate the mechanisms that result in successful or unsuccessful treatment. CONCLUSIONS: KHFAC nerve block has significant potential as a means of controlling nerve activity for the purpose of treating disease. However, early clinical studies in the use of high-frequency currents for the treatment of pain have not been designed to elucidate mechanisms or allow direct comparisons to preclinical data. We strongly encourage the careful reporting of the parameters utilized in these clinical studies, as well as the development of outcome measures that could illuminate the mechanisms of this modality.

Δ BP-Net: Monitoring "Changes" in Blood Pressure Using PPG with Self-contrastive Masking.

Estimating blood pressure (BP) values from physiological signals (e.g., photoplethysmogram (PPG)) using deep learning models has recently received increased attention, yet challenges remain in terms of models' generalizability. Here, we propose taking a new approach by framing the problem as tracking the "changes" in BP over an interval, rather than directly estimating its value. Indeed, continuous monitoring of acute changes in BP holds promising implications for clinical applications (e.g., hypertensive emergencies). As a solution, we first present a self-contrastive masking (SCM) model, designed to perform pair-wise temporal comparisons within the input signal. We then leverage the proposed SCM model to introduce ΔBPNet, a model trained to detect elevations/drops greater than a given threshold in the systolic blood pressure (SBP) over an interval, from PPG. Using data from PulseDB, 1) we evaluate the performance of ΔBP-Net on previously unseen subjects, 2) we test ΔBP-Net's ability to generalize across domains by training and testing on different datasets, and 3) we compare the performance of ΔBP-Net with existing PPG-based BP-estimation models in detecting over-threshold SBP changes. Formulating the problem as a binary classification task (i.e., over-threshold SBP elevation/ drop or not), ΔBP-Net achieves 75.97%/73.19% accuracy on data from subjects unseen during training. Additionally, the proposed ΔBP-Net outperforms ΔSBP estimations derived from existing PPG-based BP-estimation methods. Overall, by shifting the focus from estimating the value of SBP to detecting overthreshold "changes" in SBP, this work introduces a new potential for using PPG in clinical BP monitoring, and takes a step forward in addressing the challenges related to the generalizability of PPG-based BP-estimation models.

Closed-Loop Multimodal Neuromodulation of Vagus Nerve for Control of Heart Rate.

The use of electrical current to modulate neurons for autonomic regulation requires the ability to both up-regulate and down-regulate the nervous system. An implanted system employing this electrical neuromodulation would also need to adapt to changes in autonomic state in real-time. Stimulation of autonomic nerves at frequencies in the range 1-30 Hz has been a well-established technique for increasing neural activity. Vagus nerve stimulation (VNS) has been shown to be sensitive to frequency adjustments, which can be used to more precisely control the effect as compared to amplitude modulation. Kilohertz frequency alternating current (KHFAC) is a proven technique for blocking action potential conduction to reduce neural activity. Additionally, KHFAC can be reliably modulated by simple amplitude modulation. Although there are many types of commonly used closed-loop controllers, many conventional methods do not respond well to long system delays or discontinuities. Fuzzy logic control (FLC) is a state-based controller that can describe the discontinuities of the system linguistically and then translate the state transition to a continuous output signal. In our preparation, a single bipolar electrode was placed on the vagus nerve and controlled by a fuzzy logic controller to deliver both stimulation and KHFAC to control heart rate. The FLC was able to both change the heart rate to selected values and maintain the heart rate at a constant value in response to a physiological perturbation.

First-In-Human Demonstration of High Frequency Electrical Motor Nerve Block: Case Report.

ABSTRACT: This feasibility study tested the capability of high frequency stimulation (HFS) to block muscle contractions elicited by electrical stimulation of the same nerve proximally. During a tendon lengthening surgery in the forearm, the anterior interosseous nerve (AIN) was exposed. A specialized nerve cuff electrode was placed around the nerve, and a stimulating probe held on the nerve 1 cm proximal to the cuff electrode delivered pulses of current causing the pronator quadratus muscle to contract. Through the cuff electrode, 20 kHz HFS was delivered to the nerve for 10 seconds during proximal stimulation. HFS amplitudes between 5 and 10 mA peak-to-peak were tested to determine which produced complete and partial block of the electrically induced contractions. The minimum HFS amplitude that produced complete block was 8 mA, with lower amplitudes producing partial block. In all trials, muscle contractions resumed immediately after HFS was turned off. This demonstration of high frequency electrical nerve block is a milestone in the road to clinical implementation of HFS mediated motor block for spasticity.

Corticospinal inhibition investigated in relation to upper extremity motor function in cervical spinal cord injury.

OBJECTIVE: Corticospinal inhibitory mechanisms are relevant to functional recovery but remain poorly understood after spinal cord injury (SCI). Post-injury characteristics of contralateral silent period (CSP), a measure of corticospinal inhibition evaluated using transcranial magnetic stimulation (TMS), is inconsistent in literature. We envisioned that investigating CSP across muscles with varying degrees of weakness may be a reasonable approach to resolve inconsistencies and elucidate the relevance of corticospinal inhibition for upper extremity function following SCI. METHODS: We studied 27 adults with chronic C1-C8 SCI (age 48.8 ± 16.1 years, 3 females) and 16 able-bodied participants (age 33.2 ± 11.8 years, 9 females). CSP characteristics were assessed across biceps (muscle power = 3-5) and triceps (muscle power = 1-3) representing stronger and weaker muscles, respectively. We assessed functional abilities using the Capabilities of the Upper Extremity Test (CUE-T). RESULTS: Participants with chronic SCI had prolonged CSPs for biceps but delayed and diminished CSPs for triceps compared to able-bodied participants. Early-onset CSPs for biceps and longer, deeper CSPs for triceps correlated with better CUE-T scores. CONCLUSIONS: Corticospinal inhibition is pronounced for stronger biceps but diminished for weaker triceps muscle in SCI indicating innervation relative to the level of injury matters in the study of CSP. SIGNIFICANCE: Nevertheless, corticospinal inhibition or CSP holds relevance for upper extremity function following SCI.

Demographic Information Fusion Using Attentive Pooling In CNN-GRU Model For Systolic Blood Pressure Estimation.

Fusing demographic information into deep learning models has become of interest in recent end-to-end cuff-less blood pressure (BP) estimation studies in order to achieve improved performance. Conventionally, the demographic feature vector is concatenated with the pooled embedding vector. Here, using an attention-based convolutional neural network-gated recurrent unit (CNN-GRU), we present a new approach and fuse the demographic information into the attentive pooling module. Our results demonstrate that, under calibration-based testing protocol, the proposed approach provides improved systolic blood pressure (SBP) estimation accuracy (with R2=0.86 and mean absolute error (MAE)=4.90 mmHg) compared to both the baseline model with no demographic information fused, and the conventional approach of fusing demographic information. Our work showcases the feasibility of using attention-based methods to combine demographic features with deep learning models, and suggests new ways for fusing demographic information in deep learning models to achieve improved BP estimation accuracy.

Neuroprosthesis for individuals with spinal cord injury.

OBJECTIVE: Individuals who sustain a traumatic spinal cord injury (SCI) often have a loss of multiple body systems. Significant functional improvement can be gained by individual SCI through the use of neuroprostheses based on electrical stimulation. The most common actions produced are grasp, overhead reach, trunk posture, standing, stepping, bladder/bowel/sexual function, and respiratory functions. METHODS: We review the fundamental principles of electrical stimulation, which are established, allowing stimulation to be safely delivered through implanted devices for many decades. We review four common clinical applications for SCI, including grasp/reach, standing/stepping, bladder/bowel function, and respiratory functions. Systems used to implement these functions have many common features, but are also customized based on the functional goals of each approach. Further, neuroprosthetic systems are customized based on the needs of each user. RESULTS & CONCLUSION: The results to date show that implanted neuroprostheses can have a significant impact on the health, function, and quality of life for individuals with SCI. A key focus for the future is to make implanted neuroprostheses broadly available to the SCI population.

Can the electrically stimulated manual muscle test differentiate upper from lower motor neuron injury in persons with acute SCI?

OBJECTIVE: To determine if the motor response on the stimulated manual muscle test (SMMT) in muscles with a grade 0 motor score on the manual muscle test (MMT) can differentiate lower motor neuron (LMN) from upper motor neuron (UMN) injury based on the presence of spontaneous activity (SA) with needle EMG. DESIGN: Prospective Study. PARTICIPANTS/METHODS: Twenty-one subjects with acute traumatic cervical SCI. METHODS: An upper extremity International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) evaluation was completed on all subjects. A needle EMG and an electrically stimulated manual muscle test (SMMT) were completed on all key upper extremity muscles with a MMT motor score of zero. RESULTS: The MMT, SMMT and Needle EMG were done on 77 muscles. The SMMT motor score was 0 on 10 muscles and >1 on 67 muscles. The needle EMG identified spontaneous activity (SA) in 55/77 muscles. Seventy percent (7/10) of the muscles with MMT and SMMT motor score of zero demonstrated SA on EMG. Seventy-two percent (48/67) of the muscles with MMT motor score = 0 and SMMT motor score ≥1 demonstrated SA on EMG. CONCLUSION: In our study, 70% of the muscles with a SMMT motor response of zero and 72% of the muscles with a SMMT motor response greater than or equal to one demonstrated SA on EMG. The use of the SMMT as a clinical measure to differentiate LMN from UMN integrity may be limited when applied.

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.

Surgical restoration of arm and hand function in people with tetraplegia.

Improved hand and arm function is the most sought after function for people living with a cervical spinal cord injury (SCI). Surgical techniques have been established to increase upper extremity function for tetraplegics, focusing on restoring elbow extension, wrist movement, and hand opening and closing. Additionally, more innovative treatments that have been developed (implanted neuroprostheses and nerve transfers) provide more options for improving function and quality of life. One of the most important steps in the process of restoring upper extremity function in people with tetraplegia is identifying appropriate candidates - typically those with American Spinal Injury Association (ASIA) motor level C5 or greater. Secondary complications of SCI can pose barriers to restoring function, particularly upper extremity spasticity. A novel approach to managing spasticity through high-frequency alternating currents designed to block unwanted spasticity is being researched at the Cleveland FES Center and may improve the impact of reconstructive surgery for these individuals. The impact of these surgeries is best measured within the framework of the World Health Organization's International Classification of Function, Disability and Health. Outcome measures should be chosen to reflect changes within the domains of body functions and structures, activity, and participation. There is a need to strengthen the evidence in the area of reconstructive procedures for people with tetraplegia. Research continues to advance, providing more options for improved function in this population than ever before. The contribution of well-designed outcome studies to this evidence base will ultimately help to address the complications surrounding access to the procedures.

Cuff-Less Blood Pressure Estimation From Photoplethysmography via Visibility Graph and Transfer Learning.

This paper presents a new solution that enables the use of transfer learning for cuff-less blood pressure (BP) monitoring via short duration of photoplethysmogram (PPG). The proposed method estimates BP with low computational budget by 1) creating images from segments of PPG via visibility graph (VG), hence, preserving the temporal information of the PPG waveform, 2) using pre-trained deep convolutional neural network (CNN) to extract feature vectors from VG images, and 3) solving for the weights and bias between the feature vectors and the reference BPs with ridge regression. Using the University of California Irvine (UCI) database consisting of 348 records, the proposed method achieves a best error performance of 0.00±8.46 mmHg for systolic blood pressure (SBP), and -0.04±5.36 mmHg for diastolic blood pressure (DBP), respectively, in terms of the mean error (ME) and the standard deviation (SD) of error, ranking grade B for SBP and grade A for DBP under the British Hypertension Society (BHS) protocol. Our novel data-driven method offers a computationally-efficient end-to-end solution for rapid and user-friendly cuff-less PPG-based BP estimation.

PulseDB: A large, cleaned dataset based on MIMIC-III and VitalDB for benchmarking cuff-less blood pressure estimation methods.

There has been a growing interest in developing cuff-less blood pressure (BP) estimation methods to enable continuous BP monitoring from electrocardiogram (ECG) and/or photoplethysmogram (PPG) signals. The majority of these methods have been evaluated using publicly-available datasets, however, there exist significant discrepancies across studies with respect to the size, the number of subjects, and the applied pre-processing steps for the data that is eventually used for training and testing the models. Such differences make conducting performance comparison across models largely unfair, and mask the generalization capability of various BP estimation methods. To fill this important gap, this paper presents "PulseDB," the largest cleaned dataset to date, for benchmarking BP estimation models that also fulfills the requirements of standardized testing protocols. PulseDB contains 1) 5,245,454 high-quality 10 -s segments of ECG, PPG, and arterial BP (ABP) waveforms from 5,361 subjects retrieved from the MIMIC-III waveform database matched subset and the VitalDB database; 2) subjects' identification and demographic information, that can be utilized as additional input features to improve the performance of BP estimation models, or to evaluate the generalizability of the models to data from unseen subjects; and 3) positions of the characteristic points of the ECG/PPG signals, making PulseDB directly usable for training deep learning models with minimal data pre-processing. Additionally, using this dataset, we conduct the first study to provide insights about the performance gap between calibration-based and calibration-free testing approaches for evaluating generalizability of the BP estimation models. We expect PulseDB, as a user-friendly, large, comprehensive and multi-functional dataset, to be used as a reliable source for the evaluation of cuff-less BP estimation methods.

The Effects of Filtering PPG Signal on Pulse Arrival Time-Systolic Blood Pressure Correlation.

Pulse arrival time (PAT), evaluated from electro-cardiogram (ECG) and photoplethysmogram (PPG) signals, has been widely used for cuff-less blood pressure (BP) estimation due to its high correlation with BP. However, the question of whether filtering the PPG signal impacts the extracted PAT values and consequently, the correlation between PAT and BP, has not been investigated before. In this paper, using data from 18 subjects, changes in the PAT values, and in the subject-specific PAT-systolic BP (SBP) correlation caused by filtering the PPG signal with variable cutoff frequencies in the range of 2 to 15 Hz are studied. For PAT extraction, three PPG characteristic points (foot, maximum slope and systolic peak) are considered. Results show that differences in the cutoff frequency can shift the PAT values and introduce a worst-case error of over 8.2 mmHg for SBP estimation, indicating that PPG signal filter settings can impact PAT-based BP estimations. Our study suggests that extracting the PAT from the maximum slope point of PPG signal filtered at 10 Hz provides the most stable correlation with SBP.

Electrical conduction block in large nerves: high-frequency current delivery in the nonhuman primate.

Recent studies have made significant progress toward the clinical implementation of high-frequency conduction block (HFB) of peripheral nerves. However, these studies were performed in small nerves, and questions remain regarding the nature of HFB in large-diameter nerves. This study in nonhuman primates shows reliable conduction block in large-diameter nerves (up to 4.1 mm) with relatively low-threshold current amplitude and only moderate nerve discharge prior to the onset of block.