Magnetoencephalogram-based brain-computer interface for hand-gesture decoding using deep learning.

Advancements in deep learning algorithms over the past decade have led to extensive developments in brain-computer interfaces (BCI). A promising imaging modality for BCI is magnetoencephalography (MEG), which is a non-invasive functional imaging technique. The present study developed a MEG sensor-based BCI neural network to decode Rock-Paper-scissors gestures (MEG-RPSnet). Unique preprocessing pipelines in tandem with convolutional neural network deep-learning models accurately classified gestures. On a single-trial basis, we found an average of 85.56% classification accuracy in 12 subjects. Our MEG-RPSnet model outperformed two state-of-the-art neural network architectures for electroencephalogram-based BCI as well as a traditional machine learning method, and demonstrated equivalent and/or better performance than machine learning methods that have employed invasive, electrocorticography-based BCI using the same task. In addition, MEG-RPSnet classification performance using an intra-subject approach outperformed a model that used a cross-subject approach. Remarkably, we also found that when using only central-parietal-occipital regional sensors or occipitotemporal regional sensors, the deep learning model achieved classification performances that were similar to the whole-brain sensor model. The MEG-RSPnet model also distinguished neuronal features of individual hand gestures with very good accuracy. Altogether, these results show that noninvasive MEG-based BCI applications hold promise for future BCI developments in hand-gesture decoding.

Effects of Noninvasive Cervical Vagal Nerve Stimulation on Cognitive Performance But Not Brain Activation in Healthy Adults.

OBJECTIVES: While preliminary evidence suggests that noninvasive vagal nerve stimulation (nVNS) may enhance cognition, to our knowledge, no study has directly assessed the effects of nVNS on brain function and cognitive performance in healthy individuals. The aim of this study was therefore to assess whether nVNS enhances complex visuospatial problem solving in a normative sample. Functional magnetic resonance imaging (fMRI) was used to examine underlying neural substrates. MATERIAL AND METHODS: Participants received transcutaneous cervical nVNS (N = 15) or sham (N = 15) stimulation during a 3 T fMRI scan. Stimulation lasted for 2 min at 24 V for nVNS and at 4.5 V for sham. Subjects completed a matrix reasoning (MR) task in the scanner and a forced-choice recognition task outside the scanner. An analysis of variance (ANOVA) was used to assess group differences in cognitive performance. And linear mixed effects (LMEs) regression analysis was used to assess main and interaction effects of experimental groups, level of MR task difficulty, and recall accuracy on changes in blood oxygen level-dependent (BOLD) signal. RESULTS: Subjects who received nVNS showed higher accuracy for both easy (p = 0.017) and hard (p = 0.013) items of the MR task, slower reaction times for hard items (p = 0.014), and fewer false negative errors during the forced-choice recognition task (p = 0.047). MR task difficulty related to increased activation in frontoparietal regions (p < 0.001). No difference between nVNS and sham stimulation was found on BOLD response during performance of the MR task. CONCLUSIONS: We hypothesize that nVNS increased attention compared to sham, and that this effect led to enhanced executive functions, and consequently to better performance on visuospatial reasoning and recognition tasks. Results provide initial support that nVNS may be a low-risk, low-cost treatment for cognitive disorders.

Resting-state magnetoencephalography source magnitude imaging with deep-learning neural network for classification of symptomatic combat-related mild traumatic brain injury.

Combat-related mild traumatic brain injury (cmTBI) is a leading cause of sustained physical, cognitive, emotional, and behavioral disabilities in Veterans and active-duty military personnel. Accurate diagnosis of cmTBI is challenging since the symptom spectrum is broad and conventional neuroimaging techniques are insensitive to the underlying neuropathology. The present study developed a novel deep-learning neural network method, 3D-MEGNET, and applied it to resting-state magnetoencephalography (rs-MEG) source-magnitude imaging data from 59 symptomatic cmTBI individuals and 42 combat-deployed healthy controls (HCs). Analytic models of individual frequency bands and all bands together were tested. The All-frequency model, which combined delta-theta (1-7 Hz), alpha (8-12 Hz), beta (15-30 Hz), and gamma (30-80 Hz) frequency bands, outperformed models based on individual bands. The optimized 3D-MEGNET method distinguished cmTBI individuals from HCs with excellent sensitivity (99.9 ± 0.38%) and specificity (98.9 ± 1.54%). Receiver-operator-characteristic curve analysis showed that diagnostic accuracy was 0.99. The gamma and delta-theta band models outperformed alpha and beta band models. Among cmTBI individuals, but not controls, hyper delta-theta and gamma-band activity correlated with lower performance on neuropsychological tests, whereas hypo alpha and beta-band activity also correlated with lower neuropsychological test performance. This study provides an integrated framework for condensing large source-imaging variable sets into optimal combinations of regions and frequencies with high diagnostic accuracy and cognitive relevance in cmTBI. The all-frequency model offered more discriminative power than each frequency-band model alone. This approach offers an effective path for optimal characterization of behaviorally relevant neuroimaging features in neurological and psychiatric disorders.

Marked Increases in Resting-State MEG Gamma-Band Activity in Combat-Related Mild Traumatic Brain Injury.

Combat-related mild traumatic brain injury (mTBI) is a leading cause of sustained impairments in military service members and veterans. Recent animal studies show that GABA-ergic parvalbumin-positive interneurons are susceptible to brain injury, with damage causing abnormal increases in spontaneous gamma-band (30-80 Hz) activity. We investigated spontaneous gamma activity in individuals with mTBI using high-resolution resting-state magnetoencephalography source imaging. Participants included 25 symptomatic individuals with chronic combat-related blast mTBI and 35 healthy controls with similar combat experiences. Compared with controls, gamma activity was markedly elevated in mTBI participants throughout frontal, parietal, temporal, and occipital cortices, whereas gamma activity was reduced in ventromedial prefrontal cortex. Across groups, greater gamma activity correlated with poorer performances on tests of executive functioning and visuospatial processing. Many neurocognitive associations, however, were partly driven by the higher incidence of mTBI participants with both higher gamma activity and poorer cognition, suggesting that expansive upregulation of gamma has negative repercussions for cognition particularly in mTBI. This is the first human study to demonstrate abnormal resting-state gamma activity in mTBI. These novel findings suggest the possibility that abnormal gamma activities may be a proxy for GABA-ergic interneuron dysfunction and a promising neuroimaging marker of insidious mild head injuries.

MEG Working Memory N-Back Task Reveals Functional Deficits in Combat-Related Mild Traumatic Brain Injury.

Combat-related mild traumatic brain injury (mTBI) is a leading cause of sustained cognitive impairment in military service members and Veterans. However, the mechanism of persistent cognitive deficits including working memory (WM) dysfunction is not fully understood in mTBI. Few studies of WM deficits in mTBI have taken advantage of the temporal and frequency resolution afforded by electromagnetic measurements. Using magnetoencephalography (MEG) and an N-back WM task, we investigated functional abnormalities in combat-related mTBI. Study participants included 25 symptomatic active-duty service members or Veterans with combat-related mTBI and 20 healthy controls with similar combat experiences. MEG source-magnitude images were obtained for alpha (8-12 Hz), beta (15-30 Hz), gamma (30-90 Hz), and low-frequency (1-7 Hz) bands. Compared with healthy combat controls, mTBI participants showed increased MEG signals across frequency bands in frontal pole (FP), ventromedial prefrontal cortex, orbitofrontal cortex (OFC), and anterior dorsolateral prefrontal cortex (dlPFC), but decreased MEG signals in anterior cingulate cortex. Hyperactivations in FP, OFC, and anterior dlPFC were associated with slower reaction times. MEG activations in lateral FP also negatively correlated with performance on tests of letter sequencing, verbal fluency, and digit symbol coding. The profound hyperactivations from FP suggest that FP is particularly vulnerable to combat-related mTBI.

Spinal Cord Stimulator Related Infections: Findings From a Multicenter Retrospective Analysis of 2737 Implants.

INTRODUCTION: Surgical site infection is a potential complication of spinal cord stimulator (SCS) implantation. Current understanding of the epidemiology, diagnosis, and treatment of these infections is based largely on small clinical studies, many of which are outdated. Evidence-based guidelines for management of SCS-related infections thus rely instead on expert opinion, case reports, and case series. In this study, we aim to provide a large scale retrospective study of infection management techniques specifically for SCS implantation. METHODS: A multicenter retrospective study of SCS implants performed over a seven-year period at 11 unique academic and non-academic institutions in the United States. All infections and related complications in this cohort were analyzed. RESULTS: Within our study of 2737 SCS implant procedures, we identified all procedures complicated by infection (2.45%). Localized incisional pain and wound erythema were the most common presenting signs. Laboratory studies were performed in the majority of patients, but an imaging study was performed in less than half of these patients. The most common causative organism was Staphylococcus aureus and the IPG pocket was the most common site of an SCS-related infection. Explantation was ultimately performed in 52 of the 67 patients (77.6%). Non-explantation salvage therapy was attempted in 24 patients and was successful in resolving the infection in 15 patients without removal of SCS hardware components. DISCUSSION: This study provides current data regarding SCS related infections, including incidence, diagnosis, and treatment.

Spinal Cord Stimulator Implant Infection Rates and Risk Factors: A Multicenter Retrospective Study.

OBJECTIVES: Spinal cord stimulation is an evidence-based treatment for a number of chronic pain conditions. While this therapy offers improvement in pain and function it is not without potential complications. These complications include device failure, migration, loss of therapeutic paresthesia, and infection. This article looked to establish a modern infection rate for spinal cord stimulators, assess the impact of known risk factors for surgical site infections and to determine the impact of certain preventative measures on the rate of infection. METHODS: After institutional review board approval, a multisite, retrospective review was conducted on 2737 unique implants or revisions of SCS systems. Patient demographics, risk factors including diabetes, tobacco use, obesity, revision surgery, trial length, implant location, implant type, surgeon background, prophylactic antibiotic use, utilization of a occlusive dressing, and post-operative antibiotic use were recorded and analyzed. RESULTS: The overall infection rate was 2.45% (n = 67). Diabetes, tobacco use, and obesity did not independently increase the rate of infection. Revision surgeries had a trend toward higher infection rate; however, this did not meet statistical significance. There was no difference in the rate of infection between implants performed by physicians of different base specialties, cylinder leads vs. paddle leads, or between different prophylactic antibiotics. Implants performed at academic centers had a higher rate of infection when compared to implants performed in nonacademic settings. When patients received an occlusive dressing or post-operative antibiotics they had a lower rate of infection. CONCLUSIONS: The infection rate (2.45%) reported in this study is lower than the previously reported rates (3-6%) and are on par with other surgical specialties. This study did not show an increased rate of infection for patients that used tobacco, had diabetes or were obese. It's possible that given the low overall infection rate a larger study is needed to establish the true impact of these factors on infection. In addition, this study did not address the impact of poorly controlled diabetes mellitus (elevated hemoglobin A1c) vs. well-controlled diabetes. It can be concluded from this study that utilizing an occlusive dressing over the incision in the post-operative period decreases the rate of infection and should become the standard of care. This study also demonstrated the positive impact of post-operative antibiotics in decreasing the rate of infection. Studies in other surgical specialties have not shown this impact which would suggest that further research is needed.

Noninvasive Transcutaneous Vagus Nerve Stimulation Decreases Whole Blood Culture-Derived Cytokines and Chemokines: A Randomized, Blinded, Healthy Control Pilot Trial.

OBJECTIVES: The purpose of this study was to test the transcutaneous noninvasive vagus nerve stimulator (nVNS) (gammaCore©) device to determine if it modulates the peripheral immune system, as has been previously published for implanted vagus nerve stimulators. MATERIALS AND METHODS: A total of 20 healthy males and females were randomized to receive either nVNS or sham stimulation (SST). All subjects underwent an initial blood draw at 8:00 am, followed by stimulation with nVNS or SST at 8:30 am. Stimulation was repeated at 12:00 pm and 6:00 pm. Additional blood samples were withdrawn 90 min and 24 hour after the first stimulation session. After samples were cultured using the Myriad RBM TruCulture (Austin, TX) system (WBCx), levels of cytokines and chemokines were measured by the Luminex assay and statistical analyses within and between groups were performed using the Wilcoxon Signed Ranks Test and Mann-Whitney U with the statistical program R. RESULTS: A significant percent decrease in the levels of the cytokine interleukin [IL]-1ß, tumor necrosis factor [TNF] levels, and chemokine, interleukin [IL]-8 IL-8, macrophage inflammatory protein [MIP]-1α, and monocyte chemoattractant protein [MCP]-1 levels was observed in the nVNS group non-lipopolysaccharide (LPS)-stimulated whole blood culture (n-WBCx) at the 24-hour time point (p < 0.05). In SST group, there was a significant percent increase in IL-8 at 90 min post-stimulation (p < 0.05). At 90 min, the nVNS group had a greater percent decrease in IL-8 concentration (p < 0.05) compared to SST group. The nVNS group had a greater percent decrease in cytokines (TNF, IL-1ß) and chemokines (MCP-1 and IL-8) at 24 hour (p < 0.05) in comparison to SST. LPS-stimulated whole blood cultures (L-WBCx) did not show a significant decrease in cytokine levels in either the nVNS or SST group across any time points. The nVNS group showed a significant percent increase in LPS-stimulated IL-10 levels at the 24-hour time point in comparison to SST. CONCLUSIONS: nVNS downregulates inflammatory cytokine release suggesting that nVNS may be an effective anti-inflammatory treatment.

Novel High-Frequency Peripheral Nerve Stimulator Treatment of Refractory Postherpetic Neuralgia: A Brief Technical Note.

OBJECTIVES: The study aims to describe an ultrasound (US)-guided peripheral nerve stimulation implant technique and describe the effect of high-frequency peripheral nerve stimulation on refractory postherpetic neuralgia. MATERIALS AND METHODS: Following a cadaver pilot trial using US and confirmatory fluoroscopic guidance, a 52-year-old man with refractory left supraorbital neuralgia underwent combined US and fluoroscopic-guided supraorbital peripheral nerve stimulator trial. The patient was subsequently implanted with a percutaneous lead over the left supraorbital and supratrochlear nerve utilizing a high-frequency stimulation paradigm. RESULTS: At 9 months follow-up, the pain intensity had declined from a weekly average of 8/10 to 1/10 on the pain visual analog scale (VAS). After implant, both nerve conduction and blink reflex studies were performed, which demonstrated herpetic nerve damage and frequency-specific peripheral nerve stimulation effects. The patient preferred analgesia in the supraorbital nerve distribution accomplished with high-frequency paresthesia-free stimulation (HFS) at an amplitude of 6.2 mA, a frequency of 100-1200 Hz, and a pulse width of 130 µsec, to paresthesia-mediated pain relief associated with low-frequency stimulation. CONCLUSION: We report the implant of a supraorbital peripheral nerve stimulating electrode that utilizes a high-frequency program resulting in sustained suppression of intractable postherpetic neuralgia.

Non-invasive ventral cervical magnetoneurography as a proxy of in vivo lipopolysaccharide-induced inflammation.

Maintenance of autonomic homeostasis is continuously calibrated by sensory fibers of the vagus nerve and sympathetic chain that convey compound action potentials (CAPs) to the central nervous system. Lipopolysaccharide (LPS) intravenous challenge reliably elicits a robust inflammatory response that can resemble systemic inflammation and acute endotoxemia. Here, we administered LPS intravenously in nine healthy subjects while recording ventral cervical magnetoneurography (vcMNG)-derived CAPs at the rostral Right Nodose Ganglion (RNG) and the caudal Right Carotid Artery (RCA) with optically pumped magnetometers (OPM). We observed vcMNG RNG and RCA neural firing rates that tracked changes in TNF-α levels in the systemic circulation. Further, endotype subgroups based on high and low IL-6 responders segregate RNG CAP frequency (at 30-120 min) and based on high and low IL-10 response discriminate RCA CAP frequency (at 0-30 min). These vcMNG tools may enhance understanding and management of the neuroimmune axis that can guide personalized treatment based on an individual's distinct endophenotype.

EMG-projected MEG high-resolution source imaging of human motor execution: Brain-muscle coupling above movement frequencies.

Magnetoencephalography (MEG) is a non-invasive functional imaging technique for pre-surgical mapping. However, movement-related MEG functional mapping of primary motor cortex (M1) has been challenging in presurgical patients with brain lesions and sensorimotor dysfunction due to the large numbers of trials needed to obtain adequate signal to noise. Moreover, it is not fully understood how effective the brain communication is with the muscles at frequencies above the movement frequency and its harmonics. We developed a novel Electromyography (EMG)-projected MEG source imaging technique for localizing early-stage (-100 to 0 ms) M1 activity during ~l min recordings of left and right self-paced finger movements (~1 Hz). High-resolution MEG source images were obtained by projecting M1 activity towards the skin EMG signal without trial averaging. We studied delta (1-4 Hz), theta (4-7 Hz), alpha (8-12 Hz), beta (15-30 Hz), gamma (30-90 Hz), and upper-gamma (60-90 Hz) bands in 13 healthy participants (26 datasets) and three presurgical patients with sensorimotor dysfunction. In healthy participants, EMG-projected MEG accurately localized M1 with high accuracy in delta (100.0%), theta (100.0%), and beta (76.9%) bands, but not alpha (34.6%) or gamma/upper-gamma (0.0%) bands. Except for delta, all other frequency bands were above the movement frequency and its harmonics. In three presurgical patients, M1 activity in the affected hemisphere was also accurately localized, despite highly irregular EMG movement patterns in one patient. Altogether, our EMG-projected MEG imaging approach is highly accurate and feasible for M1 mapping in presurgical patients. The results also provide insight into movement-related brain-muscle coupling above the movement frequency and its harmonics.

Elevated C-Reactive Protein in Older Men With Chronic Pain: Association With Plasma Amyloid Levels and Hippocampal Volume.

BACKGROUND: Chronic pain leads to tau accumulation and hippocampal atrophy, which may be moderated through inflammation. In older men, we examined associations of chronic pain with Alzheimer's disease (AD)-related plasma biomarkers and hippocampal volume as moderated by systemic inflammation. METHODS: Participants were men without dementia. Chronic pain was defined as moderate-to-severe pain in 2+ study waves at average ages 56, 62, and 68. At age 68, we measured plasma amyloid-beta (Aß42, n = 871), Aß40 (n = 887), total tau (t-tau, n = 841), and neurofilament light chain (NfL, n = 915), and serum high-sensitivity C-reactive protein (hs-CRP, n = 968), a marker of systemic inflammation. A subgroup underwent structural MRI to measure hippocampal volume (n = 385). Analyses adjusted for medical morbidities, depressive symptoms, and opioid use. RESULTS: Chronic pain was related to higher Aß40 (ß = 0.25, p = .009), but hs-CRP was unrelated to AD-related biomarkers (ps > .05). There was a significant interaction such that older men with both chronic pain and higher levels of hs-CRP had higher levels of Aß42 (ß = 0.36, p = .001) and Aß40 (ß = 0.29, p = .003). Chronic pain and hs-CRP did not interact to predict levels of Aß42/Aß40, t-tau, or NfL. Furthermore, there were significant interactions such that Aß42 and Aß40 were associated with lower hippocampal volume, particularly when levels of hs-CRP were elevated (hs-CRP × Aß42: ß = -0.19, p = .002; hs-CRP × Aß40: ß = -0.21, p = .001), regardless of chronic pain status. CONCLUSIONS: Chronic pain was associated with higher plasma Aß, especially when hs-CRP was also elevated. Higher hs-CRP and Aß levels were both related to smaller hippocampal volumes. Chronic pain, when accompanied by systemic inflammation, may elevate the risk of neurodegeneration in AD-vulnerable regions.

Multi-path decoder U-Net: A weakly trained real-time segmentation network for object detection and localization in ultrasound scans.

Detecting and localizing an anatomical structure of interest within the field of view of an ultrasound scan is an essential step in many diagnostic and therapeutic procedures. However, ultrasound scans suffer from high levels of variabilities across sonographers and patients, making it challenging for sonographers to accurately identify and locate these structures without extensive experience. Segmentation-based convolutional neural networks (CNNs) have been proposed as a solution to assist sonographers in this task. Despite their accuracy, these networks require pixel-wise annotations for training; an expensive and labor-intensive operation that requires the expertise of an experienced practitioner to identify the precise outline of the structures of interest. This complicates, delays, and increases the cost of network training and deployment. To address this problem, we propose a multi-path decoder U-Net architecture that is trained on bounding box segmentation maps; not requiring pixel-wise annotations. We show that the network can be trained on small training sets, which is the case in medical imaging datasets; reducing the cost and time needed for deployment and use in clinical settings. The multi-path decoder design allows for better training of deeper layers and earlier attention to the target anatomical structures of interest. This architecture offers up to a 7% relative improvement compared to the U-Net architecture in localization and detection performance, with an increase of only 0.75% in the number of parameters. Its performance is on par with, or slightly better than, the more computationally expensive U-Net++, which has 20% more parameters; making the proposed architecture a more computationally efficient alternative for real-time object detection and localization in ultrasound scans.

EMG-projected MEG High-Resolution Source Imaging of Human Motor Execution: Brain-Muscle Coupling above Movement Frequencies.

Magnetoencephalography (MEG) is a non-invasive functional imaging technique for pre-surgical mapping. However, movement-related MEG functional mapping of primary motor cortex (M1) has been challenging in presurgical patients with brain lesions and sensorimotor dysfunction due to the large numbers of trails needed to obtain adequate signal to noise. Moreover, it is not fully understood how effective the brain communication is with the muscles at frequencies above the movement frequency and its harmonics. We developed a novel Electromyography (EMG)-projected MEG source imaging technique for localizing M1 during ~1 minute recordings of left and right self-paced finger movements (~1 Hz). High-resolution MEG source images were obtained by projecting M1 activity towards the skin EMG signal without trial averaging. We studied delta (1-4 Hz), theta (4-7 Hz), alpha (8-12 Hz), beta (15-30 Hz), and gamma (30-90 Hz) bands in 13 healthy participants (26 datasets) and two presurgical patients with sensorimotor dysfunction. In healthy participants, EMG-projected MEG accurately localized M1 with high accuracy in delta (100.0%), theta (100.0%), and beta (76.9%) bands, but not alpha (34.6%) and gamma (0.0%) bands. Except for delta, all other frequency bands were above the movement frequency and its harmonics. In both presurgical patients, M1 activity in the affected hemisphere was also accurately localized, despite highly irregular EMG movement patterns in one patient. Altogether, our EMG-projected MEG imaging approach is highly accurate and feasible for M1 mapping in presurgical patients. The results also provide insight into movement related brain-muscle coupling above the movement frequency and its harmonics.

Non-invasive cervical vagus nerve stimulation effects on reaction time and valence image anticipation response.

BACKGROUND: Norepinephrine (NE) driven noninvasive vagus nerve stimulation (nVNS), which improves attention and reduces reaction time, augments learning. Equally important, endogenous NE mediated arousal is highly dependent on the valence (positive or negative) of the exogenous stimulus. But to date, no study has measured valence specific effects of nVNS on both functional magnetic resonance imaging (fMRI) anticipation task response and reaction time in healthy individuals. Therefore, the aim of this pilot study was to assess whether nVNS vs sham modulates valence cortical anticipation task response and reaction time in a normative sample. METHODS: Participants received right sided transcutaneous cervical nVNS (N = 12) or sham (N = 12) stimulation during a 3T fMRI scan. Subjects first performed a continuous performance task (CPT) and then a cued anticipation task to images of positively and negatively valenced events during fMRI. Reaction times to cues and Blood oxygen level dependent (BOLD) response were examined over phase to identify effects of nVNS/sham over time. RESULTS: nVNS reduced reaction time for all valenced image anticipation trials. With the fMRI anticipation task, we observed a valence-specific effect; nVNS increased responsivity to images with negative valence and decreased responsivity to images with positive valence, whereas sham showed an inverse valence response. CONCLUSIONS: nVNS was linked to reduced reaction time during the anticipation task. In tandem, nVNS consistently enhanced responsivity to negatively valenced images and diminished responsivity to positively valenced images, suggesting specific nVNS driven endogenous neurotransmitter signaling may contribute.

Sex-specific differences in the efficacy of traditional low frequency versus high frequency spinal cord stimulation for chronic pain.

INTRODUCTION: Spinal cord stimulation (SCS), an FDA-approved therapy for chronic pain, uses paresthesia (low frequency SCS (LF-SCS)) or paresthesia-free (such as high-frequency SCS (HF-SCS)) systems, providing analgesia through partially-elucidated mechanisms, with recent studies indicating a sexual dimorphism in pain pathogenesis (Bretherton et al., Neuromodulation, 2021; Paller et al., Pain Med 10:289-299, 2009; Slyer et al., Neuromodulation, 2019; Van Buyten et al., Neuromodulation 20:642-649, 2017; Mekhail et al., Pain Pract, 2021). We aim to evaluate SCS therapy sex effects based on paradigm, utilizing visual analog scores (VAS), perceived pain reduction (PPR), and opioid use. METHODS: A retrospective cohort study of SCS patients implanted between 2004 and 2020 (n = 237) was conducted. Descriptive statistics and linear mixed methods analyses were used. RESULTS: HF-SCS (10 kHz) was implanted in 94 patients (40 females, 54 males), and LF-SCS in 143 (70 females, 73 males). At 3 months and 6 months, HF-SCS (p < 0.001) and LF-SCS (p < 0.005) had lower VAS scores compared to baseline (p < 0.005), with no differences across groups. PPR improved in both post-implantation (p < 0.006) and at 3 months (p < 0.004 respectively), compared to baseline persisting to 6 (p < 0.003) and 12 months (p < 0.01) for HF-SCS, with significantly better PPR for HF-SCS at 3 (p < 0.008) and 6 (p < 0.001) months compared to LF-SCS. There were no differences in opioid use from baseline for either modality; however LF-SCS patients used more opioids at every time point (p < 0.05) compared to HF-SCS. VAS was improved for all modalities in both sexes at 3 months (p = 0.001), which persisted to 6 months (p < 0.05) for HF-SCS males and females, and LF-SCS females. Female HF-SCS had improved PPR at 3 (p = 0.016) and 6 (p = 0.022) months compared to baseline, and at 6 (p = 0.004) months compared to LF-SCS. Male HF-SCS and LF-SCS had improved PPR post-implantation (p < 0.05) and at 3 months (p < 0.05), with HF-SCS having greater benefit at 3 (p < 0.05) and 6 (p < 0.05) months. LF-SCS males but not females used less opioids at 6 months (p = 0.017) compared to baseline; however this effect did not persist. On linear mixed model analyses, including age, sex and stimulator type, VAS decreased with age, at each timepoint, and had a trend towards increasing with female sex, while PPR increased at 3 and 6 months and lastly HF-SCS was associated with decreased opioid use. DISCUSSION: PPR at 3 and 6 months improved to a greater extent in HF-SCS. HF-SCS females had improved PPR at 3 and 6 months, and only LF-SCS males used less opioids at 6 months, potentially indicating sex-based pathway. Future studies should further elucidate differences in sex-based pathways and identify optimal SCS opioid-sparing paradigms for chronic pain patients.

Peripheral Nerve Magnetoneurography With Optically Pumped Magnetometers.

Electrodiagnosis is routinely integrated into clinical neurophysiology practice for peripheral nerve disease diagnoses, such as neuropathy, demyelinating disorders, nerve entrapment/impingement, plexopathy, or radiculopathy. Measured with conventional surface electrodes, the propagation of peripheral nerve action potentials along a nerve is the result of ionic current flow which, according to Ampere's Law, generates a small magnetic field that is also detected as an "action current" by magnetometers, such as superconducting quantum interference device (SQUID) Magnetoencephalography (MEG) systems. Optically pumped magnetometers (OPMs) are an emerging class of quantum magnetic sensors with a demonstrated sensitivity at the 1 fT/√Hz level, capable of cortical action current detection. But OPMs were ostensibly constrained to low bandwidth therefore precluding their use in peripheral nerve electrodiagnosis. With careful OPM bandwidth characterization, we hypothesized OPMs may also detect compound action current signatures consistent with both Sensory Nerve Action Potential (SNAP) and the Hoffmann Reflex (H-Reflex). In as much, our work confirms OPMs enabled with expanded bandwidth can detect the magnetic signature of both the SNAP and H-Reflex. Taken together, OPMs now show potential as an emerging electrodiagnostic tool.

Toward Composite Pain Biomarkers of Neuropathic Pain-Focus on Peripheral Neuropathic Pain.

Chronic pain affects ~10-20% of the U.S. population with an estimated annual cost of $600 billion, the most significant economic cost of any disease to-date. Neuropathic pain is a type of chronic pain that is particularly difficult to manage and leads to significant disability and poor quality of life. Pain biomarkers offer the possibility to develop objective pain-related indicators that may help diagnose, treat, and improve the understanding of neuropathic pain pathophysiology. We review neuropathic pain mechanisms related to opiates, inflammation, and endocannabinoids with the objective of identifying composite biomarkers of neuropathic pain. In the literature, pain biomarkers typically are divided into physiological non-imaging pain biomarkers and brain imaging pain biomarkers. We review both types of biomarker types with the goal of identifying composite pain biomarkers that may improve recognition and treatment of neuropathic pain.

A flexible adhesive surface electrode array capable of cervical electroneurography during a sequential autonomic stress challenge.

This study introduces a flexible, adhesive-integrated electrode array that was developed to enable non-invasive monitoring of cervical nerve activity. The device uses silver-silver chloride as the electrode material of choice and combines it with an electrode array consisting of a customized biopotential data acquisition unit and integrated graphical user interface (GUI) for visualization of real-time monitoring. Preliminary testing demonstrated this electrode design can achieve a high signal to noise ratio during cervical neural recordings. To demonstrate the capability of the surface electrodes to detect changes in cervical neuronal activity, the cold-pressor test (CPT) and a timed respiratory challenge were employed as stressors to the autonomic nervous system. This sensor system recording, a new technique, was termed Cervical Electroneurography (CEN). By applying a custom spike sorting algorithm to the electrode measurements, neural activity was classified in two ways: (1) pre-to-post CPT, and (2) during a timed respiratory challenge. Unique to this work: (1) rostral to caudal channel position-specific (cephalad to caudal) firing patterns and (2) cross challenge biotype-specific change in average CEN firing, were observed with both CPT and the timed respiratory challenge. Future work is planned to develop an ambulatory CEN recording device that could provide immediate notification of autonomic nervous system activity changes that might indicate autonomic dysregulation in healthy subjects and clinical disease states.