Improved Selectivity in Eliciting Evoked Electromyography Responses With High-Resolution Spinal Cord Stimulation.

BACKGROUND AND OBJECTIVES: As spinal cord stimulation (SCS) offers a therapy for increasing numbers of patients with chronic pain and spinal cord injury, it becomes increasingly important to better understand its somatotopy. In this prospective study, we investigate whether high-resolution SCS (HR-SCS) offers improved selectivity assessed through elicitation of evoked electromyography (EMG) responses as compared with commercial paddle leads. METHODS: Vertical tripole configurations were used to elicit EMG responses in both types of paddles placed for standard-of-care indications between T6 and T10. In HR-SCS, evoked EMG responses in lower extremity/abdominal muscle groups were monitored at 6 to 8 mediolateral sites. All commercial paddle columns were tested. Percentage change in the maximum root mean square value was calculated at a group level. Heat maps were generated to identify responders for each muscle group. Responders were considered patients who had a >50% change in root mean square over baseline. RESULTS: We demonstrated significantly greater motor responses across medial and lateral contacts and greater responder rates consistently at the T6 and T9 levels with HR-SCS as compared with commercial paddles in 18 patients. Distal muscle groups (gastrocnemius and tibialis anterior) and proximal muscle groups (biceps femoris and quadriceps) were selectively activated at both levels. CONCLUSION: We demonstrate that HR-SCS has greater selectivity in eliciting evoked EMG responses in an intraoperative setting. HR-SCS offers recruitment of muscle groups at lateral contacts concurrently with medial contacts. We provide data that HR-SCS may provide higher spatial resolution, which has the potential to allow for personalization of care and treatment of pain syndromes/symptoms which to date have not been effectively treated.

Multiocular defect in the Old English Sheepdog: A canine form of Stickler syndrome type II associated with a missense variant in the collagen-type gene COL11A1.

Multiocular defect has been described in different canine breeds, including the Old English Sheepdog. Affected dogs typically present with multiple and various ocular abnormalities. We carried out whole genome sequencing on an Old English Sheepdog that had been diagnosed with hereditary cataracts at the age of five and then referred to a board-certified veterinary ophthalmologist due to owner-reported visual deterioration. An ophthalmic assessment revealed that there was bilateral vitreal degeneration, macrophthalmos, and spherophakia in addition to cataracts. Follow-up consultations revealed cataract progression, retinal detachment, uveitis and secondary glaucoma. Whole genome sequence filtered variants private to the case, shared with another Old English Sheepdog genome and predicted to be deleterious were genotyped in an initial cohort of six Old English Sheepdogs (three affected by multiocular defect and three control dogs without evidence of inherited eye disease). Only one of the twenty-two variants segregated correctly with multiocular defect. The variant is a single nucleotide substitution, located in the collagen-type gene COL11A1, c.1775T>C, that causes an amino acid change, p.Phe1592Ser. Genotyping of an additional 14 Old English Sheepdogs affected by multiocular defect revealed a dominant mode of inheritance with four cases heterozygous for the variant. Further genotyping of hereditary cataract-affected Old English Sheepdogs revealed segregation of the variant in eight out of nine dogs. In humans, variants in the COL11A1 gene are associated with Stickler syndrome type II, also dominantly inherited.

Investigation of the intraoperative cortical responses to spinal motor mapping in a patient with chronic pain.

Intraoperative neurophysiological monitoring (IONM) in spinal cord stimulation (SCS) surgery for chronic pain is shown to provide effective guidance during device placement. Electromyography (EMG) is used to determine the laterality of the paddle. In some SCS cases, laterality cannot be obtained via EMG due to patient physiology. Electroencephalography (EEG) is already used in IONM to monitor cortical responses. Here, we show proof-of-concept of assessing the responses of epidurally evoked EMGs simultaneously with EEGs to determine laterality during IONM using a high-resolution (HR) SCS paddle. An 8-column HR-SCS paddle was acutely placed at T9-T10 interspace in patients with failed back surgery syndrome. EMG signals from 18 muscle groups were recorded simultaneously with 60-channel EEG signals at various stimulation amplitudes (0-10 mA). Particular attention was paid to regions associated with pain including the somatosensory cortex (S1), prefrontal cortex (PFC), and motor cortex (M1). When left and right lateral contacts were stimulated at low amplitudes (1-2 mA), significant changes were seen in θ, α, and ß powers in the contralateral PFC but not in M1 or S1. There was a significant correlation between M1 and contralateral contacts in α power. At higher currents (7-8 mA), right-sided contacts resulted in α power change. We found significant differences in α, θ, and ß powers in PFC for contralateral stimulation of the lateral SCS contacts at low amplitudes and in α power at higher amplitudes. The changes in PFC suggest the potential of EEG for understanding a cortical mechanism of action of SCS and provide insight into the pathophysiology of chronic pain.NEW & NOTEWORTHY Here, we present proof of concept of assessing the responses of epidurally evoked electromyography simultaneously with scalp electroencephalography to determine whether both laterality and insights into pain mechanisms can be elucidated. With stimulation, significant changes were seen in θ, α, and ß band power in the contralateral prefrontal cortex and in α power in the motor cortex. We provide insight into the mechanism of action of SCS in preventing pain in this patient.

Spatiotemporal Distribution of Electrically Evoked Spinal Compound Action Potentials During Spinal Cord Stimulation.

OBJECTIVES: Recent studies using epidural spinal cord stimulation (SCS) have demonstrated restoration of motor function in individuals previously diagnosed with chronic spinal cord injury (SCI). In parallel, the spinal evoked compound action potentials (ECAPs) induced by SCS have been used to gain insight into the mechanisms of SCS-based chronic pain therapy and to titrate closed-loop delivery of stimulation. However, the previous characterization of ECAPs recorded during SCS was performed with one-dimensional, cylindrical electrode leads. Herein, we describe the unique spatiotemporal distribution of ECAPs induced by SCS across the medial-lateral and rostral-caudal axes of the spinal cord, and their relationship to polysynaptic lower-extremity motor activation. MATERIALS AND METHODS: In each of four sheep, two 24-contact epidural SCS arrays were placed on the lumbosacral spinal cord, spanning the L3 to L6 vertebrae. Spinal ECAPs were recorded during SCS from nonstimulating contacts of the epidural arrays, which were synchronized to bilateral electromyography (EMG) recordings from six back and lower-extremity muscles. RESULTS: We observed a triphasic P1, N1, P2 peak morphology and propagation in the ECAPs during midline and lateral stimulation. Distinct regions of lateral stimulation resulted in simultaneously increased ECAP and EMG responses compared with stimulation at adjacent lateral contacts. Although EMG responses decreased during repetitive stimulation bursts, spinal ECAP amplitude did not significantly change. Both spinal ECAP responses and EMG responses demonstrated preferential ipsilateral recruitment during lateral stimulation compared with midline stimulation. Furthermore, EMG responses were correlated with stimulation that resulted in increased ECAP amplitude on the ipsilateral side of the electrode array. CONCLUSIONS: These results suggest that ECAPs can be used to investigate the effects of SCS on spinal sensorimotor networks and to inform stimulation strategies that optimize the clinical benefit of SCS in the context of managing chronic pain and the restoration of sensorimotor function after SCI.

Caught in a Dangerous World: Problematic News Consumption and Its Relationship to Mental and Physical Ill-Being.

This study adds to the growing body of literature on problematic media behavior by introducing and explicating the concept of problematic news consumption, which we define as involving transportation, preoccupation, misregulation, underregulation, and interference. Using survey data from a national sample of U.S. adults, we examine the factor structure of a problematic news consumption measure, the existence of latent classes derived from the expected factors, and differences in mental and physical health across the emerging classes. Results show support for the proposed factor structure as well as the existence of four latent classes, which appear to be stratified according to severity of problematic news consumption. Results also show greater mental and physical ill-being among those with higher levels of problematic news consumption compared to those with lower levels, even after controlling for demographics, personality traits, and overall news use. Implications for designing effective media literacy campaigns to raise awareness of the potential for news consumption to develop into a problematic behavior as well as the development of intervention strategies are discussed.

High-density spinal cord stimulation selectively activates lower urinary tract nerves.

Objective.Epidural spinal cord stimulation (SCS) is a potential intervention to improve limb and autonomic functions, with lumbar stimulation improving locomotion and thoracic stimulation regulating blood pressure. Here, we asked whether sacral SCS could be used to target the lower urinary tract (LUT) and used a high-density epidural electrode array to test whether individual electrodes could selectively recruit LUT nerves.Approach. We placed a high-density epidural SCS array on the dorsal surface of the sacral spinal cord and cauda equina of anesthetized cats and recorded the stimulation-evoked activity from nerve cuffs on the pelvic, pudendal and sciatic nerves.Main results. Here we show that sacral SCS evokes responses in nerves innervating the bladder and urethra and that these nerves can be activated selectively. Sacral SCS always recruited the pelvic and pudendal nerves and selectively recruited both of these nerves in all but one animal. Individual branches of the pudendal nerve were always recruited as well. Electrodes that selectively recruited specific peripheral nerves were spatially clustered on the arrays, suggesting anatomically organized sensory pathways.Significance.This selective recruitment demonstrates a mechanism to directly modulate bladder and urethral function through known reflex pathways, which could be used to restore bladder and urethral function after injury or disease.

High-Density, Actively Multiplexed µECoG Array on Reinforced Silicone Substrate.

Simultaneous interrogation of electrical signals from wide areas of the brain is vital for neuroscience research and can aid in understanding the mechanisms of brain function and treatments for neurological disorders. There emerges a demand for development of devices with highly conformal interfaces that can span large cortical regions, have sufficient spatial resolution, and chronic recording capability while keeping a small implantation footprint. In this work, we have designed 61 channel and 48 channel high-density, cortical, micro-electrocorticographic electrode arrays with 400 µm pitch on an ultra-soft but durable substrate. We have also developed a custom multiplexing integrated circuit (IC), methods for packaging the IC in a water-tight liquid crystal polymer casing, and a micro-bonding method for attaching the electronics package to the electrode array. With the integrated multiplexer, the number of external wire connections can be reduced to 16 wires, thereby diminishing the invasive footprint of the device. Both the electrode array and IC were tested in vivo in a rat model to demonstrate the ability to sense finely-localized electrophysiological signals.

High-Resolution Spinal Motor Mapping Using Thoracic Spinal Cord Stimulation in Patients With Chronic Pain.

BACKGROUND: High-resolution spinal cord stimulation (HR-SCS) paddle can stimulate medial-dorsal columns and extend stimulation coverage to the laterally positioned spinal targets. OBJECTIVE: To investigate the medio-lateral selectivity of an HR-SCS paddle in patients with chronic pain. METHODS: During standard-of-care spinal cord stimulation (SCS) placement, epidurally evoked electromyography and antidromic dorsal column-evoked potentials were recorded in 12 subjects using an HR-SCS paddle with 8 medio-lateral sites spanning the full epidural width at thoracic T9-12 and a commercial paddle consecutively. RESULTS: Recruitment maps were aligned with respect to physiological midline which was overlapping with anatomic midline in 10 of 11 cases. Overlapping contacts between the HR-SCS and commercial paddles exhibited similar patterns while HR-SCS demonstrated higher precision targeting of certain dermatomes. Spinal motor maps showed that the lateral contacts triggered stronger responses in medial gastrocnemius, adductor magnus, and tibialis anterior while the medial contacts triggered stronger responses in gluteus maximus and adductor hallucis. The time-locked popliteal fossa responses indicated ipsilateral activation by HR-SCS at the lateral contacts and bilateral activation at the medial contacts with stronger ipsilateral responses. CONCLUSION: This study is the first to perform high-resolution medio-lateral SCS mapping in patients with chronic pain. These results show promise that HR-SCS may provide additional ipsilateral recruitment within the extremities which improve targeting of focal pain in the lower extremities. Furthermore, this study supports the functional use of intraoperative neuromonitoring as a decision tool to determine physiological midline in thoracic SCS surgeries and provides a full methodological framework.

Rapid Visualization Tool for Intraoperative Dorsal Column Mapping Triggered by Spinal Cord Stimulation in Chronic Pain Patients.

Spinal cord stimulation (SCS) is a widely accepted effective treatment for managing chronic pain. SCS outcomes depend highly on accurate placement of SCS electrodes at the appropriate spine level for a desired pain relief. Intraoperative neurophysiological monitoring (IONM) under general anesthesia provides an objective real-time mapping of the dorsal columns, and has been shown to be a safe and effective tool. IONM applies stimulation to multiple electrode contacts at various intensities and monitors the triggered electromyography (EMG) responses in several muscle groups simultaneously. Therefore, it requires dynamic communication between neurosurgeon and neurophysiologist and continuous real-time annotations of the responses, which makes the procedure complex and experience-based. Here, we describe an automated data visualization tool that generates patient specific activity maps using intraoperatively collected signals. Responses were collected using a High-resolution (HR)-SCS lead with 8 columns of electrodes spanning the dorsal columns. Our JavaScript/Python based graphical user interface (GUI) provides a fast and robust visualization of EMG activity via denoising, feature extraction, normalization, and overlaying of the activity maps on body images in selected colormaps. In contrast to reviewing series of EMG signals, our user-friendly tool provides a rapid and robust analysis of stimulation effects on various muscle groups and direct comparison across subjects and/or stimulation settings. Future work includes expanding analytics capabilities and operating room implementation as a real-time processing tool that can be used in conjunction with the current IONM techniques.

Surgical placement of customized abdominal vagus nerve stimulating and gastrointestinal serosal surface recording electrodes.

Bioelectronic medical approaches to control vagus nerve-to-organ signaling have the potential to treat cardiac, respiratory, gastrointestinal (GI) and metabolic diseases, such as obesity. Unlike cervical vagus nerve stimulation (VNS), abdominal VNS could provide specific therapeutic control of the GI tract without off-target effects on thoracic organs; however, surgical approaches for abdominal VNS electrode placement are not well established. Moreover, optimal device configurations and additional placement of GI recording electrodes for closed-loop control are largely unknown. We designed VNS cuff and GI planar serosal electrodes and tested placement of these devices in laparoscopic surgery in two cadavers. We determined that electrode positioning on the ventral abdominal vagus nerve and gastric antrum was feasible but other sites, such as the duodenum and proximal stomach, were more difficult. The current investigation can guide potential placement and design of VNS cuff and GI electrodes for development of closed-loop GI therapeutic devices.

Selective stimulation of the ferret abdominal vagus nerve with multi-contact nerve cuff electrodes.

Dysfunction and diseases of the gastrointestinal (GI) tract are a major driver of medical care. The vagus nerve innervates and controls multiple organs of the GI tract and vagus nerve stimulation (VNS) could provide a means for affecting GI function and treating disease. However, the vagus nerve also innervates many other organs throughout the body, and off-target effects of VNS could cause major side effects such as changes in blood pressure. In this study, we aimed to achieve selective stimulation of populations of vagal afferents using a multi-contact cuff electrode wrapped around the abdominal trunks of the vagus nerve. Four-contact nerve cuff electrodes were implanted around the dorsal (N = 3) or ventral (N = 3) abdominal vagus nerve in six ferrets, and the response to stimulation was measured via a 32-channel microelectrode array (MEA) inserted into the left or right nodose ganglion. Selectivity was characterized by the ability to evoke responses in MEA channels through one bipolar pair of cuff contacts but not through the other bipolar pair. We demonstrated that it was possible to selectively activate subpopulations of vagal neurons using abdominal VNS. Additionally, we quantified the conduction velocity of evoked responses to determine what types of nerve fibers (i.e., Aδ vs. C) responded to stimulation. We also quantified the spatial organization of evoked responses in the nodose MEA to determine if there is somatotopic organization of the neurons in that ganglion. Finally, we demonstrated in a separate set of three ferrets that stimulation of the abdominal vagus via a four-contact cuff could selectively alter gastric myoelectric activity, suggesting that abdominal VNS can potentially be used to control GI function.

Machine learning prediction of emesis and gastrointestinal state in ferrets.

Although electrogastrography (EGG) could be a critical tool in the diagnosis of patients with gastrointestinal (GI) disease, it remains under-utilized. The lack of spatial and temporal resolution using current EGG methods presents a significant roadblock to more widespread usage. Human and preclinical studies have shown that GI myoelectric electrodes can record signals containing significantly more information than can be derived from abdominal surface electrodes. The current study sought to assess the efficacy of multi-electrode arrays, surgically implanted on the serosal surface of the GI tract, from gastric fundus-to-duodenum, in recording myoelectric signals. It also examines the potential for machine learning algorithms to predict functional states, such as retching and emesis, from GI signal features. Studies were performed using ferrets, a gold standard model for emesis testing. Our results include simultaneous recordings from up to six GI recording sites in both anesthetized and chronically implanted free-moving ferrets. Testing conditions to produce different gastric states included gastric distension, intragastric infusion of emetine (a prototypical emetic agent), and feeding. Despite the observed variability in GI signals, machine learning algorithms, including k-nearest neighbors and support vector machines, were able to detect the state of the stomach with high overall accuracy (>75%). The present study is the first demonstration of machine learning algorithms to detect the physiological state of the stomach and onset of retching, which could provide a methodology to diagnose GI diseases and symptoms such as nausea and vomiting.

An intronic LINE-1 insertion in MERTK is strongly associated with retinopathy in Swedish Vallhund dogs.

The domestic dog segregates a significant number of inherited progressive retinal diseases, several of which mirror human retinal diseases and which are collectively termed progressive retinal atrophy (PRA). In 2014, a novel form of PRA was reported in the Swedish Vallhund breed, and the disease was mapped to canine chromosome 17. The causal mutation was not identified, but expression analyses of the retinas of affected Vallhunds demonstrated a 6-fold increased expression of the MERTK gene compared to unaffected dogs. Using 24 retinopathy cases and 97 controls with no clinical signs of retinopathy, we replicated the chromosome 17 association in Swedish Vallhunds from the UK and aimed to elucidate the causal variant underlying this association using whole genome sequencing (WGS) of an affected dog. This revealed a 6-8 kb insertion in intron 1 of MERTK that was not present in WGS of 49 dogs of other breeds. Sequencing and BLASTN analysis of the inserted segment was consistent with the insertion comprising a full-length intact LINE-1 retroelement. Testing of the LINE-1 insertion for association with retinopathy in the UK set of 24 cases and 97 controls revealed a strong statistical association (P-value 6.0 x 10-11) that was subsequently replicated in the original Finnish study set (49 cases and 89 controls (P-value 4.3 x 10-19). In a pooled analysis of both studies (73 cases and 186 controls), the LINE-1 insertion was associated with a ~20-fold increased risk of retinopathy (odds ratio 23.41, 95% confidence intervals 10.99-49.86, P-value 1.3 x 10-27). Our study adds further support for regulatory disruption of MERTK in Swedish Vallhund retinopathy; however, further work is required to establish a functional overexpression model. Future work to characterise the mechanism by which this intronic mutation disrupts gene regulation will further improve the understanding of MERTK biology and its role in retinal function.

Expression and Reception: An Analytic Method for Assessing Message Production and Consumption in CMC.

This article presents an innovative methodology to study computer-mediated communication (CMC), which allows analysis of the multi-layered effects of online expression and reception. The methodology is demonstrated by combining the following three data sets collected from a widely tested eHealth system, the Comprehensive Health Enhancement Support System (CHESS): 1) a flexible and precise computer-aided content analysis; 2) a record of individual message posting and reading; and 3) longitudinal survey data. Further, this article discusses how the resulting data can be applied to online social network analysis and demonstrates how to construct two distinct types of online social networks - open and targeted communication networks - for different types of content embedded in social networks.

Identifying With a Stereotype: The Divergent Effects of Exposure to Homosexual Television Characters.

Scholars examining homosexual television characters have typically come to one of two conclusions: either exposure to homosexual characters can lead to increased acceptance, or homosexual characters serve to reaffirm negative stereotypes. We seek to bridge these two bodies of research by introducing the concept of stereotyped identification-the idea that cognitively and emotionally identifying with fictional characters can increase acceptance of minorities, while reinforcing implicit stereotypes about how they look, act, and talk. Results from our national survey (N = 972) offer support for this hypothesis.

The Effects of Expressing Religious Support Online for Breast Cancer Patients.

The growth of online support groups has led to an expression effects paradigm within the health communication literature. Although religious support expression is characterized as a typical subdimension of emotional support, we argue that in the context of a life-threatening illness, the inclusion of a religious component creates a unique communication process. Using data from an online group for women with breast cancer, we test a theoretical expression effects model. Results demonstrate that for breast cancer patients, religious support expression has distinct effects from general emotional support messages, which highlights the need to further theorize expression effects along these lines.

When women attack.

The common assumption that female candidates on the campaign trail should not go on the attack, because such tactics contradict gender stereotypes, has not received consistent support. We argue that in some circumstances gender stereotypes will favor female politicians going negative. To test this proposition, this study examines how gender cues affect voter reactions to negative ads in the context of a political sex scandal, a context that should prime gender stereotypes that favor females. Using an online experiment involving a national sample of U.S. adults (N = 599), we manipulate the gender and partisan affiliation of a politician who attacks a male opponent caught in a sex scandal involving sexually suggestive texting to a female intern. Results show that in the context of a sex scandal, a female candidate going on the attack is evaluated more positively than a male. Moreover, while female participants viewed the female sponsor more favorably, sponsor gender had no effect on male participants. Partisanship also influenced candidate evaluations: the Democratic female candidate was evaluated more favorably than her Republican female counterpart.

Providing a sense of touch to prosthetic hands.

Each year, approximately 185,000 Americans suffer the devastating loss of a limb. The effects of upper limb amputations are profound because a person's hands are tools for everyday functioning, expressive communication, and other uniquely human attributes. Despite the advancements in prosthetic technology, current upper limb prostheses are still limited in terms of complex motor control and sensory feedback. Sensory feedback is critical to restoring full functionality to amputated patients because it would relieve the cognitive burden of relying solely on visual input to monitor motor commands and provide tremendous psychological benefits. This article reviews the latest innovations in sensory feedback and argues in favor of peripheral nerve interfaces. First, the authors examine the structure of the peripheral nerve and its importance in the development of a sensory interface. Second, the authors discuss advancements in targeted muscle reinnervation and direct neural stimulation by means of intraneural electrodes. The authors then explore the future of prosthetic sensory feedback using innovative technologies for neural signaling, specifically, the sensory regenerative peripheral nerve interface and optogenetics. These breakthroughs pave the way for the development of a prosthetic limb with the ability to feel.

Optogenetic control of nerve growth.

Due to the limited regenerative ability of neural tissue, a diverse set of biochemical and biophysical cues for increasing nerve growth has been investigated, including neurotrophic factors, topography, and electrical stimulation. In this report, we explore optogenetic control of neurite growth as a cell-specific alternative to electrical stimulation. By investigating a broad range of optical stimulation parameters on dorsal root ganglia (DRGs) expressing channelrhodopsin 2 (ChR2), we identified conditions that enhance neurite outgrowth by three-fold as compared to unstimulated or wild-type (WT) controls. Furthermore, optogenetic stimulation of ChR2 expressing DRGs induces directional outgrowth in WT DRGs co-cultured within a 10 mm vicinity of the optically sensitive ganglia. This observed enhancement and polarization of neurite growth was accompanied by an increased expression of neural growth and brain derived neurotrophic factors (NGF, BDNF). This work highlights the potential for implementing optogenetics to drive nerve growth in specific cell populations.