Superficial Peroneal Neuromodulation of Nonobstructive Urinary Retention Induced by Prolonged Pudendal Afferent Activity in Cats

The purpose of this study is to determine if superficial peroneal nerve stimulation (SPNS) can improve nonobstructive urinary retention (NOUR) induced by prolonged pudendal nerve stimulation (PNS). In this exploratory acute study using 8 cats under anesthesia, PNS and SPNS were applied by nerve cuff electrodes. Skin surface electrodes were also used for SPNS. A double lumen catheter was inserted via the bladder dome for bladder infusion and pressure measurement and to allow voiding without a physical urethral outlet obstruction. The voided and postvoid residual (PVR) volumes were also recorded. NOUR induced by repetitive (4-13 times) application of 30-min PNS significantly (p<0.05) reduced voiding efficiency by 49.5±16.8% of control (78.3±7.9%) with a large PVR volume at 208.2±82.6% of control bladder capacity. SPNS (1 Hz, 0.2 ms) at 1.5 to 2 times threshold intensity (T) for inducing posterior thigh muscle contractions was applied either continuously (SPNSc) or intermittently (SPNSi) during cystometrograms to improve the PNS-induced NOUR. SPNSc and SPNSi applied by nerve cuff electrodes significantly (p<0.05) increased voiding efficiency to 74.5±18.9% and 67.0±15.3%, respectively, and reduced PVR volume to 54.5±39.0% and 88.3±56.0%, respectively. SPNSc and SPNSi applied non-invasively by skin surface electrodes also improved NOUR similar to the stimulation applied by a cuff electrode. This study indicates that abnormal pudendal afferent activity could be a pathophysiological cause for the NOUR occurring in Fowler's syndrome and a noninvasive superficial peroneal neuromodulation therapy might be developed to treat NOUR in patients with Fowler's syndrome.

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.

Superficial Peroneal Neuromodulation of Persistent Bladder Underactivity Induced by Prolonged Pudendal Afferent Nerve Stimulation in Cats

The purpose of this study is to determine if superficial peroneal nerve stimulation (SPNS) can reverse persistent bladder underactivity induced by prolonged pudendal nerve stimulation (PNS). In 16 α‐chloralose anesthetized cats, PNS and SPNS were applied by nerve cuff electrodes. Skin surface electrodes were also used for SPNS. Bladder underactivity consisting of a significant increase in bladder capacity to 157.8±10.9% of control and a significant reduction in bladder contraction amplitude to 56.0±5.0% of control was induced by repetitive (4-16 times) application of 30-min PNS. SPNS (1 Hz, 0.2 ms) at 1.5 to 2 times threshold intensity (T) for inducing posterior thigh muscle contractions was applied either continuously (SPNSc) or intermittently (SPNSi) during a cystometrogram (CMG) to determine if the stimulation can reverse the PNS-induced bladder underactivity. SPNSc or SPNSi applied by nerve cuff electrodes during the prolonged PNS inhibition significantly reduced bladder capacity to 124.4±10.7% and 132.4±14.2% of control, respectively, and increased contraction amplitude to 85.3±6.2% and 75.8±4.7%, respectively. Transcutaneous SPNSc and SPNSi also significantly reduced bladder capacity and increased contraction amplitude. Additional PNS applied during the bladder underactivity further increased bladder capacity, while SPNSc applied simultaneously with the PNS reversed the increase in bladder capacity. This study indicates that a non-invasive superficial peroneal neuromodulation therapy might be developed to treat bladder underactivity caused by abnormal pudendal nerve somatic afferent activation that is hypothesized to occur in patients with Fowler's syndrome.

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 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 is was possible to selectively activate subpopulations of vagal afferents 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.

All-Polymer Printed Low-Cost Regenerative Nerve Cuff Electrodes

Neural regeneration after lesions is still limited by several factors and new technologies are developed to address this issue. Here, we present and test in animal models a new regenerative nerve cuff electrode (RnCE). It is based on a novel low-cost fabrication strategy, called “Print and Shrink”, which combines the inkjet printing of a conducting polymer with a heat-shrinkable polymer substrate for the development of a bioelectronic interface. This method allows to produce miniaturized regenerative cuff electrodes without the use of cleanroom facilities and vacuum based deposition methods, thus highly reducing the production costs. To fully proof the electrodes performance in vivo we assessed functional recovery and adequacy to support axonal regeneration after section of rat sciatic nerves and repair with RnCE. We investigated the possibility to stimulate the nerve to activate different muscles, both in acute and chronic scenarios. Three months after implantation, RnCEs were able to stimulate regenerated motor axons and induce a muscular response. The capability to produce fully-transparent nerve interfaces provided with polymeric microelectrodes through a cost-effective manufacturing process is an unexplored approach in neuroprosthesis field. Our findings pave the way to the development of new and more usable technologies for nerve regeneration and neuromodulation.

Compensation Strategies for Bioelectric Signal Changes in Chronic Selective Nerve Cuff Recordings: A Simulation Study

Peripheral nerve interfaces (PNIs) allow us to extract motor, sensory, and autonomic information from the nervous system and use it as control signals in neuroprosthetic and neuromodulation applications. Recent efforts have aimed to improve the recording selectivity of PNIs, including by using spatiotemporal patterns from multi-contact nerve cuff electrodes as input to a convolutional neural network (CNN). Before such a methodology can be translated to humans, its performance in chronic implantation scenarios must be evaluated. In this simulation study, approaches were evaluated for maintaining selective recording performance in the presence of two chronic implantation challenges: the growth of encapsulation tissue and rotation of the nerve cuff electrode. Performance over time was examined in three conditions: training the CNN at baseline only, supervised re-training with explicitly labeled data at periodic intervals, and a semi-supervised self-learning approach. This study demonstrated that a selective recording algorithm trained at baseline will likely fail over time due to changes in signal characteristics resulting from the chronic challenges. Results further showed that periodically recalibrating the selective recording algorithm could maintain its performance over time, and that a self-learning approach has the potential to reduce the frequency of recalibration.

Compensation Strategies for Bioelectric Signal Changes in Chronic Selective Nerve Cuff Recordings: A Simulation Study

Peripheral nerve interfaces (PNIs) allow us to extract motor, sensory and autonomic information from the nervous system and use it as control signals in neuroprosthetic and neuromodulation applications. Recent efforts have aimed to improve the recording selectivity of PNIs, including by using spatiotemporal patterns from multi-contact nerve cuff electrodes as input to a convolutional neural network (CNN). Before such a methodology can be translated to humans, its performance in chronic implantation scenarios must be evaluated. In this simulation study, approaches were evaluated for maintaining selective recording performance in the presence of two chronic implantation challenges: the growth of encapsulation tissue and rotation of the nerve cuff electrode. Performance over time was examined in three conditions: training the CNN at baseline only, supervised re-training with explicitly labeled data at periodic intervals, and a semi-supervised self-learning approach. This study demonstrated that a selective recording algorithm trained at baseline will likely fail over time due to changes in signal characteristics resulting from the chronic challenges. Results further showed that periodically recalibrating the selective recording algorithm can maintain its performance over time, and that a self-learning approach has the potential to reduce the frequency of recalibration.