scholarly journals Graded recruitment of pupil-linked neuromodulation by parametric stimulation of the vagus nerve

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zakir Mridha ◽  
Jan Willem de Gee ◽  
Yanchen Shi ◽  
Rayan Alkashgari ◽  
Justin Williams ◽  
...  
Keyword(s):  
Vagus Nerve ◽  
Basal Forebrain ◽  
Pupil Dilation ◽  
Brain State ◽  
Cognitive Enhancer ◽  
Treatment Resistant ◽  
Stimulation Parameters ◽  
The Moment ◽  
Target Effects ◽  
Stimulation Of

AbstractVagus nerve stimulation (VNS) is thought to affect neural activity by recruiting brain-wide release of neuromodulators. VNS is used in treatment-resistant epilepsy, and is increasingly being explored for other disorders, such as depression, and as a cognitive enhancer. However, the promise of VNS is only partially fulfilled due to a lack of mechanistic understanding of the transfer function between stimulation parameters and neuromodulatory response, together with a lack of biosensors for assaying stimulation efficacy in real time. We here develop an approach to VNS in head-fixed mice on a treadmill and show that pupil dilation is a reliable and convenient biosensor for VNS-evoked cortical neuromodulation. In an ‘optimal’ zone of stimulation parameters, current leakage and off-target effects are minimized and the extent of pupil dilation tracks VNS-evoked basal-forebrain cholinergic axon activity in neocortex. Thus, pupil dilation is a sensitive readout of the moment-by-moment, titratable effects of VNS on brain state.

scholarly journals Graded recruitment of pupil-linked neuromodulation by parametric stimulation of the vagus nerve

2019 ◽  
Author(s):  
Z. Mridha ◽  
J. W. de Gee ◽  
Y. Shi ◽  
R. Alkashgari ◽  
J. Williams ◽  
...  
Keyword(s):  
Vagus Nerve ◽  
Basal Forebrain ◽  
Pupil Dilation ◽  
Brain State ◽  
Brain Disorders ◽  
Treatment Resistant ◽  
Stimulation Parameters ◽  
The Moment ◽  
The Brain ◽  
Target Effects

AbstractVagus nerve stimulation (VNS) is thought to alter the state of the brain by recruiting global neuromodulators. VNS is used in treatment-resistant epilepsy, and is increasingly being explored for other brain disorders, such as depression, and as a cognitive enhancer. However, the promise of VNS is only partially fulfilled due to a lack of mechanistic understanding of the transfer function between stimulation parameters and neuromodulatory response, together with a lack of biosensor for assaying stimulation efficacy in real time. We here develop an approach to VNS in head-fixed mice on a treadmill, and use it to show that pupil dilation is a biosensor for VNS-evoked cortical neuromodulation. In a ‘goldilocks’ zone of stimulation parameters, current leakage and off-target effects are minimized and the extent of pupil dilation tracks VNS-evoked basal-forebrain cholinergic axon activity in auditory cortex. Thus, pupil dilation is a sensitive readout of the moment-by-moment titratable effects of VNS on brain state.

scholarly journals Serum cytokine levels are modulated by specific frequencies, amplitudes, and pulse widths of vagus nerve stimulation

2020 ◽  
Author(s):  
Téa Tsaava ◽  
Timir Datta-Chaudhuri ◽  
Meghan E. Addorisio ◽  
Emily Battinelli Masi ◽  
Harold A. Silverman ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Inflammatory Cytokine ◽  
Serum Cytokine ◽  
Stimulation Parameters ◽  
Cytokine Levels ◽  
Selection Of ◽  
Stimulation Of

ABSTRACTElectrical stimulation of peripheral nerves is a widely used technique to treat a variety of conditions including chronic pain, motor impairment, headaches, and epilepsy. Nerve stimulation to achieve efficacious symptomatic relief depends on the proper selection of electrical stimulation parameters to recruit the appropriate fibers within a nerve. Recently, electrical stimulation of the vagus nerve has shown promise for controlling inflammation and clinical trials have demonstrated efficacy for the treatment of inflammatory disorders. This application of vagus nerve stimulation activates the inflammatory reflex, reducing levels of inflammatory cytokines during inflammation. Here, we wanted to test whether altering the parameters of electrical vagus nerve stimulation would change circulating cytokine levels of normal healthy animals in the absence of increased inflammation. To examine this, we systematically tested a set of electrical stimulation parameters and measured serum cytokine levels in healthy mice. Surprisingly, we found that specific combinations of pulse width, pulse amplitude, and frequency produced significant increases of the pro-inflammatory cytokine tumor necrosis factor alpha (TNFα), while other parameters selectively lowered serum TNFα levels, as compared to sham-stimulated mice. In addition, serum levels of the anti-inflammatory cytokine interleukin-10 (IL-10) were significantly increased by select parameters of electrical stimulation but remained unchanged with others. These results indicate that electrical stimulation parameter selection is critically important for the modulation of cytokines via the cervical vagus nerve and that specific cytokines can be increased by electrical stimulation in the absence of inflammation. As the next generation of bioelectronic therapies and devices are developed to capitalize on the neural regulation of inflammation, the selection of nerve stimulation parameters will be a critically important variable for achieving cytokine-specific changes.

Phosphene perceptions and safety of chronic visual cortex stimulation in a blind subject

2020 ◽  
Vol 132 (6) ◽  
pp. 2000-2007 ◽  
Author(s):  
Soroush Niketeghad ◽  
Abirami Muralidharan ◽  
Uday Patel ◽  
Jessy D. Dorn ◽  
Laura Bonelli ◽  
...  
Keyword(s):  
Visual Cortex ◽  
Adverse Events ◽  
Clinical Intervention ◽  
Occipital Cortex ◽  
Neuronal Population ◽  
Serious Adverse Events ◽  
Stimulation Parameters ◽  
The Right ◽  
Visual Cortical ◽  
Stimulation Of

Stimulation of primary visual cortices has the potential to restore some degree of vision to blind individuals. Developing safe and reliable visual cortical prostheses requires assessment of the long-term stability, feasibility, and safety of generating stimulation-evoked perceptions.A NeuroPace responsive neurostimulation system was implanted in a blind individual with an 8-year history of bare light perception, and stimulation-evoked phosphenes were evaluated over 19 months (41 test sessions). Electrical stimulation was delivered via two four-contact subdural electrode strips implanted over the right medial occipital cortex. Current and charge thresholds for eliciting visual perception (phosphenes) were measured, as were the shape, size, location, and intensity of the phosphenes. Adverse events were also assessed.Stimulation of all contacts resulted in phosphene perception. Phosphenes appeared completely or partially in the left hemifield. Stimulation of the electrodes below the calcarine sulcus elicited phosphenes in the superior hemifield and vice versa. Changing the stimulation parameters of frequency, pulse width, and burst duration affected current thresholds for eliciting phosphenes, and increasing the amplitude or frequency of stimulation resulted in brighter perceptions. While stimulation thresholds decreased between an average of 5% and 12% after 19 months, spatial mapping of phosphenes remained consistent over time. Although no serious adverse events were observed, the subject experienced mild headaches and dizziness in three instances, symptoms that did not persist for more than a few hours and for which no clinical intervention was required.Using an off-the-shelf neurostimulator, the authors were able to reliably generate phosphenes in different areas of the visual field over 19 months with no serious adverse events, providing preliminary proof of feasibility and safety to proceed with visual epicortical prosthetic clinical trials. Moreover, they systematically explored the relationship between stimulation parameters and phosphene thresholds and discovered the direct relation of perception thresholds based on primary visual cortex (V1) neuronal population excitation thresholds.

Tetrodotoxin-resistant release of ATP from superfused rabbit detrusor muscle during electrical field stimulation in the presence of luciferin–luciferase

1984 ◽  
Vol 62 (1) ◽  
pp. 153-156 ◽  
Author(s):  
Archana Chaudhry ◽  
John W. Downie ◽  
Thomas D. White
Keyword(s):  
Action Potentials ◽  
Electrical Field Stimulation ◽  
Detrusor Muscle ◽  
Electrical Field ◽  
Stimulation Parameters ◽  
Rabbit Bladder ◽  
Firefly Luciferin ◽  
Rabbit Urinary Bladder ◽  
Stimulation Of

The present study was carried out to assess the possible role of ATP in the noncholinergic, nonadrenergic transmission in the rabbit urinary bladder. When rabbit detrusor muscle strips were superfused with medium containing firefly luciferin–luciferase and stimulated transmurally at low stimulation parameters, tetrodotoxin-sensitive contractions were obtained but no release of ATP could be detected. However, at somewhat higher stimulation parameters, release of ATP was observed. This release of ATP was not diminished by tetrodotoxin indicating that ATP was not likely released as a result of propagated action potentials in nerves. Because contractions persisted in the presence of tetrodotoxin, it is possible that the ATP might have been released as a result of direct electrical stimulation of the muscle. These results do not support the idea that ATP is released as a neurotransmitter in the rabbit bladder.

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

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jonathan A. Shulgach ◽  
Dylan W. Beam ◽  
Ameya C. Nanivadekar ◽  
Derek M. Miller ◽  
Stephanie Fulton ◽  
...  
Keyword(s):  
Vagus Nerve ◽  
Nerve Fibers ◽  
The Body ◽  
Evoked Responses ◽  
Gi Tract ◽  
Selective Stimulation ◽  
Nerve Cuff ◽  
Cuff Electrodes ◽  
Nerve Cuff Electrodes ◽  
Stimulation Of

AbstractDysfunction 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.

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