We wish to thank Pradeep Dumpala, DVM PhD, Sarah Blair, MA, and the husbandry staff at SUNY Upstate Medical University for their dedication and attention to caring for the rabbits. NIH-NINDS (1R61NS133273), Department of Pharmacology, SUNY Upstate Medical University

Continuous EEG/ECG Recordings in Rabbits Using Subdermal Electrode Placement

<ol><li>Bosinski, C., Wagner, K., Zhou, X., Liu, L., Auerbach, D. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Multi-system+monitoring+for+identification+of+seizures%2C+arrhythmias+and+apnea+in+conscious+restrained+rabbits%5BTitle%5D)+AND+%22J+Vis+Exp%22%5BJournal%5D)">Multi-system monitoring for identification of seizures, arrhythmias and apnea in conscious restrained rabbits.</a> J Vis Exp. (169), e62256(2021).</li>
<li>Finlay, M. C., Lambiase, P. D., Ben-Simon, R., Taggart, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Effect+of+mental+stress+on+dynamic+electrophysiological+properties+of+the+endocardium+and+epicardium+in+humans%5BTitle%5D)+AND+%22Heart+Rhythm%22%5BJournal%5D)">Effect of mental stress on dynamic electrophysiological properties of the endocardium and epicardium in humans.</a> Heart Rhythm. 13 (1), 175-182 (2016).</li>
<li>Shen, M. J., Zipes, D. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Role+of+the+autonomic+nervous+system+in+modulating+cardiac+arrhythmias%5BTitle%5D)+AND+%22Circulation+Res%22%5BJournal%5D)">Role of the autonomic nervous system in modulating cardiac arrhythmias.</a> Circulation Res. 114 (6), 1004-1021 (2014).</li>
<li>Xu, L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Juvenile+myoclonic+epilepsy+and+sleep%5BTitle%5D)+AND+%22Epilepsy+Behav%22%5BJournal%5D)">Juvenile myoclonic epilepsy and sleep.</a> Epilepsy Behav. 80, 326-330 (2018).</li>
<li>Bazil, C. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Seizure+modulation+by+sleep+and+sleep+state%5BTitle%5D)+AND+%22Brain+Res%22%5BJournal%5D)">Seizure modulation by sleep and sleep state.</a> Brain Res. 1703, 13-17 (2019).</li>
<li>Ryan, J. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Heart+rate+and+autonomic+biomarkers+distinguish+convulsive+epileptic+vs.+Functional+or+dissociative+seizures%5BTitle%5D)+AND+%22Seizure%22%5BJournal%5D)">Heart rate and autonomic biomarkers distinguish convulsive epileptic vs. Functional or dissociative seizures.</a> Seizure. 111, 178-186 (2023).</li>
<li>Brunner, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Mechanisms+of+cardiac+arrhythmias+and+sudden+death+in+transgenic+rabbits+with+long+QT+syndrome%5BTitle%5D)+AND+%22J+Clin+Invest%22%5BJournal%5D)">Mechanisms of cardiac arrhythmias and sudden death in transgenic rabbits with long QT syndrome.</a> J Clin Invest. 118, 2246-2259 (2008).</li>
<li>Edwards, A. G., Louch, W. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Species-dependent+mechanisms+of+cardiac+arrhythmia%3A+A+cellular+focus%5BTitle%5D)+AND+%22Clin+Med+Insights+Cardiol%22%5BJournal%5D)">Species-dependent mechanisms of cardiac arrhythmia: A cellular focus.</a> Clin Med Insights Cardiol. 11, 1179546816686061(2017).</li>
<li>Kaha Sciences. , Ad instruments. 
 <a target="_blank" href="http://https://www.adinstruments.com/kaha?creative=524197312959&keyword=kaha%20telemetry&matchtype=e&network=g&device=c&gad_source=1&gclid=CjwKCAjw8fu1BhBsEiwAwDrsjJLJeUjMCwMe-kCxFg2QdpP94gaAOd8qS6UBE6iU-IdP2XGxMvbT7hoCDZAQAvD_BwE">http://https://www.adinstruments.com/kaha?creative=524197312959&keyword=kaha%20telemetry&matchtype=e&network=g&device=c&gad_source=1&gclid=CjwKCAjw8fu1BhBsEiwAwDrsjJLJeUjMCwMe-kCxFg2QdpP94gaAOd8qS6UBE6iU-IdP2XGxMvbT7hoCDZAQAvD_BwE</a> (2024).</li>
<li>Stellar telemetry. , TSE Systems. 
 <a target="_blank" href="https://www.tse-systems.com/products/stellar-implantable-telemetry/">https://www.tse-systems.com/products/stellar-implantable-telemetry/</a> (2024).</li>
<li>Dsi implantable telemetry. , DSI. 
 <a target="_blank" href="https://www.datasci.com/products/implantable-telemetry">https://www.datasci.com/products/implantable-telemetry</a> (2024).</li>
<li>Stellar telemetry. , Kruuse televet ii, telemetric ecg & holter. 
 <a target="_blank" href="https://kruuse.com/products/consultation/examination/ekg/kruuse-televet-ii-telemetric-ecg-holter">https://kruuse.com/products/consultation/examination/ekg/kruuse-televet-ii-telemetric-ecg-holter</a> (2024).</li>
<li>Mishra, V., Gautier, N. M., Glasscock, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Simultaneous+Video-EEG-ECG+monitoring+to+identify+neurocardiac+dysfunction+in+mouse+models+of+epilepsy%5BTitle%5D)+AND+%22J+Vis+Exp%22%5BJournal%5D)">Simultaneous Video-EEG-ECG monitoring to identify neurocardiac dysfunction in mouse models of epilepsy.</a> J Vis Exp. (131), 57300(2018).</li>
<li>eeg/emg systems. , Pinnacle technology. 
 <a target="_blank" href="https://www.pinnaclet.com/eeg-emg-systems.html">https://www.pinnaclet.com/eeg-emg-systems.html</a> (2024).</li>
</ol>

The authors have nothing to disclose. A portion of the information contained within this manuscript is also present in the first author's Master's thesis (Laura Williams) with suitable permission.

We present a detailed protocol for the generation of a custom wire harness, the in-house fabrication of an implant, and the procedure for the sterile implantation of the EEG/ECG electrodes, wires, and port. This setup facilitates the collection of continuous, high quality EEG/ECG recordings in an efficient, safe, and financially feasible way. This protocol generates a system in which both EEG and ECG data can be collected in rabbits without the need for restrainers or&#160;constant supervision. Continuous long-term EEG a...

We previously developed a protocol to collect acute (&#60; 5 h) video/EEG/ECG recordings from rabbits. It involves the use of nine subdermal EEG and ECG pin electrodes, placement of the rabbit in a restrainer, and the investigator closely monitoring the rabbit for the entire duration of the recording1. While this system provides high-quality video/EEG/ECG recordings, it has several limitations. Arrhythmias, epileptic seizures, and other EEG/ECG abnormalities may be triggered by various physiological and environmental substrates, so these events may be missed when conducting intermittent recordings. Thus, this recording platform does not facilitate comprehensive and accurate assessments of neuro-cardiac electrical function throughout the day, during various physiological states, or in the rabbits&#39; normal housing environment.
Continuous video/EEG/ECG monitoring is important for evaluating cardiac and neuronal electrical function during various physiological states. It facilitates accurate assessment&#160;of the prevalence and incidence of epileptiform activity and arrhythmias, as well as the concordance and progression of multi-system changes surrounding episodic events. For example, circadian fluctuations in autonomic function, as well as stress and activity-mediated autonomic changes, greatly influence heart rate and ECG metrics and can provide a trigger for arrhythmias2,3. In certain types of epilepsy (e.g., juvenile myoclonic epilepsy), seizures are more likely to occur during sleep or within 1-2 h of waking up4. The dynamic changes in electrical activity in the brain during sleep can influence the susceptibility, origin, and spread of seizures5.
Stress, activity, and motor seizures can cause muscle artifacts and dislodgement of the electrodes, which influences the quality and stability of the recordings. In particular, during pro-convulsant studies, rabbits experience myoclonic, clonic, tonic, and clonic-tonic seizures. The tonic phase involves the involuntary extension of the neck, which can dislodge the pin electrodes and thus interrupt the signal during a critical phase of the experiment. As such, the temporary system involving pin electrodes has critical limitations that must be addressed. Moreover, as the rabbits are in a restrainer, documenting the full extent of the motor manifestations is difficult.
Therefore, it is important to develop a procedure to implant electrodes for long-term continuous and stable multi-system recordings when the animal is in its normal unrestrained environment. This will facilitate detailed assessments during a wide range of physiological states and in response to environmental triggers. It will also be valuable for capturing rare episodic events. As the setup does not require the investigator to be present during the recording, it increases the efficiency and throughput of the research platform. It also minimizes the frequency of people disturbing the rabbits. Finally, as this procedure allows for the animals to stay in their natural housing environment throughout the recording, it improves the quality of life for the rabbits and improves overall animal welfare.

<table><tbody><tr><td>3:1 heat shrink wrap with adhesive</td><td>N/A</td><td>Wirefly</td><td>Adhesive lined polyolefin tubing designed to shrink 1/3 diameter when heated. Isolate electrodes when connecting wires and plugs, connecting pieces of the wire harness together</td></tr><tr><td>Absorbent Pads</td><td>-</td><td>any</td><td>Absorbent pads for Fluid collection</td></tr><tr><td>BD E-Z Scrub 116 Surgical Scrub Brush/Sponge</td><td>371163</td><td>BD E-Z Scrub</td><td>3% PCMX Surgical Scrub Brush/Sponge To scrub prior to operating for aseptic technique</td></tr><tr><td>Biopsy Punches</td><td>1315</td><td>ARGENT, McKesson</td><td>6 mm circular cutting blade for circular incision for port</td></tr><tr><td>Buprenorphine</td><td>-</td><td>-</td><td>0.3 mg/mL Buprenorphine For post-operative pain control</td></tr><tr><td>Butt connectors</td><td>X003C7S38P</td><td>SVAAR</td><td>Tinned copper butt splice 26-22 AWG non-insulated butt connectors Connecting carbon fiber wires from the electrodes to the plug</td></tr><tr><td>Cautery Pen</td><td>https://jorvet.com/product/cautery-kit-accessories/</td><td>Jorgensen Laboratories, Inc.</td><td>Hand-held Bovie Cautery Pen For controlling bleeding</td></tr><tr><td>Coaxial cable through-wall bushing</td><td>COAX BUSH WH</td><td>Commercial Electric</td><td>Plastic bushing with 6.9mm inner diameter opening and 1cm+ post Wire port</td></tr><tr><td>Cohesiant Wrap</td><td>https://healthypets.com/vetone-cohesiant-wrap-blue-2x5yd/</td><td>AmerisourceBergen</td><td>4in x 5yd self-adherent wrap For post-operative wound protection</td></tr><tr><td>Disposable Scalpel with Handle</td><td>https://www.securos.com/</td><td>Securos Surgical AmerisourceBergen</td><td>Sterile disposable scalpels For making incisions</td></tr><tr><td>Electrical Slip Ring</td><td></td><td>Taidacent</td><td>High Speed Ball Conductive Slip Ring 12 way 2A Collector ring rotary joint rotary connector, Electrical slip ring to allow free movement of animal without binding up the wire harness</td></tr><tr><td>Eye lube pro</td><td>https://domespharma.us/eye-lube-pro-detailer-final-v6/</td><td>Sentrx</td><td>Lubricating Gel Prevents eye drying/damage during anesthesia</td></tr><tr><td>GLUture</td><td>503763</td><td>World Precision Instrument</td><td>Topical Tissue Adhesive For closure of incision sites&amp;nbsp;</td></tr><tr><td>Isoflurane</td><td>ANADA # 200-129</td><td>Isospire</td><td>Isoflurane For anesthesia</td></tr><tr><td>Isopropyl alcohol</td><td>500205</td><td>VETone</td><td>70% isopropyl alcohol Topical antiseptic</td></tr><tr><td>Jet Liquid</td><td>1403</td><td>Lang Dental Mfg. Co., Inc.</td><td>Fast curing acrylic resin liquid Dental acrylic resin liquid for sealing the bushing and the wires for the wire exit port.&amp;nbsp; Also used to seal the port to the skin.</td></tr><tr><td>Jet Tooth Shade Powder</td><td>1420</td><td>Lang Dental Mfg. Co., Inc.</td><td>Fast curing provisional crown and bridge acrylic resin powder. Dental acrylic powder for sealing the bushing and the wires for the wire exit port.&amp;nbsp; Also used to seal the port to the skin.</td></tr><tr><td>Ketamine</td><td>-</td><td>-</td><td>100 mg/mL Ketamine For sedation</td></tr><tr><td>Metal shower sheathing</td><td>HOS-960M</td><td>Waterpik</td><td>Ultra-Flexible Replacement Metal Shower Hose, Extra Long for Handheld Shower Heads, 96-inch, Chrome Metal sheathing for wire harness</td></tr><tr><td>MR Conditional/CT Electrodes Array and Extension Set</td><td>MRQW32415</td><td>RhythmLink</td><td>Quick connect system with male-female plugs and 8 leads. Plugs used for port-wire harness connection.&amp;nbsp; Wires and DIN connectors used for the wire harness</td></tr><tr><td>Polypropylene Blue Monofilament Sutures</td><td>P8665</td><td>SECUROPRO</td><td>3-0, FS-2, 18&amp;rdquo; reverse cutting suture. Close any surgical incisions</td></tr><tr><td>Retractor cable</td><td>&amp;lrm;0487-013</td><td>West Coast Manufacturing Company</td><td>Industrial Retractable Reel with 48&quot; Stainless Steel Cable, Steel Bracket Back, Chrome Front, 8 oz. Retraction, Plastic Hose Clamp. Pulls excess wire harness up and away from animal</td></tr><tr><td>Rubber gasket</td><td>E-3603 NSF-51</td><td>Saint Gobain</td><td>Clear rubber tubing cut to 1.5 cm width. Gasket for protection/maintaining a seal.&amp;nbsp;</td></tr><tr><td>Small Webb Electrodes</td><td>SWEBB1215</td><td>RhythmLink</td><td>6mm, flat disc [WEBB*] electrode, silver-chloride, wire, Subdermal electrodes</td></tr><tr><td>Sterile Latex Surgical Gloves</td><td>10122</td><td>AmerisourceBergen</td><td>Sterile Latex Gloves, Powder-Free, Donned for sterile surgical technique</td></tr><tr><td>Sterile marker</td><td>DYNJSM01</td><td>Medline</td><td>Sterile Marker, Mark incision/electrode sites&amp;nbsp;</td></tr><tr><td>Sterile surgical drapes with adhesive</td><td>-</td><td>any</td><td>Sterile surgical drapes with adhesive strip on one side, Create a fixed sterile field&amp;nbsp;</td></tr><tr><td>Veterinary anesthesia masks</td><td>-</td><td>any</td><td>Plastic cones with rubber gaskets to seal over rabbit&amp;rsquo;s face. Various sizes. Delivery of inhaled anesthesia</td></tr><tr><td>Veterinary Betadine Surgical Scrub</td><td>NDC 67618-154-16</td><td>Betadine</td><td>Povidone-iodine, 7.5%, Antiseptic Sudsing Skin Cleanser</td></tr><tr><td>Xylazine</td><td>-</td><td>-</td><td>100 mg/mL Xylazine, For sedation</td></tr></tbody></table>

surgical implant procedure and wiring configuration for continuous long-term eeg/ecg monitoring in rabbits

A multi-system approach that includes the continuous collection of electroencephalogram (EEG) and electrocardiogram (ECG) recordings facilitates a comprehensive assessment of electrical activity in the brain and heart, particularly leading up to and surrounding episodic events. Building on our previous protocol that facilitates the collection of intermittent EEG/ECG recordings from conscious restrained rabbits, we developed a protocol for the collection of continuous EEG/ECG recordings from unrestrained rabbits. This new method enables high-quality 24/7 recordings in the housing cage, which captures the normal range of physiological states and enables the rabbits to move, eat, drink, and sleep freely. It enables comprehensive assessments of the prevalence, incidence, and susceptibility to EEG/ECG abnormalities, seizures, arrhythmias, and sudden death. This procedure involves the surgical placement of subdermal electrodes and the design and manufacturing of a robust wiring system that is impervious to damage by the rabbits. The surgical procedure includes two incisions and the sub-dermal tunneling of nine electrodes and wires that exit through a custom-made port. The external connector attaches to a wire harness that includes an electrical swivel, which allows for&#160;free range of rabbit motion throughout its cage. Additionally, the wires are enclosed in a metal sheath suspended by a retractor cable from the ceiling of the rabbit&#39;s cage. The wires are then connected to an amplifier/digitizer for the acquisition of high-quality continuous EEG/ECG recordings.

Using this surgical technique, there were not any cases of mortality during or after the surgery. There is a risk of infection and incomplete wound healing, particularly if the rabbit scratches or bites at the incision site. Pre-/post-operative antibiotics, covering the incision with a dry sterile piece of gauze, and fitting the rabbit with a vest help protect the surgical site and allow for better healing. All recordings are conducted in the rabbit&#39;s standard housing cage, which is w...

Surgical Implant Procedure and Wiring Configuration for Continuous Long-Term EEG/ECG Monitoring in Rabbits

The study outlines a protocol for the design, manufacturing, and placement of a novel continuous EEG/ECG recording system in rabbits. This hard-wired system allows for continuous EEG/ECG recordings from nine distinct electrodes on the head and chest, which facilitates comprehensive assessments of electrical activity in the brain and heart.

A multi-system approach that includes the continuous collection of electroencephalogram (EEG) and electrocardiogram (ECG) recordings facilitates a ...

surgical-implant-procedure-wiring-configuration-for-continuous-long

Research

JoVE Journal

Medicine

393 Views.  SUNY Upstate Medical University. Met behulp van continue EEG- en ECG-opnames is het doel van het onderzoek om tegelijkertijd de elektrische activiteit in zowel de hersenen als het hart te monitoren. Dit biedt een platform om ons in staat te stellen de multisysteemcascade van gebeurtenissen rond hartritmestoornissen, epileptische aanvallen en uiteindelijk leidend tot een plotselinge dood te onderzoeken. Dit registratiesysteem verkrijgt 24/7 EEG's en ECG's van meerdere ongeremde konijnen tijde...

Video: Chirurgische implantaatprocedure en bedradingsconfiguratie voor continue langdurige EEG/ECG-monitoring bij konijnen

Implantation and Recording of Wireless Electroretinogram and Visual Evoked Potential in Conscious Rats

The full-field electroretinogram (ERG) and visual evoked potential (VEP) are useful tools to assess retinal and visual pathway integrity in both laboratory and clinical settings. Currently, preclinical ERG and VEP measurements are performed with anesthesia to ensure stable electrode placements. However, the very presence of anesthesia has been shown to contaminate normal physiological responses. To overcome these anesthesia confounds, we develop a novel platform to assay ERG and VEP in conscious rats. Electrodes are surgically implanted sub-conjunctivally on the eye to assay the ERG and epidurally over the visual cortex to measure the VEP. A range of amplitude and sensitivity/timing parameters are assayed for both the ERG and VEP at increasing luminous energies. The ERG and VEP signals are shown to be stable and repeatable for at least 4 weeks post surgical implantation. This ability to record ERG and VEP signals without anesthesia confounds in the preclinical setting should provide superior translation to clinical data.

We show surgical implantation and Recording procedures to measure visual electrophysiological signals from the eye (electroretinogram) and brain (visual evoked potential) in conscious rats, which is more analogous to the human condition where recordings are conducted without anesthesia confounds.

The full-field electroretinogram (ERG) and visual evoked potential (VEP) are useful tools to assess retinal and visual pathway integrity in both ...

Behavior

Long-term Continuous EEG Monitoring in Small Rodent Models of Human Disease Using the Epoch Wireless Transmitter System

Many progressive neurologic diseases in humans, such as epilepsy, require pre-clinical animal models that slowly develop the disease in order to test interventions at various stages of the disease process. These animal models are particularly difficult to implement in immature rodents, a classic model organism for laboratory study of these disorders. Recording continuous EEG in young animal models of seizures and other neurological disorders presents a technical challenge due to the small physical size of young rodents and their dependence on the dam prior to weaning. Therefore, there is not only a clear need for improving pre-clinical research that will better identify those therapies suitable for translation to the clinic but also a need for new devices capable of recording continuous EEG in immature rodents. Here, we describe the technology behind and demonstrate the use of a novel miniature telemetry system, specifically engineered for use in immature rats or mice, which is also effective for use in adult animals.

Here we demonstrate the use of a wireless enabling technology for electroencephalogram (EEG) in neonatal rodent models of human disease. With telemetry, there are no encumbering connections, thus allowing natural behaviors.

Many progressive neurologic diseases in humans, such as epilepsy, require pre-clinical animal models that slowly develop the disease in order to test ...

Neuroscience

Simultaneous Recordings of Cortical Local Field Potentials, Electrocardiogram, Electromyogram, and Breathing Rhythm from a Freely Moving Rat

Monitoring the physiological dynamics of the brain and peripheral tissues is necessary for addressing a number of questions about how the brain controls body functions and internal organ rhythms when animals are exposed to emotional challenges and changes in their living environments. In general experiments, signals from different organs, such as the brain and the heart, are recorded by independent recording systems that require multiple recording devices and different procedures for processing the data files. This study describes a new method that can simultaneously monitor electrical biosignals, including tens of local field potentials in multiple brain regions, electrocardiograms that represent the cardiac rhythm, electromyograms that represent awake/sleep-related muscle contraction, and breathing signals, in a freely moving rat. The recording configuration of this method is based on a conventional micro-drive array for cortical local field potential recordings in which tens of electrodes are accommodated, and the signals obtained from these electrodes are integrated into a single electrical board mounted on the animal's head. Here, this recording system was improved so that signals from the peripheral organs are also transferred to an electrical interface board. In a single surgery, electrodes are first separately implanted into the appropriate body parts and the target brain areas. The open ends of all of these electrodes are then soldered to individual channels of the electrical board above the animal's head so that all of the signals can be integrated into the single electrical board. Connecting this board to a recording device allows for the collection of all of the signals into a single device, which reduces experimental costs and simplifies data processing, because all data can be handled in the same data file. This technique will aid the understanding of the neurophysiological correlates of the associations between central and peripheral organs.

This study introduces a method for the simultaneous recording of local field potentials in the brain, electrocardiograms, electromyograms, and breathing signals of a freely moving rat. This technique, which reduces experimental costs and simplifies data analysis, will contribute to the understanding of the interactions between the brain and peripheral organs.

Monitoring the physiological dynamics of the brain and peripheral tissues is necessary for addressing a number of questions about how the brain controls ...

Subdural Soft Electrocorticography (ECoG) Array Implantation and Long-Term Cortical Recording in Minipigs

Neurological impairments and diseases can be diagnosed or treated using electrocorticography (ECoG) arrays. In drug-resistant epilepsy, these help delineate the epileptic region to resect. In long-term applications such as brain-computer interfaces, these epicortical electrodes are used to record the movement intention of the brain, to control the robotic limbs of paralyzed patients. However, current stiff electrode grids do not answer the need for high-resolution brain recordings and long-term biointegration. Recently, conformable electrode arrays have been proposed to achieve long-term implant stability with high performance. However, preclinical studies for these new implant technologies are needed to validate their long-term functionality and safety profile for their translation to human patients. In this context, porcine models are routinely employed in developing medical devices due to their large organ sizes and easy animal handling. However, only a few brain applications are described in the literature, mostly due to surgery limitations and integration of the implant system on a living animal.
Here, we report the method for long-term implantation (6 months) and evaluation of soft ECoG arrays in the minipig model. The study first presents the implant system, consisting of a soft microfabricated electrode array integrated with a magnetic resonance imaging (MRI)-compatible polymeric transdermal port that houses instrumentation connectors for electrophysiology recordings. Then, the study describes the surgical procedure, from subdural implantation to animal recovery. We focus on the auditory cortex as an example target area where evoked potentials are induced by acoustic stimulation. We finally describe a data acquisition sequence that includes MRI of the whole brain, implant electrochemical characterization, intraoperative and freely moving electrophysiology, and immunohistochemistry staining of the extracted brains.
This model can be used to investigate the safety and function of novel design of cortical prostheses; mandatory preclinical study to envision translation to human patients.

Subdural Soft Electrocorticography ECoG Array Implantation and Long-Term Cortical Recording in Minipigs

Here, we present a method for the long-term performance and safety assessment of soft subdural electrode arrays in a minipig model, describing surgical method and tools, postoperative magnetic resonance imaging, electrophysiology of the auditory cortex, electrochemical properties of the implant, and postmortem immunochemistry.

Neurological impairments and diseases can be diagnosed or treated using electrocorticography (ECoG) arrays. In drug-resistant epilepsy, these help ...

Bioengineering

Multi-system Monitoring for Identification of Seizures, Arrhythmias and Apnea in Conscious Restrained Rabbits

Patients with ion channelopathies are at a high risk of developing seizures and fatal cardiac arrhythmias. There is a higher prevalence of heart disease and arrhythmias in people with epilepsy (i.e., epileptic heart.) Additionally, cardiac and autonomic disturbances have been reported surrounding seizures. 1:1,000 epilepsy patients/year die of sudden unexpected death in epilepsy (SUDEP). The mechanisms for SUDEP remain incompletely understood. Electroencephalograms (EEG) and electrocardiograms (ECG) are two techniques routinely used in the clinical setting to detect and study the substrates/triggers for seizures and arrhythmias. While many studies and descriptions of this methodology are in rodents, their cardiac electrical activity differs significantly from humans. This article provides a description of a non-invasive method for recording simultaneous video-EEG-ECG-oximetry-capnography in conscious rabbits. As cardiac electrical function is similar in rabbits and humans, rabbits provide an excellent model of translational diagnostic and therapeutic studies. In addition to outlining the methodology for data acquisition, we discuss the analytical approaches for examining neuro-cardiac electrical function and pathology in rabbits. This includes arrhythmia detection, spectral analysis of EEG and a seizure scale developed for restrained rabbits.

Using simultaneous video-EEG-ECG-oximetry-capnography, we developed a methodology to evaluate the susceptibility of rabbit models to develop provoked arrhythmias and seizures. This novel recording system establishes a platform to test the efficacy and safety of therapeutics and can capture the complex cascade of multi-system events that culminate in sudden death.

Patients with ion channelopathies are at a high risk of developing seizures and fatal cardiac arrhythmias. There is a higher prevalence of heart disease ...

Implantation of Electroencephalogram and Electrocardiogram Telemetry Devices in Neonatal Rabbit Kits

Pathogenic variants in ion channel genes are associated with a high rate of sudden unexpected death in epilepsy (SUDEP). Mechanisms of SUDEP are poorly understood but may involve autonomic dysfunction and cardiac arrhythmias in addition to seizures. Some ion-channel genes are expressed in both the brain and the heart, potentially increasing the risk of SUDEP in patients with ion-channelopathies associated with epilepsy and cardiac arrhythmias. Transgenic rabbits expressing epilepsy variants provide a whole organism to study the complex physiology of SUDEP. Importantly, rabbits more closely replicate human cardiac physiology than do mouse models. However, rabbit models have additional health and anesthesia considerations when undergoing invasive monitoring procedures. We have developed a novel method to surgically implant a telemetry device for long-term simultaneous electroencephalogram (EEG) and electrocardiogram (ECG) monitoring in neonatal rabbit kits. Here, we demonstrate surgical methods to implant a telemetry device in P14 (weight range 175-250 g) kits with detailed attention to surgical approach, appropriate anesthesia and monitoring, and postoperative care, resulting in a low complication rate. This method allows for continuous monitoring of neural and cardiac electrophysiology during critical points in the development of cardiac arrhythmias, seizures, and potential SUDEP in rabbit models of genetic or acquired epilepsies.

Mechanisms of sudden unexpected death in epilepsy (SUDEP) are poorly understood and challenging to translate from current models. Transgenic rabbits may offer insights into these mechanisms. We describe a method for long-term, continuous electroencephalography and electrocardiography recordings in transgenic rabbit kits to evaluate serious events that may lead to death.

Pathogenic variants in ion channel genes are associated with a high rate of sudden unexpected death in epilepsy (SUDEP). Mechanisms of SUDEP are poorly ...

Multisystem Monitoring of Epileptic Abnormalities in Rabbit: A Method for Simultaneous Video EEG, ECG, Capnography, and Oximetry Recording During Induced Seizures

Source: Bosinski, C., et al. <a href="https://www.jove.com/v/62256">Multi-system Monitoring for Identification of Seizures, Arrhythmias and Apnea in Conscious Restrained Rabbits.</a> J. Vis. Exp. (2021).
In this video, we demonstrate a multisystem monitoring method to evaluate neurological and cardiorespiratory abnormalities during intravenous injection of a seizure-inducing drug. The simultaneous monitoring of video EEG, ECG, oximetry, and capnography parameters helps to understand the real-time physiological changes associated with epileptic seizures.

Source: Bosinski, C., et al. Multi-system Monitoring for Identification of Seizures, Arrhythmias and Apnea in Conscious Restrained Rabbits. J. Vis. Exp. ...

JoVE Encyclopedia of Experiments

Biology

Large Animal Models

Leporine

Subdural Implantation of a Soft Electrocorticography Array for Cortical Electrophysiology Recording in Minipigs

Source: Fallegger, F. et al., <a href="https://app.jove.com/v/64997">Subdural Soft Electrocorticography (ECoG) Array Implantation and Long-Term Cortical Recording in Minipigs.</a>&#160;J. Vis. Exp. (2023).
This video demonstrates the implantation of a soft electrocorticography array and the long-term cortical recordings in a minipig. It outlines the steps involved in surgically implanting the array over the minipig&#39;s auditory cortex and recording both baseline and sound stimulus-evoked neuronal action potentials.

All procedures involving animal models have been reviewed by the local institutional animal care committee and the JoVE veterinary review board.
1. ...

Neurophysiology

Electrophysiology Techniques

Implanting an On-Head Electrode System in a Rat Model for Real-Time Seizure Detection

Source: Koz&#225;k, G., et al. <a href="https://app.jove.com/v/56669">Chronic Transcranial Electrical Stimulation and Intracortical Recording in Rats.</a> J. Vis. Exp. (2018).
This video demonstrates the method of implanting an on-head electrode system in an anesthetized rat for real-time seizure detection. The procedure includes placing stimulation and recording electrodes, securing them with dental cement, and connecting them to a head-mounted amplifier.

Prepping Conscious Rabbit Model for Simultaneous Video-EEG-ECG-Oximetry-Capnography for Experimental Interventions: A Procedure to Implant EEE-ECG Electrodes and Attach Respiratory Probes in Rabbit Model

For implantation of the ECG electrodes, secure a rabbit in the supine position with the head at the investigator&#39;s knees and lower than the rest of its body. With a second investigator spreading the fur to expose the underlying skin, subdermally insert 35-degree angle bent electrodes into each axilla. Place leads on the chest, posterior to the right and left forelimbs, and on the abdomen, anterior to the left hind limb. Then, place a ground pin-electrode anterior to the right hind limb on the abdomen.
When all of the ECG leads have been properly placed, secure the rabbit in an appropriately-sized restrainer, with the hind limbs under the animal. Using a 45-degree angle approach, insert subdermal straight pin-electrodes into the scalp.
Place one EEG lead on the right anterior, left anterior, right occipital, and left occipital regions of the head, and place a central reference lead at the central point between the other four leads. Run the wires between the ears, and loosely tether them to the restrainer behind the head.
To monitor respiration during the experiment, attach a pulse oximeter to one ear over the marginal ear vein, and gently secure a face mask with capnography tubing over the mouth and nose of the animal. Then, attach the other end of the tubing to the vital signs monitor.
To record video EEG ECG, open an appropriate commercially available EEG software program, and adjust the video such that all of the rabbits can be observed within the field of view. Perform a baseline recording for the animal for a minimum of 10 to 20 minutes or until the heart rate stabilizes to 200 to 250 beats per minute for at least five minutes. Set the low-frequency filter to 1 Hertz and the high-frequency filter to 59 Hertz.
Add time-locked notes in real-time to indicate the timing of interventions, neurocardiac events, and motor or investigator artifacts.

Surgical Implant Procedure and Wiring Configuration for Continuous Long-Term EEG/ECG Monitoring in Rabbits

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