Investigating the Brain and the Peripheral Nervous System

27.02.2018 Uncategorized Kommentare geschlossen

With its 86 billion neurons, communicating with each other through about 150 trillion connections the brain is the most complex organ we know. Up until today its diverse functions are far from being understood.

The malfunctions of the brain do already cause about one third of the health care costs in the developed world – a proportion that will only grow in the future. To address this problem it is essential to further explore the functioning of the brain.

The Potential of Neurotechnology

Neurotechnological devices such as electrodes or comprehensive systems for recording and stimulation enable interactions with the brain and the nervous system. In this way neurotechnology helps to gain deeper insights into their functioning and to explore potential therapeutic applications.

The Current State of Research and Technology

Recent research employing – amongst other technologies – the high-resolution °AirRay Grid Electrodes has already shown that the functional organization of the cerebral cortex is much more finely structured than findings based on previous technologies had suggested (Wang et al., 2017; Gierthmuehlen et al., 2014). Knowledge about what brain areas are involved in which body functions is for instance essential for planning surgical procedures on the brain.

Promising results have been provided by the young research field of bioelectronic medicine (link to application Bioelectronic Medicine). In this approach researchers attempt to treat diseases as close as possible to the point of origin by directly interacting with individual nerves with the aid of nerve cuff electrodes like °AirRay Cuff Electrodes.

Closed-loop interactions with the brain have already been tested successfully using for example the CorTec Brain Interchange system (Kohler et al., 2017). Studies based on other technologies have also shown that closed-loop interactions can alter the interconnections of the brain (e.g., Zanos et al., 2018). This can for instance be exploited for restoring body functions after damage to the nervous system (e.g., Ganzer et al., 2018).

Solutions supported by CorTec Technology

CorTec’s °AirRay Grid Electrodes offer novel options for recording and stimulating electrical activity of larger parts of the brain without invading the sensitive brain tissue. The electrode contacts are placed on the surface of the brain tissue and enable communication with the underlying local groups of nerve cells.

The product variant of °AirRay Micro Cuff Electrodes is specially designed to enclose nerves without applying mechanical pressure to them. The electrodes can be used for recording, stimulating as well as for blocking nerves, and thus extend research options to gentle interactions with the peripheral nervous system. At the same time this technology opens up new possibilities for therapeutic applications in the field of bioelectronic medicine.

CorTec’s °AirRay Electrode technology allows manufacturing electrodes with a high density of contacts and in individualized and miniaturized arrangements. This enables investigating neuronal functions in a much more accurate way than with previous electrodes.

Combining the °AirRay Electrodes with the Brain Interchange system offers new possibilities to explore brain-computer interfaces for future clinical applications, e.g. as assistive systems for paralyzed people.

Furthermore, the system can be used to investigate and develop long-term closed-loop interactions with the nervous system: The technology is capable of reacting to the individual physiological condition of the patient adapting its activities to this at any time. These features can be beneficial for a variety of therapies such as for Parkinson’s disease or for epilepsy intervention.

Further Readings

General Background Literature

Scientific Literature

Bioelectronic modulation of carotid sinus nerve activity in the rat: a potential therapeutic approach for type 2 diabetes

Sacramento, J.F., Chew, D.J., Melo, B.F. et al.

Diabetologia (2018) 61: 700. https://doi.org/10.1007/s00125-017-4533-7

 

Mapping the fine structure of cortical activity with different micro-ECoG electrode array geometries.

Wang X, Gkogkidis A, Iljina O, Fiederer L, Henle C, Mader I, Kaminsky J, Stieglitz T, Gierthmuehlen M, Ball T.

J Neural Eng. 2017 Jun 9. doi: 10.1088/1741-2552/aa785e. [Epub ahead of print]

 

Mapping of sheep sensory cortex with a novel microelectrocorticography grid.

Gierthmuehlen M, Wang X, Gkogkidis A, Henle C, Fischer J, Fehrenbacher T, Kohler F, Raab M, Mader I, Kuehn C, Foerster K, Haberstroh J, Freiman TM, Stieglitz T, Rickert J, Schuettler M, Ball T.

J Comp Neurol. 2014 Nov 1;522(16):3590-608. doi: 10.1002/cne.23631. Epub 2014 Jun 16.

 

Evaluation of μECoG electrode arrays in the minipig: experimental procedure and neurosurgical approach.

Gierthmuehlen M, Ball T, Henle C, Wang X, Rickert J, Raab M, Freiman T, Stieglitz T, Kaminsky J.

J Neurosci Methods. 2011 Oct 30;202(1):77-86. doi: 10.1016/j.jneumeth.2011.08.021. Epub 2011 Aug 30.

 

First long term in vivo study on subdurally implanted micro-ECoG electrodes, manufactured with a novel laser technology.

Henle C, Raab M, Cordeiro JG, Doostkam S, Schulze-Bonhage A, Stieglitz T, Rickert J.

Biomed Microdevices. 2011 Feb;13(1):59-68. doi: 10.1007/s10544-010-9471-9.

 

Closed-loop interaction with the cerebral cortex: a review of wireless implant technology

Fabian Kohler, C. Alexis Gkogkidis, Christian Bentler, Xi Wang, Mortimer

Gierthmuehlen , Joerg Fischer, Christian Stolle, Leonhard M. Reindl, Joern Rickert, Thomas

Stieglitz, Tonio Ball & Martin Schuettler (2017)

Brain-Computer Interfaces, 4:3, 146-154, DOI:10.1080/2326263X.2017.1338011

http://www.tandfonline.com/doi/full/10.1080/2326263X.2017.1338011

 

Phase-Locked Stimulation during Cortical Beta Oscillations Produces Bidirectional Synaptic Plasticity in Awake Monkeys.

Zanos S1, Rembado I2, Chen D3, Fetz EE4.

Curr Biol. 2018 Aug 3. pii: S0960-9822(18)30908-4. doi: 10.1016/j.cub.2018.07.009. [Epub ahead of print]

 

Closed-loop interaction with the cerebral cortex using a novel micro-ECoG-based implant: the impact of beta vs. gamma stimulation frequencies on cortico-cortical spectral responses.
Gkogkidis, Alexis C, et al.; Brain-Computer Interfaces (2017), 4:4, 214-224

 

First long term in vivo study on subdurally implanted Micro-ECoG electrodes, manufactured with a novel laser technology
Henle C, Raab M, Doostkam S, Cordeiro J, Schulze-Bonhage A, Stieglitz T, Rickert J (2010)
Biomedical Microdevices (in press) DOI: 10.1007/s10544-010-9471-9

 

Closedloop neuromodulation restores network connectivity and motor control after spinal cord injury.

Ganzer PD, Darrow MJ, Meyers EC, Solorzano BR, Ruiz AD, Robertson NM, Adcock KS, James JT, Jeong HS, Becker AM, Goldberg MP, Pruitt DT, Hays SA, Kilgard MP, Rennaker RL 2nd.Elife. 2018 Mar 13;7. pii: e32058. doi: 10.7554/eLife.32058.

Bioelectronic Medicine

17.10.2017 Uncategorized Kommentare geschlossen

A variety of serious chronic diseases are controlled by the nervous system. Activating or inhibiting peripheral nerves can affect a variety of body functions. This effect can be used for therapeutic treatment – especially in cases where pharmaceuticals are unavailable or insufficiently successful.

The Potential of Neurotechnology

The electric stimulation of nerves for the treatment of diseases provides attractive opportunities for directly interacting with neurophysiological control mechanisms and for tackling complex diseases at their roots. Given that the development of new or improved pharmaceuticals in many cases has been stagnating in recent years this option becomes increasingly important.

The benefits of such a “bioelectronic medicine” (Tracey 2014) are manifold:

  • Electrically influencing nerve activity is a novel treatment modality that can access new mechanisms of action beyond drug treatment.
  • Modulating individual nerves or nerve branches can induce very specific effects and may reduce side effects, e.g. on other body parts.
  • Electrical signals can be immediately effective and exert their action directly at the target location since they bypass the digestive tract.

Bioelectronic medicine could address many up to now only poorly treatable medical problems like chronic and acute inflammatory diseases (e.g. irritable bowel and Crohn’s disease, rheumatoid arthritis, sepsis, lupus), diabetes, hypertension, paralysis, stress, bleeding, obesity and metabolic syndrome and possibly even cancer.

Status of Research and Technology

In recent years a large number of research initiatives have begun to explore and systematically develop possibilities for bioelectronic therapies. Amongst others, the Feinstein Institute in New York and the new company Galvani Bioelectronics, a joint venture of the pharmaceutical company GlaxoSmithKline and the Google life-science subsidiary Verily, are particularly active in this area.

 

First research successes have been achieved in several areas:

  • Bladder emptying:
    Electrical stimulation of the nerves controlling the bladder sphincter could enable paraplegics to achieve better bladder emptying with less risk of infection (Langdale et al., 2016).

 

  • Inflammation:
    Studying neuronal control of inflammatory responses aims to treat chronic (e.g., inflammatory bowel disease) or acute and life-threatening (sepsis) inflammations via electrical stimulation of the corresponding nerves.
    First pilot studies have already shown for example that inflammatory bowel disease can be treated by stimulating the vagus nerve (Kalcun et al., 2017).
  • Restoration of mobility in paralyzes, e.g. after paraplegia:

It is being investigated if electrical stimulation of peripheral motor nerves can restore the mobility of people with spinal cord injury and other paralytic conditions (Tigra et al., 2019).

 

  • High blood pressure:
    Increased blood pressure can be lowered by stimulating the vagus nerve. Nerve signals that provide information about current blood pressure may be used to automatically control the stimulation to the patient’s situation (Secencu et al., 2018).

Solutions supported by CorTec Technology

The °AirRay cuff electrodes by CorTec are made of soft and flexible silicone. In various forms and with variable closing mechanisms, they gently enclose the nerve while ensuring good electrical insulation. They are perfect interfaces to measure the activity of nerves and to modulate their activity through electrical stimulation, both in the short and the long term.

CorTec’s °AirRay electrode technology makes it possible to produce electrodes in individualized and miniaturized forms. With this technology CorTec supports both worldwide pioneering research as well as the development of first therapies with specially adapted °AirRay Cuff electrodes.

Further Readings

Scientific literature

 

Implanted Nerve Electrical Stimulation allows to Selectively Restore Hand and Forearm Movements in Patients with a Complete Tetraplegia

Wafa Tigra, Christine Azevedo, Jacques Teissier, Anthony Gelis, Bertrand Coulet, Jean-Louis Divoux, David Guiraud (2019)

 

The revolutionary  future  of  bioelectronic  medicine.

Bioelectron. Med. 1:1; Tracey KJ. (2014)

 

Phasic activation of the external urethral sphincter increases voiding efficiency in the rat and the cat

Christopher L. Langdale, Warren M. Grill; Experimental Neurology 285 (Pt B) 2016 Nov, 173-181

Neurosurgery. 2017 Nov 1;81(5):N38-N40. doi: 10.1093/neuros/nyx451.

 

Vagal Nerve Stimulation for Inflammatory Bowel Disease.

Kolcun JPG1, Burks SS1, Wang MY1.

 

An Intraneural Electrode for Bioelectronic Medicines for Treatment of Hypertension.

Sevcencu C, Nielsen TN, Struijk JJ.

Neuromodulation. 2018 Feb 14. doi: 10.1111/ner.12758. [Epub ahead of print]

 

Exploring selective neural electrical stimulation for upper limb functions restoration

Tigra, David Guiraud, David Andreu, Bertrand Coulet, Anthony Gelis, Charles Fattal, Pawel Maciejasz, Chloé Picq, Olivier Rossel, Jacques Teissier, Christine Azevedo Coste; European Journalf of Translational Myology 2016 26(2), 161-164

 

Spatial and activity-dependent catecholamine release in rat adrenal medulla under native neuronal stimulation

Kyle Wolf, Georgy Zarkua, ShyueAn Chan, Arun Sridhar, Corey Smith; Physiological Reports Vol. 4, Iss. 27 (2016 ), 1-13

 

Cytokine-specific Neurograms In the Sensory Nerve

Benjamin E. Steinberg, Harold A Silverman, Sergio Robbiati, Manoj K Gunasekaran, Téa Tsaava, Emily Battinelli, Andrew Stiegler, Chad E Bouton, Sangeeta S Chavan, Kevin J Tracey, Patricio T Huerta ; Bioelectronic Medicine 2016, 7-17

Spinal Cord Stimulation

27.03.2018 Uncategorized Kommentare geschlossen

Certain types of chronic pain are caused by irritation of the nervous system. These so-called neuropathic pains often manifest as pain in the lower back or the legs.

According to studies of the German Pain Association e.V. and the German Pain Society e.V.  with 69% back pain is the most common kind of chronic pain. 8 to 10 million Germans live with chronic back pain. The American National Institutes of Health (NIH) estimate that more than 10% of the US population are affected by chronic pain.

The Potential of Neurotechnology

Such pain can often be treated by physiotherapy, surgery, or alternative therapies. In cases where no other therapy is effective in reducing pain electrical stimulation of the spinal cord or the dorsal root ganglia can help (Dones & Levi 2018; Hunter et al., 2018).

For this purpose electrodes are implanted in the space above the spinal cord or in the vicinity of the spinal ganglia and connected to stimulation generators. The electrical stimulation pulses delivered to the tissue provide relief from pain sensation.

Status of Research and Technology

There are already a number of commercially available and clinically approved neurostimulators for spinal cord stimulation. About 15,000 patients receive such an implant every year. Spinal cord stimulation is currently the most commonly used form of neurostimulation.

Some implant systems are already able to work in a so-called closed loop with a small number of channels. In these cases stimulation intensity is adjusted either to the body position (Denison & Litt, 2014) or to measured electrical nerve activity (Russo et al., 2018). At the same time the numbers of channels of the clinically approved systems continuously.

High-channel and more complex closed-loop interactions with the nerve tissue could probably further improve therapeutic efficiency.

Solutions supported by CorTec Technology

The CorTec electrodes, especially the flat °AirRay Grid Electrodes are suitable for spinal cord stimulation. As components of complete systems they can be customized and optimized in high-resolution designs to the application at hand. This provides greater spatial resolution of the area to be stimulated, which can help to hit the pain mediating areas and to develop new and more accurate therapies.

Applying °AirRay electrodes in conjunction with the Brain Interchange System also offers the option of combining specially designed electrode designs with long-term closed-loop pain therapy: The Brain Interchange technology is able to respond to neural activity and adjust the stimulation accordingly.

With its high number of channels, combined with the ability to both record and stimulate at all contacts, the Brain Interchange System provides maximum technical flexibility for a therapy that can adapt to the needs of the patient.

The CorTec °AirRay electrodes can be used in a variety of designs in scientific studies and as components of complete therapeutic systems. The Brain Interchange System is currently under development. Initial clinical pilot studies are in preparation to demonstrate safety and functionality of the system.

Further Readings

Scientific Literature

Spinal Cord Stimulation

Spinal Cord Stimulation for Neuropathic Pain: Current Trends and Future Applications.

Dones I, Levi V.

Brain Sci. 2018 Jul 24;8(8). pii: E138. doi: 10.3390/brainsci8080138. Review.

 

Dorsal root ganglion Stimulation

DRG FOCUS: A Multicenter Study Evaluating Dorsal Root Ganglion Stimulation and Predictors for Trial Success.

Hunter CW, Sayed D, Lubenow T, Davis T, Carlson J, Rowe J, Justiz R, McJunkin T, Deer T, Mehta P, Falowski S, Kapural L, Pope J, Mekhail N.

Neuromodulation. 2018 Aug 7. doi: 10.1111/ner.12796. [Epub ahead of print]

 

Closed-Loop Stimulation

Effective Relief of Pain and Associated Symptoms With Closed-Loop Spinal Cord Stimulation System: Preliminary Results of the Avalon Study.

Russo M, Cousins MJ, Brooker C, Taylor N, Boesel T, Sullivan R, Poree L, Shariati NH, Hanson E, Parker J.

Neuromodulation. 2018 Jan;21(1):38-47. doi: 10.1111/ner.12684. Epub 2017 Sep 18.

 

Closed-loop neurostimulation: the clinical experience.

Sun FT, Morrell MJ.

Neurotherapeutics. 2014 Jul;11(3):553-63. doi: 10.1007/s13311-014-0280-3. Review.

 

Advancing neuromodulation through control systems: a general framework and case study in posture-responsive stimulation.

Denison T, Litt B.

Neuromodulation. 2014 Jun;17 Suppl 1:48-57. doi: 10.1111/ner.12170.