Investigating the Brain and the Peripheral Nervous System
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.
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.
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).
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.
– for seizure control in Epilepsy
Epilepsy is one of the most common neurological disorders. Approximately 1% of all people experience one or more epileptic seizures during their lifetime. The symptoms of these seizures vary ranging from short mental “absences” to the dreaded “grand mal” attacks, accompanied by falls and uncontrolled twitching.
Since seizures are usually unpredictable those affected live in constant fear and are significantly impaired in their everyday lives. Many epilepsy patients are not allowed to drive a car or operate certain machines because of the constant danger of a seizure.
The cause of epilepsy are states of excessive excitation in the brain that reinforce each other until it comes to a simultaneous discharge of many nerve cells which can affect large parts of the brain. In this state the brain can no longer function normally nor process information or control movements.
Drug therapies for the treatment of epilepsy have existed for a long time, but fail or work only insufficiently in about one third of all epilepsy patients (Pohlmann-Eden & Weaver, 2013). Also, the existing drugs are commonly associated with side effects during their continued use.
With the help of targeted electrical stimulation, the spread of uncontrolled states of excitation in the brain can be contained. This way a beginning epileptic seizure can be interrupted or even prevented (Hartshorn & Jobst 2018). Crucial for such a therapeutic approach, however, is an early and reliable detection of seizure onset, which can then serve as a trigger for stimulation.
Constant deep brain stimulation with clinically approved systems is already used in some types of epilepsy (e.g., Krishna et al., 2016). However, this approach is not adaptable to the therapeutic needs of the patient.
For a demand-dependent stimulation of the cerebral cortex that intercepts emerging seizures through a closed-loop interaction with the brain up to date only one neurostimulation system exists (Geller et al., 2017). This device, however, has a small number of channels and can only perform very simple analyses of brain activity so that a treatment precisely tailored to the needs of an individual patient is not yet possible.
A more flexible, high-channel closed-loop interaction with the brain, in which more complex brain signals can be evaluated online could significantly improve therapeutic success.
The flat °AirRay Grid electrodes by CorTec can record and stimulate brain activity. They are especially well suited for this application since they can be custom made in high channel designs and tailored to the specific patient. They are especially useful, if they are employed as components in a complete neuromodulation device.
The combination of the °AirRay electrodes with the Brain Interchange System also offers the option of combining specially designed electrode designs with long-term closed-loop therapy: The Brain Interchange technology is able to respond to the physiological state of the patient and adjust the stimulation accordingly. It could thus be used to detect emerging epileptic seizures and control or even prevent them with timely stimulation impulses.
With its high number of channels, along with the ability to both record and stimulate at all contacts, the Brain Interchange System offers unprecedented technical flexibility for a therapy that is specifically tailored to the needs of the patient.
The CorTec °AirRay Grid electrodes can be produced in a wide range of designs and can be applied in scientific studies and as components of complete therapeutic systems. The Brain Interchange System is currently still under development. Initial clinical pilot studies are in preparation to demonstrate safety and functionality of the system.
General background literature
Miniature electroparticle-cuff for wireless peripheral neuromodulation
Hernandez-Reynoso, Ana G. et al.; J. Neural Eng. 2019 16 046002
Identification of hypoglycemia-specific neural signals by decoding murine vagus nerve activity
Masi, Emiliy Battinelli et al.; Bioelectronic Medicine (2019) 5:9
Signal quality of simultaneously recorded endovascular, subdural and epidural signals are comparable
John, Sam E. et al.; Scientific Reports (2018) 8:8427
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
Phase-Locked Stimulation during Cortical Beta Oscillations Produces Bidirectional Synaptic Plasticity in Awake Monkeys.
Zanos S, Rembado I, Chen D, Fetz EE; 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
Closed-loop 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.