Investigating the Brain and the Peripheral Nervous System

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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.

Presurgical Diagnostics

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Some brain diseases may require surgical removal of the affected parts of the brain. Examples of such cases include pharmacologically resistant epilepsy and brain tumors.

In order to precisely locate the diseased brain tissue and to protect healthy areas that mediate important brain functions, the brain must be “mapped” before surgery. The aim of this mapping is to determine the location and extent of different brain areas and the abnormal tissue as precisely as possible.

The Potential of Neurotechnology

Implanted depth electrodes as well as grid-like foil electrodes (also called grid and strip electrodes) are the most precise way to map the brain. Depth electrodes measure the brain activity in deeper brain regions. Grid and strip electrodes are located on the surface of the brain tissue and enable communication with the underlying local groups of nerve cells.

Because they are in direct contact with brain tissue both types of electrodes can detect the electrical signals of the brain with better resolution than external electrodes that are used in electroencephalogram (EEG) for example (Enatsu & Mikuni, 2016).

To ensure a reliable diagnosis, electrodes are implanted over a period of several days to weeks, during which they are used to record electrophysiological signals and sometimes also electrically stimulate. In some cases, e.g. in the process of removing brain tumors, the electrodes are usually used only during the surgery in which the diseased brain tissue is resected.

State of Research and Technology

Grid and strip electrodes as well as depth electrodes have been successfully used to map the brain in pre-surgical diagnostics for several decades. Recent research indicates that electrodes with higher contact densities could yield even more accurate diagnostic results (Hermiz et al., 2018, Wang et al., 2017).

The grid and strip electrodes that are used in clinical practice to date are manufactured mostly by hand. The conventional production techniques render those electrodes in high contact densities very hard and stiff.

Solutions supported by CorTec Technology

The °AirRay Cortical Electrode includes a set of grid and strip electrodes for presurgical diagnostics. They are manufactured in a patented laser-assisted process and their properties make them ideal for brain mapping:

  • The electrodes are thin and soft, so that they can very well adapt to the curved surface of the brain.
  • A special interlocking mechanism of the materials prevents a detachment of the contacts from the grid. The electrodes can thus provide an increased level of patient safety.

 

The °AirRay Cortical Electrode to be submitted to the FDA for approval for clinical use is in preparation. In individual cases, the electrode technologie has already been used successfully in patient-individual custom-made products for presurgical diagnostics.

The special production technology of CorTec allows in principle high contact densities without making the electrodes very hard and stiff. The current FDA submission of the °AirRay Cortical Electrode, however, does not include such designs yet.

Further Readings

Scientific Literature

Invasive Evaluations for Epilepsy Surgery: A Review of the Literature.

Enatsu R, Mikuni N.

Neurol Med Chir (Tokyo). 2016 May 15;56(5):221-7. doi: 10.2176/nmc.ra.2015-0319. Epub 2016 Mar 4. Review.

 

Sub-millimeter ECoG pitch in human enables higher fidelity cognitive neural state estimation.

Hermiz J, Rogers N, Kaestner E, Ganji M, Cleary DR, Carter BS, Barba D, Dayeh SA, Halgren E, Gilja V.

Neuroimage. 2018 Aug 1;176:454-464. doi: 10.1016/j.neuroimage.2018.04.027. Epub 2018 Apr 18.

 

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

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

J Neural Eng. 2017 Oct;14(5):056004. doi: 10.1088/1741-2552/aa785e. Epub 2017 Jun 9.

Brain Stimulation

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Since the 1990s electrical brain stimulation has been used successfully for the treatment of neurological diseases, in particular motor disorders like Morbus Parkinson or dystonia. Since then, further research has revealed indications that this type of therapy may be useful in an ever-growing number of other applications.

In particular adaptive brain stimulation which is based on the patient’s individual and momentary need for treatment is a promising approach for new innovative therapies. A prerequisite for such therapies is first of all the ability to determine neuronal or behavioral biomarkers from which the current condition of the patient can be deduced. Then the required therapeutic stimulation must be derived from these data.

Some examples of such therapies are described below.

– for better Treatment of Movement Disorders, e.g., Morbus Parkinson

Parkinson’s disease affects over a million people worldwide. This makes it the second most common neurodegenerative disease after Alzheimer’s disease. Due to prominent patients such as Michael J. Fox, Muhammad Ali, or Pope John Paul II the disease and its symptoms have become well-known to the general public: stiffness, tremor, unsteady, crooked gait and a mask-like facial expression.

The Potential of Neurotechnology

To date, there is no causal therapy that could stop the progression of Parkinson’s disease. The symptoms are usually suppressed with the help of pharmaceuticals (L-Dopa). As the disease progresses, however, patients will require ever-increasing doses of the medication, and strong fluctuations between states of exaggerated movement and rigidity arise.

At this stage, many patients can benefit from brain stimulation treatment through an active neuroimplant through which electrodes stimulate certain areas deep inside the brain. Electrical stimulation affects brain function and reduces the symptoms of the disease. Tremor is suppressed and mobility is restored (Fasano & Lozano, 2015).

Deep brain stimulation can also treat other movement disorders, such as dystonia, essential tremor or Tourette syndrome, as well as certain forms of epilepsy and depression (Fasano & Lozano, 2015; Rossi et al., 2016; Schlaefer et al., 2013; Bewernick et al., 2017; Zhou et al., 2018).

State of Research and Technology

About 20 years ago the first stimulation systems for the treatment of advanced Parkinson’s disease were approved for clinical use. They are based on pacemaker technologies, combined with deep brain electrodes. To date more than 100,000 Parkinson’s patients worldwide have been supplied with such brain stimulators.

The brain stimulation systems currently used in clinical practice are adjusted by the attending physician. After that they stimulate continuously with constant parameters. If the symptoms fluctuate, stimulation cannot be adjusted on a short-term basis and without intervention of a trained physician. Moreover, stimulation can produce side effects or sometimes fails to alleviate certain symptoms (Højlund et al., 2016; Nassery et al., 2016). These problems compromise therapeutic success and patient satisfaction.

Experience with the brain stimulation systems currently in use shows that, while in principle successful the therapy can still be improved. Research from recent years suggest that so-called closed-loop systems such as CorTec Brain Interchange could reach a next level of improved “adaptive” therapy (Ganzer et al., 2018; Swann et al., 2018; Mohammed et al., 2018). Such systems are able to adapt to the momentary therapeutic need of the patient.

Solutions supported by CorTec Technology

To improve the quality of stimulation therapy and to adjust it better to the needs of the patient, it is first of all important to detect brain signals in a reliable way in order to provide information about the current condition of the patient. The flat °AirRay Grid Electrodes are particularly well suited for this task because they can be customized and optimized in high-resolution designs to the specific application and the individual patient.

Applying °AirRay Electrodes connected to 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. It measures the brain signals of the patient, evaluates the data and autonomously adjusts stimulation to the current condition of the patient. This will allow a therapy that can be specifically adapted to the momentary needs of the individual 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.

– 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.

The Potential of Neurotechnology

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.

State of Research and Technology

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.

Solutions supported by CorTec Technology

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.

– for the Therapy of Chronic Pain

Certain types of chronic pain have no physiological cause that requires treatment, but nevertheless they severely affect patients due to their enormous intensity. Such pain may be of central nervous origin, e.g. after stroke. Or it can occur as a consequence of neuropathies, e.g. of the trigeminal nerve.

Ursache der Epilepsie sind unkontrollierbare Erregungszustände im Gehirn, die sich gegenseitig aufschaukeln, bis es zur gleichzeitigen Erregung vieler Nervenzellen kommt, die ihrerseits weite Teile des Gehirns erfassen können. In diesem Zustand kann das Gehirn nicht mehr normal funktionieren und etwa Informationen verarbeiten oder Bewegungen kontrollieren.

Zwar gibt es medikamentöse Therapien, jedoch wirken sie bei ca. einem Drittel der Epilepsiepatienten nicht oder nur unzureichend. Zudem sind die Medikamente, die dauerhaft genommen werden müssen, meist mit Nebenwirkungen verbunden.

The Potential of Neurotechnology

Medication generally does not help patients suffering from these kinds of chronic pain. But electrical stimulation of the motor part of the cerebral cortex can in some cases offer relief (Ostergard et al., 2014).

For this purpose, grid-like foil electrodes (also called grid electrodes) are fixed to the outer meninges over the motor cortex and are connected to a neurostimulator. Electrical stimulation delivered to the tissue provides significant pain relief.

State of Research

Motor cortex stimulation with electrodes and stimulators already approved for clinical use has been widely used in clinical practice.

Solutions supported by CorTec Technology

The flat °AirRay Grid electrodes by CorTec are suitable for stimulating brain tissue. In particular as components of complete systems, they can be individualized and optimized in high-resolution designs to the application at hand.

The combination of °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.

With its high number of channels, along with the ability to reactively 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.

Further Readings

Scientific Literature

Morbus Parkinson

Systems for deep brain stimulation: review of technical features.

Amon A, Alesch F.

J Neural Transm (Vienna). 2017 Sep;124(9):1083-1091. doi: 10.1007/s00702-017-1751-6. Epub 2017 Jul 13. Review.

 

Deep brain stimulation for movement disorders: 2015 and beyond.

Fasano A, Lozano AM.

Curr Opin Neurol. 2015 Aug;28(4):423-36. doi: 10.1097/WCO.0000000000000226. Review.

 

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

 

Scheduled, intermittent stimulation of the thalamus reduces tics in Tourette syndrome.

Rossi PJ, Opri E, Shute JB, Molina R, Bowers D, Ward H, Foote KD, Gunduz A, Okun MS.

Parkinsonism Relat Disord. 2016 Aug;29:35-41. doi: 10.1016/j.parkreldis.2016.05.033. Epub 2016 Jun 7.

 

Worsening of Verbal Fluency After Deep Brain Stimulation in Parkinson’s Disease: A Focused Review.

Højlund A, Petersen MV, Sridharan KS, Østergaard K.

Comput Struct Biotechnol J. 2016 Nov 27;15:68-74. eCollection 2017. Review.

 

Psychiatric and Cognitive Effects of Deep Brain Stimulation for Parkinson’s Disease.

Nassery A, Palmese CA, Sarva H, Groves M, Miravite J, Kopell BH.

Curr Neurol Neurosci Rep. 2016 Oct;16(10):87. doi: 10.1007/s11910-016-0690-1. Review.

 

Open-loop deep brain stimulation for the treatment of epilepsy: a systematic review of clinical outcomes over the past decade (2008-present).

Zhou JJ, Chen T, Farber SH, Shetter AG, Ponce FA.

Neurosurg Focus. 2018 Aug;45(2):E5. doi: 10.3171/2018.5.FOCUS18161.

 

Deep brain stimulation to the medial forebrain bundle for depression- long-term outcomes and a novel data analysis strategy.

Bewernick BH, Kayser S, Gippert SM, Switala C, Coenen VA, Schlaepfer TE.

Brain Stimul. 2017 May – Jun;10(3):664-671. doi: 10.1016/j.brs.2017.01.581. Epub 2017 Feb 9.

 

Rapid effects of deep brain stimulation for treatment-resistant major depression.

Schlaepfer TE, Bewernick BH, Kayser S, Mädler B, Coenen VA.

Biol Psychiatry. 2013 Jun 15;73(12):1204-12. doi: 10.1016/j.biopsych.2013.01.034. Epub 2013 Apr 3. Review.

 

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.

 

Adaptive deep brain stimulation for Parkinson’s disease using motor cortex sensing.

Swann NC, de Hemptinne C, Thompson MC, Miocinovic S, Miller AM, Gilron R, Ostrem JL, Chizeck HJ, Starr PA.J Neural Eng. 2018 Aug;15(4):046006. doi: 10.1088/1741-2552/aabc9b. Epub 2018 May 9.

 

Toward adaptive deep brain stimulation in Parkinson’s disease: a review.

Mohammed A, Bayford R, Demosthenous A.Neurodegener Dis Manag. 2018 Apr;8(2):115-136. doi: 10.2217/nmt-2017-0050. Epub 2018 Apr 25.

 

Epilepsie

The puzzle(s) of pharmacoresistant epilepsy.

Pohlmann-Eden B, Weaver DF.

Epilepsia. 2013 May;54 Suppl 2:1-4. doi: 10.1111/epi.12174.

 

Kontinuierliche Tiefenhirnstimulation bei Epilepsie

Anterior Nucleus Deep Brain Stimulation for Refractory Epilepsy: Insights Into Patterns of Seizure Control and Efficacious Target.

Krishna V, King NK, Sammartino F, Strauss I, Andrade DM, Wennberg RA, Lozano AM.

Neurosurgery. 2016 Jun;78(6):802-11. doi: 10.1227/NEU.0000000000001197.

 

Bedarfsgerechte Stimulation der Hirnrinde mit kommerziell erhältlichem System

Brain-responsive neurostimulation in patients with medically intractable mesial temporal lobe epilepsy.

Geller EB, et. al.

Epilepsia. 2017 Jun;58(6):994-1004. doi: 10.1111/epi.13740. Epub 2017 Apr 11.

 

Brain-responsive neurostimulation in patients with medically intractable seizures arising from eloquent and other neocortical areas.

Jobst BC, et. al.

Epilepsia. 2017 Jun;58(6):1005-1014. doi: 10.1111/epi.13739. Epub 2017 Apr 7.

 

Responsive brain stimulation in epilepsy.

Hartshorn A, Jobst B.

Ther Adv Chronic Dis. 2018 Jul;9(7):135-142. doi: 10.1177/2040622318774173. Epub 2018 May 7. Review.

 

Neuropace study

Brain-responsive neurostimulation in patients with medically intractable mesial temporal lobe epilepsy.

Geller EB, Skarpaas TL, Gross RE, Goodman RR, Barkley GL, Bazil CW, Berg MJ, Bergey GK, Cash SS, Cole AJ, Duckrow RB, Edwards JC, Eisenschenk S, Fessler J, Fountain NB, Goldman AM, Gwinn RP, Heck C, Herekar A, Hirsch LJ, Jobst BC, King-Stephens D, Labar DR, Leiphart JW, Marsh WR, Meador KJ, Mizrahi EM, Murro AM, Nair DR, Noe KH, Park YD, Rutecki PA, Salanova V, Sheth RD, Shields DC, Skidmore C, Smith MC, Spencer DC, Srinivasan S, Tatum W, Van Ness PC, Vossler DG, Wharen RE Jr, Worrell GA, Yoshor D, Zimmerman RS, Cicora K, Sun FT, Morrell MJ.

Epilepsia. 2017 Jun;58(6):994-1004. doi: 10.1111/epi.13740. Epub 2017 Apr 11.

 

Chronische Schmerzen

Motor cortex stimulation for chronic pain.

Ostergard T, Munyon C, Miller JP.

Neurosurg Clin N Am. 2014 Oct;25(4):693-8. doi: 10.1016/j.nec.2014.06.004. Epub 2014 Aug 3. Review.

 

Motor cortec stimulation for Refractory Benign Pain

Clinical Neurosurgery 54, Chapter 12, 2007

Machado A, Azmi H, Rezai A

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.

Brain-Computer Interface (BCI)

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Brain Computer Interfaces (BCI) hold great fascination for technology and science. In medicine, they refer to systems that detect neural activity and use it as a trigger for certain medically relevant actions.

Medical applications of this technology that are particularly intensively explored include neuronally controlled assistive systems for severely paralyzed people. They provide patients with means for communication or motor assistance for example through robot arms. In recent years, more and more scientific evidence suggests that such systems can also be used for rehabilitation purposes.

In research environment, these technologies have already achieved remarkable successes. However, there are currently no such systems yet that would be suitable for everyday use.

– As assistive systems for severely paralyzed patients, e.g. with ALS or spinal cord injury

Paralyses that occur, e.g. after severe strokes, spinal cord injuries, or in the progressive muscular atrophy disease ALS (by which the well-known physicist Stephen Hawking was afflicted, for example) can be so severe that patients can no longer communicate in a normal way. This case is called locked-in syndrome.

When even eye movements or twitching of individual muscles become impossible, the patients are completely “locked in” (complete Locked-in syndrome).

The inability to control their environment and to communicate with relatives and caregivers makes this state especially difficult for the patients – in particular, because they can at the same time remain fully conscious.

The Potential of Neurotechnology

In many cases, the brains of paralyzed patients are still intact. In these cases, neurotechnological devices can be used to create so-called brain-computer interfaces. Patients can control these independently from any remaining muscle activity – only through the power of their thoughts.

The easiest way to capture brain activity is by the encephalogram (EEG). A recently found alternative is functional near-infrared spectroscopy (fNIRS). However, the amount of information that can be collected through the skull by these two noninvasive methods is very limited. The same applies to the stability of the recorded signals. Moreover, both methods are highly susceptible to environmental disturbances, such as radio or cell phone signals (Rosenfeld & Wong, 2017, Shih et al., 2012).

Stronger and more stable signals with better spatial resolution can be recorded by electrodes that are placed within the skull. They sit directly on the brain or the meninges, or are inserted into the brain tissue. For such systems to be suitable for everyday use, however, fast and secure data processing must be guaranteed, and the applied hardware must be compact and portable.

Interfacing motor nerves potentially can restore the mobility of muscles. The bioelectronic medicine recently has begun to research this approach.

State of Research and Technology

There is a number of different kinds of assistive systems that severely paralyzed persons can use in everyday life. All of them, however, are based on remaining motor functions of the patient. Wheelchairs and other devices can be controlled by the movement of the eyes, the tongue or even by breathing (so-called “sip and puff” control). Locked-In patients who do not have any of such residual functions, therefore, cannot use these systems.

In neuroscientific research there are many approaches to enable neuronal control of wheelchairs, orthoses, communication systems, and other aids, just through neuronal signals.

While impressive results haven been achieved by such non-invasive (Chaudary et al., 2016) or invasive BCIs (Bacher et al., 2015; Branco et al., 2017; Collinger at al., 2014; Wang et al., 2013), these systems are still far from being fit for everyday use and being certified for broad clinical application.

Solutions supported by CorTec Technology

CorTec’s °AirRay Electrodes can be used both for both recording and stimulating brain activity, and can thus transmit information in both directions. Thanks to CorTec’s flexible manufacturing technology the shape, spacing, and number of electrode contacts can be adapted to the application at hand as well as to the individual patient. °AirRay Cuff Electrodes can also target motor nerves with the goal of restoring natural mobility.

Combined with intelligent decoding software as applied through CorTec’s Brain Interchange technology a direct link between the human brain and artificial intelligence can be created that could allow even the most severely paralyzed to interact again with their environments.

With its large number of currently 32 channels, the Brain Interchange System is engineered to support unprecedented intensities of information transfer. This will allow exploring a neural control of precise assistive devices as well as restoration of mobility through the body’s own muscles.

 

CorTec °AirRay Grid and Cuff Electrodes can be used in a wide range of designs, 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. A collaborative project (link to the R & D Projects page) conducted in cooperation with the University Medical Center in Freiburg investigates brain-computer interfaces as assistive systems for the paralyzed.

– For Rehabilitation, e.g., after stroke

After a stroke, many patients are left with paralyses, that permanently affect them in their daily lives, and which sometimes cannot even be remedied by intensive rehabilitation.

The Potential of Neurotechnology

By visualizing certain movements these stroke patients can frequently still generate the brain signals that – under healthy conditions – would elicit those movements. Brain-computer interfaces that detect such movement intentions in the electrical signals of the brain and based on this data control assistive devices such as orthoses could – at least partially – restore patients’ mobility.

By training with the brain-computer interface the patients can learn to move their limbs with the aid of the assistive device. Pilot studies have already achieved remarkable successes in BCI-mediated motor rehabilitation after stroke (Frolov et al., 2017; Bundy  et al., 2017; Monge-Pereira et al., 2017; Chaudhary et al., 2016).

Research results also suggest that successful training helps to establish new neuronal connections that can improve natural mobility even without the assistive devices (Biasiucci et al., 2018).

Neurotechnology could, thus, open up new ways of rehabilitation and positively affect motor disabilities that previously could not be addressed by existing measures.

State of Research and Technology

Currently, stroke rehabilitation mainly consists of passive movement therapy in which the patient follows a certain movement rhythm.

In addition brain-computer interfaces are being used to explore potential new forms of rehabilitation, mainly using non-invasively recorded signals such as the electroencephalogram (EEG; see Frolov et al., 2017; Bundy et al., 2017; Monge-Pereira et al., 2017; Chaudhary et al., 2016).

However, the accuracy and informational content of neuronal signals – and, thus, also the decodability for brain-computer interfaces – become better, if signals from within the skull, recorded directly from the surface of the brain, are used for their control (Rosenfeld & Wong, 2017; Shih et al., 2012).

Therefore, also using invasively derived brain signals for brain-computer interfaces for stroke rehabilitation is currently considered (Gharabaghi ​​et al., 2014; Wang et al., 2010). To date, however, there is no stroke rehabilitation system based on brain-computer interfaces yet that would be approved for general clinical use.

A different approach to stroke rehabilitation is based on electrical stimulation of the motor cortex during motor training. The US company Northstar Neuroscience which developed a corresponding neurostimulator achieved promising results in the 2000s with such an electrically assisted rehabilitation scheme (Brown et al., 2003; Brown et al., 2006). A subsequent larger clinical trial revealed positive long-term improvements, but no short-term benefits (Levy et al., 2016). Future studies (possibly with better technology, better trial design and improved patient selection criteria) are needed to clarify the potential of cortical stimulation in stroke rehabilitation.

Solutions supported by CorTec Technology

CorTec’s flat °AirRay Grid electrodes are useful for both recording and stimulating brain activity and can thus transmit information in both directions. Thanks to CorTec’s flexible manufacturing technology, the shape, spacing and number of electrode contacts can be individually adapted to the application at hand as well as to the individual patient.

 

Combining the °AirRay electrodes with the CorTec Brain Interchange Implant System it is possible to wirelessly transfer the data to a computing unit outside of the body. This unit analyzes the data and processes them further to derive movement control signals. In this way, the system enables fast interactions between the brain and the limbs.

 

The CorTec °AirRay Grid electrodes can be used in a wide range of designs, 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. A collaborative project (link to the R & D projects page) conducted with the University Medical Center in Tübingen, Germany, aims to explore the foundations for novel rehabilitation systems for paralyzed people.

Further Readings

Scientific Literature

As assistive systems for severely paralyzed patients

Brain-computer interfaces in the completely locked-in state and chronic stroke.

Chaudhary U, Birbaumer N, Ramos-Murguialday A.

Prog Brain Res. 2016;228:131-61. doi: 10.1016/bs.pbr.2016.04.019. Epub 2016 Aug 8. Review.

 

Neurobionics and the brain-computer interface: current applications and future horizons.

Rosenfeld JV, Wong YT.

Med J Aust. 2017 May 1;206(8):363-368. Review.

 

Brain-computer interfaces in medicine.

Shih JJ, Krusienski DJ, Wolpaw JR.

Mayo Clin Proc. 2012 Mar;87(3):268-79. doi: 10.1016/j.mayocp.2011.12.008. Epub 2012 Feb 10. Review.

 

Neural Point-and-Click Communication by a Person With Incomplete Locked-In Syndrome.

Bacher D, Jarosiewicz B, Masse NY, Stavisky SD, Simeral JD, Newell K, Oakley EM, Cash SS, Friehs G, Hochberg LR.

Neurorehabil Neural Repair. 2015 Jun;29(5):462-71. doi: 10.1177/1545968314554624. Epub 2014 Nov 10.

 

Decoding hand gestures from primary somatosensory cortex using high-density ECoG.

Branco MP, Freudenburg ZV, Aarnoutse EJ, Bleichner MG, Vansteensel MJ, Ramsey NF.

Neuroimage. 2017 Feb 15;147:130-142. doi: 10.1016/j.neuroimage.2016.12.004. Epub 2016 Dec 5.

 

Collaborative approach in the development of high-performance brain-computer interfaces for a neuroprosthetic arm: translation from animal models to human control.

Collinger JL, Kryger MA, Barbara R, Betler T, Bowsher K, Brown EH, Clanton ST, Degenhart AD, Foldes ST, Gaunt RA, Gyulai FE, Harchick EA, Harrington D, Helder JB, Hemmes T, Johannes MS, Katyal KD, Ling GS, McMorland AJ, Palko K, Para MP, Scheuermann J, Schwartz AB, Skidmore ER, Solzbacher F, Srikameswaran AV, Swanson DP, Swetz S, Tyler-Kabara EC, Velliste M, Wang W, Weber DJ, Wodlinger B, Boninger ML.

Clin Transl Sci. 2014 Feb;7(1):52-9. doi: 10.1111/cts.12086. Epub 2013 Aug 27.

 

An electrocorticographic brain interface in an individual with tetraplegia.

Wang W, Collinger JL, Degenhart AD, Tyler-Kabara EC, Schwartz AB, Moran DW, Weber DJ, Wodlinger B, Vinjamuri RK, Ashmore RC, Kelly JW, Boninger ML.

PLoS One. 2013;8(2):e55344. doi: 10.1371/journal.pone.0055344. Epub 2013 Feb 6.

For Rehabilitation

Post-stroke Rehabilitation Training with a Motor-Imagery-Based Brain-Computer Interface (BCI)-Controlled Hand Exoskeleton: A Randomized Controlled Multicenter Trial.

Frolov AA, Mokienko O, Lyukmanov R, Biryukova E, Kotov S, Turbina L, Nadareyshvily G, Bushkova Y.

Front Neurosci. 2017 Jul 20;11:400. doi: 10.3389/fnins.2017.00400. eCollection 2017.

 

Contralesional Brain-Computer Interface Control of a Powered Exoskeleton for Motor Recovery in Chronic Stroke Survivors.

Bundy DT, Souders L, Baranyai K, Leonard L, Schalk G, Coker R, Moran DW, Huskey T, Leuthardt EC.

Stroke. 2017 Jul;48(7):1908-1915. doi: 10.1161/STROKEAHA.116.016304. Epub 2017 May 26.

 

Use of Electroencephalography Brain-Computer Interface Systems as a Rehabilitative Approach for Upper Limb Function After a Stroke: A Systematic Review.

Monge-Pereira E, Ibañez-Pereda J, Alguacil-Diego IM, Serrano JI, Spottorno-Rubio MP, Molina-Rueda F.

PM R. 2017 May 13. pii: S1934-1482(17)30581-6. doi: 10.1016/j.pmrj.2017.04.016.

 

Brain-computer interfaces in the completely locked-in state and chronic stroke.

Chaudhary U, Birbaumer N, Ramos-Murguialday A.

Prog Brain Res. 2016;228:131-61. doi: 10.1016/bs.pbr.2016.04.019. Epub 2016 Aug 8. Review.

 

Brain-actuated functional electrical stimulation elicits lasting arm motor recovery after stroke.

Biasiucci A, Leeb R, Iturrate I, Perdikis S, Al-Khodairy A, Corbet T, Schnider A, Schmidlin T, Zhang H, Bassolino M, Viceic D, Vuadens P, Guggisberg AG, Millán JDR.

Nat Commun. 2018 Jun 20;9(1):2421. doi: 10.1038/s41467-018-04673-z.

 

From assistance towards restoration with epidural brain-computer interfacing.

Gharabaghi A, Naros G, Walter A, Grimm F, Schuermeyer M, Roth A, Bogdan M, Rosenstiel W, Birbaumer N.

Restor Neurol Neurosci. 2014;32(4):517-25. doi: 10.3233/RNN-140387.

 

Neural interface technology for rehabilitation: exploiting and promoting neuroplasticity.

Wang W, Collinger JL, Perez MA, Tyler-Kabara EC, Cohen LG, Birbaumer N, Brose SW, Schwartz AB, Boninger ML, Weber DJ.

Phys Med Rehabil Clin N Am. 2010 Feb;21(1):157-78. doi: 10.1016/j.pmr.2009.07.003. Review.

 

Northstar study papers:

Brown JA, Lutsep H, Cramer SC, Weinand M. Motor cortex stimulation for enhancement of recovery after stroke: case report. Neurol Res. 2003 Dec;25(8):815-8.

Brown JA, Lutsep HL, Weinand M, Cramer SC. Motor cortex stimulation for the enhancement of recovery from stroke: a prospective, multicenter safety study. Neurosurgery. 2006 Mar;58(3):464-73.

Levy RM, Harvey RL, Kissela BM, Winstein CJ, Lutsep HL, Parrish TB, Cramer SC, Venkatesan L. Epidural Electrical Stimulation for Stroke Rehabilitation: Results of the Prospective, Multicenter, Randomized, Single-Blinded Everest Trial. Neurorehabil Neural Repair. 2016 Feb;30(2):107-19. doi: 10.1177/1545968315575613. Epub 2015 Mar 6.

Novel Therapies for neurological disorders

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From Alzheimer’s disease, depression, post-traumatic stress disorder, compulsive obsessive disorders up to eating disorders – diseases of the central nervous system deeply disturb and threaten our nature and wellbeing as humans. Up until today adequate therapeutic options to effectively address many of these conditions are still lacking.

 

The Potential of Neurotechnology

Neurotechnology offers a wealth of novel opportunities to address this problem. Recent scientific research suggests that many diseases of the central nervous system respond to electrical stimulation (see literature below).

Therefore, implantable electrodes and corresponding neuromodulation systems could provide new and improved therapies for these diseases.

State of Research and Technology

So far, novel neuromodulation therapies are mainly being tested with implant systems that are already approved for clinical use usually in combination with deep brain electrodes. However, these systems are functionally limited to pre-specified stimulation patterns.

While the therapeutic use of flat grid electrodes to stimulate the cerebral cortex and the exploration of adaptive neurostimulation therapies are still in their beginnings research results suggest that they hold great promises (e.g. Fasano & Lozano, 2015).

Solutions supported by CorTec Technology

CorTec’s implantable AirRay Electrodes can be valuable tools and components for novel neuromodulation systems as well as for central nervous as for peripheral applications. The flexibility of the electrode with regard to individualized and high-resolution designs enables them to be optimized precisely to the respective application.

 

Using the °AirRay Electrodes in conjunction with the Brain Interchange System also allows combining custom-made electrode designs with long-term closed-loop therapy: The Brain Interchange technology is able to respond to the patients’ states. It measures their brain signals, evaluates the data and can autonomously adjust to their moment-to-moment state. This will enable therapies that can be adapted exactly to the needs of the patient.

 

The CorTec °AirRay Electrodes from can be used in a wide range of designs 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.

Further Readings

Publications

 

Review of the Deep Brain Stimulation Technology and possible future applications and technologies:

 Deep brain stimulation for movement disorders: 2015 and beyond.

Fasano A, Lozano AM.

Curr Opin Neurol. 2015 Aug;28(4):423-36. doi: 10.1097/WCO.0000000000000226. Review.

 

Deep Brain Stimulation in Anorexia Nervosa:

Deep brain stimulation of the subcallosal cingulate for treatment-refractory anorexia nervosa: 1 year follow-up of an open-label trial.

Lipsman N, Lam E, Volpini M, Sutandar K, Twose R, Giacobbe P, Sodums DJ, Smith GS, Woodside DB, Lozano AM.

Lancet Psychiatry. 2017 Apr;4(4):285-294. doi: 10.1016/S2215-0366(17)30076-7. Epub 2017 Feb 24.

 

Deep Brain Stimulation in Alzheimer’s Disease

A Phase II Study of Fornix Deep Brain Stimulation in Mild Alzheimer’s Disease.

Lozano AM, Fosdick L, Chakravarty MM, Leoutsakos JM, Munro C, Oh E, Drake KE, Lyman CH, Rosenberg PB, Anderson WS, Tang-Wai DF, Pendergrass JC, Salloway S, Asaad WF, Ponce FA, Burke A, Sabbagh M, Wolk DA, Baltuch G, Okun MS, Foote KD, McAndrews MP, Giacobbe P, Targum SD, Lyketsos CG, Smith GS.

J Alzheimers Dis. 2016 Sep 6;54(2):777-87. doi: 10.3233/JAD-160017.

 

Deep Brain Stimulation in Depression

Deep Brain Stimulation Modulates Gamma Oscillations and Theta-Gamma Coupling in Treatment Resistant Depression.

Sun Y, Giacobbe P, Tang CW, Barr MS, Rajji T, Kennedy SH, Fitzgerald PB, Lozano AM, Wong W, Daskalakis ZJ.

Brain Stimul. 2015 Nov-Dec;8(6):1033-42. doi: 10.1016/j.brs.2015.06.010. Epub 2015 Jun 26.

 

Deep brain stimulation to the medial forebrain bundle for depression- long-term outcomes and a novel data analysis strategy.

Bewernick BH, Kayser S, Gippert SM, Switala C, Coenen VA, Schlaepfer TE.

Brain Stimul. 2017 May – Jun;10(3):664-671. doi: 10.1016/j.brs.2017.01.581. Epub 2017 Feb 9.