Brain Stimulation

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 (HĂžjlund 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 ErregungszustÀnde 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 mĂŒssen, 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.

HÞjlund 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, MĂ€dler 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 erhÀltlichem 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