16.10.2019

Why Closed Loop?

About the advantages of responsive approaches for personalized therapies |

Neuromodulation can be an effective treatment for a variety of neurological and neuropsychiatric disorders, such as Parkinson’s Disease, epilepsy, traumatic brain injury, and obsessive-compulsive disorder (Swann et al., 2018). The treatment uses electrical stimulation pulses that are transmitted to underlying nerve tissue and can be differentiated into either open- or closed-loop (Gardner 2013; Ghasemi et al., 2018). Of particular interest for personalization of therapy, and further advancement of the field, are closed-loop approaches.

 

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Neuromodulation today uses a device similar to a pacemaker, typically also placed near the chest, to deliver continuous electrical stimulation to regions of the brain. The history of applying electric currents for the treatment of brain disorders dates back as early as 1757; however, current methods of neuromodulation were pioneered by researchers 200 years later (Benabid et al., 1987; Delgado et al., 1952; Bekthereva et al., 1963; Sam-Jacobsen, 1965). These methods often involve stimulation of deeper cortical and subcortical brain regions through one or more electrodes penetrating the brain tissue, known as Deep Brain Stimulation (DBS). In 1989, the first neuromodulatory device – based on early DBS technology – received approval from the US Food and Drug Administration (FDA) for the treatment of chronic pain. Continued developments within DBS research prompted the FDA to approve the use of this treatment for tremor and Parkinson’s Disease throughout the early 2000s (Gardner 2013).

 

DBS and other forms of neuromodulation use open- or closed-loop methods to provide stimulation to the neural tissue (Ghasemi et al., 2018). Today, open-loop stimulation is most common. In this method, electrodes provide a level of stimulation, pre-determined by a clinician, to the patient. The parameters of the stimulation, i.e. duration, amplitude, and frequency of the pulse train, remain constant. These parameters can be readjusted in a trial-and-error method by a clinician based on the patient’s condition and previous treatment results, allowing for effective treatment with minimum side effects (Rosin et al., 2011).  These open-loop paradigms are rather successful and well-established. However, great potential exists for a more personalized approach with closed-loop stimulation.

 

Scientific studies suggest that the closed-loop approach may improve existing therapies and/or enable the development of new therapies (Rosin et al., 2011; Ghasemi et al., 2018). The closed-loop system automatically and dynamically adjusts the electrical pulse and stimulation parameters without manual intervention. It accounts for patient variability through a system that receives continuous feedback from the patient’s nervous system via a programmed algorithm (Parastarfeizabadi et al., 2017). To implement closed-loop neuromodulation, a sensor that records a signal linked to symptoms of the patient is essential: this sensor detects physiological changes in real-time and allows for individualized variability in the stimulation parameters, thus decreasing the risk of adverse side effects and increasing efficacy.

 

Closed-loop studies, as for example used in the treatment of Parkinson’s Disease, show specific examples of demonstrated symptom improvement, with substantial power savings and a reduction in side effects attributable to stimulation. Swann et al., 2018 demonstrated closed-loop, or “adaptive”, brain stimulation using a fully implanted neural prosthesis in two patients with Parkinson’s Disease. This prosthesis used an algorithm to detect a cortical physiological neural signature associated with dyskinesia and updated the stimulation voltage per patient, as needed (Swann et al., 2018). Other studies, such as Malekmohammadi et al., 2016, clinical trials from the University of Florida, and groups involved in the Proceedings of the DBS Think Tank, advocate for closed-loop DBS in treating tremor and freezing of gait in patients with Parkinson’s. Various groups in the BRAIN Initiative are also investigating the use of closed-loop in Parkinson’s tremor, motor recovery post stroke, and in learning.

 

While standard open-loop neuromodulation already shows high efficacy for diseases such as Parkinson’s Disease, the closed-loop approach allows for improvement of the therapy. Through closed-loop approaches, there are benefits for the patient, such as a reduction in stimulation current without loss of therapeutic benefits, allowing for reduced stimulation-induced adverse events and prolonged battery life of implantable devices. Furthermore, the lessons learned from a broader adaptive approach allows for the development of customized therapeutic strategies as patients continue on their individual road to recovery and/or disease management.

 


 

The CorTec Brain Interchange Technology Platform is dedicated to the research and development of closed-loop therapies.

Learn more about the technological features of Brain Interchange

 


Literature:

BEKHTEREVA, N P, et al. “Utilization of Multiple Electrodes Implanted in the Subcortical Structure of the Human Brain for the Treatment of Hyperkinesis.” Zhurnal Nevropatologii i Psikhiatrii Imeni S.S. Korsakova (Moscow, Russia : 1952), U.S. National Library of Medicine, 1963, www.ncbi.nlm.nih.gov/pubmed/13970358/.

Benabid, A L, et al. “Combined (Thalamotomy and Stimulation) Stereotactic Surgery of the VIM Thalamic Nucleus for Bilateral Parkinson Disease.” Applied Neurophysiology, U.S. National Library of Medicine, 1987, www.ncbi.nlm.nih.gov/pubmed/3329873.

DELGADO, J M R, et al. “Technique of Intracranial Electrode Implacement for Recording and Stimulation and Its Possible Therapeutic Value in Psychotic Patients.” Confinia Neurologica, U.S. National Library of Medicine, 1952, www.ncbi.nlm.nih.gov/pubmed/13010010/.

Gardner, John. “A History of Deep Brain Stimulation: Technological Innovation and the Role of Clinical Assessment Tools.” Social Studies of Science, SAGE Publications, Oct. 2013, www.ncbi.nlm.nih.gov/pmc/articles/PMC3785222/.

Ghasemi, P, et al. “Closed- and Open-Loop Deep Brain Stimulation: Methods, Challenges, Current and Future Aspects.” Journal of Biomedical Physics & Engineering, Journal of Biomedical Physics and Engineering, 1 June 2018, www.ncbi.nlm.nih.gov/pmc/articles/PMC6015649/.

Herron, Jeffrey, et al. “Kinematic Adaptive Deep Brain Stimulation for Resting Tremor in Parkinson’s Disease.” Wiley Online Library, John Wiley & Sons, Ltd, 27 Jan. 2016, onlinelibrary.wiley.com/doi/abs/10.1002/mds.26482.

Kouzani1, Abbas Z. “Advances in Closed-Loop Deep Brain Stimulation Devices.” Journal of NeuroEngineering and Rehabilitation, BioMed Central, 11 Aug. 2017, jneuroengrehab.biomedcentral.com/articles/10.1186/s12984-017-0295-1.

Ramirez-Zamora, et al. “Evolving Applications, Technological Challenges and Future Opportunities in Neuromodulation: Proceedings of the Fifth Annual Deep Brain Stimulation Think Tank.” Frontiers, Frontiers, 15 Dec. 2017, www.frontiersin.org/articles/10.3389/fnins.2017.00734/full.

Rosin, Boris, et al. “Closed-Loop Deep Brain Stimulation Is Superior in Ameliorating Parkinsonism.” Neuron, U.S. National Library of Medicine, 20 Oct. 2011, www.ncbi.nlm.nih.gov/pubmed/22017994/.

Sem-Jacobsen, C W. “Depth Electrographic Stimulation and Treatment of Patients with Parkinson’s Disease Including Neurosurgical Technique.” Acta Neurologica Scandinavica. Supplementum, U.S. National Library of Medicine, 1965, www.ncbi.nlm.nih.gov/pubmed/5320070/.

Sironi, Vittorio A. “Origin and Evolution of Deep Brain Stimulation.” Frontiers in Integrative Neuroscience, Frontiers Research Foundation, 18 Aug. 2011, www.ncbi.nlm.nih.gov/pmc/articles/PMC3157831/.

Swann, Nicole C, et al. “Adaptive Deep Brain Stimulation for Parkinson’s Disease Using Motor Cortex Sensing.” Journal of Neural Engineering, U.S. National Library of Medicine, Aug. 2018, www.ncbi.nlm.nih.gov/pubmed/29741160.