Study Rationale:
Currently deep brain stimulation (DBS) is limited to “open-loop” stimulation, without real-time adjustment to the patient’s state of activity, fluctuations and types of motor symptoms, medication dosages or neural markers of the disease. Changes to DBS settings only occur during clinical appointments or within small ranges by the patient at home. These limitations may contribute to sometimes dangerous and uncomfortable side effects, such as dyskinesia, as well as mood and cognitive impairment.
Hypothesis:
Our aim is to determine if an adaptive DBS system — responding to patient-specific, clinically relevant brain or movement signal feedback — is more effective than the currently available, continuous DBS therapy in Parkinson’s disease (PD) as measured by the motor Unified Parkinson’s Disease Rating Scale (UPDRS III) and specific phenotypic measures.
Study Design:
We will use an investigational research tool (Nexus-D System, Medtronic INC) to establish a connection between the implanted neurostimulator (Activa PC+S®, Medtronic INC) and an external computer. This will allow for recording of brain activity in real time and adjustment of stimulation within clinically safe limits using prewritten algorithms that respond to real-time recordings of patients’ movement and brain activity.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
Adaptive or “intelligent” deep brain stimulation will allow for the continuous optimization of therapy on an individual basis, maximizing motor symptom improvement and minimizing adverse effect. Adaptive stimulation will also prolong battery life and reduce number of battery replacement surgeries.
Next Steps for Development:
If the project is successful, the algorithms created and tested throughout clinical trials will be used for the development of the next generation of embedded adaptive neurostimulators.
Progress Report
This study is recruiting volunteers. Learn more at https://foxtrialfinder.michaeljfox.org/trial/3592/.
March 2015
Final Outcome
We implanted Activa PC+S, a type of brain stimulation device that can both stimulate the brain and record its electrical signals, in the brain of 21 people with Parkinson's disease (PD). We have successfully recorded brain signals while study participants were sitting, lying, standing or freely moving and receiving deep brain stimulation of the subthalamic nucleus, a key part of the brain involved in PD. Deep brain stimulation was delivered when its recipient had tremor. Ten people with tremor-dominant PD received closed-loop DBS (clDBS). As a result of the treatment, tremor reduced by 36%. Mean voltage used during clDBS was 76.4% lower than that used during continuous open-loop DBS (olDBS) voltage, with clDBS lasting on average 51.5% of the olDBS duration. One of the striking findings of this study was the variation among participants in the duration of adaptive DBS. The duration of adaptive DBS ranged from 11% to 99% of the time that continuous DBS would have lasted. Additionally, with their consent, 18 participants successfully received the embedded adaptive DBS algorithms (Nexus-E/D3). Safety and tolerability of adaptive DBS using Nexus E/D3 has been successfully tested. We have performed the first fully embeded closed-loop DBS experiment and demonstrated that it was superior to open-loop DBS in providing relief from progressive bradykinesia.
Publications
Trager MH, Miller Koop M, Velisar A, et al. Subthalamic Beta Oscillations Are Attenuated after Withdrawal of Chronic High Frequency Neurostimulation in Parkinson's Disease. Neurobiol Dis. 2016;96:22-30.
Blumenfeld Z, Koop MM, Prieto T E, et al. Sixty-hertz stimulation improves bradykinesia and amplifies subthalamic low-frequency oscillations. Mov Disord. 2017;32(1):80-88.
Herron J, Velisar A, Malekmohammadi M, Bronte-Stewart H, Chizeck HJ. A metric for evaluating and comparing closed-loop deep brain stimulation algorithms. http://arxiv.org/abs/1605.09312
Malekmohammadi M, Herron J, Velisar A, et al. Kinematic Adaptive Deep Brain Stimulation for Resting Tremor in Parkinson's Disease. Mov Disord. 2016;31:426-428.
Deeb W, Giordano JJ, Rossi PJ, et al. Proceedings of the Fourth Annual Deep Brain Stimulation Think Tank - A Review of Emerging Issues and Technologies. Front Integr Neurosci. 2016; 22;10-38.
Houston B, Blumenfeld Z, Quinn E, Bronte-Stewart H, Chizeck H. Long-term detection of Parkinsonian tremor activity from subthalamic nucleus local field potentials. Conf Proc IEEE Eng Med Biol Soc. 2015; 2015:3427-3431.
Quinn EJ, Blumenfeld Z, Velisar A, Beta oscillations in freely moving Parkinson's subjects are attenuated during deep brain stimulation. Mov Disord. 2015;30:1750-1758.
Invited Lectures
2014 Stanford TEDMED talk - 'Physiological sensors will revolutionize the way we live in the next 10 years" Palace of the Legion of Honor San Francisco
2015 The Bay Area Basal Ganglia Consortium, Research speaker. "The Stanford Brain Radio Project," January 25th, San Francisco CA
2015 Virginia Tech Carlton Research Institute and School of Medicine, invited Faculty Scholar, "Neuromodulation of the sensorimotor network in Parkinson's disease, a therapy and an investigative tool." April 2/3, Roanoke, Virginia
2015 OptoDBS 2015, Invited speaker "Electrical recordings during DBS," May 7, Geneva, Switzerland
2015 American Neurological Association - Invited speaker 'Sensing brain and kinematic signals for closed loop deep brain stimulation for Parkinson's disease,' September 27 - 29. Chicago, USA
2016 Gordon Research Conference - Invited speaker. 'Challenges and Opportunities for Modulating Basal Ganglia Circuitry: A Clinician's Perspective.' February 29 - March 4. Ventura, USA
2016 DBS think tank - Invited speaker, 'Closed loop deep brain stimulation for tremor'. March 9-11. Gainesville, USA
2016 Seattle Neuroscience Symposium- invited speaker September 9th 2016, Swedish Neurosciences Institute, Seattle WA
2016 Neural Prosthesis(NP) Seminar Series, Invited speaker, September 30th Case Western Reserve University, Ohio.
2016 Stanford Neurosciences Institute Symposium, invited speaker. October 13th, Stanford University
2016 Michael J Fox Foundation, Advances in Therapeutics Conference, invited poster presentation; October 24th, New York, New York
2016 Neurology Grand Rounds, invited speaker; October 26th Salt Lake City, Utah
2016 Stanford Neurosciences Institute - invited research presentation, October 27th, Pacific Pallisades, Los Angeles CA
2016 Breakthroughs in Neurological Therapies - invited speaker. October 29th, San Francisco CA, 2017 Deep Brain Stimulation Research Symposium, keynote speaker March 23rd, Baylor College of Medicine, Houston, Tx
2017 Neurosurgery Grand Rounds, invited speaker, March 24th, Department of Neurosurgery, Baylor College of Medicine, Houston, Tx
2017 FDA ELP for Brain Computing Interface, Invited speaker, March 28-29th, Minneapolis, MN
2017 DBS Leaders Forum, invited speaker, April 6-8th, Scottsdale Arizona
2017 Translational research in Neuromodulation, invited speaker, University of Chicago, May 12th, Chicago IL
2017 DBS Think Tank, invited speaker, "Closed Loop DBS for tremor", Atlanta, Georgia
2017 A World without Parkinson's Disease, 200th Anniversary of James Parkinson's essay, invited speaker, "Neuromodulation for Parkinson;s disease, the present and the future"; The Parkinson's Disease Foundation, June 1st 2017, NYC, NY
2017 OptoDBS 2017 - invited session moderator June 22-24 Geneva, Switzerland
2017 First European Workshop in Human Intracranial Electrophysiology, invited speaker. Oct 3-4 The Brain and Spine Institute, The Pitie Salpetrere Hospital, Paris, France
2018 Gordon Research Conference - invited session organizer and moderator, Ventura, CA
Presentations at academic meetings
Velisar A., Herron J.A., Syrkin-Nikolau J., Blumenfeld Z., Trager M.H., Martin T., Chizeck H.J., Bronte-Stewart H. Closed Loop STN DBS for Tremor in Parkinson's disease using a Neural or Kinematic Signal. 21st International Congress of Parkinson's Disease and Movement Disorders, 2017, June 4-8, Vancouver BC - in review
Haddock A, Velisar A, Herron J, Bronte-Stewart H, Chizeck H, Model Predictive Control of Deep Brain Stimulation for Parkinsonian Tremor. 8th International IEEE EMBS Neural Engineering Conference, 2017, May 25-28, Shanghai China
Velisar A, Herron J. A. , Syrkin-Nikolau J., Blumenfeld Z., Trager M. , Martin T., Chizeck H. J., Bronte-Stewart H. Kinematic and neural triggered adaptive deep brain stimulation for tremor dominant Parkinson's disease. Program No. 041.07. 2016 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2016. Online.
A. Velisar MS, L. A. Shreve BS, E. J. Quinn BS, J. A. Syrkin-Nikolau BS, M. Trager BS, Z. Blumenfeld BS, M. Miller-Koop PhD, M. Malekmohammadi PhD, H. Bronte-Stewart MD MSE. Adaptive Closed Loop Neuromodulation and Neural Signatures of Parkinson's Disease. MJFFox 2016 Parkinson's disease Therapeutics Conference, New York, NY, 2016
A. Velisar, J. A. Syrkin-Nikolau, M. Trager, Z. Blumenfeld, M. Miller-Koop, M. Malekmohammadi, J. Heron, H. Chizeck, H. Bronte-Stewart. Kinematic versus Neural triggered Adaptive DBS in a tremor dominant Parkinson's disease patient. 4th World Parkinson Congress, 2016, Portland, OR - [abstract], Journal of Parkinson's Disease, vol. 6, no. s1, pp. 83, 2016, doi:10.3233/JPD-169900