Neuroethics of aDBS Systems Targeting Neuropsychiatric and Movement Disorders

The NIH BRAIN Initiative has made a substantial investment to accelerate the development of adaptive deep brain stimulation (aDBS) systems for improving clinical management of treatment-resistant psychiatric and motor disorders.

aDBS systems have emerged as a promising alternative to address significant limitations in conventional open-loop DBS treatment of neuropsychiatric and movement disorders. Studies suggest that open-loop DBS systems can effectively manage treatment-resistant obsessive-compulsive disorder, depression, Parkinson’s disease, Tourette syndrome, and essential tremor, among other disorders.

Unlike DBS, aDBS can record neural activity or other symptom-related markers to adjust stimulation in real time. Therefore, aDBS could provide stimulation only when necessary, avoid overtreatment, and minimize programming trial and error, and potential side effects (e.g. hypomania, changes in personality). In addition, aDBS can lead to improved clinical responses over DBS because it adjusts automatically, thus, it avoids the delay between suboptimal symptom management and adjustment of stimulation in a clinical encounter.

Safe and effective aDBS systems would be a welcomed advance for many patients with neuropsychiatric and movement disorders, but these systems potentially generate difficult ethical challenges that require attention.

Many of the features that make aDBS promising may exacerbate some of the ethical, legal, and social (“neuroethics”) concerns that have been raised about conventional open-loop DBS (e.g. dehumanization, changes in personal identity/personality, changes in participants’ sense of authenticity). aDBS also raises novel issues, which may impact uptake of this new technology, such as the privacy and ownership of recorded neural activity, and if patients have some control over stimulation, the potential for human enhancement by excessive manipulation of symptoms.

The long-term goal of our research program is to develop an ethically-justified and empirically-informed policy framework for the responsible research and translation of aDBS. The objective of this project, which is the first logical step in pursuit of that goal, is to critically evaluate whether pressing neuroethics issues related to aDBS, as identified by key stakeholders, are adequately addressed by current policy and what new policies are needed.

We have received two diversity supplements as part of this work

• An administrative supplement to help enhance diversity in neuroethics by training Katrina Munoz from Baylor College of Medicine in neuroethics research
• An administrative supplement to help enhance diversity in neuroethics by training Professor Demetrio Sierra from the University of Puerto Rico School of Medicine in neuroethics research. The goal is to help launch this professor’s career as an independent neuroethics researcher and help develop a neuroethics program at the University of Puerto Rico.
   

Supported by: R01 MH114854, National Institute of Mental Health, NIH

Gabriel Lázaro-Muñoz, J.D., Ph.D., M.B.E., Co-Principal Investigator
Amy McGuire, J.D., Ph.D., Co-Principal Investigator
Wayne Goodman, M.D., Co-Principal Investigator
Kristin Kostick-Quenet, Ph.D.
Stacey Pereira, Ph.D.

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Kostick-Quenet K, Kalwani L, Koenig B, et al. Researchers' Ethical Concerns About Using Adaptive Deep Brain Stimulation for Enhancement. Front Hum Neurosci. 2022;16:813922. Published 2022 Apr 14. doi:10.3389/fnhum.2022.813922

Outram S, Muñoz KA, Kostick-Quenet K, et al. Patient, Caregiver, and Decliner Perspectives on Whether to Enroll in Adaptive Deep Brain Stimulation Research. Front Neurosci. 2021;15:734182. Published 2021 Oct 7. doi:10.3389/fnins.2021.734182 

Zuk P, Sanchez C, Kostick K, Torgerson L, Muñoz KA, Hsu R, Kalwani L, Sierra Mercado D, Outram S, Koenig BA, Pereira S, McGuire AL, Lázaro-Muñoz G. Researcher Perspectives on Data Sharing in Deep Brain Stimulation. Frontiers in Human Neuroscience.  

Muñoz KA, Kostick K, Sanchez C, Kalwani L, Torgerson L, Hsu R, Sierra-Mercado D, Outram S, Koenig BA, Pereira S, McGuire A, Zuk P, Lázaro-Muñoz G (Accepted). Researcher Perspectives on Ethical Considerations in Adaptive Deep Brain Stimulation Trials. Frontiers in Human Neuroscience.

Wu H, Hariz M, Visser-Vandewalle V, Zrinzo L, Coenen V, Sheth S, Bervoets C, Naesström M, Blomstedt P, Coyne T, Hamani C, Slavin K, Krauss JK, Kahl KG, Taira T, Zhang C,
Sun B, Toda H, Schlaepfer T, Chang JW, Régis J, Schuurman R, Schulder M, Doshi P, Mosley P, Poologaindran A, Lazaro-Munoz G, Pepper J, Schechtmann G, Fytagoridis A, Huys D, Gonçalves-Ferreira A, D’Haese PF, Neimat J, Broggi G,
Vilela-Filho O, Voges J, Alkhani A, Nakajima T, Richieri R, Djurfeldt D, Fontaine P, Martinez-Alvarez R, Okamura Y, Chandler J, Watanabe K, Lozano A, Gabriëls L, De Salles A, Halpern C, Matthews K, Fins J, Nuttin B. (2020). Deep Brain Stimulation for Refractory Obsessive-Compulsive Disorder (OCD): Emerging or Established Therapy? Molecular Psychiatry.

   
Storch EA, Cepeda SL, Lee E, Goodman S.L.V., Robinson AD, De Nadai A.S., Schneider S.C., Sheth S, Torgerson L, Lázaro-Muñoz G (2020). Parental Attitudes Toward Deep Brain Stimulation in Adolescents with Treatment-Resistant Conditions. J Child Adolescent Psychopharmacol Mar;30(2):97-103.
  
Ramirez-Zamora A, Giordano JJ, Boyden ES, Gradinaru V, Gunduz A, Starr PA, Sheth SA, McIntyre CC, Fox MD, Vitek JL, Vedam-Mai V, Akbar U, Almeida L, Bronte-Stewart HM,
Mayberg HS, Pouratian N, Gittis A, Singer AC, Creed MC, Lázaro-Muñoz G, Richardson MR, Rossi MA, Cendejas-Zaragoza L, D'Haese P-F, Chiong W, Gilron R, Chizeck H, Ko A, Baker KB, Wagenaar J, Harel N, Deeb W, Foote KD, Okun MS (2019) Proceedings of the Sixth Deep Brain Stimulation Think Tank Modulation of Brain Networks and Application of
Advanced Neuroimaging, Neurophysiology, and Optogenetics. Frontiers in Neuroscience Vol. 13, 936.
   
Zuk P & Lázaro-Muñoz G (2019). DBS and Autonomy: Clarifying the Role of Theoretical Neuroethics. Neuroethics.
    
Zuk P & Lázaro-Muñoz G (2019). Ethical Analysis of “Mind Reading” or “Neurotechnological Thought Apprehension”: Keeping Potential Limitations in Mind. AJOB neuroscience 10(1): 32-34.

Kostick KM, Sierra-Mercado D, Lázaro-Muñoz G (2019) Ethical and Social Considerations for Increasing Use of DTC Neurotechnologies. AJOB neuroscience Oct;10(4):183-185.

Sierra-Mercado D, Zuk P, Beauchamp MS, Sheth SA, Yoshor D, Goodman, WK, McGuire AL, Lázaro-Muñoz G (2019). Device Removal Following Brain Implant Research. Neuron 105(5):759-61.

Lázaro-Muñoz G, Zuk P, Pereira, Kostick K, Torgerson L, Sierra-Mercado D, Majumder M, Blumenthal-Barby J, Storch EA, Goodman WK, McGuire AL (2019). Neuroethics at 15: Keep the Kant but Add More Bacon.  American Journal of Bioethics: Neuroscience 10(3):97-100.
     
Lázaro-Muñoz G, Zuk P, Pereira S, Kostick K, Torgerson L, Sierra-Mercado D, Robinson J, Majumder M, Blumenthal-Barby J, Storch E, Sheth SA, Yoshor D, Goodman, WK,
McGuire AL.  (2019) Comment on:  Neuroethics Roadmap. Advisory Committee to the Director Working Group on BRAIN 2.0 Neuroethics Subgroup (BNS).

Lázaro-Muñoz G, Yoshor D, Beauchamp M, Goodman WK, McGuire AL (2018). Continued Access to Investigational Brain Implants. Nature Reviews Neuroscience doi: 10.1038/s41583-018-0004-5.

Zuk P, Torgerson L, Sierra-Mercado D, Lázaro-Muñoz G (2018). Neuroethics of Neuromodulation: An Update. Current Opinion in Biomedical Engineering 8:45-50 doi: 10.1016/j.cobme.2018.10.003.

Zuk P, McGuire AL, Lázaro-Muñoz G (2018). Alienation, Quality of Life, and DBS for Depression. AJOB Neuroscience 9(4):223-25.  

Sierra-Mercado D, Lázaro-Muñoz G (2018). Enhance Diversity Among Researchers to Promote Participant Trust in Precision Medicine Research. American Journal of Bioethics 18(4):44-46.  

Brannan C, Foulkes AS, Lázaro-Muñoz G (2018). Preventing Discrimination Based on Psychiatric Risk Biomarkers. AJMG Part B: Neuropsychiatric Genetics doi: 10.1002/ajmg.b.32629.
 

Sierra-Mercado D, Lázaro-Muñoz G. (2018) Enhance Diversity Among Researchers to Promote Participant Trust in Precision Medicine Research. American Journal of Bioethics 18(4):44-46.

Lázaro-Muñoz G, McGuire AL, Goodman WK. "Should We Be Concerned About Preserving Agency and Personal Identity in Patients with Adaptive Deep Brain Stimulation Systems?" AJOB Neuroscience. 2017;8(2):73-75.

Life and Health Decisions with Experimental Brain Implants. International Neuroethics Society Annual Meeting; Virtual. Lázaro-Muñoz, G. (October 2020).

Neuroethics Methodology and the Is-Ought Gap. International Neuroethics Society, Poster Session, Online.  Zuk, P. (October 2020).

Researchers’ Perspectives on Changes in Personality, Mood, and Behavior in Adaptive Deep Brain Stimulation Trials. International Neuroethics Society, Poster Session, Online.  Zuk, P., Sanchez, C., Lavingia, R., Torgerson, L., Kostick, K., Muñoz, K., et al. (October 2020).

Will cultural beliefs and attitudes lead to social disparities in neurotechnology use? International Neuroethics Society, Virtual. Kostick K, Kalwani, L, Zuk P, Muñoz K, Torgerson L, Sanchez C, Hsu Rebecca, Sierra-Mercado D, Outram S, Koenig B, Pereira S, McGuire A, Lázaro-Muñoz G (October 2020)

Researcher Perspectives on Ethical Considerations in Adaptive Deep Brain Stimulation Trials. International Neuroethics Society Annual Meeting, Poster Presentation, Washington, D.C. Muñoz, K.A., Kostick, K., Sanchez, C., Kalwani, L., Torgerson, L., Hsu, R., Sierra-Mercado, D., Robinson, J.O., Outram, S., Koenig, B.A., Pereira, S., McGuire, A., Zuk, P., Lázaro-Muñoz, G. (October 2020). 

Researchers’ views on device removal following brain implant research. International Neuroethics Society Annual Meeting; Virtual. Sierra-Mercado, D, Kostick K, Torgerson L, Hsu R, Outram S, Koenig BA, Pereira S, McGuire A, Zuk P, Lázaro-Muñoz G (October 2020).

Brain Organoids and Uncertainty. American Society for Bioethics and Humanities. Panel Session, Online.  Zuk, P. (October 2020). 

Researcher Perspectives on Ethical Considerations in Adaptive Deep Brain Stimulation Trials. American Society for Bioethics and Humanities Annual Meeting, Talk Presentation, Baltimore, MD. Muñoz, K.A., Kostick, K., Sanchez, C., Kalwani, L., Torgerson, L., Hsu, R., Sierra-Mercado, Robinson, J.O., D., Outram, S., Koenig, B.A., Pereira, S., McGuire, A., Zuk, P., Lázaro-Muñoz, G. (October 2020). 
 
Beyond treatment: Researchers’ perspectives on the use of adaptive deep brain stimulation (aDBS) for enhancement. American Society for Bioethics and Humanities 22nd Annual  Meeting, Virtual. Kostick K, Kalwani L, Torgerson L, McGuire A, Zuk P, Lázaro-Muñoz G (October 2020).

Researchers’ Perspectives on Changes in Personality, Mood, and Behavior in Adaptive Deep Brain Stimulation. BRAIN Initiative PI Meeting, Poster Session, Online.  Zuk, P., Sanchez, C., Torgerson, L., Kostick, K., Muñoz, K., Kalwani, L., et al. (June 2020).
 
Researchers’ Perspectives on Continued Access to Deep Brain Stimulation at the End of Trials. DBS Think Tank; Virtual. Lázaro-Muñoz G (2020).

How do you treat DBS patients during a pandemic?: Ethical and practical challenges to consider. COVID Research Seminar Series, Baylor College of Medicine, Virtual. Kostick K, Storch E, Lázaro-Muñoz G (June 2020).

How Does Neuroethics Contributes to Advances in Neurosciences? University of Puerto Rico NeuroBoricuas Seminar; Virtual. Lázaro-Muñoz G (2020).

Patients’ Perspectives on Closed-Loop Deep Brain Stimulation Devices. Texas Association of Neurological Surgeons Annual Meeting; Dallas, TX. Lázaro-Muñoz G (2020).

Post-trial Obligations Following Brain Implant Research. Texas Association of Neurological Surgeons Annual Meeting; Dallas, TX. Lázaro-Muñoz G (2020).

Continued Access to Investigational Brain Implants: Neuroethics, Policy, and Stakeholder Perspectives. Columbia University, New York, NY. Lázaro-Muñoz G (2020).

Post-trial Obligations Following Implantable Neural Device Research. Stanford Center for Bioethics Seminar Series; Palo Alto, CA. Lázaro-Muñoz G (2019).

Researchers’ Perspectives on Continued Access to Neural Devices Following Adaptive Deep Brain Stimulation Trials. International Neuroethics Society Annual Meeting; Chicago, IL. Lázaro-Muñoz G, Kostick K, Zuk P, Torgerson L, Hsu R, Robinson JO, Sierra-Mercado D, Outram S, Koenig B, Pereira S, McGuire AL (2019).

The Neuroethics of Consciousness Research: A Call for Empirical Investigation. International Neuroethics Society Annual Meeting; Chicago, IL. Zuk P, Lázaro-Muñoz G (2019).

Patients’ reasons for declining to participate in adaptive Deep Brain Stimulation trials.  International Neuroethics Society Annual Meeting; Chicago, IL. Kalwani L, Sierra-Mercado D, Outram S, Kostick K, Zuk P, Torgerson L, Hsu R, Robinson JO, Koenig B, Pereira S, McGuire AL, Lázaro-Muñoz G (2019).

Deep Brain Stimulation (DBS) Registries: Is there an Ethical Obligation to Share Data? American Society for Bioethics and Humanities Annual Meeting; Pittsburgh, PA. Lázaro-Muñoz G, Peter Zuk P, McGuire AL (2019).

Data Sharing for Deep Brain Stimulation: Researcher Perspectives. American Society for Bioethics and Humanities Annual Meeting; Pittsburgh, PA. Zuk P, Kostick K, Torgerson L, Hsu R, Robinson JO, Sierra-Mercado D, Outram S, Koenig B, Pereira S, McGuire AL, Lázaro-Muñoz G (2019).

Device Removal Following Brain Implant Research. International Neuroethics Society Annual Meeting; San Diego, CA. Sierra-Mercado D, Zuk P, McGuire AL, Lázaro-Muñoz G. (2018).

aDBS, Automaticity, and Autonomy: In Search of a Way Forward. International Neuroethics Society Annual Meeting; San Diego, CA. Zuk P, Lázaro-Muñoz G (2018).

Right or Privilege?: Continued Access to Investigational Brain Implants. American Society for Bioethics and Humanities Annual Meeting; Anaheim, CA. Lázaro-Muñoz G, Yoshor D, Beauchamp M, Goodman WK, McGuire AL (2018).

Explantation and Continued Access to Investigational Brain Implants. BCM Neurology Grand Rounds; Houston, TX. Lázaro-Muñoz G, Yoshor D, Beauchamp M, Goodman WK, McGuire AL (2018).

Continued Access to Investigational Brain Implants. National Autonomous University of Mexico; Mexico City, MX. Lázaro-Muñoz G, Yoshor D, Beauchamp M, Goodman WK, McGuire AL (2018).

Continued Access to Investigational Brain Implants. VI DBS Think Tank; Atlanta, GA. Lázaro-Muñoz G, Yoshor D, Beauchamp M, Goodman WK, McGuire AL (2018).

Continued Access to Investigational Brain Implants. 4th BRAIN PI Meeting; Rockville, MD. Lázaro-Muñoz G, Yoshor D, Beauchamp M, Goodman WK, McGuire AL (2018).

Managing Return of Results in Genomics Research: Early lessons from psychiatric genetics research. Hispanic Community Health Study / Study of Latinos (HCHS/SOL) Genomic Reporting Committee; teleconference. Lázaro-Muñoz G (2018).

BRAIN Initiative: Neurotechnologies and Neuroethics. University of Puerto Rico School of Medicine, Institute of Bioethics; San Juan, PR. Lázaro-Muñoz G (2018).

Should Researchers Return Clinically Relevant Findings Generated in the Course of Psychiatric Genomics Studies? University of Puerto Rico, Río Piedras NEURO ID; San Juan, PR. Lázaro-Muñoz G (2018).

Right or Privilege? Continued Access to Investigational Brain Implants. University of Puerto Rico School of Law; San Juan, PR. Lázaro-Muñoz G (2018).