Deep brain stimulation (DBS) conducted for routine clinical care has opened an opportunity to explore the possible collection of a brain biopsy for research purposes. Attention has recently been drawn to brain biopsies collected purely for investigative purposes, without serving any immediate diagnostic purpose or eliciting any therapeutic benefit. Such biopsies are frequently performed in oncology¹ and are not inherently unethical. However, these protocols have not been routinely used in neurosurgery, and this raises concerns about the amount and content of the detail that should be provided to patients concerning the benefits, burdens, and risks of a brain biopsy and about who is the most appropriate to deliver this information.

There are several relevant challenges regarding the ethics of brain biopsy during DBS implantation surgery. First, it is difficult to know what specific or generalized physiological, cognitive, and behavioral functions even small volumes of brain tissue may serve, and to what extent. Second, the target of the brain biopsy may be remote from the target of the care-based surgery. This is the case in DBS surgery, for example. Finally, the true effect of the biopsy on brain networks is not fully known. There should be sound justification for a nontherapeutic brain biopsy to both support the potential value of the tissue sought and balance any potential harms to the patient. Current and emerging techniques and technologies in imaging and biophysical modeling could—and should—be developed and used to maximize understanding of the brain networks involved. This effort will likely enable a natural evolution toward more precise and safer remote-site brain biopsy.

The unknowns of any procedure should be carefully explained to patients during the consenting process. Informed consent is an ethical staple of any contemporary medical intervention, whether for therapeutic or research purposes. The focus of consent is the provision of information about major burdens and risks of the procedure and how these risks balance with the intended, most probable, or possible benefits. Central to this process is transparency in and veracity of any and all information provided.² In this way, informed consent serves to empower the patient by sustaining their autonomous right to refuse any and all procedures offered and enables clinicians and researchers to conduct procedures with ethical probity.³ Consent for neurosurgical procedures like DBS, which may involve both a therapeutic procedure and collection of a brain biopsy for research purposes, must acknowledge all unknowns. Furthermore, consent must clarify whether continued study and care of patients undergoing biopsy will remain available.⁴

Often, it is the attending clinician who both provides information to and obtains consent from the patient to be treated. However, research consent must be obtained without coercion to be valid. The attending surgeon and principal research investigator are powerful figures that may exert considerable influence over patients’ decision-making.^3,5 Although these parties can provide information and answer questions about the research procedure, protocols, benefits, burdens, and risks involved, they should not be directly present when the patient renders his or her decision for consent or refusal of a nontherapeutic brain biopsy. Creating a safe space apart from the treating clinician to allow patients to decide on a nontherapeutic biopsy can help lessen possible feelings of coercion.

Who might be best to obtain consent, and what process would be most effective for obtaining informed consent for a DBS surgery that also involves a brain biopsy collected for the sole purpose of research? The principal research investigator, not the surgeon, should ensure that the patient comprehends the protocols and procedures and their attendant benefits, burdens, and risks. The principal research investigator should answer all questions asked by the patient and/or their family or legal proxy. In addition, there should be another independent proxy, which is endorsed by the institutional review board as appropriate, who obtains the actual consent (Figure).

Moreover, when requesting informed consent to biopsy brain tissue for research and during DBS implantation surgery, it is advocated that the consent form should ideally include check boxes to grant a research participant the opportunity to request more information and greater clarification about several factors, including the size of the biopsy; possible short-term and long-term risks; the research questions to be addressed; and whether and how the biopsy materials will be made available to outside investigators. Another suggestion would be adding an additional check box on the informed consent form for research subjects to request discussion with the surgeon to define the specifics, burdens, and risks of the biopsy, over and above those inherent to the DBS implantation procedure itself. Of course, some of the risks are unknown, and this must be communicated to patients in the spirit of intellectual honesty and veracity, which are cornerstones of the moral practice of medicine.² This discussion should occur prior to the day of the procedure.

Benevolent aims are central to both treatment and research. But given that the good aims and ends of research (ie, successful experimental outcomes) are axiomatically tentative, the secondary maxim of clinical medicine—nonharm—is actually the primary realistic obligate of research. It may well be that biopsies taken during DBS implantation surgery will be valuable to the furtherance of research and the knowledge it affords. However, this remains to be demonstrated. Thus, thorough provision of information about all aspects of the investigational protocols, inclusive of the benefits, uncertainties, burdens, and risks of obtaining the tissue necessary for forthcoming studies, should be afforded to subjects to sustain the rectitude of all domains and dimensions of research-in-practice.

Corresponding Author: Michael S. Okun, MD, Norman Fixel Institute for Neurological Diseases, University of Florida Health, 3011 SW Williston Rd, Gainesville, FL 32608 (okun@neurology.ufl.edu).

Published Online: September 16, 2024. doi:10.1001/jamaneurol.2024.3018

Conflict of Interest Disclosures: Dr Okun reported grants from the US National Institutes of Health (NIH), the Michael J. Fox Foundation, the Tourette Association of America, the Parkinson’s Foundation, the Smallwood Foundation, the Bachmann-Strauss Dystonia & Parkinson Foundation, and the University of Florida Foundation; serving as a medical advisor for the Parkinson’s Foundation, as principal investigator of the NIH R25NS108939 training grant, and as an associate editor for New England Journal of Medicine Journal Watch Neurology; research support from grants R01NS131342, NIH R01NR014852, R01NS096008, UH3NS119844, UH3NS095553, and U01NS119562 (University of Florida); receiving royalties for publications with Hachette Book Group, Demos, Manson, Amazon, Smashwords, Books4Patients, Perseus, Robert Rose, Oxford, and Cambridge; and participating in continued medical education and educational activities on movement disorders in the past 12 to 24 months sponsored by WebMD/Medscape, RMEI Medical Education, the American Academy of Neurology, the Movement Disorders Society, Mediflix, and Vanderbilt University. No other disclosures were reported.

Additional Contributions: We thank Alfonso Enrique Martinez Nunez, MD (University of Florida), for assistance with the artwork provided in the figure. Dr Martinez Nunez was compensated for his contribution.