Prefrontal cortex biopsies taken for research purposes during deep brain stimulation (DBS) procedures appeared to be safe, new research has suggested.

Investigators found no significant differences in rates of intracranial hemorrhage (ICH), seizures, or infection between 1152 DBS procedures performed with or without research biopsies of healthy tissue. Cognitive performance also remained stable in a subset of patients who underwent pre- and postprocedure testing.

These findings, they say, support the safety of taking biopsies as part of the DBS protocol in the Living Brain Project at Mount Sinai Hospital and the Icahn School of Medicine at Mount Sinai in New York City.

Study investigator Alexander W. Charney, MD, PhD, associate professor of psychiatry, neuroscience, neurosurgery, and genetic and genomic sciences at Mount Sinai, said the team wanted to use its own data to determine whether the procedure was associated with any adverse effects on brain function or cognition.

“This procedure is as safe as the standard one, but with the huge added benefit that we are able to advance science by obtaining these biopsies for research,” study investigator told Medscape Medical News.

He noted that neither the research team nor regulatory authorities had concerns about the safety of performing biopsies during DBS surgery and that after hundreds of procedures, they observed no evidence of increased risk compared with standard DBS alone.

The study was published online on September 3 in Neurosurgery.

Media Controversy

Founded in 2013, the Living Brain Project was established to study living human brain tissue collected during DBS surgery, allowing researchers to compare it with postmortem samples and link these findings to detailed clinical and cognitive assessments to advance understanding of neurologic disorders.

The project includes patients undergoing DBS for various indications. DBS is an elective, well-controlled procedure performed frequently. The same brain region is sampled in each patient, enabling direct comparison of living tissue with postmortem samples.

Project participants also undergo comprehensive preoperative evaluations — including behavior, movement, and cognitive assessments — along with neuroimaging and intraoperative monitoring of brain electrical activity.

In 2024, the removal of healthy prefrontal cortex tissue from one or both hemispheres during DBS generated some controversy. A report by STAT News questioned the ethics of the technique and size of the biopsies taken. STAT reported the technique included removal of biopsies up to 1 cc from each hemisphere.

However, Charney said the STAT report was not factually correct. The 1 cc was an upper estimate of the amount of tissue that could be lost during traditional DBS without a biopsyas outlined in consent forms. For example, if bleeding required more cauterization than usual, that could lead to up to 1 cm² of tissue loss, he explained.

In the study, the actual mean biopsy size was 0.04 cc, with an outlier of 0.064 cc, which may have resulted from a measuring error, the researchers noted.

The biopsies were no larger than the amount of tissue removed with cauterization prior to electrode placement, Charney added. “We wouldn’t have done this study if we thought there was more tissue being lost as part of the research,” he said.

Charney noted that while media coverage last year influenced the timing of the current study, it did not affect the analysis. “We’ve had these data for years,” he said. He and his colleagues have been monitoring safety and presenting findings at conferences since 2013, with no peers raising concerns, he said.

Nonetheless, the original STAT article and a follow-up piece “created a lot of buzz within our small field of DBS,” Charney said. The coverage was “almost traumatic for me. You know you’re doing something for the greater good, and to see it portrayed in such a dark way was staggering.”

No Differences in Outcomes

The study included 1152 procedures in 590 individuals. Of the 409 participants enrolled in the Living Brain Project, 384 underwent biopsies in 652 procedures. The nonbiopsy group comprised 500 procedures in 384 individuals, including 98 who had multiple DBS procedures, at least one of which included a biopsy.

All procedures were performed by Brian H. Kopell, MD, at Mount Sinai from 2013 to 2024. Kopell is a professor of neurosurgery, neurology, psychiatry, and neuroscience, and a neurosurgical editor for Medscape.

CT scans were performed within hours of each procedure. Patients were assessed for ICH, seizures, and infections around the time of DBS and up to 90 days following the surgery.

A subset of 144 participants completed cognitive and mental health testing at baseline and at 1 year.

There was no significant difference between the 11 ICHs in the biopsy group and the 7 in the nonbiopsy cohort (1.7% vs 1.4% rate; chi-square test P = .88). Similarly, investigators found no significant difference between the one seizure in the biopsy group and two seizures in the nonbiopsy group (0.2% vs 0.4% rate; chi-square test P = .82).

Tissue volume estimates were based on 231 biopsies. The authors noted that biopsy size was unlikely to exceed 0.75 cc, the technical limit of the sampling instrument.

In a subset of participants, neuropsychological testing at baseline and 1 year assessed general intelligence, language, visuospatial skills, attention, processing speed, executive function, memory, and affective state.

Of the 144 participants who completed this testing, 92 underwent at least one biopsy, and 52 were in the nonbiopsy group.

The investigators found no significant correlation between cognitive performance and the number of biopsies taken, after adjusting for 26 neuropsychiatric tests. They did observe a nominal association between the number of biopsies and clinical improvement over time on the Parkinson’s Disease Questionnaire-8 (PDQ-8) communication subscale and total scores.

A ‘Treasure Trove’ of Data

Similarly, no significant correlation emerged between cohorts regarding changes in test scores over time using the Student t-test. A nominally significant improvement in clinical outcomes in the biopsy group was observed on the PDQ-8 activities of daily living and the PDQ-8 total score.

In the full cohort of 144 participants, scores on the FAS test and the animal naming test significantly declined over time, as assessed by paired Student t-tests. Apathy ratings on the Starkstein scale also showed a significant increase over time.

The potential advances from studying these living brain samples justify asking people who are about to undergo neurosurgery if they would be willing to consider participating in the research, Charney said. Not all studies are the same, he added, and “you want the type of research you propose to do…to answer a really important question. We take this very seriously.”

A related study, published online on August 23 in Molecular Psychiatry, showed differences in the majority of gene and protein expression between living brain biopsies and postmortem samples. Charney, a coauthor of the study, noted that these findings are controversial in the field, as many researchers rely on postmortem tissue — but that is what their data indicate.

The investigators are seeking continued funding from the National Institutes of Health. “Unfortunately. STAT News has changed the future prospects for the study,” Charney said. “As scientists, we don’t have a platform to respond quickly. Our publication process takes longer.”

“Hopefully, the narrative will change based on data and as opposed to incorrect information,” he added.

Charney noted his team has several hundred samples in the freezer that have never been studied. “It’s a treasure trove of information that could help us understand a variety of brain conditions.” With renewed funding, he hopes to analyze those samples “and get back to focusing on the science.”

Commenting for Medscape Medical News, Alberto Priori, MD, PhD, full professor of neurology at the University of Milan, Milan, Italy, who was not involved in the study, described the research as a strong and interesting demonstration that modern methods confirm the safety of cortical biopsy.

Also commenting for Medscape Medical News, Kim Burchiel, MD, professor and chairman emeritus of the Department of Neurological Surgery at Oregon Health & Science University in Portland — and one of the neurologists quoted in the STAT News article — noted that retrospective studies have limitations. He added that when the same group performing the biopsies also tracks their safety, “it always introduces the possibility of bias, but the result is still important.” 

Consent Dispute Addressed

“Given the location of the biopsies, I am not surprised that the outcomes were comparable from the standpoint of safety,” he said. 

“The problem I have always had with this study was that the biopsies were performed without the explicit consent of the patients,” Burchiel added. He clarified that this was his impression up until the 2024 media coverage of the technique.

However, a spokesperson for Mt. Sinai countered that “for the entirety of the 11 years this study has been going on, there has always been a consent form in place that includes language and detail around the biopsy. Biopsy has been the seminal aspect of the [Living Brain Project] from its inception. The idea that a separate consent for biopsy only happened after 2024 is absurd and counterfactual.”

The study was supported by a grant for Charney from the National Institute on Aging. Kopell serves as a consultant for Medtronic, Abbott Neuromodulation, and Turing Medical. Priori and Burchiel reported having no relevant financial disclosures.