Two BRAIN-funded studies in small groups of individuals demonstrate inclusion of DBS in therapy may improve treatment. A third BRAIN-supported paper explores questions regarding posttrial needs of study participants living with neural implanted devices and highlights the importance of integrating a neuroethical strategy from the beginning of a research project.
Deep brain stimulation (DBS) is a neurosurgical procedure that involves implanting tiny wires into specific areas of the brain to treat various disorders and diseases. Since its initial approval in the late 1990’s to treat tremors associated with certain neurological diseases, DBS has been expanded to many more disorders. The National Institutes of Health (NIH)’s Brain Research Through Advancing Innovative Neurotechnologies® Initiative, or The BRAIN Initiative®, is at the forefront of supporting the acceleration of neurotechnologies, like DBS. The NIH BRAIN Initiative aims to improve our understanding of the human brain and ensure that the ethical considerations that accompany these studies are thoughtfully integrated. Specifically, two separate studies that were funded by the NIH BRAIN Initiative demonstrate how DBS can be incorporated into clinical settings—one study explored the safety and feasibility of DBS in post-stroke therapy and a second study examined the benefit of DBS as a potential treatment for individuals living with treatment-resistant depression.
Cerebellar post-stroke deep brain stimulation appears safe and feasible in a small trial
Stroke is a common physical and neurologically debilitating disease impacting nearly 800,000 Americans each year that is caused by the interruption of blood flow to the brain. In a study published last month in Nature Medicine, an in-human phase I trial to treat post-stroke motor deficits at the Cleveland Clinic Main Campus observed that continual DBS delivered to the dentate nucleus (DN), a cluster of neurons within the cerebellum, was safe and feasible [1]. In this study, twelve individuals with moderate-to-severe upper limb impairment received DBS for four-to-eight months with physical therapy prior, during, and after stimulation. Improvements were even seen in participants who were as much as three years removed from their stroke, which is well outside the time window typically associated with functional recovery. Specifically, nine of the twelve participants showed improved motor function, which aligned with having some preservation of motor function post-stroke. The findings of this trial, while preliminary, suggest that the addition of DBS to physical therapy post-stroke is promising and informative for subsequent larger randomized-controlled studies. Read more about this DBS study here.
Researchers discover biomarker for tracking depression recovery
Recently published last week, a novel experimental study for treatment-resistant depression conducted at Emory University, Georgia Institute of Technology, and the Icahn School of Medicine at Mount Sinai found that DBS coupled with an artificial intelligence (AI) recording tool identified a brain activity signature, known as a biomarker [2]. Treatment-resistant depression is a type of major depressive disorder (MDD) that is unresponsive to at least two different antidepressants and effects 30% of individuals diagnosed with it. In this study, ten participants with treatment-resistant depression received the same stimulation to start, which became personalized across a 6-month period that was targeted to the subcallosal cingulate cortex (SCC), a brain region involved in emotional behavior. Nine of the ten participants demonstrated significant clinical response, while 70% achieved treatment-resistant depression remission. The use of AI tools to observe a treatment-resistant depression biomarker before and after DBS provides an objective neurotechnology that can improve the treatment of a traditionally subjectively and variable clinical disorder. For more about this study, read the press release.
Continuing trial responsibilities for implantable neural devices
The NIH BRAIN Initiative supports research projects that examine the neuroethical and societal implications of BRAIN-funded tools and technologies, such as DBS. A portion of a multi-part strategy that seeks to achieve proactive management and ongoing assessment of the neuroethical implications of BRAIN-supported work includes the neuroethical considerations researchers should examine regarding continuing responsibilities to participants of implanted neural device trials, after the trial has ended. A new paper, highlighted in a recent BRAIN Blog post and published in Neuron, takes an in-depth look at the posttrial needs of study participants, including posttrial-associated care, continued access to the device and maintenance, and/or removal of the device [3]. The authors suggest several strategies for approaching posttrial needs, along with specific points to consider when planning a trial. To further explore the details of these recommendations, read the complete article in Neuron.
Together, these BRAIN-funded studies highlight how expanding the use of DBS neurotechnology may have a direct impact on human health, with the potential to treat brain disorders and diseases. As these technologies continue to advance, BRAIN is also leading the way in ensuring that neuroethical questions that may arise in human studies and posttrial care are well integrated with the science.
References
[1] Baker KB, et al. “Cerebellar deep brain stimulation for chronic post-stroke motor rehabilitation: a phase I trial.” August 14, 2023. Nature Medicine. DOI: 10.1038/s41591-023-02507-0
[2] Alagapan, S, et al. “Cingulate dynamics track depression recovery with deep brain stimulation.” September 20, 2023. Nature. DOI: 10.1038/s41586-023-06541-3
[3] Hendriks, S, et al. "Continuing trial responsibilities for implantable neural devices." August 14, 2023. Neuron. DOI: https://doi.org/10.1016/j.neuron.2023.07.008