Deep brain stimulation tested as a means of restoring lost function following traumatic brain injury

A BRAIN-funded study explores a novel approach of applying deep brain stimulation (DBS) to treat the symptoms associated with traumatic brain injury. A second BRAIN-funded study examines the continued integration and understanding about the ethical implications of technologies like DBS. 

Deep brain stimulation (DBS), a procedure where clinicians implant very fine wires into specific regions of the brain to change activity at those areas, has shown remarkable potential to help treat neurological disorders and injury. Since issuing its first awards in 2014, the NIH’s Brain Research Through Advancing Innovative Neurotechnologies® Initiative, or The BRAIN Initiative®, has been at the forefront in driving the development of innovative neurotechnologies like DBS. A recent BRAIN Initiative-funded study took the novel approach of applying DBS treatment to treat the symptoms associated with traumatic brain injury [1]. This trial highlights the potential of research funded by the BRAIN Initiative and serves as a reminder of both the hopes and limitations of current technologies.

In December 2023, a team of researchers and clinicians from multiple institutions, published a paper in Nature Medicine showing that DBS delivered to a part of the brain called the thalamus helped five people recover some measure of higher brain processing that had been lost following traumatic brain injury.

Six participants were enrolled in this trial and implanted with a DBS device designed to stimulate nerves leaving the central lateral nucleus of the thalamus. The thalamus can be thought of as the brain’s Grand Central Station. Nearly all motor and sensory inputs (except for smell) pass through the thalamus where they are routed to other parts of the brain for additional processing and interpretation. One specific area of the thalamus, the central lateral nucleus, plays an important role in tying the prefrontal cortex and striatum into the “frontostriatal” networks that perform executive functions like planning and organization, problem-solving, and emotion regulation.

The researchers were able to confirm that the implanted electrodes were located correctly and were able to stimulate nerve fibers leaving the thalamus. Although one participant had to leave the study after developing an infection following implantation, each of the five remaining participants showed improvements in a variety of behavioral assessments designed to test various executive functions once the devices were turned on.

It has been suggested that, following brain injury, the central lateral nucleus becomes less active, which can impact the ability of frontostriatal networks to function. In this trial, the central lateral nucleus was directly stimulated by DBS, and this was accompanied by improved cognitive abilities in the participants.

The biggest caveat to these findings was their preliminary nature. The primary goal of the research, a phase 1 feasibility study, was to determine whether the treatment can be performed in a safe and effective manner. While it is impossible to draw definitive conclusions from such a small sample size (five participants), the results are nevertheless encouraging.

Neuroethics of DBS and other technologies that alter the brain

In addition to the cutting-edge science it supports, the NIH BRAIN Initiative has a multi-part strategy to achieve proactive, ongoing assessment and management of the neuroethical implications of the development and application of BRAIN-funded tools and neurotechnologies. This strategy includes a commitment to supporting explorations of the ethical and societal implications of BRAIN-funded tools and technologies through its neuroethics program. DBS, along with other implanted neural devices, has had a long history of discussions related to its ethical considerations, with topics ranging from continued access to treatment to responsibilities for long-term maintenance of implanted devices to the potential impact of the device on personality and personal identity. These latter concerns are particularly relevant in DBS interventions like the one described here, which aims to directly affect how a participant’s brain processes information—in essence potentially changing how they think about and/or perceive the world.

These and other questions were addressed directly by the team in a second paper describing conversations with trial participants and their families following the conclusion of the device trial [2]. While specific experiences varied, some common themes emerged. Some of the relevant neuroethical considerations in this space focus on the potential impact neuromodulation could have on a person’s identity, yet the consensus among the trial participants was that it was their brain injury that was the cause of any alterations in their personality—neuromodulation simply helped preserve or restore their personal identity.

That said, there was considerable emphasis made by the interviewees about the importance of having psychosocial support, for both the participants and their loved ones. Sudden impacts on brain function, even when they are perceived as positive, can profoundly impact a person’s view of the world and their relationships. For example, one participant remarked that she needed “smarter friends” now that her cognitive abilities had improved. Some family members (and some participants themselves) also remarked that seeing such radical and quick improvement brought on a renewed sense of mourning as they thought back on the years between the initial traumatic brain injury and the DBS trial as time that was lost.

Other concerns related to the post-trial obligations of the investigators. Questions about insurance coverage for device maintenance and the long-term effects of implantation were common, as were questions related to whether they would be allowed to continue with treatment even if insurance wouldn’t cover maintenance costs. Finally, because this was a short-term feasibility study that took place over three months, concerns were raised about the longevity of the treatment’s efficacy. While the investigators view this type of intervention as a potential chronic therapy, longer term follow-up is needed to determine if the effects will persist or wane over time. The loss of efficacy in chronic DBS treatment for disorders such as Parkinson’s disease would support the importance of this type of study. Many of the questions raised in these interviews closely track with work done by the BRAIN Neuroethics Working Group (NEWG), including a workshop on continuing trial responsibilities(pdf, 459 KB), as well as a related discussion of post-trial needs related to implantable neural devices that was published in October 2023 [3] and described in a previous BRAIN Blog post.

Studies such as the work described in this blog post show the remarkable potential that DBS neurotechnologies can have on human health. This type of research also raises ethical questions that only a few years ago seemed out of the realm of possibility by neuroscientists and clinicians. By both supporting research projects that develop groundbreaking neurotechnologies and driving conversations that facilitate continued integration and understanding about the ethical implications of those technologies, the NIH BRAIN Initiative is leading the way in integrating cutting-edge science and the ethical questions that can and will arise.

References

[1] Schiff ND, et al. “Thalamic deep brain stimulation in traumatic brain injury: a phase 1, randomized feasibility study.” December 4, 2023. Nature Medicine. DOI: 10.1038/s41591-023-02638-4

[2] Fins JJ et al. “Subject and family perspectives from the central thalamic deep brain stimulation trial for traumatic brain injury: part II.” October 18, 2023. Cambridge Quarterly of Healthcare Ethics. DOI: 10.1017/S0963180123000518

[3] Hendriks S et al. “Continuing trial responsibilities for implantable neural devices.” October 18, 2023. Neuron. DOI: 10.1016/j.neuron.2023.07.008

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