The zapping of the brain worked. Scientists have tried and failed for decades to prove that zapping the brain can treat depression. The findings of a current deep brain stimulation trial suggest that it might work. Since childhood, Sarah, a 36-year-old woman, has suffered from chronic, unremitting depression. “Depression had made my everyday existence so constrained and deprived that each day I forced myself to resist the suicidal thoughts that overcame me several times an hour,” she adds. Up to 30% of patients who receive depression medication are considered treatment-resistant, which indicates they’ve tried at least two different drug courses to address their condition but have seen little or no improvement in symptoms. One of these people was Sarah.
Her sorrow prompted her to enrol in a UCSF study evaluating the use of deep brain stimulation to treat treatment-resistant depression. The results of the trial were published today in Nature Medicine in a new paper. Deep brain stimulation, or DBS, is the implantation of a device that sends tiny electrical pulses to specific areas of the brain. It was first created to treat persons with Parkinson’s disease control their tremors, and the FDA first approved its use in 1997.Its rapid effectiveness sparked interest in using it to treat other neurological disorders like depression and OCD. So far, no trial has proven it to be effective. However, the findings of this study suggest that it might be possible.
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Previous attempts to use DBS to treat depression tended to target the same part of the brain in each patient, with pulses administered at a steady rate. However, because no two brains are alike, a one-size-fits-all approach to DBS may not be the best option. Knowing this, UCSF researchers modified the technology to allow it to be tailored to an individual brain for the first time. This entailed zapping the part of her brain that provided the most effective and long-lasting relief.
The researchers had to first figure out where Sarah’s sweet spot was. They implanted temporary electrodes in her brain and stimulated different areas for ten days while measuring her cerebral activity. Sarah completed surveys about her mood during this time, including depression, anxiety, and energy levels, indicating that a pattern of brain activity could be related to a specific mood fluctuation. Sarah’s ventral striatum, a portion of the brain that activates while mediating the sense of reward, proved to be the source of the most consistent and long-lasting alleviation. Scientists also discovered that by tracking activity in the amygdala, a brain region involved in emotional processing, they could forecast when Sarah’s symptoms would be at their most acute.
The device was then put in Sarah’s brain. (The battery, which is roughly the size of a matchbox, is kept in a hole doctors drilled in her right side of her head’s skull bone.)Sarah’s ventral striatum received a pulse if the device recognised that the activity in her amygdala followed a specific pattern. “The aha moment arrived,” she says of the moment she received the first stimulus. “For a little while, I felt the most overwhelmingly joyful experience, and my depression was a distant nightmare,” she recalls. “I realised that my despair was not a moral flaw as a result of the [experience].” There was hope for my recovery because it was a treatable condition.” Her suicidal ideas had fully vanished after only a few weeks of treatment. She is stimulated roughly 300 times every day, for a total of about thirty minutes of stimulation. Sarah is still reaping the same benefits fifteen months after the device was first placed.
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Scientists have been attempting to use DBS to treat treatment-resistant depression for the past two decades, but there has never been solid evidence that it helps. Like any treatment that involves opening up the brain and implanting a device, its history is littered with heated debates and failed attempts. Helen Mayberg, a professor of neurology and psychiatry at Mount Sinai’s Icahn School of Medicine, is one of the pioneers in this field. For more than a decade, Mayberg has been a forerunner in the field of DBS and depression, and he is undoubtedly its poster child. She ultimately conducted a trial, termed the BROADEN research, in 2008, to considerable fanfare and scrutiny, in which her gadget was evaluated in 200 people with TRD.
The trial was abruptly ended after funding was withheld a few years into it. Mayberg and her team are still exploring the strategy despite the trial’s poor outcome. However, she claims that the experience has made her more realistic. “That enthusiasm has been dampened, mitigated, it has matured – this is difficult.”Mayberg is excited by the new studies, but she is apprehensive. She’s curious as to what will happen next with this patient. Will she still require the gadget if she improves? Could she develop a tolerance to the stimulations and require a higher dose in the future?
Will it cause her brain to change? And while the device is based on changes in Sarah’s mood, Mayberg’s patients experience no variation in their sickness; their despair is persistent and unrelenting – a heavy vibrating hum hovering over their heads at all times. She wants to know if the device can tell the difference between the normal ups and downs of life – a difficult day at work, missing the bus, getting a surprise bill – and the clinical depression disorder. DBS, according to Mayberg, is unlikely to ever be used as a first-line treatment for depression. “DBS and invasive brain surgery will always be limited,” she explains. “If you have to break into someone’s head to leave something, it’ll always be saved for people who can’t get well any other way.
” One thorny ethical problem with DBS is whether implanting a device in someone’s brain can cause personality changes. But, as Jonathan Pugh, a senior research fellow at the Oxford Uehiro Centre for Practical Ethics, who has studied the ethics of DBS, points out, modifying abnormal moods is the precise purpose of using DBS to treat a mental disease like depression, which confuses things even more. “Trying to distinguish between what are potentially ethically problematic personality changes and what are the improvements that we truly wish to help these people attain is extremely challenging.”
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Frederic Gilbert, a neuroethicist at the University of Tasmania, is concerned that the technique will overlook all of the disorder’s complexity and variations. “Reducing depression to a biomarker-driven closed-loop therapy may not be the best way for discovering and analysing the pathology’s phenomenological costs,” he argues. He also wants to know what happens to people who are unable to generate a biomarker. Is this to say that they will be barred from therapy, thus resulting in indirect discrimination?
The experts are quick to point out that just because the treatment worked for Sarah doesn’t guarantee it would work for everyone. “To be clear, this is not an evidence of this approach’s effectiveness. “This is truly the first instance of this working in someone,” says Edward Chang, a neurosurgeon at UCSF and a senior author on the research. The researchers intend to enroll more patients in the study, which will necessitate finding the individualised brain region and circuit to target in each individual. “I believe that in the future, there will be potential to make it scalable and more generalizable to a bigger population.” However, it is still in its early stages,” Chang explains.
