Brain stimulation tested to wake coma patients

IIt’s a lot of soap operas and other fictions that a long-term coma can serve as a kind of time travel that quickly takes a character into a future where they will spontaneously awaken and come to terms with the changes that happened while they were in the coma slept. In fact, contrary to what one might get while watching television during the day, it is very rare for people to stay in a coma for long periods. Martin Monti, a neuroscientist at the University of California at Los Angeles, says that it is estimated that the number of people who have been in what is known as a vegetative state for more than a few months is between 50 and 150 per 1 million. For these few patients and their families, “these are all very difficult situations,” he says.

Most people with impaired consciousness, which doctors refer to as the vegetative states and the less severe, minimally conscious state, both of which are characterized by a lack of vigilance and a lack of consciousness, awaken within months. But for a small subset of people who have had a severe brain injury and are then in a coma for a year or more: “If they don’t spontaneously recover – they don’t step on the recovery path – there isn’t much we can do for them when they remain stable in a disorder of consciousness, ”he says.

Monti tries to change that. In a study published online last month in Brain stimulationMonti and colleagues report preliminary results from a study in which they used ultrasound to non-invasively stimulate an area known as the thalamus in patients with long-term impaired consciousness. Of the three patients included in the study, two showed behavioral improvements, e.g. B. reacting to simple commands and on the one hand the ability to answer yes or no when answering questions.

“I think that creates cautious optimism,” says Shy Shoham, a neural engineer at NYU Langone Health. “It’s a nice preliminary result.”

The idea of ​​stimulating the brain to treat coma goes back decades, and the thalamus – an area deep in the organ that, among other things, regulates vigilance – was a goal before. For example, in 2007 a team reported in nature that they had implanted an electrode in the brain of a patient who had been in a coma for six years to stimulate the thalamus. After the treatments, the authors wrote, the patient responded better to commands than before and even spoke intelligibly for the first time. A later study by another group of three patients found some improvement in movement and brain activity after electrode stimulation of the thalamus, although none of the patients regained consciousness.

Overall, the effects of such interventions were “difficult to determine,” says Ziv Williams, a neuroscientist at Massachusetts General Hospital and Harvard Medical School, who was not involved in any of the studies.

Monti and his colleagues saw the results of thalamic stimulation as promising, but he says, “It is difficult to stick an electrode into a person’s brain, especially after a serious brain injury.” The team therefore investigated whether non-invasive stimulation of the thalamus with ultrasound could induce signs of consciousness in coma patients, and in 2015 started a clinical study with the aim of recruiting and treating 30 patients. In their first report, published in 2016, they described the treatment of a man who had been in a state of minimal consciousness for several weeks after a traffic accident with a session of ten 30-second ultrasound pulses with the waves being MRI on the thalamus were directed. The man showed signs of improvement immediately after treatment – he was reaching for objects, for example – and three days later he was able to fully understand the language and respond by nodding or shaking his head, the authors wrote.

The most recent study reports the cases of three more patients from the same study, all over 50 years old and in a state of minimal consciousness for more than a year. There were no signs of treatment safety issues, the study authors write, and two of the patients showed “clinically significant increases in behavioral reactivity” after the intervention, although one of the patients had decreased to their pre-treatment response level at follow-up. Reviews a few months later. The other patient maintained the improvement over time – she could respond to simple commands and recognize objects – but was still rated as minimally conscious.

The clinical trial was canceled last spring due to the pandemic, Monti says, and his team is in the process of writing down the results of a handful of other patients who were recruited and treated before the shutdown. Their results were similar to those of the three patients in the previous report, and he hopes to receive funding to start a new study that will use brain imaging and EEG to assess whether ultrasound is not just changing behavior – a somewhat subjective one Measure. Williams notices – but also the underlying functions of the brain.

While the non-invasive approach has clear advantages, Williams says it could also have disadvantages if it turns out that ultrasound needs to be used constantly to maintain its advantages. “These ultrasound devices are big machines – at least not at the moment [easily] carry around, ”he says.

JA Cain et al., “Ultrasonic thalamic stimulation for chronic disorders of consciousness” Brain stimulation14, 301-3, 2021.



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