A groundbreaking NHS trial will try to improve patients’ moods using a brain-computer interface that directly changes brain activity using ultrasound.
The device, designed to be implanted under the skull but outside the brain, maps activity and delivers targeted ultrasound pulses to “activate” groups of neurons. Its safety and tolerability will be tested in around 30 patients in a £6.5 million trial, funded by the UK’s Advanced Research and Invention Agency (Aria).
In the future, doctors hope this technology could revolutionize the treatment of diseases such as depression, drug addiction, OCD and epilepsy by rebalancing disrupted patterns of brain activity.
Jacques Carolan, program director at Aria, said: “Neurotechnologies can help a much wider range of people than we thought. Helping to combat treatment-resistant depression, epilepsy, substance abuse and eating disorders is the huge opportunity here. We are at a turning point in both the conditions we hope to treat and the new types of technologies that are emerging to do so.
The trial follows rapid advances in brain-computer interface (BCI) technology, with Elon Musk’s company Neuralink last year launching a clinical trial on paralyzed patients and another study restoring communication in stroke patients by translating their thoughts directly into speech.
However, these technologies raise important ethical questions regarding data ownership and privacy, the possibility of enhancement and the risk of neuro-discrimination, where brain data can be used to judge a person’s suitability for a employment or medical insurance.
Clare Elwell, professor of medical physics at UCL, said: “These innovations could move very quickly from a technical point of view, but we are lagging behind in solving the neuroethical problems. We are now accessing neural pathways in ways we never could before. We must therefore carefully consider the clinical impact of any intervention and ensure that we always act in the best interests of the patient.
The final trial will test a device developed by the American non-profit organization Forest Neurotech. Unlike invasive implants, in which electrodes are inserted into a specific location in the brain, Forest 1 uses ultrasound to read and modify activity. Aria describes the device as “the world’s most advanced BCI” due to its ability to modify activity in multiple regions simultaneously.
This expands potential future applications to a broad population of patients affected by conditions such as depression, anxiety, and epilepsy, all of which are “circuit-level” conditions rather than localized to a specific region of the brain.
Aimun Jamjoom, consultant neurosurgeon at Barking, Havering and Redbridge University Hospitals NHS, who is leading the project, said: “This is a less invasive technique and the ability to offer a safer form of surgery is very exciting. When considering conditions such as depression or epilepsy, (up to) a third of these patients simply do not improve. These are the groups for whom technology like this could be a life-changing solution.
The NHS trial will recruit patients who, due to brain injury, have had part of their skull temporarily removed to relieve a critical build-up of pressure in the brain. This means that the device can be tested without resorting to surgery.
When placed under the skull or in individuals with a skull abnormality, ultrasound can detect tiny changes in blood flow to produce 3D maps of brain activity with a spatial resolution approximately 100 times greater than that of a typical fMRI. The same implant can deliver focused ultrasound to mechanically nudge neurons toward firing, providing a way to increase activity remotely at precise locations.
Participants will wear the device on their scalp over the cranial defect site for two hours. Their brain activity will be measured and researchers will test whether patients’ mood and sense of motivation can be reliably changed.
There are safety considerations, as ultrasound can cause tissue heating. Professor Elsa Fouragnan, a neuroscientist at the University of Plymouth, who is collaborating on the project, said: “What we are trying to minimize is the heat. There is a trade-off between security and efficiency.
She added that it would also be important to ensure that personality or decision-making is not altered in unintentional ways – for example by making someone more impulsive.
The study will last three and a half years starting in March, with the first eight months dedicated to obtaining regulatory approval. If successful, Forest hopes to launch into a full clinical trial for a disease such as depression.
The Forest 1 trial is one of 19 projects announced on Monday as part of Aria’s £69m Precision Neurotechnologies programme, others including research into neural robots for the treatment of epilepsy, genetic engineering of brain cells and laboratory-grown brain organoids. Aria, the UK equivalent of the US Defense Advanced Research Projects Agency (Darpa) and the brainchild of Dominic Cummings, was established in 2023 with the mission of funding high-risk, high-return science projects.
