New non-invasive form of deep brain stimulation could provide alternative treatment for brain diseases

New non-invasive form of deep brain stimulation could provide alternative treatment for brain diseases

• Scientists developed a technology called temporal interference that allows for the first time the stimulation of deep brain structures without brain surgery. 
• This study validates the technology in humans, showing that when people perform a memory task whilst receiving temporal interference stimulation of the hippocampus, it can improve memory accuracy. 
• These results give a solid rationale to develop it into a therapy for Alzheimer’s disease, which the researchers are now testing in a clinical trial.

Researchers at the UK Dementia Research Institute have developed a new form of deep brain stimulation that does not require surgery and could provide an alternative treatment option for brain diseases such as Alzheimer’s.

The exciting new technology has been successfully trialled with 20 healthy volunteers for the first time by Dr Nir Grossman and Dr Ines Violante and the team at the UK Dementia Research Institute (UK DRI) at Imperial College London and the University of Surrey.

Known as temporal interference (TI), it works by safely delivering differing frequencies of electrical field through electrodes placed on the scalp and different parts of the head. The overlapping electrical fields enable a deep region of the brain known as the hippocampus to be targeted by electrical stimulation, without affecting the surrounding areas – a procedure that until now required brain surgery.

The research, published today (Thursday) in the journal Nature Neuroscience, and funded by the UK DRI, showed that the technology was able to focally stimulate the hippocampus and improve memory function in healthy adults. Scientists now hope it could soon be used to improve symptoms of memory loss in people living with Alzheimer’s disease and have begun trialling the technique in people with early Alzheimer’s.

The technology was first described by the team at Imperial College London in 2017 and shown to work in principle in mice. The new study shows for the first time that TI is effective at stimulating deep regions within the human brain. This has broad applications, and will allow scientists to stimulate different deep brain regions to discover their functional roles for the first time – accelerating the discovery of new therapeutic targets.

In the new study, the researchers first used post-mortem brain measurements to validate that the TI electric fields can be remotely focused in the hippocampus. They then applied the TI stimulation to healthy volunteers while they were memorising pairs of faces and names – a process heavily dependent on the hippocampus. Using an imaging technique called functional magnetic resonance imaging (fMRI) they showed that the TI stimulation selectively affected the hippocampal activity evoked by the memory task. Finally, the researchers repeated the procedure for a longer period of 30 minutes to show that the stimulation leads to improved memory accuracy. 

Study leader Dr Nir Grossman, Group Leader at the UK Dementia Research Institute at Imperial College London, said:

“Until now, if we wanted to electrically stimulate structures deep inside the brain, we needed to surgically implant electrodes into the brain, which of course carries risk for the patient, and can lead to complications.

“With our new technique we have shown for the first time, that it is possible to remotely stimulate specific regions deep within the human brain without the need for surgery. This opens up an entirely new avenue of treatment for brain diseases like Alzheimer’s which affect deep brain structures. We hope it will help to scale up the availability of deep brain stimulation therapies by drastically reducing cost and risk.

“We are now testing whether repeated treatment with the stimulation over the course of a number of days could benefit people in the early stages of Alzheimer’s. We hope that this will restore normal brain activity in the affected areas, which could improve symptoms of memory impairment.”

The study is published simultaneously with a second study led by researchers in École polytechnique fédérale de Lausanne (EPFL), Switzerland which independently validated the technology. In the EPFL study, the researchers used the TI technology to focally stimulate a different deep brain area called the striatum and improve motor memory function in healthy volunteers.

Next, the researchers at the UK DRI at Imperial College London are trialling the technology in people in the early stages of Alzheimer’s disease. In the clinical trial, funded by the Alzheimer’s Association and the Bill Gates Foundation, participants receive multiple sessions of non-invasive TI brain stimulation, to test whether it could be effective at restoring activity in affected areas of the brain and improving symptoms of memory loss¹.

First author Dr Ines Violante, Senior Lecturer in Psychological Neuroscience at the University of Surrey, said:

“The ability to selectively target deep brain areas of the brain using a non-invasive approach is very exciting as it provides a tool to investigate how the human brain operates and opens possibilities for clinical applications.

“The combination of non-invasive imaging and brain stimulation will help us unravel the processes that support our cognitive functions, such as memory and learning. Knowledge of these processes and how they can be altered is essential to develop better individualised strategies to treat or delay the onset of diseases.”

Luca De Freitas, 24, was one of the healthy volunteers who took part in the study. He said:

“The procedure was easy and straightforward, I felt very calm, and it wasn’t at all painful. The research team were really efficient and kind, and made sure to explain the whole process behind the study thoroughly. It helped to understand exactly why the team were conducting the study, and the process by which the study was conducted was very well organised. I work for a company which produces diagnostics for dementia, so I was really keen to take part in the study to help advance research in this area.”

Dr Joanna Latimer, Head of Neuroscience and Mental Health at the Medical Research Council (MRC), part of UK Research and Innovation, added:

“Alzheimer’s disease is a devastating condition for which effective treatments are very much needed. Memory impairment is a key feature of the disease and these initial results present an innovative treatment option for people diagnosed with Alzheimer’s.

“The results from the next stage of this highly promising treatment cannot come fast enough, and reaffirm the importance of the commitment the MRC has made to support the UK DRI and its role in advancing dementia research.”