Memory loss caused by Alzheimer's disease and other forms of dementia may soon be treatable drug-free with non-surgical electrical stimulation of the brain, new research suggests.

A successful trial in healthy young adults confirmed the technique can improve memory, and researchers have now begun trials in people with early Alzheimer's.

This painless, non-invasive treatment called 'temporal interference' uses electric fields of multiple frequencies to stimulate neurons in the hippocampus, a deep brain region involved in the formation, storage, and recall of memories.

"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," says neuroscientist Nir Grossman from Imperial College London.

"This opens up an entirely new avenue of treatment for brain diseases like Alzheimer's which affect deep brain structures."

Our neurons communicate using electrical signals. Among its complex processes, Alzheimer's impacts this communication between neurons in the hippocampus, embedded deep inside the brain's temporal lobe.

Deep brain stimulation is one way to fix these electrical activity imbalances and could potentially treat brain conditions like Alzheimer's. Like a pacemaker for the brain, implanted electrodes can monitor activity and carry small electric currents into malfunctioning regions.

Obsessive-compulsive disorder and movement disorders like Parkinson's are already treated with deep brain stimulation. But the surgical procedure to implant the electrodes is risky, making it difficult to research its usefulness in other brain conditions.

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

In temporal interference, high-frequency electric fields are sent into the brain through electrodes attached to the outside of the scalp.

Two electric fields, one at 2,000 Hz and the other at 2,005 Hz, are targeted to overlap (interfere) in the temporal lobe, creating a low-frequency difference current at 5 Hz. This current is in the same frequency range as neural activity in learning and memory.

The low-frequency 5 Hz electric fields work in the hippocampus by making it easier for cells to coordinate the activities needed to create memories.

Electrodes are placed on the side of a person's head. The torso and arms of a physician standing behind are visible
Temporal interference delivers electrical stimulation through electrodes placed on the head. (Imperial College London)

"The ability to selectively target deep brain areas 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," says first author, neuroscientist Ines Violante from the University of Surrey.

Before attempting to remotely target the hippocampus with electric fields, the researchers used postmortem brain experiments and computer modeling to confirm this was possible.

Next, they used temporal interference stimulation on 20 volunteers without Alzheimer's symptoms while they memorized sets of faces and names, a task that requires extensive hippocampus activity.

Functional magnetic resonance imaging (fMRI) showed that temporal interference only changed the parts of the hippocampus activated by the memory task.

They repeated the process on another 21 volunteers for a full 30 minutes, and it was clear that temporal interference during the task enhanced memory performance.

Trial participants were mostly young, aged in their 20s on average. However, another new study has validated the technique on a different deep area of the brain, the striatum, and participants in that trial included 15 older adults aged 61–71, also without Alzheimer's symptoms.

"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," Grossman says.

Participants aged 50–100 with mild cognitive impairment and likely early-stage, non-genetic Alzheimer's disease have been enrolled in the new trial.

Scientists are keeping their fingers crossed that the 5 Hz current can revive diseased neurons in the hippocampus. They hope it will repair Alzheimer's damage to the area's mitochondria – the cells' energy generators.

"Knowledge of these processes and how they can be altered is essential to develop better individualized strategies to treat or delay the onset of diseases," says Violante.

Grossman adds, "We hope this work will help to scale up the availability of deep brain stimulation therapies by drastically reducing cost and risk."

The study has been published in Nature Neuroscience.