Dr. Andres Lozano
An observed memory flashback by half the patients in a deep brain stimulation clinical trial prompted the research team to publish a Letter to the Editor in The New England Journal of Medicine. The unexpected finding may help researchers better understand human memory. (Photo: UHN)

Research, especially medical and health research, can be a funny thing.

It often yields expected results, but sometimes turns expectations on their head.

And then there are the unexpected results, the ones that leave scientists thinking, "well, that's interesting."

For Toronto Western Hospital (TW) neurosurgeon, Dr. Andres Lozano, one such observation was so interesting it became the subject of a Letter to the Editor published last week in The New England Journal of Medicine (NEJM).

Dr. Lozano serves as Principal Investigator in a multi-centre trial with researchers across North America, studying deep brain stimulation (DBS) in order to improve overall brain cognition in patients with Alzheimer's disease (AD) – a potential treatment invented in Toronto and first announced to the world in 2010.

Back then, the research results were broad: DBS – a procedure where electrodes are surgically implanted in the brain to deliver an electrical pulse – seemed to enhance memory.

Almost half of patients experienced memory flashback

A decade later, researchers are working to home in on what part of the brain will benefit most from DBS and which type of AD patients will respond best to this treatment. During their most recent clinical trial of 42 patients, the study looked at the fornix – a bundle of nerves in the brain – as the target for improved cognition.

 "We observed that, when the electrodes were turned on after DBS surgery, almost half the patients in this trial experienced a memory flashback," says Dr. Lozano, who also holds the R.R. Tasker Chair in Functional Neurosurgery at UHN.

"This was largely unexpected and is very interesting as it may help us better understand human memory."

Electrodes are usually turned on a couple of weeks after DBS surgery and tested to determine what level of stimulation is most comfortable for a patient.

As the candidates had their stimulators programmed and were randomized for this trial, not only did these patients experience a flashback of what seemed to be a true memory, but more details associated with that particular memory were recalled as the voltage of the electrodes was increased. Patients were able to remember emotions, smells and even temperatures related to the flashback.

'This could lead us to restoring memory function'

It's an observation that could have many implications in our understanding of human memory – and not just for AD patients.

"It's really establishing a new path for discovery – it shows how memories are potentially formed, where they're stored in the brain, how to retrieve buried memories and how to activate the areas in the brain that hold them," says Dr. Lozano.

"This could lead us to restoring memory function in not only Alzheimer's patients, but also those who suffer head injuries, strokes or any condition that affects memory."

It's a significant discovery that needed to be recognized. But since the actual clinical trial wasn't designed to investigate the location of memory, a Letter to the Editor detailing the observation was submitted to NEJM in place of a manuscript.

The team, which includes TW neurologist Dr. David Tang Wai and neuropsychologist Mary Pat McAndrews, is now actively recruiting patients with AD to launch a phase III clinical trial of DBS. This trial will look at optimizing stimulation parameters to see whether DBS could be both safe and effective to improve memory and slow down the progress of AD.  

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