Biomarker-guided neuromodulation alleviates memory loss in traumatic brain injury patients

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A collaborative study published in the journal Brain Stimulation has shown that targeted electrical stimulation in epilepsy patients with traumatic brain injury (TBI) can improve memory—more specifically, the recalling of words—by an average of 19%.

Led by Michael Jacob Kahana (University of Pennsylvania, Philadelphia, USA), a team of neuroscientists studied TBI patients with implanted electrodes, analysed neural data as patients studied words, and used a machine learning algorithm to predict momentary memory lapses.

Other co-authors of this research include Paul Wanda and Ramon Diaz-Arrastia—both of Penn Medicine (Philadelphia, USA)—and Youssef Ezzyat of Wesleyan University (Middletown, USA).

“The last decade has seen tremendous advances in the use of brain stimulation as a therapy for several neurological and psychiatric disorders including epilepsy, Parkinson’s disease, and depression,” said Kahana. “Memory loss, however, represents a huge burden on society. We lack effective therapies for the 27 million Americans suffering.”

Diaz-Arrastia added that the technology Kahana and his team developed delivers “the right stimulation at the right time, informed by the wiring of the individual’s brain and that individual’s successful memory retrieval”.

This study builds on previous work from Kahana, Ezzyat and their collaborators. Publishing their findings in 2017, they showed that stimulation delivered when memory is expected to fail can improve memory, whereas stimulation administered during periods of good functioning worsens memory. The stimulation in that study was ‘open loop’, meaning it was applied by a computer without regard for the state of the brain.

In a study with 25 epilepsy patients that was published the following year, the researchers monitored brain activity in real time and used closed-loop, biomarker-guided stimulation, applying electrical pulses to the left lateral temporal cortex only when memory was expected to fail. They found a 15% improvement in the probability of recalling a word from a list.

Their new study, however, specifically focuses on eight people with a history of moderate-to-severe TBI who were recruited from a larger group of patients undergoing neurosurgical evaluation for epilepsy—seven of whom are male. Diaz-Arrastia noted that 80% of people who get hospitalised for TBI overall are male.

Kahana emphasised the importance of addressing TBI-related memory loss, noting that “these patients are often relatively young and physically healthy, but they face decades of impaired memory and executive function”.

The researchers’ primary question was whether stimulation could improve memory across entire lists of words when only some words were stimulated, whereas prior studies only considered the effect of stimulation on individual words. Ezzyat stated that this development is important because “this suggests that an eventual real-life therapy could provide more generalised memory improvement—not just at the precise moment when stimulation is triggered”.

The researchers note that more work remains before this kind of stimulation can be applied in a therapeutic setting, and scientists need to study physiological responses to stimulation to better understand the neural mechanisms behind improved memory performance. As Diaz-Arrastia said, “these are still early days in the field”.

“I think eventually what we would need is a self-contained, implantable system, where you could implant the electrodes into the brain of someone who had a brain injury,” he concluded.


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