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A New Study Suggests Non-Invasive Brain Stimulation Can Improve Working Memory

Article In Brief

Researchers found that directing non-invasive alternating current to specific brain regions could reverse the disrupted synchronicity of old age and return the brain to a state of a more youthful working memory.

Scientists at Boston University used non-invasive electrical brain stimulation with alternating current to strengthen working memory—how people retain information over a short period of time so that they can act on it or remember it—in older adults, and it seemed to work.

The study, published in the May issue of Nature Neuroscience, suggests that disrupted and non-synchronized brain circuits may play a role in impaired working memory, and that a noninvasive stimulation technique could potentially help synchronize those brain circuits to help the aging brain regain its ability to communicate across networks and improve working memory.

Using EEG to measure brain wave activity in both young and older adults, the study authors—Robert M.G. Reinhart, PhD, assistant professor in thedepartment of psychological and brain sciences atBoston University, and John A. Nguyen, a doctoral candidatein thelab—found that older people had more disorganized electrical rhythms in the brain than younger people.

They wanted to determine whether directing non-invasive alternating current to specific brain regions could reverse the disrupted synchronicity of old age and return the brain to a state of a more youthful working memory.

They designed the study to answer these and other questions: Do working memory impairments of older people arise from disconnected or desynchronized brain mechanisms involving prefrontal and temporal regions? Can scientists use external electrical current to noninvasively and safely stimulate frontotemporal brain regions in the elderly to strengthen the neural communication and plasticity of this brain network?

Study Methods, Findings

To explore these questions, the researchers recruited both young and older volunteers: 42 people, aged 60 through 76, and 42 younger people between 20 and 30 years old.

On testing day, scientists measured each elderly person's brain synchronization patterns using an EEG before the experiment to identify each individual's specific brain network so they could design the High-Definition transcranial alternating-current stimulation (HD-tACS), according to their EEG synchronization. They were then asked to perform a series of working memory tasks: For example, they were shown a familiar object, which was brought back a few seconds later with or without slight modifications and asked whether it was the same object or different; they performed the task while they underwent 25 minutes of HD-tACS. HD-tACS drives an electrical current through the scalp, skin, dura, and cerebrospinal fluid. They used the same design to stimulate younger people in a subsequent experiment.

The EEG and the HD-tACS were applied concurrently to ensure they delivered the stimulation to the prefrontal and left temporal cortex, brain regions involved in working memory, and to measure functional connectivity. The investigators continued to measure brain waves for an additional 50 minutes after the stimulation was stopped.

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“We strongly suspect that the integrity of brain synchronization plays a key role in how well people remember things. It looks promising that large-scale synchronization may be a window into learning more about the aging brain and cognition more broadly.”

—DR. ROBERT M.G. REINHART

They were interested in the relationship between the timing of the theta waves and the amplitude of gamma waves in the temporal areas of the brain, and the relationship between the timing of theta waves in the prefrontal and temporal areas. The scientists explained that this precise temporal code might be required for optimal cognition and plasticity.

“For example, bursts of high-frequency spikes locked to the theta rhythm have been shown to activate the calcium-dependent protease calpain, which plays an important role in the induction of long-term potentiation, the cellular basis of learning and memory. From a disease standpoint, aberrations in this temporal code exist in many brain disorders and our findings suggest that modulating this temporal code could potentially have therapeutic benefits,” said Dr. Reinhart.

The research team conducted the same study on a sham day when both young and old study volunteers did not know whether the stimulation was on or off. They identified deficits in the synchronization in older people. They were also slower and less accurate on the working memory tests than younger people.

When the stimulation was on, the older cohort members were as accurate in their tasks as the more youthful group. And there was more synchronous activity in the stimulated regions—the effect was evident when measured for another 50 minutes.

Dr. Reinhart said that neurons in the prefrontal and temporal regions play an important role in the storage and processing of real-world information. These areas are thought to work in concert to allow us to effectively store information in memory.

The prefrontal and temporal regions are also hard hit in Alzheimer's disease, Dr. Reinhart noted. He speculated that the frontal lobe is no longer in perfect alignment with the temporal regions and that is why older people and potentially those with dementia may have great difficulty keeping objects in memory.

“Stimulation allows these regions to come back online,” said Dr. Reinhart.

“High definition-tACS appears to improve working memory in older adults in a stable and enduring manner,” said Dr. Reinhart. “It appears to eliminate age-related impairment in working-memory accuracy. We strongly suspect that the integrity of brain synchronization plays a key role in how well people remember things. It looks promising that large-scale synchronization may be a window into learning more about the aging brain and cognition more broadly.”

Expert Commentary

Independent experts agreed that the study offered important insights into the role of synchronized brain circuits in memory. But some questioned the effectiveness of the stimulation method used in the study.

Some experts said they prefer to usetranscranial magnetic stimulation (TMS), which useselectromagnetic forces that are turned on and off very quickly, inducing the electrical current to reach neurons in the cerebral cortex.

And others told Neurology Today that TMS overdrives brain regions and HD-tACS provides more nuanced control. HD-tACS is a hundred times lower in intensity.

“Rather than overriding the network, HD-tACS modulates it,” said Marom Bikson, PhD, a scientist in the department of biomedical engineering at the City College of New York. Dr. Bikson was not directly involved in the study in Nature Neuroscience, but he invented thehigh-definition stimulation used in the experiments.

Many researchers are using high-definition technology to study the brain,” explained Dr. Bikson. “In this study, thestimulation was designed to reverse the brain's electrical deficits that they observed in some older adults. A more robust working memory was revived by rhythmically synchronizing brain circuits.”

“They used these tools in a very clever way,” he continued. “They are not claiming that they proved this treatment enhances memory. A lot more work needs to bedone,but this study provides support for moving ahead with such clinical trials.”

Joel L. Voss, PhD, associate professor at Northwestern University Feinberg School of Medicine, works with TMS because he is not convinced that HD-tACS is sufficient to influence neural activity in the cortex.

“There is evidence to show that the technology influences peripheral nerves and that can lead to any number of effects, including arousal. That arousal could have led to better performance on memory studies after stimulation.”

Dr. Reinhart and his colleagues said that they controlled for the effects of arousal and transcutaneous effects on nerves in the scalp.

Dr. Voss and his colleagues published a study in the April issue of Neurology showing the rescue of long-term/episodic memory and corresponding brain activity in older adults to young-adult levels using TMS. They stimulated 30 minutes daily for five days and then looked at the effects of the stimulation on day six.

“We show we can have a beneficial effect on memory but more work is needed in all these types of studies to understand what is actually useful,” said Dr. Voss. “I am a basic scientist and focus on what is possible and not what is practical.”

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“There is evidence to show that the technology influences peripheral nerves and that can lead to any number of effects, including arousal. That arousal could have led to better performance on memory studies after stimulation.”

—DR. JOEL L. VOSS

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“I expect that improving brain activity rhythms across multiple brain regions might be helpful for improving a wide range of cognitive tasks, not just working memory, but perhaps also helping with spatial navigation, attention, reasoning, or decision making.”

—DR. BETTINA BUHRING

Putting the study in a practical context, Bettina Buhring, PhD, chief of the learning and memory program in the division of neuroscience and basic behavioral science at the National Institute of Mental Health, said: “The [current] study highlights the possible therapeutic potential of fine-tuning brain activity rhythms simultaneously at multiple brain regions.

“The investigators showed that the particular stimulation frequencies matter; that the location of stimulation matters; that multiple nodes of the brain network can be stimulated to work together more efficiently; and that the brain uses nested rhythms (rhythms within rhythms) to hold information in memory.

“I expect that improving brain activity rhythms across multiple brain regions might be helpful for improving a wide range of cognitive tasks, not just working memory, but perhaps also helping with spatial navigation, attention, reasoning, or decision making,” she said. “It would also be interesting to see whether this type of intervention could help people with cognitive problems in other brain disorders, such as autism, schizophrenia, or mood disorders.

“Another interesting aspect of this work is that it had its effect within about 12 minutes and lasted at least 50 minutes after the end of stimulation,” said Dr. Buhring.

“This is in contrast to the long effect lags that pharmacological interventions often have, which can take months to show an effect. This study illustrates that the brain is a finely-tuned network where millisecond-level timing is crucial. Thus, electrical, magnetic, or other rhythmic treatment modalities provide a different way of addressing brain disorders, whereas traditional pharmacological treatments intrinsically do not have a rhythm, and whose effects on brain rhythms are rarely tested.”

Disclosures

Drs. Reinhart, Voss, and Buhring had no disclosures. Dr. Bikson is an inventor on patents, co-founder, and has equity in Soterix Medical. Soterix Medical produces neuromodulation devices including High-Definition tACS. He also consults for consults for Boston Scientific Inc., GlaxoSmithKline, and METCA.

Link Up for More Information

•. Reinhart RMG, Nguyen JA. Working memory revived in older adults by synchronizing rhythmic brain circuits https://www.nature.com/articles/s41593-019-0371-x. Nat Neurosci 2019; 22(5):820–827.