This fall, Robert Reinhart of Boston University published a study finding that electrical stimulation can boost memory - and Reinhart was surprised to discover the effects lasted a full month.
Scientists believe brain circuits tend to uncouple as we age. Since brain neurons communicate by exchanging electrical impulses with each other, the breakdown of these links and associations could be what causes the “senior moment”—when you can’t remember the name of the movie you just watched.
In 2019, Boston University researchers led by Robert Reinhart, director of the Cognitive and Clinical Neuroscience Laboratory, showed that memory loss in healthy older adults is likely caused by these disconnected brain networks. When Reinhart and his team stimulated two key areas of the brain with mild electrical current, they were able to bring the brains of older adult subjects back into sync — enough so that their ability to remember small differences between two images matched that of much younger subjects for at least 50 minutes after the testing stopped.
Reinhart wowed the neuroscience community once again this fall. His newer study in Nature Neuroscience presented 150 healthy participants, ages 65 to 88, who were able to recall more words on a given list after 20 minutes of low-intensity electrical stimulation sessions over four consecutive days. This amounted to a 50 to 65 percent boost in their recall.
Even Reinhart was surprised to discover the enhanced performance of his subjects lasted a full month when they were tested again later. Those who benefited most were the participants who were the most forgetful at the start.
An older person participates in Robert Reinhart's research on brain stimulation.
Robert Reinhart
Reinhart’s subjects only suffered normal age-related memory deficits, but NIBS has great potential to help people with cognitive impairment and dementia, too, says Krista Lanctôt, the Bernick Chair of Geriatric Psychopharmacology at Sunnybrook Health Sciences Center in Toronto. Plus, “it is remarkably safe,” she says.
Lanctôt was the senior author on a meta-analysis of brain stimulation studies published last year on people with mild cognitive impairment or later stages of Alzheimer’s disease. The review concluded that magnetic stimulation to the brain significantly improved the research participants’ neuropsychiatric symptoms, such as apathy and depression. The stimulation also enhanced global cognition, which includes memory, attention, executive function and more.
This is the frontier of neuroscience.
The two main forms of NIBS – and many questions surrounding them
There are two types of NIBS. They differ based on whether electrical or magnetic stimulation is used to create the electric field, the type of device that delivers the electrical current and the strength of the current.
Transcranial Current Brain Stimulation (tES) is an umbrella term for a group of techniques using low-wattage electrical currents to manipulate activity in the brain. The current is delivered to the scalp or forehead via electrodes attached to a nylon elastic cap or rubber headband.
Variations include how the current is delivered—in an alternating pattern or in a constant, direct mode, for instance. Tweaking frequency, potency or target brain area can produce different effects as well. Reinhart’s 2022 study demonstrated that low or high frequencies and alternating currents were uniquely tied to either short-term or long-term memory improvements.
Sessions may be 20 minutes per day over the course of several days or two weeks. “[The subject] may feel a tingling, warming, poking or itching sensation,” says Reinhart, which typically goes away within a minute.
The other main approach to NIBS is Transcranial Magnetic Simulation (TMS). It involves the use of an electromagnetic coil that is held or placed against the forehead or scalp to activate nerve cells in the brain through short pulses. The stimulation is stronger than tES but similar to a magnetic resonance imaging (MRI) scan.
The subject may feel a slight knocking or tapping on the head during a 20-to-60-minute session. Scalp discomfort and headaches are reported by some; in very rare cases, a seizure can occur.
No head-to-head trials have been conducted yet to evaluate the differences and effectiveness between electrical and magnetic current stimulation, notes Lanctôt, who is also a professor of psychiatry and pharmacology at the University of Toronto. Although TMS was approved by the FDA in 2008 to treat major depression, both techniques are considered experimental for the purpose of cognitive enhancement.
“One attractive feature of tES is that it’s inexpensive—one-fifth the price of magnetic stimulation,” Reinhart notes.
Don’t confuse either of these procedures with the horrors of electroconvulsive therapy (ECT) in the 1950s and ‘60s. ECT is a more powerful, riskier procedure used only as a last resort in treating severe mental illness today.
Clinical studies on NIBS remain scarce. Standardized parameters and measures for testing have not been developed. The high heterogeneity among the many existing small NIBS studies makes it difficult to draw general conclusions. Few of the studies have been replicated and inconsistencies abound.
Scientists are still lacking so much fundamental knowledge about the brain and how it works, says Reinhart. “We don’t know how information is represented in the brain or how it’s carried forward in time. It’s more complex than physics.”
Lanctôt’s meta-analysis showed improvements in global cognition from delivering the magnetic form of the stimulation to people with Alzheimer’s, and this finding was replicated inan analysis in the Journal of Prevention of Alzheimer’s Disease this fall. Neither meta-analysis found clear evidence that applying the electrical currents, was helpful for Alzheimer’s subjects, but Lanctôt suggests this might be merely because the sample size for tES was smaller compared to the groups that received TMS.
At the same time, London neuroscientist Marco Sandrini, senior lecturer in psychology at the University of Roehampton, critically reviewed a series of studies on the effects of tES on episodic memory. Often declining with age, episodic memory relates to recalling a person’s own experiences from the past. Sandrini’s review concluded that delivering tES to the prefrontal or temporoparietal cortices of the brain might enhance episodic memory in older adults with Alzheimer’s disease and amnesiac mild cognitive impairment (the predementia phase of Alzheimer’s when people start to have symptoms).
Researchers readily tick off studies needed to explore, clarify and validate existing NIBS data. What is the optimal stimulus session frequency, spacing and duration? How intense should the stimulus be and where should it be targeted for what effect? How might genetics or degree of brain impairment affect responsiveness? Would adjunct medication or cognitive training boost positive results? Could administering the stimulus while someone sleeps expedite memory consolidation?
Using MRI or another brain scan along with computational modeling of the current flow, a clinician could create a treatment that is customized to each person’s brain.
While Sandrini’s review reported improvements induced by tES in the recall or recognition of words and images, there is no evidence it will translate into improvements in daily activities. This is another question that will require more research and testing, Sandrini notes.
Scientists are still lacking so much fundamental knowledge about the brain and how it works, says Reinhart. “We don’t know how information is represented in the brain or how it’s carried forward in time. It’s more complex than physics.”
Where the science is headed
Learning how to apply precision medicine to NIBS is the next focus in advancing this technology, says Shankar Tumati, a post-doctoral fellow working with Lanctôt.
There is great variability in each person’s brain anatomy—the thickness of the skull, the brain’s unique folds, the amount of cerebrospinal fluid. All of these structural differences impact how electrical or magnetic stimulation is distributed in the brain and ultimately the effects.
Using MRI or another brain scan along with computational modeling of the current flow, a clinician could create a treatment that is customized to each person’s brain, from where to put the electrodes to determining the exact dose and duration of stimulation needed to achieve lasting results, Sandrini says.
Above all, most neuroscientists say that largescale research studies over long periods of time are necessary to confirm the safety and durability of this therapy for the purpose of boosting memory. Short of that, there can be no FDA approval or medical regulation for this clinical use.
Lanctôt urges people to seek out clinical NIBS trials in their area if they want to see the science advance. “That is how we’ll find the answers,” she says, predicting it will be 5 to 10 years to develop each additional clinical application of NIBS. Ultimately, she predicts that reigning in Alzheimer’s disease and mild cognitive impairment will require a multi-pronged approach that includes lifestyle and medications, too.
Sandrini believes that scientific efforts should focus on preventing or delaying Alzheimer’s. “We need to start intervention earlier—as soon as people start to complain about forgetting things,” he says. “Changes in the brain start 10 years before [there is a problem]. Once Alzheimer’s develops, it is too late.”
NASA astronaut Frank Rubio floats by the International Space Station’s “window to the world.” Yesterday, he returned from the longest single spaceflight by a U.S. astronaut on record - over one year. Exploring deep space will require even longer missions.
Yesterday, NASA astronaut Frank Rubio returned to Earth after over one year, the longest single spaceflight for a U.S. astronaut. But this is just the start; longer and more complex missions into deep space loom ahead, from returning to the moon in 2025 to eventually sending humans to Mars. To ensure that these missions succeed, NASA is increasing efforts to study the biological effects and prevent harm.
The dangers of microgravity are real
A NASA report published in 2016 details a long list of incidents and near-misses caused – at least partly – by space-induced changes in astronauts’ vision and coordination. These issues make it harder to move with precision and to judge distance and velocity.
According to the report, in 1997, a resupply ship collided with the Mir space station, possibly because a crew member bumped into the commander during the final docking maneuver. This mishap caused significant damage to the space station.
Returns to Earth suffered from problems, too. The same report notes that touchdown speeds during the first 100 space shuttle landings were “outside acceptable limits. The fastest landing on record – 224 knots (258 miles) per hour – was linked to the commander’s momentary spatial disorientation.” Earlier, each of the six Apollo crews that landed on the moon had difficulty recognizing moon landmarks and estimating distances. For example, Apollo 15 landed in an unplanned area, ultimately straddling the rim of a five-foot deep crater on the moon, harming one of its engines.
Spaceflight causes unique stresses on astronauts’ brains and central nervous systems. NASA is working to reduce these harmful effects.
NASA
Space messes up your brain
In space, astronauts face the challenges of microgravity, ionizing radiation, social isolation, high workloads, altered circadian rhythms, monotony, confined living quarters and a high-risk environment. Among these issues, microgravity is one of the most consequential in terms of physiological changes. It changes the brain’s structure and its functioning, which can hurt astronauts’ performance.
The brain shifts upwards within the skull, displacing the cerebrospinal fluid, which reduces the brain’s cushioning. Essentially, the brain becomes crowded inside the skull like a pair of too-tight shoes.
That’s partly because of how being in space alters blood flow. On Earth, gravity pulls our blood and other internal fluids toward our feet, but our circulatory valves ensure that the fluids are evenly distributed throughout the body. In space, there’s not enough gravity to pull the fluids down, and they shift up, says Rachael D. Seidler, a physiologist specializing in spaceflight at the University of Florida and principal investigator on many space-related studies. The head swells and legs appear thinner, causing what astronauts call “puffy face chicken legs.”
“The brain changes at the structural and functional level,” says Steven Jillings, equilibrium and aerospace researcher at the University of Antwerp in Belgium. “The brain shifts upwards within the skull,” displacing the cerebrospinal fluid, which reduces the brain’s cushioning. Essentially, the brain becomes crowded inside the skull like a pair of too-tight shoes. Some of the displaced cerebrospinal fluid goes into cavities within the brain, called ventricles, enlarging them. “The remaining fluids pool near the chest and heart,” explains Jillings. After 12 consecutive months in space, one astronaut had a ventricle that was 25 percent larger than before the mission.
Some changes reverse themselves while others persist for a while. An example of a longer-lasting problem is spaceflight-induced neuro-ocular syndrome, which results in near-sightedness and pressure inside the skull. A study of approximately 300 astronauts shows near-sightedness affects about 60 percent of astronauts after long missions on the International Space Station (ISS) and more than 25 percent after spaceflights of only a few weeks.
Another long-term change could be the decreased ability of cerebrospinal fluid to clear waste products from the brain, Seidler says. That’s because compressing the brain also compresses its waste-removing glymphatic pathways, resulting in inflammation, vulnerability to injuries and worsening its overall health.
The effects of long space missions were best demonstrated on astronaut twins Scott and Mark Kelly. This NASA Twins Study showed multiple, perhaps permanent, changes in Scott after his 340-day mission aboard the ISS, compared to Mark, who remained on Earth. The differences included declines in Scott’s speed, accuracy and cognitive abilities that persisted longer than six months after returning to Earth in March 2016.
By the end of 2020, Scott’s cognitive abilities improved, but structural and physiological changes to his eyes still remained, he said in a BBC interview.
“It seems clear that the upward shift of the brain and compression of the surrounding tissues with ventricular expansion might not be a good thing,” Seidler says. “But, at this point, the long-term consequences to brain health and human performance are not really known.”
NASA astronaut Kate Rubins conducts a session for the Neuromapping investigation.
NASA
Staying sharp in space
To investigate how prolonged space travel affects the brain, NASA launched a new initiative called the Complement of Integrated Protocols for Human Exploration Research (CIPHER). “CIPHER investigates how long-duration spaceflight affects both brain structure and function,” says neurobehavioral scientist Mathias Basner at the University of Pennsylvania, a principal investigator for several NASA studies. “Through it, we can find out how the brain adapts to the spaceflight environment and how certain brain regions (behave) differently after – relative to before – the mission.”
To do this, he says, “Astronauts will perform NASA’s cognition test battery before, during and after six- to 12-month missions, and will also perform the same test battery in an MRI scanner before and after the mission. We have to make sure we better understand the functional consequences of spaceflight on the human brain before we can send humans safely to the moon and, especially, to Mars.”
As we go deeper into space, astronauts cognitive and physical functions will be even more important. “A trip to Mars will take about one year…and will introduce long communication delays,” Seidler says. “If you are on that mission and have a problem, it may take eight to 10 minutes for your message to reach mission control, and another eight to 10 minutes for the response to get back to you.” In an emergency situation, that may be too late for the response to matter.
“On a mission to Mars, astronauts will be exposed to stressors for unprecedented amounts of time,” Basner says. To counter them, NASA is considering the continuous use of artificial gravity during the journey, and Seidler is studying whether artificial gravity can reduce the harmful effects of microgravity. Some scientists are looking at precision brain stimulation as a way to improve memory and reduce anxiety due to prolonged exposure to radiation in space.
Other scientists are exploring how to protect neural stem cells (which create brain cells) from radiation damage, developing drugs to repair damaged brain cells and protect cells from radiation.
To boldly go where no astronauts have gone before, they must have optimal reflexes, vision and decision-making. In the era of deep space exploration, the brain—without a doubt—is the final frontier.
Additionally, NASA is scrutinizing each aspect of the mission, including astronaut exercise, nutrition and intellectual engagement. “We need to give astronauts meaningful work. We need to stimulate their sensory, cognitive and other systems appropriately,” Basner says, especially given their extreme confinement and isolation. The scientific experiments performed on the ISS – like studying how microgravity affects the ability of tissue to regenerate is a good example.
“We need to keep them engaged socially, too,” he continues. The ISS crew, for example, regularly broadcasts from space and answers prerecorded questions from students on Earth, and can engage with social media in real time. And, despite tight quarters, NASA is ensuring the crew capsule and living quarters on the moon or Mars include private space, which is critical for good mental health.
Exploring deep space builds on a foundation that began when astronauts first left the planet. With each mission, scientists learn more about spaceflight effects on astronauts’ bodies. NASA will be using these lessons to succeed with its plans to build science stations on the moon and, eventually, Mars.
“Through internally and externally led research, investigations implemented in space and in spaceflight simulations on Earth, we are striving to reduce the likelihood and potential impacts of neurostructural changes in future, extended spaceflight,” summarizes NASA scientist Alexandra Whitmire. To boldly go where no astronauts have gone before, they must have optimal reflexes, vision and decision-making. In the era of deep space exploration, the brain—without a doubt—is the final frontier.
Swiss researchers have found a type of brain cell that appears to be a hybrid of the two other main types — and it could lead to new treatments for brain disorders.
A new brain cell: Researchers at the Wyss Center for Bio and Neuroengineering and the University of Lausanne believe they’ve definitively proven that some astrocytes do actively participate in neurotransmission, making them a sort of hybrid of neurons and glial cells.
According to the researchers, this third type of brain cell, which they call a “glutamatergic astrocyte,” could offer a way to treat Alzheimer’s, Parkinson’s, and other disorders of the nervous system.
“Its discovery opens up immense research prospects,” said study co-director Andrea Volterra.
The study: Neurotransmission starts with a neuron releasing a chemical called a neurotransmitter, so the first thing the researchers did in their study was look at whether astrocytes can release the main neurotransmitter used by neurons: glutamate.
By analyzing astrocytes taken from the brains of mice, they discovered that certain astrocytes in the brain’s hippocampus did include the “molecular machinery” needed to excrete glutamate. They found evidence of the same machinery when they looked at datasets of human glial cells.
Finally, to demonstrate that these hybrid cells are actually playing a role in brain signaling, the researchers suppressed their ability to secrete glutamate in the brains of mice. This caused the rodents to experience memory problems.
“Our next studies will explore the potential protective role of this type of cell against memory impairment in Alzheimer’s disease, as well as its role in other regions and pathologies than those explored here,” said Andrea Volterra, University of Lausanne.
But why? The researchers aren’t sure why the brain needs glutamatergic astrocytes when it already has neurons, but Volterra suspects the hybrid brain cells may help with the distribution of signals — a single astrocyte can be in contact with thousands of synapses.
“Often, we have neuronal information that needs to spread to larger ensembles, and neurons are not very good for the coordination of this,” researcher Ludovic Telley told New Scientist.
Looking ahead: More research is needed to see how the new brain cell functions in people, but the discovery that it plays a role in memory in mice suggests it might be a worthwhile target for Alzheimer’s disease treatments.
The researchers also found evidence during their study that the cell might play a role in brain circuits linked to seizures and voluntary movements, meaning it’s also a new lead in the hunt for better epilepsy and Parkinson’s treatments.
“Our next studies will explore the potential protective role of this type of cell against memory impairment in Alzheimer’s disease, as well as its role in other regions and pathologies than those explored here,” said Volterra.
