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.”
A drone hovers over Tacuarembó hospital in Uruguay, carrying its precious cargo: breast milk intended for children in remote parts of the country.
But these children need breast milk throughout their first six months, if not longer, to prevent malnutrition and other illnesses that are prevalent in rural Tacuarembó. Ground transport isn't quick or reliable enough to meet this goal. It can take several hours, during which the milk may spoil due to a lack of refrigeration.
The battery-powered drones have been the difference-maker. The project to develop them, financed by the UNICEF Innovation Fund, is the first of its kind in Latin America. To Castelli, it's nothing short of a revolution. Tacuarembó Hospital, along with three rural clinics in the most impoverished part of Uruguay, are its leaders.
"This marks the first occasion when the public health system has been directly impacted [by our technology]," says Sebastián Macías, the CEO and co-founder of Cielum, an engineer at the University Republic, which collaborated on the technology with a Uruguayan company called Cielum and a Swiss company, Rigitech.
The drone can achieve a top speed of up to 68 miles per hour, is capable of flying in light rain, and can withstand winds of up to 30 miles per hour at a maximum altitude of 120 meters.
"We have succeeded in embracing the mothers from rural areas who were previously slipping through the cracks of the system," says Ferreira, the hospital director. He envisions an expansion of the service so it can improve health for children in other rural areas.
Nurses load the drone for breast milk delivery.
Sebastián Macías - Cielum
The star aircraft
The drone, which costs approximately $70,000, was specifically designed for the transportation of biological materials. Constructed from carbon fiber, it's three meters wide, two meters long and weighs 42 pounds when fully loaded. Additionally, it is equipped with a ballistic parachute to ensure a safe descent in case the technology fails in midair. Furthermore, it can achieve a top speed of 68 miles per hour, fly in light rain, and withstand winds of 30 miles per hour at a height of 120 meters.
Inside, the drones feature three refrigerated compartments that maintain a stable temperature and adhere to the United Nations’ standards for transporting perishable products. These compartments accommodate four gallons or 6.5 pounds of cargo. According to Macías, that's more than sufficient to carry a week’s worth of milk for one infant on just two flights, or 3.3 pounds of blood samples collected in a rural clinic.
“From an energy perspective, it serves as an efficient mode of transportation and helps reduce the carbon emissions associated with using an ambulance,” said Macías. Plus, the ambulance can remain available in the town.
Macías, who has led software development for the drone, and three other technicians have been trained to operate it. They ensure that the drone stays on course, monitor weather conditions and implement emergency changes when needed. The software displays the in-flight positions of the drones in relation to other aircraft. All agricultural planes in the region receive notification about the drone's flight path, departure and arrival times, and current location.
The future: doubling the drone's reach
Forty-five days after its inaugural flight, the drone is now making five flights per week. It serves two routes: 34 miles to Curtina and 31 miles to Tambores. The drone reaches Curtina in 50 minutes while ambulances take double that time, partly due to the subpar road conditions. Pueblo Ansina, located 40 miles from the state capital, will soon be introduced as the third destination.
Overall, the drone’s schedule is expected to become much busier, with plans to accomplish 20 weekly flights by the end of October and over 30 in 2024. Given the drone’s speed, Macías is contemplating using it to transport cancer medications as well.
“When it comes to using drones to save lives, for us, the sky is not the limit," says Ciro Ferreira, Tacuarembó hospital director.
In future trips to clinics in San Gregorio de Polanco and Caraguatá, the drone will be pushed to the limit. At these locations, a battery change will be necessary, but it's worth it. The route will cover up to 10 rural Tacuarembó clinics plus one hospital outside Tacuarembó, in Rivera, close to the border with Brazil. Currently, because of a shortage of ambulances, the delivery of pasteurized breast milk to Rivera only occurs every 15 days.
“The expansion to Rivera will include 100,000 more inhabitants, doubling the healthcare reach,” said Ferreira, the director of the Tacuarembó Hospital. In itself, Ferreira's hospital serves the medical needs of 500,000 people as one of the largest in Uruguay's interior.
Alejandro Del Estal, an aeronautical engineer at Rigitech, traveled from Europe to Tacuarembó to oversee the construction of the vertiports – the defined areas that can support drones’ take-off and landing – and the first flights. He pointed out that once the flight network between hospitals and rural polyclinics is complete in Uruguay, it will rank among the five most extensive drone routes in the world for any activity, including healthcare and commercial uses.
Cielum is already working on the long-term sustainability of the project. The aim is to have more drones operating in other rural regions in the western and northern parts of the country. The company has received inquiries from Argentina and Colombia, but, as Macías pointed out, they are exercising caution when making commitments. Expansion will depend on the development of each country’s regulations for airspace use.
For Ferreira, the advantages in Uruguay are evident: "This approach enables us to bridge the geographical gap, enhance healthcare accessibility, and reduce the time required for diagnosing and treating rural inhabitants, all without the necessity of them traveling to the hospital,” he says. "When it comes to using drones to save lives, for us, the sky is not the limit."