BY MARC CHALUFOUR

Robert Reinhart suspected that his latest research, published in a leading journal in August, would receive some attention. Sure enough, headlines in USA Today, Nature, The Boston Globe, among others, touted his discovery that electrical stimulation to the brain can improve memory. But it was the messages that filled Reinart’s email inbox and voicemail that really blew him away. 

“A lot of them are these really personal, tragic, heartfelt stories. That just makes your heart melt—and you want to get back to everyone and you want to help them,” he says. “We had to have an emergency lab meeting the other day, just to prepare and plan to respond to so many people.” 

Reinhart, an assistant professor of psychological and brain sciences and the director of the Cognitive & Clinical Neuroscience Laboratory, studies human cognition with the goal of developing drug-free therapeutics for people suffering from brain disorders. He was recently honored for his work, receiving the 2022 Science and PINS Prize for Neuromodulation.

For his latest research, published in Nature Neuroscience on August 22, 2022, Reinhart and the members of his lab focused on adults aged 65 and older. Utilizing a soft cap covered in electrodes, they administered both low- and high-frequency electrical stimulation for 20 minutes on 4 consecutive days, while reading subjects a list of 20 words. They then tested those subjects’ immediate recall of the words as well as their memory of them one month later. The results showed improvements in both short- and long-term memory.

arts&sciences spoke with Reinhart shortly after his paper came out about his findings and what comes next for his research.  

arts&sciences: What’s been the response to your paper so far?

Robert Reinhart: It’s been a strong positive response from scientists around the country, around the world, and from the public, who’ve flooded my inbox. I love interacting with the public and I feel like it’s our responsibility as scientists to communicate what the public has bankrolled—the cost and risk is socialized for much of research. It’s a wonderful way to disseminate research. 

How do you see your research helping people? What are the clinical implications?

There are lots of problems with drugs and with current procedures—surgical procedures, behavioral and cognitive behavioral therapy—with people not responding to treatments or having side effects and persistence of symptoms. This is what our work speaks to: drug-free, novel therapeutics to help people with a wide variety of different disease states and clinical symptoms. I think there’s a real appetite for alternative drug-free approaches without the side effects. 

How far out are we from having these kinds of tools appear in a doctor’s office? There’s precedent for these types of tools, but we need bigger studies for them to be replicated and to ensure that it’s efficacious and safe.

Does the stimulation that you’re introducing to the brain mimic natural brain activity?

The brain communicates via nerve impulses. There’s rhythmic activity in the brain. We’re targeting those rhythms and causally augmenting them with the stimulation to put them into a different mode of functioning. So, for example, in schizophrenia and Alzheimer’s disease, there’s an asynchronous, rhythmic pattern. And the general idea is that we’re trying to resynchronize these patterns of activity that have been implicated in memory processing. Time is a crucial parameter in how the brain communicates with itself, and we’re going in and trying to have an effect on that dimension of brain activity.

How closely might eventual real-word use of this technology mirror your research?

We’re figuring out what parameters are the ones that we need to hone in on to maximize the benefit from the stimulation—like how intense is the stimulation within acceptable safety limits, the duration of each stimulation dose, interval spacing, optimal spacing between the sessions. We have a number of grants that we’re proposing now.

One thing we determined was that the frequency parameter is important. We’re manipulating the timing of brain activities and how they communicate. There’s processes that rise and fall in the brain at blindingly fast speed, and we can directly augment those rhythms that coordinate information flow and the timing of information to exploit the natural plasticity of the brain. We’ve known for a long time that certain pieces of brain tissue have specific functions—but the timing and the frequency of the brain activities in those regions can also be discovered and then exploited for translation. That was an important discovery with this latest work. 

Who might benefit most from your research?

Our research is geared toward people who are not responding well to drugs or first line treatments and standard care—they need something else. 

Are you beginning to understand how this might impact people with different conditions differently?

That’s a question for the future. We’re very interested in people who don’t respond to treatment and their individual differences. But condition by condition, we don’t have that much experience yet. I should say, one of the latest views in psychiatry is a dimensional approach, RDoc [Research Domain Criteria], where you view symptoms of various brain disorders along a spectrum of wellness. So, there might not be as clear of a line between what is considered “typical” versus “pathological”—there’s actually dimensions in which they overlap. And we target certain components of executive functioning which are likely to have implications across a wide variety of cognitive brain disorders and at different points along the wellness spectrum

Are there any lessons to be learned from this work with regard to preventing memory loss in the first place?

I haven’t thought of what we’re developing in the realm of prevention. When I think of prevention, with respect to Alzheimer’s, I think of radical diet and lifestyle changes. I think of whole grain, plant-based, vegan diets, low on salt, sugar, and oil, as well as adequate sleep and exercise, and stress reduction. These kinds of long-term, preventive measures are critical. But when you get to the place where you have the disease, that’s where we need pills and procedures, including drug-free procedures like the kind we’re developing.

What’s next for your lab?

We have three research threads we’re most excited about, and we’re developing a fourth. One is helping people with schizophrenia and schizoaffective disorder with cognitive deficits. Schizophrenia is the most disabling health state in the world. Number two is Alzheimer’s disease and memory, following up on this work that shows we can enhance memory for at least a month. So, we’re going to run a clinical trial—we’re submitting a grant for that now. The third is with respect to anxiety. Schizophrenia is the most disabling health state in the world, but anxiety and depression are the most prevalent. So, we’re focusing on generalized anxiety disorder as well as obsessive compulsive disorder. And then a fourth research stream—this one is really new—is in the realm of conscious and nonconscious experience. I think this is going to be really exciting and I’m eager to talk about what we’re finding, but the work is still under review.

And finally, you said your inbox filled up when this paper was published. Why do you think your work resonates with so many people?

I think our research is part of a larger scientific effort to open up an entirely new realm of treatment options for a wide variety of patients. And I think there are other factors that contribute to the appeal of not just our work, but novel pills and procedures, novel approaches to address diseases. And that might be, I’m sorry to say, because the healthcare system is not optimal in this country. If you look at the OECD countries—the most industrialized, technologically advanced countries in the world—the US ranks very low in terms of cost of healthcare and in terms of outcomes. We’re paying the most and we’re getting the worst outcomes. And so, when you have something that can potentially help people who are suffering, you get this kind of response.

This interview has been edited for brevity and clarity.