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Improving Cognition with Noninvasive, Personalized Treatments Wins Prize

image of researcher placing transcranial electrode cap on volunteer
Former Reinhart Lab Breanna Bullard demonstrates electrode placement on lab member Elena Kouvaras. | Courtesy of Robert Reinhart

For his work in utilizing new technologies to personalize noninvasive treatments for various cognitive brain disorders, such as aging-related memory decline, Robert Reinhart is the 2022 grand prize winner of the Science & PINS Prize for Neuromodulation.

Such developments are especially valuable considering the personal, social, and economic costs associated with a rapidly aging global population, as age is the greatest risk factor for cognitive decline. This new technology utilized by Reinhart and his team — high-definition transcranial alternating current stimulation (HD-tACS) — works as electrical currents are tailored to an individual's rhythmic brain activity and alter brainwaves to treat various cognitive issues.

"Today, someone in the United States develops Alzheimer's disease every 65 seconds," said Reinhart, assistant professor of psychological and brain sciences and biomedical engineering at Boston University. "We hope our research will contribute to the development of future drug-free therapeutics that can effectively slow, stop, or even reverse memory impairments in older people, and as a result, reduce the direct and indirect costs associated with cognitive aging for individuals, their families, caregivers, and society."

While cognitive brain disorders like age-related memory decline and obsessive-compulsive disorder can be disabling, the treatments that exist to ameliorate them — including pharmacological, surgical and behavioral therapeutics — are limited by slow symptom resolution and accompanying side effects.

The Need for Personalized Therapeutics

Novel therapeutic interventions capable of providing rapid, personalized and sustainable improvements with minimal side effects are urgently needed, and one class of tools that has emerged is noninvasive neuromodulation technology — the alteration of nerve activity through the targeted delivery of a stimulus. Reinhart and his team have taken advantage of developments in neuromodulation to find early success in tailoring therapeutics to individual rhythmic brain activity.

"The work by Dr. Reinhart, beautifully presented in his winning essay, highlights the potential of neuromodulation for treating cognitive impairments," write Caitlin Czajka and Mattia Maroso, senior editors at Science Translational Medicine. "Dr. Reinhart and colleagues utilized non-invasive transcranial alternating current stimulation to improve age-related memory function and to reduce symptoms of obsessive-compulsive behaviors. The results presented by Dr. Reinhart support the use of this customizable, non-pharmacological intervention to maintain cognitive abilities throughout life."

Reinhart and his team chose to work with transcranial alternating current stimulation (tACS) because tACS can noninvasively and safely align neural processes in the brain with external stimuli and give immediate control over components of human cognition. They utilized and improved upon a new neuromodulation approach known as high-definition transcranial alternating current stimulation (HD-tACS). In this approach, synchronization of currents in the brain using HD-tACS can manipulate rhythmic activity in the brain.

"My team at BU is especially interested in the rhythmic or oscillatory network activity underlying human cognition," said Reinhart. "We think that examining these large-scale brain rhythms and how they synchronize within and across different frequencies and brain areas will shed important light on the nature of human cognition."

Reinhart said that although invasive deep brain stimulation personalized to an individual's anatomy has shown some promise, his team's work is the first to show encouraging results using a completely noninvasive neuromodulation approach. The design rooted in basic neuroscience practices allows brainwaves that vary person to person to be stimulated and individually tuned to inform cognitive function — all from the outside the brain, using electrodes.

Robert Reinhart | Cydney M. Scott

The HD-tACS experimental setup his team employs involves electroencephalogram (EEG) electrodes — most of which are mounted in an elastic cap — attached to the patient. Additional electrodes are placed next to the eyes, on the forehead, or behind the ears. The electrodes are sensors enclosed in a plastic shell; they do not directly contact the skin but rather, electrical contact between the skin and the electrodes is achieved via a water-soluble electrode gel. Current is applied for about 20 minutes, during which volunteers are comfortably seated and perform cognitive tasks, including those involving responding to various stimuli on a computer screen.

Treating Memory Loss and OCD

Utilizing HD-tACS, Reinhart and his team conducted a variety of personalized treatments to work with older volunteers on improving memory and with other people to improve components of obsessive-compulsive behaviors.

In the experiments with older individuals, the frequency of synchronization of brainwaves was individually determined for each participant to maximize the likelihood of success. Volunteers monitoring a screen were briefly presented with the image of a complex real-world object before it disappeared. They then needed to hold this object in their mind's eye for several seconds. Afterwards, they were presented with an object and needed to indicate whether it was new or matched the original.

"Older adults were significantly more accurate at performing this classic visual working memory task during and after their personalized HD-tACS treatment versus the sham," Reinhart said.

In aiming to treat compulsivity, healthy volunteers exhibiting some form of compulsive behavior received carefully designed, personalized treatments of currents to the brain through the use of attached electrodes to tune their neural networks that control reward learning and repetition of behavior.

"Compulsive behavior reduced markedly immediately after the five-day procedure and these improvements remained for at least three months," said Reinhart. "In particular, we observed sustained reductions in hoarding, ordering and checking tendencies. In addition, strongest improvements were observed for those who began with the most severe behaviors."

The findings suggest this new form of personalized neuromodulation may be effective in producing long-lasting benefits in people experiencing distress due to actions such as compulsive eating, gambling and shopping, and particularly in people suffering from mental health problems.

Future of tACS

The group has tracked changes and improvements in their volunteers three months following treatment and plans to monitor tACS effects using behavioral and brain activity measures over longer periods in the future.

Reinhart and his team are also developing new HD-tACS protocols in the hopes that HD-tACS can be used to treat a wider variety of cognitive disorders with personalized therapeutics.

"We plan to continue studying aging and subclinical OCD, but we are expanding our tACS research program to include Alzheimer's dementia, clinical OCD, bipolar mania, and schizophrenia," Reinhart said. "While it is challenging to predict the future, we are optimistic that personalization rooted in the neuroscience of network dynamics will rise to the forefront of next-generation noninvasive neuromodulation and pave the way toward the future use of precision electroceuticals in neurology and psychiatry."

The Science & PINS Prize for Neuromodulation seeks to reward those who perform innovative neuromodulation research.

"Neuromodulation therapy is an emerging therapy for the treatment of functional neurological and psychiatric system diseases, which is increasingly clinically accepted. As people's understanding of the therapy becomes clearer, patient selection becomes more precise, and neuromodulation efficacy is getting better and better," said Chong Li, CEO of PINS Medical. "However, the corresponding devices approved by global regulatory agencies with observable clinical efficacy are still primarily implantable neuromodulation devices, such as deep brain stimulators. Researchers have begun to try the non-intrusive ways to modulate the established neuro-targets. Both articles [in Science] are very good attempts, they set inspiring groundworks for futural non-invasive neuromodulation therapy."

On winning, Reinhart said "I am sincerely honored to receive this prestigious prize and I am grateful for the outstanding mentors, students, and collaborators I have had the privilege of working with over the years."

2022 Finalist

Davide Folloni

Davide Folloni is a finalist for his essay "Ultrasound neuromodulation of the deep brain." Folloni received his undergraduate degree from the University of Parma, a master's degree in clinical psychology from the University of Padua, and a master's and Ph.D. in neuroscience from the University of Oxford. His research focuses on the development of multimodal approaches combining neuromodulatory, electrophysiological and imaging techniques to understand the neural mechanisms underlying learning and decision-making with the primary aim to describe how neuronal oscillations guide adaptation to the world.