Brain Dynamics
Program Highlight
Brain Dynamics
Alvaro Pascual -Leone, M.D., Ph.D., believes he can change your mind for the better. For more than a decade, this Spanish-born neurologist and neurophysiologist has been doing research at BIDMC that combines high-tech imaging with noninvasive stimulation techniques.
“I’ve always been interested in the notion of: How do we do the things we do? How do we think? How do we feel? How do we know that we are we?—these sorts of things,” he says. “Being able to stimulate the brain of awake subjects becomes a fantastic opportunity to study these kinds of questions.” It may also offer new hope for patients suffering from disorders as varied as depression, epilepsy, and stroke.
Pascual-Leone’s research capitalizes on the idea that the brain isn’t as rigid and inflexible as once thought. Back in the 80s, he was involved in pioneering work in epileptic patients that helped prove that the brain is “plastic,” adapting continuously as we go about our daily lives. While his goal at first was to map areas of the brain that controlled certain critical functions, like language and memory, Pascual-Leone became intrigued with the possibility of exploiting the brain’s adaptive abilities for therapeutic purposes. “This capacity for dynamic change is a double-edged sword,” he notes. “There is no reason to believe that the changes will be good. So the challenge is not to activate plasticity— there’s nothing to activate; it’s already on—but rather to guide it, to suppress those changes that are going to hamper recovery or promote disease and to enhance those changes that are going to promote health.”
So how exactly do you go about altering how the brain works? Because brain cells, or neurons, communicate through a process controlled by electrical and chemical signals, applying an electric current to an area of the brain can affect how these cells do their job. In the past, the only way to study these effects was to place an electrode directly on the brain itself in patients already undergoing open-skull surgery. But with the advent of high-speed electronics and advanced imaging came a new, noninvasive technique called “transcranial magnetic stimulation” (TMS), which has become the cornerstone of Pascual-Leone’s research. TMS uses a high-speed electrical device held near the head to generate a magnetic field, which in turn creates a current far below the scalp’s surface. “So really magnetic stimulation is a misnomer,” says Pascual-Leone. “It’s not the magnetic field that stimulates. It’s only bridging the skin and the skull and then inducing current in the brain.” By aiming this current at certain specific areas of the brain, researchers can stimulate or block the activity of certain neuronal pathways that may be involved in disease.
With TMS, combined with advanced imaging like MRI scans to view its impact, Pascual-Leone has gleaned a wealth of information about how brains—both healthy and ailing—function. More importantly, he has created a therapeutic option that can be guided both by the disease itself and how it manifests itself in a specific patient, reducing potential side effects and increasing efficacy. “And what is particularly appealing to me,” he notes, “is the idea that if we can do this in one condition, then I think we can assume that we can probably do it in any other condition as long as we know what the network is that needs to be targeted and in what direction it needs to be affected.” That, of course, is the trick. But already Pascual-Leone, one of a handful of U.S.-based researchers using this technology, has shown encouraging results in depression, stroke-related disorders, epilepsy, autism, and chronic pain, to name a few, and has just begun exploring new targets in addictive behaviors.
Pascual-Leone’s accomplishments have recently caught the eye of the press and philanthropists alike. Just as articles on his work graced the pages of Time and Newsweek, longstanding supporters of BIDMC, Helaine Berenson Allen and Theodore Berenson, pledged a $1 million gift to create the Berenson-Allen Center for Noninvasive Brain Stimulation at the medical center, which Pascual-Leone will direct. “My brother and I were extremely impressed with the depth and breadth of Alvaro’s work,” says Allen. “Given our long relationship with Beth Israel Deaconess, we weren’t surprised at all that this kind of innovation and creativity was taking place at the medical center.”
Pascual-Leone, who says he is “indebted” to Allen and Berenson for their generosity, believes that scientists today also need to be practical business people, who have an obligation to realize a return on any investment made on their work. “And an aspect of the return is, of course, do the ideas translate into something that helps people—at least that’s my own measure of accountability,” he says. “But the other is do they help generate more funds to train people, pursue more studies, develop new technologies, and so forth. So I see this as the kind of gift that will prove to be a fantastic return on investment at all those levels.”
While he hopes that the creation of the new center will inspire others to sponsor his work, Pascual-Leone is already thankful for the reward that few cognitive neurophysiology researchers ever receive—translation of his scientific efforts into successful clinical applications. As the FDA considers the approval of the use of TMS for the treatment of depression and other diseases, he smiles, “It’s a really unique gift that patients give us in allowing us to take care of them and to apply some novel ideas to their care.”
