McLean Hospital 115 Mill Street Belmont, MA 02478
Innovations in neuroimaging enable McLean scientists to investigate the structure and function of the brain to diagnose and develop treatments for many mental health conditions. Now two groundbreaking techniques go a step further: offering the possibility of direct relief from memories of traumatic events and bipolar or major depression.
Edward G. Meloni, PhD, assistant psychologist at McLean, and Marc J. Kaufman, PhD, director of the Translational Imaging Laboratory, knew that the gas xenon worked as an anesthetic and a diagnostic imaging agent in human beings. In 2014, they released an animal study that showed it also had the potential to reduce memories of traumatic events, setting the stage for new treatments for post-traumatic stress disorder (PTSD).
“When we reactivated a traumatic memory in rats using cues associated with the trauma, the xenon blocked the memory from being reincorporated into the brain,” said Meloni.
Xenon may have interfered with a neural process called reconsolidation. “Every time we recall a memory, it’s modified by new information in the environment before it’s re-stored in the brain,” said Meloni. Xenon appeared to hamper that reconsolidation, reducing the rats’ fear response by more than half for at least 18 days.
The results sparked the pair’s interest in using xenon to arrest some of the effects of traumatic brain injury (TBI), leading to the creation of a study made possible by philanthropic support.
Xenon works by blocking the brain’s NMDA receptors, which bind the neurotransmitter glutamate and are involved in learning and memory. Neurons exposed to an excessive amount of glutamate because of NMDA-receptor overactivation—which may happen with TBI—can be damaged. Meloni and Kaufman hypothesized that xenon would block that overactivation.
To model human TBI in rats, they administered a neurochemical that elevates brain glutamate levels and treated some of the animals with xenon immediately after the insult. Neuroimaging showed damage in the brains of the untreated animals and significant neuroprotection in the xenon-treated ones.
“The xenon effects that we can detect with neuroimaging are helping us understand some of the mechanisms at work in PTSD and TBI,” said Kaufman. “We’re enthusiastic that xenon could be a treatment for people sometime soon.”
For McLean physicist Michael Rohan, PhD, the effects from a neuroimaging machine itself led to a treatment—one provided by a 14-inch-wide tabletop low-field magnetic stimulation (LFMS) device that he designed in 2005 and continues to refine.
An expert in coil design, Rohan helped develop the first commercial functional magnetic resonance imaging machine before joining McLean’s Brain Imaging Center. His interest in how electromagnetic fields interact with nerve cells led to a pioneering 2004 study showing that LFMS brought immediate mood improvement for 23 out of 30 patients suffering from the depression phase of bipolar disorder. In 2014, using his tabletop device, he confirmed those results: a single 20-minute treatment brought significant, rapid mood elevation for patients suffering from bipolar or major depression.
“LFMS uses electromagnetic fields that are a fraction of the strength but at a much higher frequency than treatments such as electroconvulsive therapy or transcranial magnetic stimulation,” said Rohan. “It’s as if LFMS provides a nudge within the cortex—the brain’s surface layer—like a pharmaceutical would. The other treatments are analogous to pressing the reset or the override button.”
Those differences may explain the lack of side effects—and the quick response. Electroconvulsive therapy and transcranial magnetic stimulation, in contrast, require multiple treatments and, like antidepressant medications, can take four to six weeks to begin working.
Currently Rohan is developing a 10-inch-wide version of his machine and conducting a double-blind study with 72 subjects to learn how long the LFMS effects last and how multiple treatments might influence results.
“Usually you begin with a hypothesis, develop it through animal models, and work your way up to humans,” said Rohan. “Here, we saw the technology work in people first. Now we’re going backward to figure out how and why.”