Using new approaches, an interdisciplinary team of scientists at NewYork-Presbyterian Hospital/Weill Cornell Medical Center in New York City has gained a view of activity in key brain areas associated with a core difficulty in patients with borderline personality disorder -- shedding new light on this serious psychiatric condition.
"It's early days yet, but the work is pinpointing functional differences in the neurobiology of healthy people versus individuals with the disorder as they attempt to control their behavior in a negative emotional context. Such initial insights can help provide a foundation for better, more targeted therapies down the line," explains lead researcher Dr. David A. Silbersweig, the Stephen P. Tobin and Dr. Arnold M. Cooper Professor of Psychiatry and Professor of Neurology at Weill Cornell Medical College, and attending psychiatrist and neurologist at NewYork-Presbyterian Hospital/Weill Cornell Medical Center.
The findings are featured in this month's issue of the American Journal of Psychiatry.
Borderline personality disorder is a devastating mental illness that affects between 1 to 2 percent of Americans, causing untold disruption of patients' lives and relationships. Nevertheless, its underlying biology is not very well understood. Hallmarks of the illness include impulsivity, emotional instability, interpersonal difficulties, and a preponderance of negative emotions such as anger -- all of which may encourage or be associated with substance abuse, self-destructive behaviors and even suicide.
"In this study, our collaborative team looked specifically at the nexus between negative emotions and impulsivity -- the tendency of people with borderline personality disorder to 'act out' destructively in the presence of anger," Dr. Silbersweig explains. "Other studies have looked at either negative emotional states or this type of behavioral disinhibition. The two are closely connected, and we wanted to find out why. We therefore focused our experiments on the interaction between negative emotional states and behavioral inhibition."
Advanced brain-scanning technologies developed by the research team made it possible to detect the brain areas of interest with greater sensitivity.
"Previous work by our group and others had suggested that an area at the base of the brain within the ventromedial prefrontal cortex was key to people's ability to restrain behaviors in the presence of emotion," Dr. Silbersweig explains.
Unfortunately, tracking activity in this brain region has been extremely difficult using functional MRI (fMRI). "Due to its particular location, you get a lot of signal loss," the researcher explains.
However, the Weill Cornell team used a special fMRI activation probe that they developed to eliminate much of that interference. This paved the way for the study, which included 16 patients with borderline personality disorder and 14 healthy controls.
The team also used a tailored fMRI neuropsychological approach to observe activity in the subjects' ventromedial prefrontal cortex as they performed what behavioral neuroscience researchers call "go/no go" tests.
These rapid-fire tests require participants to press or withhold from pressing a button whenever they receive particular visual cues. In a twist from the usual approach, the performance of the task with negative words (related to borderline psychology) was contrasted with the performance of the task when using neutral words, to reveal how negative emotions affect the participants' ability to perform the task.
As expected, negative emotional words caused participants with borderline personality disorder to have more difficulty with the task at hand and act more impulsively -- ignoring visual cues to stop as they repeatedly pressed the button.
But what was really interesting was what showed up on fMRI.
"We confirmed that discrete parts of the ventromedial prefrontal cortex -- the subgenual anterior cingulate cortex and the medial orbitofrontal cortex areas -- were relatively less active in patients versus controls," Dr. Silbersweig says. "These areas are thought to be key to facilitating behavioral inhibition under emotional circumstances, so if they are underperforming that could contribute to the disinhibition one so often sees with borderline personality disorder."
At the same time, the research team observed heightened levels of activation during the tests in other areas of the patients' brains, including the amygdala, a locus for emotions such as anger and fear, and some of the brain's other limbic regions, which are linked to emotional processing.