Brain Structure Associated With Fear Inhibition Also May Influence Personality

"Some studies have demonstrated links between extraversion or the trait of neuroticism and the overall activity of brain regions that include the mOFC. But this is the first time anyone has looked at the potential relation of both brain structure and fear extinction to personality traits," says Mohammed Milad, PhD, of the MGH Department of Psychiatry, a co-lead author of the study.

Most individuals initially respond with physical and emotional distress to situations that bring back memories of traumatic events, but such responses usually diminish over time, as the situations are repeated without unpleasant occurrences. The ability to suppress those negative responses is called "extinction memory," and its deficiency may lead to anxiety disorders such as post-traumatic stress disorder. In their previous study, the MGH team focused on the ventromedial prefrontal cortex – an area on the lower surface of the brain that includes the mOFC and is believed to inhibit the activity of the amygdala, a structure known to be involved with fear. The current report combined the data analyzed in that study – published in the July 26, 2005, Proceedings of the National Academy of Science – with the results from a standard personality test. Since earlier research has associated levels of extraversion and neuroticism – oversensitivity and emotional instability – with vulnerability to anxiety disorders, the current experiment focused on those traits.

As described in the PNAS study, over two days 14 study participants viewed a series of digital photos that featured lamps with either a red or a blue light shining. On the first day, participants viewed the photos several times with a mild electric shock – described as annoying but not painful – delivered to their hands after one, but not the other, colored light appeared. They then viewed the photos again with no shocks administered. On the second day, participants' anxiety levels, determined by perspiration on the palm of the hand, were measured while they once again viewed the photos with both colors displayed but no shocks given. Structural magnetic resonance (MR) images of the volunteers' brains showed that those who responded with less anxiety on the second day also had a thicker mOFC, and no other areas of the brain appeared to be correlated with extinction retention.

Combining the results of the personality tests with the previously reported data revealed that both improved extinction retention and a thicker mOFC were associated with higher levels of extraversion and lower neuroticism. Using a statistical tool that analyzes whether one specific factor influences the relationship between the two other factors, the researchers found that while the relation between mOFC thickness and increased extraversion is mediated by extinction retention, the association between mOFC thickness and extinction retention does not seem to directly affect neuroticism.

"This study illustrates how measurement of a brain structure can be linked to a complex character trait like extraversion through a simpler behavioral measure like extinction retention," says Scott Rauch, MD, director of the Psychiatric Neuroscience Research Division in MGH Psychiatry and co-lead author of the paper. "Understanding how personality is based in the brain is important both for insights into personality disorders and for conditions in which personality may confer vulnerability, such as anxiety disorders."

Rauch adds, "We are in the process of studying the link between extinction retention and regional brain function and hope to investigate how developmental factors may govern the structure and function of the mOFC. The ability to modify mOFC activity may eventually prove to be of therapeutic value." Rauch is an associate professor of Psychiatry at Harvard Medical School.

The report's co-authors are Roger Pitman, MD, of MGH Psychiatry; Brian Quinn and Bruce Fischl, PhD, of MGH Radiology; and Scott Orr, PhD, of the VA Medical Center in Manchester, N.H. The study was supported by grants from the National Institute of Mental Health, the MGH Tosteson Fellowship, National Center for Research Resources, National Institute of Biomedical Imaging and Bioengineering, and the Mental Illness and Neuroscience Discovery Institute.

Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of nearly $500 million and major research centers in AIDS, cardiovascular research, cancer, cutaneous biology, medical imaging, neurodegenerative disorders, transplantation biology and photomedicine. In 1994, MGH and Brigham and Women's Hospital joined to form Partners HealthCare System, an integrated health care delivery system comprising the two academic medical centers, specialty and community hospitals, a network of physician groups, and nonacute and home health services.