News Release

Penn Medicine 'brain road maps' reflect behavior differences between males and females

Findings offer new insights for personalized medicine and treatment of particular disorders

Peer-Reviewed Publication

University of Pennsylvania School of Medicine

PHILADELPHIA -- Differences in the neural wiring across development of men and women across ages, matched behavioral differences commonly associated with each of the sexes, according to an imaging-based study from researchers at the Perelman School of Medicine at the University of Pennsylvania published February 1 in Philosophical Transactions of the Royal Society B.

The Penn team, including senior author Ragini Verma, PhD, an associate professor in the Center for Biomedical Image Computing and Analytics (CBICA), department of Radiology, performed diffusion tensor imaging (DTI) brain scans and administered a computerized neurocognitive battery (CNB) of tests on 900 randomly selected healthy and unmedicated Philadelphian children and young adults, ages 8 to 22 years, to find how structural differences in the brain may relate to male and female behavior differences such as men being more likely to be better at learning and performing a single task at hand and women being more likely to exhibit superior memory and social cognition skills. These methods allowed the team, including lead authors Birkan Tunc, PhD, a research associate, and Berkan Solmaz, PhD, a postdoctoral researcher in Radiology, CBICA, and co-authors Ruben C. Gur, PhD, a professor of psychology in the department of Psychiatry, and Raquel E. Gur, MD, PhD, professor of Psychiatry, Neurology and Radiology, to develop a structural connectome, akin to a road map of each subject's brain.

As a natural gateway to fathom the human mind and behavior, studies concentrating on the human structural connectome are an important part of efforts to investigate sex differences. Insight into brain differences between men and women offers important considerations for the growing field of personalized medicine, which U.S. President Barack Obama announced $215 million in support for in his recent State of the Union address. The findings also have potential implications for treatment of a variety of conditions.

Differences in the cause and progression of some diseases and disorders according to sex sometimes influence treatment of those conditions. For instance, men are far more likely to get autism than women are. And in schizophrenia, which is also more frequent in males, the onset and severity of the disease differ between the sexes.

"Links between brain and behavior possibly rely on a complex interplay among multiple features of the neurobiological mechanism," Verma said. "Network theoretical studies pertaining to the properties of the structural connectome may provide pioneering insights into these links."

Her team studied sex related differences in the connectivity of the subnetworks that were defined based on structural characteristics, functional systems, and finally, behavioral domains. Subnetworks are clusters of brain regions and their connectivity, which are associated with functionality or behavioral domains such as motor abilities, social motivation or cognitive control.

The team's findings build on a 2013 Proceedings of the Academy of Sciences (PNAS) study in which they found, on average, differences in the neural wiring of men and women. This latest study delves deeper, reporting that differences in the behaviors of men and women are accompanied by related differences in the brain subnetworks. According to findings of the team, stronger structural connectivity in motor, sensory, and executive functions matched higher motor and spatial skills in males. In females, subnetworks associated with social cognition, attention and memory tasks had higher connectivity and matched improved memory and social cognition skills.

"On a macro level, behavior-related disorders manifest and progress differently based on sex, and these findings should advance conversations about how we manage some of those conditions," Verma said. "Our results suggest a synchrony between sex-related differences in the brain network and behavior. Thus, in a near future, we may be able to pinpoint precisely at the subnetwork level what we know about an individual's brain and how to manage care of whatever disorders or ailments they are facing."

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Other co-authors on the study, all from Penn, include Drew Parker, Theodore D. Satterthwaite, Mark Elliott, Monica E. Calkins, and Kosha Ruparel.

This work was supported by National Institute of Mental Health (MH089983, MH089924, MH079938, and MH092862).

Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $5.3 billion enterprise.

The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 17 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $409 million awarded in the 2014 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania -- recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; Chester County Hospital; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Chestnut Hill Hospital and Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2014, Penn Medicine provided $771 million to benefit our community.


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