May 3, 2017

Interpreting complex connections

U takes a leading role in the Lifespan Human Connectome Project, phase two of a national brain mapping initiative

A closer look at the hallucinations of schizophrenia

In the middle of a conversation with his mother, he glimpsed the figure of a man from the corner of his eye. But when he turned his head, the figure was gone.

Minutes later, the figure appeared again in his peripheral vision, creating a debilitating sense of concern. Still, no man was present.

Scott Sponheim headshot
Scott Sponheim, Ph.D., will explore how and why these visual distortions occur.
Scientists don’t know exactly what causes the visual hallucinations that some 3 million people with schizophrenia experience, but a new project led by the Medical School’s Scott Sponheim, Ph.D., a professor of psychiatry and staff psychologist at the Minneapolis VA Health Care System, will explore why these episodes of visual distortion occur, potentially leading to improved treatments.

Funded by a $3 million grant from the National Institutes of Health and part of the disease arm of the Human Connectome Project, Sponheim will collaborate with the University’s Center for Magnetic Resonance Research to obtain detailed brain images of 150 people who have schizophrenia while they perform tasks that prompt activity in the brain’s visual and prefrontal cortexes. He will also scan the brains of 100 of their immediate relatives and 50 other healthy people who are not related to someone with schizophrenia.

Sponheim expects that people with schizophrenia will have abnormal activity in both the prefrontal and visual cortexes, while healthy relatives who carry genetic vulnerability for the disorder will have only abnormal activity in prefrontal areas. He thinks the interplay between both abnormalities in the brain causes the hallucinations and represents problems with brain connections that result in schizophrenia.

“By identifying mechanisms for the hallucinations, we can eventually develop more targeted treatments that might improve compromised portions of the brain,” Sponheim says.

More than six years ago, the University of Minnesota spearheaded the technological advances behind the most ambitious brain imaging study ever conducted, the Human Connectome Project. It mapped the vast network of about 90 billion neurons and trillions of interconnections in the brains of young, healthy adults at the millimeter scale.

The U’s Center for Magnetic Resonance Research (CMRR) developed the imaging methods and directions on reconstructing the images to make sense of the data. Colleagues at Washington University in St. Louis did the bulk of the brain scanning—in total, 1,200 volunteers—and, together with investigators from Oxford University, developed the image processing pipelines.

Findings from this National Institutes of Health (NIH)–funded project, now complete and celebrated as a success, are publicly available to scientists and anyone else who wants them. The insights gleaned so far are fascinating.

“Our consortium [found] that the brain networks that we can detect very much correlated with behavioral measures, lifestyle measures,” says CMRR director Kamil Ugurbil, Ph.D. “For example, they are correlated very strongly with IQ, with education, with drug use or alcoholism, etcetera.”

Brain scan images from Human Connectome Project
Image: Vu, A.T., Jamison, K., Glasser, M.F., Smith, S.M., Coalson, T., Moeller, S., Auerbach, E.J., Ugurbil, K., Yacoub, E., 2016. Tradeoffs in pushing the spatial resolution of fMRI for the 7T Human Connectome Project. Neuroimage.

Other researchers used the Human Connectome Project data to show that brain networks are unique to individuals, much like fingerprints. That’s encouraging, Ugurbil says, because if researchers can identify networks unique to individuals, they may be able to identify abnormalities unique to individuals as well.

What’s next? Extensions of this immense undertaking. The NIH is now funding a Lifespan Human Connectome Project, designed to track normal brain changes in humans from infancy to “as old as we can get,” Ugurbil says.

  • The Baby Connectome Project focuses on children from birth to early childhood to map structural and functional changes that occur in the brain during typical development. The U’s Jed Elison, Ph.D., McKnight Land Grant Professor, and Ugurbil will lead this effort with partners at the University of North Carolina.
  • The Lifespan Human Connectome Project: Development targets ages 5 to 21 and will track changes in the brain, behavior, and mood as children move through puberty. The U’s Essa Yacoub, Ph.D., and Kathleen Thomas, Ph.D., will lead this arm of the study, which will also take into account physical and mental health, thinking and decision-making skills, and behavioral and emotional regulation.
  • The Lifespan Human Connectome Project: Aging will characterize several factors that influence cognitive function alongside the comprehensive brain connectivity mapping in healthy volunteers aged 36 and up. This study—led by Ugurbil and the CMRR’s Melissa Terpstra, Ph.D.—will track risk factors for Alzheimer’s disease, cognitive symptoms associated with perimenopause, and key aspects of socioeconomic and health status.

The NIH is also funding 13 connectome projects focused on specific neuropsychiatric diseases to identify where and how alterations occur—and potentially to find ways to intervene with disease processes.

“Predominantly, this drive comes from the hypothesis that all neuropsychiatric diseases are circuitry diseases and you cannot study them with just normal magnetic resonance imaging,” says Ugurbil.

U psychiatry professor Scott Sponheim, Ph.D., is leading one such project on schizophrenia (see sidebar).

The CMRR’s experts will continue to refine and develop the technologies needed for all of the connectome studies—and they’re disseminating these techniques to scientists around the world (at nearly 300 sites total) in the name of advancing brain science.

“At the expense of sounding immodest, I think there has been a revolution in imaging the brain through the Human Connectome Project,” says Ugurbil, adding that anyone who uses functional imaging and diffusion imaging—the two imaging types used in the studies—in their research will benefit. “The technological development has been really fantastic.”

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