September 11, 2012 | 2
In a room tucked next to the reception desk in a colorful lobby of a Park Avenue office tower, kids slide into the core of a white cylinder and practice something kids typically find quite difficult: staying still. Inside the tunnel, a child lies on her back and looks up at a television screen, watching a cartoon. If her head moves, the screen goes blank, motivating her to remain motionless. This dress rehearsal, performed at The Child Mind Institute, prepares children emotionally and physically to enter a real magnet for a scan of their brain. The scan is not part of the child’s treatment; it is his or her contribution to science. What scientists learn from hundreds to thousands of brain scans from children who are ill, as well as those who are not, is likely to be of enormous benefit to children in the future.
The Child Mind Institute is a one-of-a-kind facility dedicated to the mental health of children. Its clinicians offer state-of-the-art treatments for children with psychiatric disorders. (For more on its clinical services see my previous post, “Minding Our Children’s Minds.”) In addition to spotting and treating mental illness, The Child Mind Institute is dedicated to improving both through science. Its researchers are helping build a repository of brain scans to better understand both ordinary brain development and how mental illness might warp that process.
Tracking the developmental trajectory of mental illness is a critical, overlooked enterprise. Almost three quarters of psychiatric disorders start before age 24 and psychological problems in childhood often portend bona fide, or more severe, diagnoses in adults. If scientists can pinpoint changes that forecast a mental disorder, they might be able to diagnose an incipient disease, when it might be preventable, and possibly target the troublesome circuits through therapy. Certain brain signatures might also provide information about disease risk and prognosis, and about what types of treatments might work best for an individual.
Timeline for the Brain
The first step in this process is obtaining a reliable snapshot of ordinary brain development, one based on lots of brains. The ability to recognize signs of a sick brain (or one at risk of becoming sick), after all, requires knowing what a healthy brain looks like. Toward this end, 1,000 residents of Rockland county, ages six to 85 will, in the next few years, travel to the Nathan S. Kline Institute for Psychiatric Research in Orangeburg, New York, 27 miles north of New York City, to take part in a landmark study to have their brains speed-read using state-of-the-art functional magnetic resonance imaging (fMRI) machines.
Each scan divulges the so-called “functional architecture” of the brain by gauging levels of neural activity in different regions. (fMRI devices don’t measure such activity directly, but track blood flow, under the assumption that more active neurons use more blood.) From these activity levels, software can infer how strongly two regions are connected, says Cameron Craddock, director of imaging at the Center for the Developing Brain at the Child Mind Institute, which, along with the Nathan S. Kline Institute and the National Institutes of Mental Health is supporting this unique endeavor. If two regions are abuzz at the same time, researchers assume they are connected and form part of a common network. By scanning large numbers of individuals of various ages, researchers can determine how the functional connectivity of the brain changes over time.
The resulting images will be made publicly available through the International Neuroimaging Data-Sharing Initiative, the first large-scale attempt to collect and share a large number of brain images. On December 11, 2009, the scientists behind this effort, previously dubbed the 1,000 Functional Connectomes Project, publicly released over 1,200 sets of fMRI images of the brain at rest created at 33 different sites around the world. Since then, investigators have downloaded and used this data to sketch a core architecture behind human brain function along with variations between individuals of different ages and genders—findings outlined in more than 40 publications so far.
Images of Illness
In a second project, The Child Mind Institute will explore brain development patterns in its young patients. Children who volunteer for the project will travel to Orangeburg for a brain scan. The images, stripped of identifying details, will comprise a future Child Mind Institute Biobank. As with the repository of brains from healthy individuals, Biobank curators will pair these scans with carefully collected psychological and clinical data from the same individuals to understand the significance of what they are seeing in the scans.
The hope is to find functional brain signatures of mental illness and learning disorders in children and teens. “We plan to integrate the research and the clinical,” to determine the developmental origins of ailments such as autism, depression and psychosis, says Ronald Steingard, a psychopharmacologist at The Child Mind Institute. Scientists hope such information might one day be used to develop objective medical tests for these problems and to see a patient’s response to treatment as a change in his or her brain.
This effort parallels other recent undertakings conducted with the support of the International Neuroimaging Data-Sharing Initiative. In one of these, the Autism Brain Imaging Data Exchange, investigators from 16 scattered labs have divulged brain scans, along with behavioral data, from 539 individuals with an autism spectrum disorder and 573 counterparts without autism. A separate research consortium has released brain images, along with basic clinical information, from 285 children and adolescents with attention-deficit hyperactivity disorder and 491 without the deficit for comparison.
In addition to more accurate diagnosis, a close look at the brain regions altered by illness could help doctors tailor treatment more precisely to a patient’s problem. Strategies such as electroconvulsive therapy and deep-brain stimulation (DBS) that work by revving up or shutting down neural activity can be aimed at particular brain regions or nerve fiber tracts. In some cases, medication is known to act largely on particular brain areas as well.
Focused treatment could also take the form of biofeedback, in which the patient tries to deliberately alter brain activity through conscious processes. The hubbub in a brain area or circuit could drive a visual output—say, a needle on a “brainometer.” Patients might try to move that needle one way or the other by directing their thoughts to particular topics, sensations or remembrances. (Often, patients try several strategies by trial-and-error before landing on one that works.) Craddock is now actively investigating biofeedback as a possible treatment for depression.
In addition, shedding light on the neural circuits involved in specific brain disorders might inspire the development of new therapies aimed at those circuits. Like the collaborative effort to decipher the human genome, a large-scale endeavor to uncover the vast array of connections in the human brain, their meaning, and how they change over time, is likely to yield myriad benefits, many of which we cannot yet predict.
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