Spelling Out the Link between Brain Networks and School Performance

by Aalok Mehta

June 3, 2010

Come May 2013, your child may suddenly develop a case of attention-deficit hyperactivity disorder. Or no longer be diagnosed as autistic.

That's when the American Psychiatric Association is slated to release the next version of the Diagnostic and Statistical Manual of Mental Disorders, a widely used handbook that defines psychiatric conditions such as ADHD, depression, and post-traumatic stress disorder. The specific symptoms that characterize many of these conditions are expected to change in the DSM-5, which is undergoing an extensive review and revision process.

The DSM works off a “perfect” model of mental disease; the book describes an ideal case of a condition, and people are said to have the disorder if they have a certain number of the listed symptoms. This has been controversial for as long as the DSM has been around, since what exactly constitutes a disease and how many symptoms are necessary for a diagnosis are largely subjective decisions. Also, many researchers think the manual lumps together into a single condition cases that may have vastly different root causes in the brain (such as autism, which sometimes has a genetic basis and sometimes doesn’t).

In response, some experts are pushing that any changes to the handbook should reflect this new understanding (see also the Cerebrum articles, “On the Road to DSM-V” and “Psychiatry at Stalemate”). But the practical implications of what we know now are limited: Neuroscientists have thus far failed to provide precise causes for these disorders, to isolate responsible genes, or to develop diagnostic methods that are more objective than patient interviews and observation.

Those difficulties were a central focus of many of the speakers at the Learning and the Brain conference held last month in Washington, DC., titled "Focused Minds: Enhancing Student Attention, Memory and Motivation." The conference presented teachers, administrators, and other educators with new findings about ADHD and other learning disorders that might be applied in the classroom.

The take-home message was one of tentative optimism. Even though understanding of the brain changes underlying ADHD is still in its infancy, speakers were hopeful that the new DSM would incorporate recent findings in a way that offers a more nuanced and accurate description of attention disorders. The potential changes suggested ranged from incorporating the latest results of brain imaging to guide treatment to tweaking existing testing methods to more accurately reflect the specific mental tasks that go awry in attention disorders.

“We should never design a curriculum without good science,” said Jack Naglieri, a psychology professor at George Mason University who specializes in educational test design and spoke Friday at the conference, which ran Thursday through Saturday, May 6-8, 2010.

Is ADHD real?

If there is one issue that can probably be laid to rest, it’s the issue of whether ADHD exists.

Jay Giedd, chief of the unit on brain imaging in the child psychiatry branch of the National Institute of Mental Health, described three lines of evidence supporting the argument that ADHD, which accounts for 40 percent of all child psychiatry visits, is “a real biological disorder.”

For one, even though ADHD is a “tough diagnosis,” he said on Saturday, “there is a pretty high level of agreement.” In other words, different doctors examining the same child are likely to come to the same conclusion.

The tendency for ADHD to run in families is also strongly suggestive. “Heritability is really high—around 70 percent,” he said. The exact nature of these genetic contributors, though, has proved more elusive, he added. Scientists have identified many genes that seem to influence ADHD symptoms, and they interact in complex ways that make a genetic test for ADHD unlikely in the near future.

Giedd’s work in brain imaging has demonstrated several distinctive brain markers that appear consistently in ADHD. Notably, patients show unusual activity in their frontal lobes, basal ganglia, corpus callosum, and cerebellum. They also show a delay in brain maturation, lagging several years behind healthy children in the formation of brain connections. This delay is most evident in the prefrontal cortex, the region responsible for executive control and other high-level brain functions, including attention and movement planning. By adulthood, many of the differences seem to disappear.

The problem may lie with a problem in synaptic pruning, the “Darwinian” process in which the brain produces an overabundance of connections between cells and then keeps only the most useful, Geidd said. But it will take much more research to understand what exactly goes awry and when and why someone becomes vulnerable. Thus far, the neuroscience is still too preliminary to provide any markers useful for more objective ADHD tests. “People say, ‘let’s not have to guess anymore,’” Giedd said. “That’s not going to work.”

On the other hand, the findings soon may prove useful in assessing the severity of ADHD and figuring out what treatments are likely to work. The cerebellum, for instance, shows the greatest differences in people with ADHD; by looking at its state, doctors might distinguish to some degree the severity of the disorder even in people with similar symptoms. But perhaps the best use of imaging may be to track brain development over time instead of looking at a single snapshot.

“Studies of trajectories of brain development provide the greatest discrimination from healthy controls and some degree of [treatment] outcome prediction,” Geidd said, suggesting that psychiatrists might soon be able to use brain images to choose the best treatments for their ADHD patients.

A matter of motivation

For other speakers at the conference, the new insights could inform current, imperfect methods for diagnosing ADHD. For example, based on recent findings, ADHD might be better understand as “motivation deficit disorder,” said James Swanson, a pediatrics professor at the University of California, Irvine Medical School, on Saturday.

At a cellular level, people with ADHD seem to recycle (remove from use) the neurotransmitter dopamine too quickly, possibly because they have increased levels of a dopamine transporter, he said. This results in lower levels of nerve cell activity, particularly in the prefrontal cortex.

Such a theory explains why many children with ADHD have no problems playing video games, but fall behind on less-engaging schoolwork. The drug methylphenidate—commonly known as Ritalin—may work, in fact, by enhancing the saliency, or relevance, of academic tasks. “It’s much more interesting doing math problems on methylphenidate versus placebo,” Swanson said.

Like Giedd, Swanson believes that existing definitions of ADHD fail to capture a “continuum of behavior” that ranges gradually from normally functioning children to those with the most severe cases of ADHD. This type of distribution is now also believed to occur in autism and other mental disorders. In the DSM, on the other hand, most conditions are categorical—they are either present or they are not, and the book offers only limited ability to rate the severity of a condition.

Swanson suggests that one easy way to remedy this would be to change the current diagnostic method, which focuses solely on the presence of “bad things.” Rather, psychiatrists should assess both strengths and weaknesses on a sliding scale, to provide a more thorough picture of the condition and help gauge its severity.

Naglieri, of George Mason, also supports a more nuanced method of testing for ADHD. Instead of looking at general intelligence or overall symptoms, he advocates directly assessing the specific brain functions that go astray in learning disabilities.

“Children with learning disabilities have high ability but low achievement,” he said. “Cognitive abilities have to be measured independently of achievement,” preferably with standardized, consistently applied testing methods.

For Naglieri, a natural framework for this is Alexander Luria’s PASS neuropsychological theory, which posits four primary mental tasks relevant to education: Planning, Attention, Sequential processing, and Simultaneous processing. These relate, respectively, to selecting and using efficient solutions to problems, focusing on specific things and ignoring others, using information in a specific order, and recognizing plans and seeing how parts relate to a whole.

Naglieri has developed methods to test for each and only these tasks. These tests can often distinguish ADHD from autism spectrum disorders and other mental conditions. He has also created exercises and teaching methods that specifically address each of these functions. “For instance, we should teach the child to plan, not a plan,” he said. Preliminary data shows that these teaching methods offer significant and lasting effects in children who have ADHD and other disorders.

Naglieri ackknowledged, however, that each of the PASS mental tasks is theoretical—none has yet been tied to specific brain circuits or regions. And that remains the biggest sticking point to a wholesale modification of ADHD that connects symptoms to their underlying causes in the brain.

As Swanson put it, neuroscientists need to go from symptoms to cognitive process to neural networks, but for now each of those connections remains tenuous. For all we know, ADHD may be a hodgepodge of vastly different conditions that outwardly lead to a similar set of symptoms.

But he’s also confident that those gaps will be filled, and sooner rather than later. “A decade ago, the best scientists were not working on ADHD,” he said. “Now, I think they are.”