Brain Imaging 'Growth Chart' May Flag Early Attention Problems

Nancy A. Melville

April 15, 2016

Children with attention-deficit/hyperactivity disorder (ADHD) show distinctive patterns in brain maturation that are evident on neuroimaging, suggesting the potential to develop a neurologic growth chart similar to other types of growth charts used in standard pediatric care, new research shows.

"We mapped the normative maturational trajectories of major components of the functional connectome and showed that downshifted component expression relative to the normative profile (shallow maturation) is implicated in both impaired attention task performance and ADHD," the authors write.

"Our results invite further investigation into the use of network growth charting to identify patterns of brain dysmaturation that can serve as early, objective markers of cognitive problems and disorder vulnerability," they add.

The study was published online April 13 in JAMA Psychiatry.

Deviation From Normal Trajectories

Previous neuroimaging research has shown intrinsic connectivity networks (ICNs) to be essential in the functional organization in the brain and that they are associated with attention functionality.

Importantly, the networks' interrelationships demonstrate consistent patterns of change throughout development.

In an effort to determine whether networks can be mapped as maturational profiles that reveal patterns of impaired attention function, the researchers, led by Chandra Sripada, MD, PhD, of the Department of Psychiatry at the University of Michigan, in Ann Arbor, evaluated data from the Philadelphia Neurodevelopmental Cohort. These date included prospective genomic testing data, neurocognitive assessment results, and neuroimaging data on 9498 youths obtained between 2009 and 2011.

In a sample of 519 youths aged 8 to 22 years who met the study's inclusion criteria, 25 (4.8%) met diagnostic criteria for ADHD.

Assessment of resting-state neuroimaging of those patients showed significant deviations in maturational trajectories compared with individuals showing normal, sustained attention function (P < 2.2×10-16).

Specifically, the researchers observed a downshift in ICN maturation that was linked to reduced attention performance, in contrast to a right-shifted pattern (lagged maturation) that was not linked to reductions in attention performance.

The patterns were further shown to be reliable biomarkers indicating severe attention impairment (peak receiver operating characteristic curve measured by area under the curve, 79.3%).

"We showed that when individuals deviate from normative maturational trajectories in the development of ICNs, they consistently exhibit worse sustained attention performance," the authors write.

Previous studies have shown maturational interrelationships specifically between the default mode network and task-positive networks of the brain, as as well as important roles of each in sustained attention functioning.

But the reliability in predictive patterns was unexpected, Dr Sripada told Medscape Medical News.

"Our success in predicting attention is a surprise. We are actually able to predict whether a child will be severely impaired on an attention task with good reliability.

"We have long known that brain networks mature in youth. We also know that clinically relevant dimensions, such as attention functioning, also mature. No one has previously developed brain network growth charts and shown they can predict clinically relevant dimensions."

Although the clinical implications of the research remain to be seen, the findings are encouraging, Dr Sripada noted.

"This opens the door to a brand new approach to create imaging biomarkers for clinically relevant conditions. Future studies can build on what we have done, but it is far too soon to actually use these methods today," he said.

Implications for Other Deficits

In an accompanying editorial, Philip Shaw, PhD, of the National Human Genome Research Institute, National Institute of Mental Health, in Bethesda, Maryland, said the finding that participants' maturational deviation score accounts for as much as 25% of the variance in sustained attention skills, whereas general intelligence accounts for only 7% of the variance, is particularly intriguing.

"The finding represents an impressive validation of how patterns of functional connectivity can pertain to a core cognitive skill. The question now arises of whether these functional alterations also contribute to the deficits in sustained attention found in other childhood disorders — not just ADHD," he writes.

In further comments to Medscape Medical News, Dr Shaw agreed that much remains to be known before reference charts on brain maturation may become a part of clinical practice ― including how the information could benefit patientswith ADHD.

"We know that psychostimulant medication for ADHD, which is the most widely used treatment, can correct some of the subtle differences in brain function seen in children with ADHD, but only while the medication is being taken," he said.

"Very little is known of whether medication or behavioral therapies impact on brain development in the longer term. Partly this is because the technologies to map the development of brain structure, function, and neurochemistry are relatively new.

"Ideally, to see how treatment impacts on brain development, the imaging should be done within a randomized trial, as this would allow us to make statements about causal links."

This research was supported by grants from the National Institutes of Health and the Center for Computational Medicine Pilot Grant and by the John Templeton Foundation. Dr Shaw is funded by the Intramural Programs of the National Human Genome Research Institute and the National Institute of Mental Health.

JAMA Psychiatry. Published online April 13, 2016. Full text, Editorial


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