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Brain Patterns Put ADHD in Focus

A spatial map of the cortical surface area portion of the multimodal brain pattern, demonstrating increases (red) and decreases (blue) associated with ADHD symptoms.

A spatial map of the cortical surface area portion of the multimodal brain pattern, demonstrating increases (red) and decreases (blue) associated with ADHD symptoms.

Helping Families Through Better Understanding

Tomas Elliott was 6 years old when he was diagnosed with ADHD. Now 13, the youngster can struggle to understand and manage his difficulties.

His father, David, says that identifying affected areas of the brain could lead to earlier detection, new therapies and give individuals a clearer understanding of the severity of their condition. Such knowledge would help schools, families and the children themselves.

“As a parent, you want to know about life outcomes,” David says. “Will they get a job? Will they finish school? Will they be happy? It would be empowering for families to have a more concrete picture of what’s happening in their child’s brain, and for the kids to understand themselves better.”

ADHD can be a very frustrating condition as parents grapple with the fact that standard positive parenting strategies are ineffective. Their children often need to be asked to do something many times before they respond. They are often restless and noisy, and are sometimes on the go all day, which can really wear parents down.

Having a child with ADHD can be extremely disruptive for everyone and put a real strain on relationships between family members, including between the parents. Siblings can feel left out as the child with ADHD demands so much attention.

It’s also tough on the child with ADHD, who tends to be as intelligent as his or her peers but is confronted by a series of stumbling blocks. These kids often struggle to demonstrate their intelligence because they find it so hard to focus on one task for any period of time. Their impulsivity can also really interfere with their social life as friends often find them unpredictable or annoying.

Despite increases in understanding and recognition of ADHD, the main treatment remains stimulant medications such as Ritalin, which have not changed for 50 years. Psychological and educational interventions are also treatment mainstays to target co-occurring problems, such as anxiety, oppositional behaviour and learning difficulties.

By Tim Silk, Emma Sciberras & Daryl Efron

Brain scans are revealing the neurobiology underlying specific symptoms of attention deficit hyperactivity disorder, and raising the prospect of individualised treatments.

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder affecting 5% of school-aged children. It is typically characterised by inattention, impulsivity and hyperactivity, although not all children with these behaviours will have ADHD. Similarly, not all children with ADHD show the same symptoms. We still don’t know what the underlying mechanisms are in ADHD, but it’s quite clear that it’s not isolated to one or two areas of the brain.

ADHD is a multi-faceted disorder, with a range of risk factors and related conditions adding to its complexity. Diagnostic and treatment decisions are currently made through structured questionnaires and interviews with parents, teachers and children. Specific psychological testing is also used to uncover an individual’s particular difficulties and challenges. At present there is no role for brain scans, brainwave tests or blood tests in the diagnosis of ADHD.

The fact that ADHD presents differently in children suggests there may be a combination of factors at play with specific biological foundations in the brain. In order to improve treatments or predict the likely progression of the condition, it’s important for researchers and clinicians to understand what is happening in the brain.

A Different Approach to ADHD

There have been two recent conceptual shifts in neuro­psychiatric research. First, rather than examining whether a certain outcome is categorically different between two groups, researchers are now looking at how that outcome varies with an increasing number of symptoms. The second shift examines how a trait, such as inhibition, varies on a spectrum of human behaviour from normal to dysfunctional across a range of possible disorders. It’s hoped that these approaches will elicit clinically useful sub-groupings or reveal the causes or the brain regions driving the behaviours.

Researchers have discussed the involvement of the prefrontal cortex (which is implicated in personality, decision-making and moderating social behaviour) and the striatal region (a relay station in key brain networks involved in cognitive and motor control).

However, neuroimaging studies have identified other brain regions that differ in ADHD, including the parietal and temporal cortices (which integrate sensory information, including what to pay attention to), the corpus callosum (which allows communication between the brain’s hemispheres) and the cerebellum (a hindbrain area involved in movement and balance that is increasingly recognised to have diverse functions, including cognition).

Studies have also reported differences in the volume of grey matter (possibly reflecting changes to typical development) as well as variations in white matter microstructure that appear to vary with symptom severity.

Although ADHD is increasingly considered to be a disorder of brain networks, variations have tended to be examined in isolation. While the precise interplay of these neural networks is not well understood, advances in imaging technology are allowing us to identify patterns across the brain linking specific traits and behaviours.

The Children’s Attention Project

The Children’s Attention Project is examining the long-term effects that ADHD have on children’s behaviour, learning and day-to-day living, as well as their parents’ well-being. The Children’s Attention Project is Australia’s only longitudinal study of ADHD and one of the first of its kind in the world.

Launched in 2011, the study aims to describe ADHD symptoms during the early years of school, examining mental health, academic and social functioning, and family quality of life for children with and without the disorder. The project investigates modifiable predictors of medium- to long-term outcomes in ADHD.

Beginning with Grade 1 students across 43 schools in metropolitan Melbourne, researchers at the Murdoch Children’s Research Institute and Deakin University first collected questionnaires about the child’s behaviour from both the parents and the teacher, following up with a face-to-face diagnostic interview with the parents.

To date, the Children’s Attention Project has generated findings that have enriched our understanding of many aspects of ADHD. These include academic, emotional and social ability, the presence of other conditions and their effects, quality of life, how ADHD presents in girls, the influence of maternal ADHD, the effect of trauma, and rates of diagnosis and treatment. The team has published more than 20 peer-reviewed articles using data from this cohort.

In addition to questionnaires and student assessments, the study’s third stage introduced neuroimaging to the project to look at brain development and its connection to attention. Children aged 9–12 years underwent an initial MRI scan in the hope of identifying and tracking changes in the areas of the brain responsible for attention at 18-month intervals.

Searching for Patterns

Differences in the brain’s overall structure may give rise to functional changes across brain networks that are responsible for cognitive function, sensory and motor processes. Recent advances in MRI analyses allow us to better examine these variations across tissue types and individuals.

While previous brain imaging studies have looked for differences in either the grey matter (thinking regions) or white matter (where communication between regions occurs), we looked at both. The results, published in the American Journal of Psychiatry (https://goo.gl/mw2D1u), showed distinct structural patterns across both grey and white matter (e.g. volume, cortical thickness and cortical surface area) that were associated with different ADHD problems, symptoms, development and cognition. Our findings suggest that ADHD may stem from a combination of factors that have specific biological foundations in the brain, and may help to explain why there is such variation in the way symptoms present among children.

Learning more about the underlying neurobiology, particularly differences between various groups of patients, may lead to more individualised pharmaceutical and behavioural treatments and support for the common neurodevelopmental disorder.

Patterns to Predict ADHD

Combining multiple magnetic resonance images, we examined the brains of 160 Australian children aged 9–12 years, 70 of whom met diagnostic criteria for ADHD. We identified four different structural patterns across the whole brain, each associated with unique phenotypic profiles. These covered demographic characteristics such as gender and socio-economic status, early life variables such as birth weight and smoking during pregnancy, cognitive factors such as thinking, language and academic skills, and ADHD-related factors such as typical symptoms, medication use, social difficulties and quality of life.

Two brain patterns were particularly relevant to ADHD. In one, children with less developmentally mature brains showed more hyperactive symptoms and were more likely to be receiving medication for ADHD. The second pattern reflected typical clinical features of ADHD, such as increased likelihood of being male, the presence of hyperactivity symptoms, social problems and irritability, lower cognitive and academic scores, and ADHD medication use.

Once we identified this set of brain patterns, we were able to demonstrate that they could predict ADHD symptoms in an independent group of children. This is an important step towards the ultimate long-term goal: to see if neuroimaging could provide objective measures to inform the diagnosis of ADHD and customise treatments.

What’s Next?

The next step is to understand changes in the brains of children with ADHD as they transition to adolescence. We also want to examine whether changes in the brain reflect changes in the expression of ADHD, including the presentation of symptoms associated with the condition, including social and academic difficulties. As part of the neuroimaging study we have rescanned all participants after 18 months and 36 months.

We hope to be able to be able to continue to follow-up the entire Children’s Attention Project sample through adolescence and into adulthood.

Tim Silk is Chief Investigator on the Neuroimaging of the Children’s Attention Project at Deakin University’s School of Psychology. Emma Sciberras is Chief Investigator on the Children’s Attention Project at Deakin University’s School of Psychology. Daryl Efron is Senior Research Fellow at the Murdoch Children’s Research Institute, and Consultant Paediatrician at the Royal Children’s Hospital.
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