ADDitude for Professionals

Mapping the ADHD Brain: MRI Scans May Unlock Better Treatment and Even Symptom Prevention

Brain MRI is a new and experimental tool in the world of ADHD research. Though brain scans cannot yet reliably diagnose ADHD, some scientists are using them to identify environmental and prenatal factors that affect symptoms, and to better understand how stimulant medications trigger symptom control vs. side effects.

AI (Artificial Intelligence) concept.
AI (Artificial Intelligence) concept.

Can Brain MRI Imaging Diagnose ADHD?

Can brain magnetic resonance imaging (MRI) diagnose ADHD? Unfortunately, but unequivocally, no. No brain imaging modality — MRI, SPECT scan, T.O.V.A. (Test of Variables of Attention), or other — can accurately diagnose attention deficit hyperactivity disorder (ADHD or ADD).

Despite what you may have read in the popular press, none of these tools can be used reliably as accurate, stand-alone diagnostic tools to identify ADHD. Tests like the T.O.V.A. and continuous performance task may be helpful in giving the diagnosing clinician additional information, but in isolation they are not diagnostic, and they shouldn’t be used to diagnose ADHD.

Why? An individual could do very poorly on the T.O.V.A., but not because they have ADHD. For example, someone who is profoundly depressed is also going to have impairments in attention, so this test lacks what we call the “specificity to ADHD.”

The other issue is a lack of sensitivity. In certain settings, the attention of some children with ADHD is very impaired. But when they do the T.O.V.A., their attention does not look so bad. Some parents see this in the context of playing a video game, where sometimes a child who has even the worst case of ADHD can still actually pay attention quite well.

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However, from a research perspective, brain scans — and brain MRIs, in particular — are quite important in helping us think about co-occurring conditions. And the reason for that is because, as our understanding of the brain improves, we are looking at the brain much more from the perspective of underlying circuits or brain systems. Those brain systems don’t have one-to-one relationships with psychiatric diagnosis but may underlie various conditions.

For example, the brain system that we believe is involved in the pleasure response, or what we call “reward processing,” is the same brain system associated with both ADHD and substance use disorders. As we learn more about the brain, it’s becoming clearer that certain underlying brain systems may predispose individuals to several conditions rather than one isolated condition. And that is very likely why we see so much co-occurrence of psychiatric conditions.

MRI research can help us identify and map those brain systems, and it is also helping professionals understand ADHD treatment and prevention with a new, nuanced lens.

Is ADHD Really Preventable If It’s Genetic?

In the U.S., diagnostic rates of ADHD have nearly doubled over the last 20 years. Some of this increase is attributed to increased awareness of ADHD symptoms across all of its subtypes — hyperactive/impulsive, inattentive, and combined. That said, it is unlikely that such a significant increase in the diagnostic rate of ADHD is due to increased awareness alone. There is a reasonable chance that the actual rate of ADHD is indeed going up. This underscores the need for preventive approaches.

Some cases of ADHD are purely attributable to genes, but most researchers believe that, in the lion’s share of cases, ADHD is actually caused by a gene and environment interaction. In other words, the genes set the stage, but certain environmental inputs trigger symptoms of ADHD. My research aims to better understand is the environmental component of this epigenetic equation.

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Human brain development is remarkably plastic. There are lots and lots of changes going on from birth up until the first few decades of life. And what factors ultimately influence that development increasing or decreasing risk for ADHD are still things that that we haven’t well worked out — yet.

Brain MRI Research for ADHD Prevention

Brain MRI is a new and experimental tool in the world of ADHD research. In 2017, a study published in Radiology documented differences between the MRI scans of ADHD brains and non-ADHD brains. These findings were given greater credence by a 2018 study conducted by Radboud University Nijmegen Medical Centre that used MRI brain scans to conclude that people with ADHD had smaller brain volume in five subcortical areas.

My Brain MRI Research at Columbia University

The Posner Lab at Columbia University uses MRI, among other tools, to study the impacts of prenatal exposures on ADHD. Understanding the prenatal period is crucial because of the extensive brain development that goes on during that period, and my lab’s research is supported by current epidemiological studies and animal models linking a variety of prenatal exposures to an increased risk of ADHD. Among these exposures are stress, trauma, various drugs, chemicals, and even diet or obesity.

Studies using animal models have always had an advantage over human studies in that, after animal studies conclude, researchers can see into the rat’s brains via dissection. Now, a detailed multimodal MRI approach allows labs like mine to take on human studies with a similar, heightened ability to see into the brains of our subjects. So, while MRI cannot yet be a diagnostic tool for ADHD, it is an important research tool that allows scientists to obtain a special insight into the development of the ADHD brain.

My lab obtains MRI scans for babies shortly after birth in order to get an image of the brain before any postnatal influences take hold. We are testing whether the prenatal exposure — to stress, trauma, alcohol, etc. — increases risk for ADHD above and beyond some familial or genetic effect. The overall goal is to isolate and identify via MRI those prenatal factors that increase ADHD risk and then to reduce those exposures. Things like stress will never be eliminated entirely, but if we can reduce them, research suggests that we can lower the risk of a child developing ADHD.

We use a structural MRI, which allows us to look at the size and the shapes of different brain regions, and diffusion MRI, which maps out the white matter tracts that connect different brain regions. On top of that, the functional MRI is used to assess which brain regions are active over a period of time.

In the studies that we’re conducting now, we enroll women during pregnancy. We then do a detailed assessment of various exposures during pregnancy. Shortly after birth, we obtain MRI scans on the babies. And then all throughout childhood, we continue to do detailed assessments of the development of attention and hyperactive behaviors.

Brain MRI Research Goals

My lab’s goal is to continue to follow these children up to age 6 through 10, when the ADHD diagnosis really comes to light. What that will allow us to do is to determine whether the prenatal exposures that we’re seeing are influencing brain development, and whether that continues on and predicts the subsequent development of ADHD.

My lab wants to be able to compare genetic risk for ADHD with risk induced from prenatal exposures. Another, more quantitative, approach that we’re using is genotyping. This allows us to compare genetic risk for ADHD with risk induced from prenatal exposures. There is a particular genetic profile called the Polygenic Risk Score that tries to quantify the genetic risk for ADHD. By genotyping children in our studies, we can ask the same question: Does the prenatal exposure increase risk for ADHD above and beyond that Polygenic Risk Score? Hopefully, the findings of our research will help professionals answer this question.

Why Do We Need New ADHD Treatments?

Our current medication treatments for ADHD work quite well, but unfortunately, many children stop treatment over time. We know that ADHD is a chronic condition that generally requires long-term treatment, yet the majority of teenagers with ADHD stop taking medication within two years of starting it. Why? The leading reason given for stopping treatment is side effects, underscoring the point that we need better, more refined treatments that are less prone to side effects.

The first-line medication treatment for ADHD is psychostimulants, which were first developed and used in children in the 1930s. The stimulant treatments that we use today have slightly altered delivery mechanisms, such as long-acting versions and liquid formulations. Those alterations are very helpful, but the underlying pharmacology hasn’t changed in almost a century.

Additionally, our knowledge of how psychostimulants work is surprisingly limited given the tenure of these medications. We know that psychostimulants have an immediate impact, increasing transmission of dopamine, but we don’t know what changes stimulant medications cause in the brain that alleviate ADHD symptoms. And we don’t know which of those changes are actually responsible for symptom improvement versus side effects.

How MRI Can Accelerate ADHD Treatment Development

Again, my lab is approaching this ADHD treatment quandary with MRI technology. In this case, we’re not using MRI to understand what causes ADHD, but instead we’re using MRI to understand how our treatments work, and what we can do to reduce side effects.

Ultimately, what we want to do in this line of research is identify brain changes that are responsible for symptom improvement versus brain changes that are responsible for side effects. And with that information in hand, the next step would be to then develop new medications that specifically target those brain changes leading to symptom improvement.

If you take a group of children who have ADHD and perform MRI scans on them, and then they’re treated with stimulant medication and scanned again 10 years later, you wouldn’t be able to determine which of the documented brain changes were attributable to the medication versus brain changes that were just attributable to human development. They’ve been growing for 10 years, and that process in and of itself is going to lead to substantial brain changes.

The study that my lab and other labs have done suggests that there are significant changes in brain function that are attributable to stimulant medications. But those changes are short lived. When we treat children with ADHD and a stimulant medication, we see the medications can be extremely effective in the short term. But once the medication is stopped, within a day, the symptoms reemerge.

Brain MRI are helping us understand the short-term effects of ADHD medication, and may ultimately help us understand the long-term effects as well.

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Jonathan Posner, M.D., is board certified in adult and child psychiatry and adolescent psychiatry and runs a MRI research laboratory at Columbia University. His research has received numerous awards from the American Academy of Child and Adolescent Psychiatry (AACAP) and the Depression and Bipolar Support Alliance (DBSA), continual support from the National Institutes of Health (NIH), and is widely published in prestigious journals such as JAMA and Lancet.