How Do ADHD Medications Affect Brain Connectivity During Working Memory Tasks?

What you need to know

Boys with ADHD showed abnormal brain connectivity patterns during a working memory task compared to typically developing boys.
Two common ADHD medications, methylphenidate and atomoxetine, had differing effects on brain connectivity during the task.
Methylphenidate increased connectivity in several brain networks, while atomoxetine had more subtle effects.

Background on ADHD and working memory

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental condition characterized by persistent inattention, hyperactivity, and impulsivity that interferes with daily functioning and development. Many individuals with ADHD also experience difficulties with working memory, which is the ability to temporarily hold and manipulate information in mind.

Working memory is crucial for many everyday tasks, like following multi-step instructions or doing mental math. When someone with ADHD struggles with working memory, it can make it harder to stay organized, complete assignments, or follow conversations.

Previous research has found that individuals with ADHD often show differences in brain activation and connectivity when performing working memory tasks compared to those without ADHD. In particular, they tend to show less activation in frontal and parietal brain regions involved in attention and executive function.

How ADHD medications work

Two of the most commonly prescribed medications for ADHD are methylphenidate (e.g. Ritalin, Concerta) and atomoxetine (Strattera). These medications work in slightly different ways:

Methylphenidate increases levels of dopamine and norepinephrine in the brain by blocking their reuptake. This helps improve attention, focus, and impulse control.
Atomoxetine selectively increases norepinephrine levels in the brain. It can help reduce ADHD symptoms, though it may work more gradually than stimulants like methylphenidate.

While we know these medications can improve ADHD symptoms, less is known about exactly how they impact brain function and connectivity during cognitive tasks like working memory. This study aimed to examine those effects.

About this study

The researchers recruited 19 boys with ADHD (ages 10-15) who had never taken ADHD medication before, as well as 20 typically developing boys of the same age range.

The boys with ADHD completed a working memory task called the n-back task three separate times - once after taking a single dose of methylphenidate, once after atomoxetine, and once after a placebo pill. The typically developing boys completed the task once without any medication.

During the task, participants saw a series of letters appear one at a time on a screen. In the easiest condition (0-back), they simply had to press a button whenever they saw the letter X. In harder conditions, they had to remember letters they had seen previously:

1-back: Press the button if the current letter matches the one shown 1 step back
2-back: Press if it matches the letter from 2 steps back
3-back: Press if it matches from 3 steps back

This tests the ability to hold and update information in working memory. The researchers used functional magnetic resonance imaging (fMRI) to measure brain activation and connectivity while the participants performed this task.

Key findings on brain connectivity differences

When comparing the boys with ADHD (while on placebo) to the typically developing boys, a key difference emerged in connectivity between two brain regions:

The right superior parietal gyrus (rSPG) - involved in spatial attention and working memory
The left insula/central operculum - involved in task-switching and cognitive control

The boys with ADHD showed increased connectivity between these regions compared to the typically developing boys during the working memory task.

Interestingly, this abnormal connectivity pattern was no longer seen when the boys with ADHD took either methylphenidate or atomoxetine. This suggests both medications may help normalize certain aspects of brain connectivity during working memory tasks.

Effects of methylphenidate on brain connectivity

When the boys with ADHD took methylphenidate, they showed increased connectivity in several brain networks compared to the typically developing boys, including:

Between the right middle frontal gyrus and regions involved in:
- Cognitive control (anterior cingulate cortex, insula)
- Processing sensory/emotional information (thalamus, putamen)
- Language and memory (temporal regions)
- Spatial processing (parietal regions)
Between the right superior parietal gyrus and:
- Cognitive control regions (anterior cingulate cortex)
- Regions integrating sensory information (parietal operculum)

These increases in connectivity were not seen when comparing the ADHD group on placebo to typically developing boys. This suggests methylphenidate may enhance communication between brain networks involved in executive function, attention, and information processing during working memory tasks.

Effects of atomoxetine on brain connectivity

Interestingly, when the boys with ADHD took atomoxetine, their brain connectivity patterns during the working memory task looked very similar to the typically developing boys. Unlike with methylphenidate, there were no significant differences in connectivity compared to the control group.

This suggests atomoxetine may have more subtle effects on brain network communication during working memory tasks, or that its effects may emerge more gradually with longer-term use.

What do these connectivity changes mean?

The increased connectivity seen with methylphenidate likely reflects enhanced communication between brain regions involved in different aspects of working memory and attention. This may help compensate for the under-activation often seen in ADHD in regions like the prefrontal cortex during such tasks.

However, more connectivity is not always better. The typically developing boys actually showed decreased connectivity between certain regions as the working memory task got harder. This may reflect more efficient, specialized processing.

The fact that boys with ADHD on placebo didn’t show this pattern, but instead had increased connectivity, could indicate less efficient processing or a compensatory mechanism. By enhancing connectivity in key networks, methylphenidate may be helping to optimize communication between regions to support working memory performance.

Effects on task performance

Interestingly, there were no significant differences in working memory task performance between the ADHD and typically developing groups, or between medication conditions in the ADHD group.

This highlights that differences in brain connectivity patterns don’t always translate to observable behavioral differences. The brain may find various ways to achieve similar performance levels, even if the underlying neural processes differ.

It’s also possible that performance differences might emerge with a more challenging task or larger sample size. The authors note that deficits tend to be larger for visual working memory tasks compared to verbal tasks like the one used here.

Limitations and future directions

As with any study, there are some limitations to consider:

Only boys were included, so the results may not generalize to girls with ADHD.
The study only looked at acute effects of a single dose of medication. Longer-term treatment may have different effects.
The sample size was relatively small, which limits statistical power to detect subtle effects.

Future research could examine:

Effects in larger, more diverse samples including girls/women with ADHD
How connectivity changes with long-term medication treatment
Whether connectivity patterns predict individual treatment response
Effects of non-medication treatments like cognitive training on brain connectivity

Conclusions

Both methylphenidate and atomoxetine helped normalize an atypical connectivity pattern seen in boys with ADHD during a working memory task.
Methylphenidate led to widespread increases in connectivity between brain networks involved in executive function, attention, and information processing.
Atomoxetine had more subtle effects, making brain connectivity patterns in boys with ADHD look similar to typically developing boys.
These medications may optimize communication between brain regions to support working memory, even in the absence of clear behavioral differences.

This research provides new insights into how common ADHD medications impact the functioning of brain networks involved in working memory and attention. Understanding these neural effects may eventually help clinicians predict which treatments will work best for individual patients. However, more research is needed before these findings can be applied clinically. For now, they add to our understanding of how ADHD impacts the brain and how medications may help address those differences.