How Are ADHD Genetics Related to Brain Function During Response Inhibition?

What you need to know

• Higher genetic risk for ADHD is associated with more severe ADHD symptoms, slower and more variable reaction times, and altered brain activity during response inhibition tasks.
• Reaction time measures partially explain the link between genetic risk and ADHD symptoms.
• Brain activity in certain regions during failed inhibition may help explain the relationship between genetic risk and hyperactivity-impulsivity symptoms.

Understanding ADHD and response inhibition

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental condition affecting 5-7% of children worldwide. It is characterized by persistent patterns of inattention and/or hyperactivity-impulsivity that interfere with daily functioning and development. While we know ADHD has a strong genetic component, we’re still learning about how genes influence brain function and behavior in ADHD.

One important aspect of brain function that is often impaired in ADHD is response inhibition - the ability to stop or suppress inappropriate behaviors. Response inhibition is typically measured using tasks like the “stop-signal task”, where participants have to quickly stop a planned action when given a signal. People with ADHD often struggle with these types of tasks.

This study aimed to explore how genetic risk for ADHD relates to brain activity and behavioral performance during response inhibition tasks. The researchers were particularly interested in whether certain patterns of brain activity or behavior might help explain the link between genetic risk and ADHD symptoms.

How genetic risk for ADHD was measured

To measure genetic risk for ADHD, the researchers used a method called polygenic risk scoring. This involves looking at many genetic variants across a person’s genome that have been associated with ADHD in large genetic studies. Each person gets a score that represents their cumulative genetic risk, with higher scores indicating higher risk.

Key findings on genetic risk, behavior, and brain activity

The study found several important relationships between genetic risk for ADHD, behavior on the stop-signal task, brain activity, and ADHD symptoms:

Genetic risk and ADHD symptoms

People with higher polygenic risk scores for ADHD tended to have more severe ADHD symptoms, including both inattention and hyperactivity-impulsivity. This confirms that the genetic risk score is capturing meaningful variation related to ADHD.

Genetic risk and task performance

Higher genetic risk was associated with slower and more variable reaction times on the stop-signal task. This means people at higher genetic risk for ADHD tended to respond more slowly overall and had more fluctuation in their response speed from trial to trial.

Interestingly, genetic risk was not significantly related to the main measure of inhibitory control on the task (stop-signal reaction time). This suggests genetic risk may impact general attentional processing more than inhibitory control specifically.

Genetic risk and brain activity

The study found that genetic risk for ADHD was associated with altered brain activity in several regions during the stop-signal task. These included areas in the frontal lobes, striatum, and temporal lobes - regions that are important for cognitive control, motor planning, and processing behavioral relevance.

Some key findings on brain activity:

• During successful inhibition, higher genetic risk was linked to reduced activity in left frontal and striatal regions.
• During failed inhibition, higher risk was associated with increased activity in temporal and striatal areas.
• When comparing failed to successful inhibition, higher risk related to increased activity in frontal, striatal, and temporal regions.

These patterns suggest genetic risk for ADHD impacts the function of brain networks involved in cognitive control and behavioral regulation.

Explaining the link between genetic risk and symptoms

An important goal of the study was to explore whether behavioral or brain measures might help explain how genetic risk leads to ADHD symptoms. The researchers found evidence for two such “mediating” relationships:

1. Reaction time measures partially mediated the link between genetic risk and ADHD symptoms. This means slower and more variable reaction times help explain why higher genetic risk leads to more severe symptoms.

2. Brain activity in the left temporal pole and parahippocampal gyrus during failed inhibition mediated the relationship between genetic risk and hyperactivity-impulsivity symptoms (but not inattention symptoms).

This second finding is particularly interesting, as it suggests altered neural processing when failing to inhibit a response may be one pathway through which genetic risk leads to hyperactive and impulsive behaviors specifically.

Conclusions

• Genetic risk for ADHD impacts both the severity of ADHD symptoms and the functioning of brain systems involved in cognitive control and behavioral regulation.
• Slower and more variable attention/processing speed may be one mechanism linking genetic risk to ADHD symptoms.
• Altered neural processing when failing to inhibit responses may help explain how genetic risk leads to hyperactive-impulsive symptoms specifically.
• These findings improve our understanding of how genetic factors influence brain function and behavior in ADHD, potentially pointing to future targets for treatment or prevention efforts.

While this study provides valuable insights, it’s important to note that the relationships found were only partial explanations. ADHD is a complex disorder, and many other factors beyond what was measured here likely play a role in how genetic risk manifests as symptoms. Larger studies will be needed to confirm and expand on these findings.

Understanding these brain-behavior-genetics relationships may eventually help develop more targeted treatments or early interventions for ADHD. However, more research is needed before these findings can be directly applied in clinical settings.