Genetic potential for attention-deficit/hyperactivity disorder directly predicts irregular timing of brain waves involved in concentration and goal-directed behavior. This objective link between a person’s genetic profile and neural activity provides a measurable goal for understanding how the condition progresses. This study was recently published in the journal translational psychiatry.
Cognitive control is a mental process that allows humans to prioritize relevant information and ignore distractions in order to achieve a specific goal. Problems with this ability often make it difficult to maintain focus in everyday environments. Cognitive control difficulties are common not only in autism but also in neurodevelopmental disorders such as attention-deficit/hyperactivity disorder (ADHD).
To measure this mental process, researchers look at electrical signals in the brain known as frontal-central theta activity. These are brain waves that occur at a frequency of 4 to 8 cycles per second in the front of the head. These brain waves act as neural conductors, coordinating the activity of different brain regions when a person needs to navigate conflicting information.
In people with ADHD, the timing of these brain waves is often irregular. This lack of precise temporal coordination typically leads to inconsistent reaction times during the task. People may react very quickly on one trial, but much more slowly on the next trial. This behavioral discrepancy is recognized as a hallmark of ADHD across different age groups.
The researchers wanted to know whether a person’s genetic profile could predict these specific irregularities in the timing of their brain waves. They relied on a tool called a polygenic score, which combines information from millions of small genetic variations across the genome into a single number. This score estimates an individual’s overall genetic likelihood of developing a particular condition based on traits inherited from their parents.
By examining polygenic scores, researchers can bridge the gap between abstract genetic risk and actual physical measurements of brain function. EEG measurements, which show clear familial genetic patterns, serve as a bridge between a person’s DNA and observable behavior. Understanding these connections can help experts understand exactly how genetic risk manifests as physical changes in the brain.
Umit Aydin, a researcher at the University of Reading and King’s College London, led the study. Grainne McLaughlin, a cognitive neuroscience researcher at King’s College London, served as senior author on the project. The research team wanted to test whether polygenic scores for ADHD and autism could predict irregular brainwave timing and inconsistent reaction times.
The research team recruited 454 young people, with an average age of 22, to take part in the project. These individuals had previously provided DNA samples to an ongoing registry called the Twin Early Development Study. The participant groups included those diagnosed with ADHD, those diagnosed with autism, and those without such symptoms.
To measure cognitive control, the researchers asked participants to complete an arrow-based computer exercise called the flanker task. Participants looked at the screen and pressed the left or right button indicating the direction of the central arrow. To make the exercise more challenging, other arrows pointing in opposite directions were placed on either side of the central arrow.
The human brain must exert cognitive control to ignore the misleading flanker arrows and focus only on the central target. While participants completed this exercise, researchers recorded their brain waves using an electroencephalogram (EEG). Participants wore a hat fitted with 64 sensors that received electrical signals passing through their scalp.
The research team focused specifically on the consistency of theta brainwave timing across trials. They observed the moment when participants correctly identified the direction of the arrow despite confusing visual interference. Separately, the researchers used previously collected DNA to calculate polygenic scores for ADHD and autism for each participant.
The team then ran a statistical model to see if these genetic scores matched the brainwave patterns and reaction times recorded during computer exercises. They adjusted the mathematical model to account for the participants’ age, gender, and family relationships. To ensure that the EEG measurements were completely reliable, they also called back a small group of 21 participants for a second session about a week later.
The analysis showed that participants with higher polygenic scores for ADHD had more irregular frontal-central theta wave timing. This irregular neural timing appeared to be almost completely independent of demographic factors. ADHD genetic scores directly predicted specific neural signatures associated with poor cognitive control.
McLoughlin explained the importance of linking genetic markers to physical brain activity. “For the first time, we have been able to directly link the genetic potential of ADHD to disturbances in neural timing. The brain’s theta rhythm acts like a conductor that coordinates cognitive processes. In ADHD, we now show that the timing of that conductor is irregular, and that this irregularity has a genetic origin associated with ADHD,” she said.
Physically measuring this mental process could help experts evaluate future interventions. Finding easily quantifiable brain signals gives medical professionals a concrete way to assess how effective different treatments are. As McLoughlin pointed out, “This is important because it gives us objective neural targets to develop and test treatments.”
Autism genetic scores did not predict similarly irregular brain wave timing or reaction time fluctuations. Researchers found no statistical association between autism polygenic scores and EEG measurements.
Despite the clear association between ADHD genetic scores and EEG timing, this study had several limitations. Genetic scores did not statistically predict behavioral discrepancies in participants’ actual physical reaction times. The research team noted that the number of participants may have been too small to detect smaller genetic effects related to reaction speed.
The demographics of the participant population also limits how broadly the conclusions can be applied. All 454 participants were of Caucasian origin. Future studies should include individuals from diverse ethnic backgrounds to see if the same genetic associations hold true across different populations around the world.
Additionally, polygenic scores only account for very common genetic variation. These do not capture the rare genetic variations and environmental influences that play a large role in the development of ADHD. Because of these gaps, polygenic scores provide only a partial picture of a person’s overall genetic risk.
Some of the specific genes included in the ADHD polygenic score are known to influence brain development and cell connectivity. One specific gene location identified in the score helps regulate dopamine in the brain. This is highly relevant because many common medications used to treat ADHD work by targeting the brain’s dopamine system.
The researchers will now use larger sample sizes to investigate exactly how these genetic variations disrupt the brain’s internal timing networks. They hope to uncover the exact biological pathways that translate a person’s genetic code into the brain wave abnormalities seen in ADHD. Tracking these pathways will ultimately allow experts to design personalized treatment strategies based on a patient’s unique genetic and neurological profile.
The study, “Polygenic risk for ADHD predicts neural signatures of cognitive control: Evidence from central frontal theta dynamics,” was authored by Umit Aydin, Zaie Wang, Mate Gürkovics, Amy Tong, Grace Cullen, Sumaiya Ahmed, Jason Palmer, and Grainne McLoughlin.
