King's College London

New research from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London has for the first time investigated the relationship between polygenic scores for ADHD and cognitive control – revealing that genetic variation linked to ADHD manifests directly through disrupted timing in the brain’s cognitive control systems

The research, published in Translational Psychiatry, established that polygenic scores for ADHD – but not autism – specifically predict irregularities in signals from the frontal areas of the brain.

These signals relate to cognitive control, a fundamental set of processes that allows humans to prioritise relevant information while suppressing distractions when planning behaviour in everyday life. In ADHD, these signals, known as midfrontal theta activity of the brain – which acts like a neural ‘conductor’ coordinating cognitive processes - have repeatedly been associated with cognitive control difficulties and reaction time variability, where behavioural responses fluctuate from moment to moment.

Researchers in this study investigated whether polygenic scores – which attempt to predict a person’s likelihood of developing certain traits by mapping small genetic variants in their genome - could predict variability in theta activity and response times in ADHD.

The study included 454 participants who had previously provided DNA samples as part of the Twins Early Development Study (TEDS), with 111 meeting the criteria for ADHD, 47 for autism, and 16 for both conditions. Participants completed a task designed to test cognitive control while their brain activity was measured using EEG.

In their analysis of the data, researchers found that ADHD polygenic scores predict dysregulation in midfrontal theta activity, providing robust evidence linking genetic variance, brain function and behaviour.

Dr Grainne McLoughlin, Reader in Cognitive Neuroscience at King’s IoPPN and the study’s senior author said, “For the first time, we’ve linked genetic likelihood for ADHD directly to disrupted neural timing. The brain’s theta rhythm acts like a conductor coordinating cognitive processes – in ADHD, that conductor’s timing is irregular and we have now shown that this irregularity has genetic origins linked to ADHD."

The researchers now plan to investigate the precise mechanistic pathways through which genetic variation linked to ADHD shapes cognitive control processes at the neural level. 

 

 

ADHD polygenic risk predicts neural signatures of cognitive control: Evidence from midfrontal theta dynamics (Aydin, McLoughlin et al) (DOI10.1038/s41398-026-03938-2) was published in Translational Psychiatry.

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