The adult diagnosis of Attention Deficit Hyperactivity Disorder (ADHD) is based on criteria of inattention and impulsivity. As the causes of ADHD have a biological basis, the discovery of biomarkers could help in the diagnosis and treatment of this disorder with sometimes dramatic consequences for the family, the profession, the social situation and the safety of the people concerned. Supported by the Synapsy National Research Center, neuroscientists from the University of Geneva (UNIGE), the Biomedical Imaging Center (CIBM) and the Geneva University Hospitals (HUG) are interested in a new approach to electroencephalography (EEG) called “microstates”, to identify neurological traces of ADHD. The microstate technique makes it possible to consider the spatial and temporal dimension of brain activity. Using her, the research team were able to identify that a state of brain activity, associated with sleep and attention, was longer in people with ADHD. The results, to be discovered in the journal Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, identify a new robust biomarker of ADHD and thus contribute to the evolution of psychiatry towards a precision medical discipline.
ADHD affects 5% of adults, making it one of the most common psychiatric disorders. Clinical diagnosis is currently only based on a questionnaire that revolves around the key symptoms of inattention and impulsivity. Yet the neuroscientific community agrees that the causes of ADHD, although still little known, have a biological and genetic basis, suggesting the existence of biomarkers useful for diagnosis. This is the purpose of this new study supported by Synapsy, a Swiss research center that has been working for twelve years at the meeting between neurosciences and psychiatry to understand the neural foundations of psychiatric disorders, in the hope of designing better diagnoses and treatments.
In search of a better investigative tool
The study of the human brain is laborious since it cannot be directly accessed to invest the cellular and molecular mechanisms. To do this, non-invasive means of investigation such as brain imaging or electroencephalogram (EEG) are available. The latter makes it possible, thanks to an electrode network deposited on the scalp, to measure the electric fields generated by large neural networks. Recent studies report abnormal EEG activities in ADHD patients, suggesting that brain developmental dysfunction is the cause of ADHD.
Unfortunately, the data vary too much from study to study to be used as reliable markers for ADHD. “These variations are either due to the great heterogeneity of the causes of ADHD, or to the fact that it is not the right tool to investigate the question, because it does not take into account the spatio-temporal aspects of brain states”, says Tomas Ros, researcher in the Departments of Psychiatry and Neurosciences of the Faculty of Medicine of UNIGE.
Brain microstates reveal two biomarkers
At rest, the brain successively switches from one state to another, exhibiting different spatial patterns of the EEG electric field. Neuroscientists speak most often of five states, or major configurations, lettered from A to E. These different states remain stable for a hundred milliseconds and pass from one to another, hence their name, “microstates », Or microstates. They are detectable by EEG and their frequency, their length or their order of appearance can be extracted from the recordings.
By applying this approach, the researchers found differences between adult patients with and without ADHD diagnosis. Brain micro-state A appears shorter in people with a diagnosis of ADHD. “By comparing this observation with data from clinical questionnaires, we observed that this condition is inversely correlated with disturbances in attention,” said Victor Férat, researcher at Christoph Michel’s laboratory, and first author of the study. In addition, the team observed that microstate D lasted longer in ADHD and that its level was associated with sleep disturbances, often present in these same patients.
As the scientific literature suffers from reproducibility in the field, the research team repeated their approach on a different cohort of patients to verify its accuracy. Thanks to a collaboration with Martijn Arns, head of clinic at the private Nijmegen institute in the Netherlands, the first dataset of 66 ADHD patients and 66 controls was validated by a separate dataset of 22 ADHD patients and 22 controls recorded at HUG thanks to the ADHD unit of Nader Perroud, co-author of the study. “We have confirmed the data concerning the microstate D, but not those relating to the microstate A”, indicates Victor Férat.