Brain Activity Research in Rare Genetic Disorders

 

Investigating the brain activity of people with rare genetic syndromes is important to help advance our knowledge and understanding of these syndromes. Neuroimaging tools, such as EEG (electroencephalography), can be used to non-invasively detect brain activity. Sensors are placed on the scalp to record the electrical signals arising from populations of brain cells communicating and oscillating in synchrony. The dynamic nature of brain processes means that different patterns of brain activity can always be observed whether due to external stimuli, such as hearing a sound, or due to internal processes, such as recalling a memory.

In a clinical setting, EEG has been typically used to detect and diagnose seizures/ epilepsy disorders. In research, EEG, in combination with advanced signal analysis techniques, has been used to examine the observed brain activity patterns in clinical groups in comparison to a reference (typically-developing) group. EEG research also focuses on subtle differences in brain activity that can be detected due to advanced analysis techniques. Because these studies tend to be conducted on a group level, EEG research on rare genetic syndromes has been very limited due to the challenge of identifying large numbers of participants with a particular rare genetic syndrome. However, this is rapidly changing due to the recognition of the importance of secure open-data and collaborative practices among research groups, charities, and other entities.

At ShARL, we have studied the brain activity of individuals with 16p11.2 deletions and duplications. 16p11.2 deletion refers to the rare event of having a missing segment of DNA in the ‘16p11.2’ region (i.e., short arm of chromosome 16, segment ’11.2’); and 16p11.2 duplication refers to having an extra portion of DNA at the ‘16p11.2’ region. Individuals with 16p11.2 deletions and duplications are at an increased risk of intellectual disability, developmental delays, psychiatric symptoms and other symptoms and difficulties. Prior to conducting our study, we surveyed the available resources and databases that have the permission to share anonymised EEG data of rare genetic or autism-related syndromes to approved bona fide researchers. This step is valuable as it enables studies of rare populations that otherwise would have been difficult to achieve and allows for the primary and/or further analysis of previously collected datasets by various lab groups. For our studies, we have obtained approval from the Simons Foundation Autism Research Initiative (SFARI) to analyse data previously collected by SFARI collaborators. The results showed altered brain activity at resting-state (i.e., while participants are resting) and in response to visual stimuli (i.e., when participants are viewing alternating black and white checkerboards on a computer screen) in 16p11.2 deletion and duplication carriers. The observed brain activity in the frontal and back regions of the brain was atypical in various indices of brain cell communication and function. Importantly, we have also found that certain brain activity indices were associated with increased severity of pervasive developmental problems and anxiety problems. Our study was the first to provide evidence that resting-state brain activity is altered in 16p11.2 deletion and duplication carriers and that this may be linked with the developmental and psychiatric problems observed in this population. Although challenging, EEG brain research aims to further our understanding of the specific brain alterations found in rare genetic syndromes - and how these changes in brain activity may contribute to certain symptoms. Findings from this line of research could also produce reliable intermediate indicators of prognosis and treatment progression in these syndromes. 

 Dr Reem (Eema) Al-Jawahiri

Post-doctoral research associate

 

 

 

References:

 

Al-Jawahiri R., Jones M., Milne E. (in press). Spontaneous neural activity relates to psychiatric traits in 16p11.2 deletion carriers: an analysis of EEG spectral power and multi-scale entropy. Journal of Psychiatric Research. https://doi.org/10.1016/j.jpsychires.2020.10.036

Al-Jawahiri R., Jones M., Milne E. (2019). Atypical neural variability in carriers of 16p11.2 copy number variants. Autism Research. https://doi.org/10.1002/aur.2166

The simons vip consortium. (2012). Simons Variation in Individuals Project (Simons VIP): A Genetics- First Approach to Studying Autism Spectrum and Related Neurodevelopmental Disorders. Neuron, 73(6), 1063-1067. https://doi.org/10.1016/j.neuron.2012.02.014