To accompany the Neurodevelopmental Disorders Annual Seminar, Emily Farran and the CoGDeV lab arranged a workshop on Overcoming and Considering Difficulties of Research with Neurodevelopmental Disorders. After a hectic day of engaging with lots of different research talks at the conference on the previous day, a smaller group of 60 delegates had the chance to get together and listen to speakers present their ideas regarding current and prominent issues in researching Neurodevelopmental Disorders. The aim of the workshop was to initiate discussion on the addressed issues, to think about how they might relate to their own research practices and what can be done to overcome the shortfalls of working with neurodevelopmental disorders known for their mixed etiologies and phenotypes.
The first session of the Neurodevelopmental Disorders Workshop was presented by Hana D’Souza of Birkbeck, University of London, who discussed the importance of understanding individual differences when working with neurodevelopmental disorders, presenting specific evidence from Down Syndrome. Hana began the talk by presenting evidence that there is a great deal of variability within groups of typically developing children, for example, some children walk at 9 months, and others at 24 months, but both are considered to be within the typical range. She then went on to present a lot of interesting evidence of heightened individual variability within atypical groups such as Williams Syndrome and Down Syndrome, and importantly, that this variability extends to the individual themselves (intra-individual variability). One example that Hana presented was in the case of WS and DS infants and toddlers who show much more variability on tests of facilitation and disengagement than typical infants and toddlers. This highlighted to the group the importance of looking closely at individual differences when examining data from atypical populations, as some individuals may score well below typical, whereas others may be within the typical range on a certain task, making it difficult to interpret results as some extreme scores may skew the data.
The second session was given by Megan Freeth, from University of Sheffield, who discussed “Capturing and exploring rich data: considerations for neurodevelopmental disorder research using behavioural, eye-tracking and EEG paradigms”. Megan began her talk by directing focus towards a mixed methods design; i.e. using both qualitative and quantitative methods when gathering data from NDD populations. She says that we should look at the “lived experience” of the individual, how the participant makes sense of their experiences and how they feel about these experiences. One way to do this would be to use Interpretive Phenomenological Analysis, where you would select a specific set of individuals from a wider population (for example ASD) who have a shared set of experiences, and perform a thematic analysis on the data collected to gather themes to direct research. This puts the participant at the centre of the research process, and Megan stated that a lot of careful planning has to go into conducting qualitative research with atypical populations, for example with participants with ASD the interview schedule should be consistent and clearly delivered throughout. Megan then went on to talk about eye tracking data in developmental research, and how we can go beyond the standard approach of reporting fixation durations. Comprehensive models have been implemented in research conducted by Megan (Heaton & Freeth, 2016), investigating visual exploration strategies in ASD. These models used time course analysis of the eye movements of participants when free-viewing natural photographic scenes to reveal that participants with ASD displayed significantly less exploration of new areas over time compared with typically developing peers. Studies such as these provide insight into visual attention and perception by using more comprehensive models of eye movement, focusing on the combination of temporal and spatial data. Finally, Megan concluded her talk by discussing the challenges of implementing EEG in with researching populations with neurodevelopmental disorders. The challenges of obtaining ‘clean’ EEG data were addressed, and Megan suggested use of Independent Component Analysis (ICA), which attempts to reduce the ‘noise’ by separating the EEG data into mutually independent scalp maps (or components). Being able to isolate components of interest is more beneficial, as the data can be collected from all electrodes as opposed to just a few, thus creating the ‘bigger picture’.
After the lunch break, we heard from Gaia Scerif, from University of Oxford,who spoke about her collaboration with Kate Baker on “Rare genotypes and small sample sizes: discussing strategies”. This talk began by highlighting to the group what the challenges are, and some potential solutions. This should be done by studying mechanisms across functional gene networks in rare disorders and understanding variability in outcomes in small sample sizes. For example, Gaia presented evidence that there is a link between Williams Syndrome and Fragile X Syndrome’s behavioural symptoms due to different affected genes lying along the same pathway (Fung et al, 2012). This highlights a need for more work into cross syndrome analysis. Another interesting point that was highlighted in this talk was the need for more longitudinal research as snapshot cross-sectional research does not always present an accurate picture of an individual’s true potential. For example, in Fragile X Syndrome, when looking at 3-10 year olds performance on a cognitive task at time 1, there seems to be no improvement between 3 and 10 years, but if we look at the same 3 year olds a few years later, their performance has improved. This could be due to younger children having better interventions due to more research.
Our fourth and final speaker, Eva Loth of King’s College, London spoke about identifying true stratification biomarkers for autism, referring to the efforts adopted in the EU-AIMS Longitudinal European Autism Project (LEAP) to increase analysis transparency and reproducibility. The difficulties of dealing with the heterogeneous nature of ASD were discussed by Eva, in relation to the differences found at all levels of presentation (genetic, neural, cognitive, behavioural etc.). We heard in great detail from Eva about the LEAP project, which is a huge collaboration between academic, pharmaceutical and charity-based partners from across all of Europe with aim of developing an infrastructure that will underpin new treatments for ASD, new training opportunities and new analytical approaches. However, variability makes stratification research difficult, and in ASD it is very much in its infancy. Stratification is used to form categories, in this instance the first level is based on population criteria (e.g. comorbidity or sex), then the next step is to establish whether some biomarkers (e.g. performance on certain cognitive test or brain anatomical indices) may only be detectable at certain developmental stages. Once the cut off points for stratification biomarkers have been established for different developmental levels, the groups are further divided according to differences in brain development and function. The final stage adopts network-based stratification approaches, to identify molecular ASD subgroups on the basis of the entire genetic profile. Subgroups are built from the bottom up, to neurological biomarkers and phenotypes. Eva described the research protocol, including the recruitment and testing of ASD and typically developing volunteers, who are all comprehensively tested to identify clinical and neurocognitive profiles, brain structure and function and biochemical biomarkers and genomics. The scale of the project is massive (N=400 ASD participants across seven centres), as are the implications for the lives of those living, working with and experiencing ASD.
In summary, all of the talks and prompted discussions were insightful and thought-provoking, and left us all with plenty to think about regarding our own research. One of the recurring themes of the day was that the diversity in the presentation of many Neurodevelopmental Disorders should be embraced in our research, and that we need to develop our methods to accommodate individual differences. When working with atypical populations, we shouldn’t just be looking what they cannot do, but in fact it is important to highlight they can do!
Written by Emma Campbell and Leighanne Mayall
