The 4D lab is continuing its blog series on transdiagnostic research approaches to better understand neurodivergent children. These approaches aim to cross diagnostic boundaries and better understand the brains of people whose experience of the world is neurodivergent without necessarily pathologising these differences. Here, we will focus on the very first task a neuroscientist embarks upon when constructing a transdiagnostic research project: finding the right question(s) to ask.
Surely finding a good question to ask is the easiest part of being a scientist? But what determines whether the question we are asking is ‘good’?
An initial research question commonly has personal resonance. This is important as it motivates the researcher in the face of hardship, such as when experiments don’t work, or grant applications are rejected (i.e. most of the time!). For example, my own experience at school and witnessing my friend diagnosed with dyslexia struggle with anxiety naturally led me to seek answers to the question: what is the effect of anxiety on learning? How does anxiety interact with neurodevelopmental disorders and in which contexts can anxiety ‘worsen’ symptoms?
Scientific rationale: posing a theoretical and/or methodological question
It is then vital to determine if the question has already been answered before. Sometimes it has, but typically only partially. This is one of the most important phases of a research project: reviewing the existing literature. Allowing time for the absorption of information by letting it sink in over several weeks usually reveals potential obstacles that were not initially anticipated. These obstacles usually take one of two forms: theory-related and method-related.
Going back to my own experience, my literature review on anxiety and neurodevelopmental disorders slowly got me out of the idea of looking at the effect of anxiety on cognition and learning: half the papers showed a detrimental effect of anxiety on learning and cognitive metrics while the other half showed a facilitatory effect… In fact, anxiety seemed to be responsible for other behaviours such as difficulty concentrating, which themselves were barriers to learning. This led me to the idea that it would be more pertinent to study co-occurrence of anxiety with other behavioural difficulties. Reading more, I realised that the developmental trajectory of anxiety was not well understood, partly due to subtypes of anxiety, with different ages of onset and both a homotypic (e.g. anxiety in early childhood leads to anxiety in adolescence) and heterotypic presentation (e.g. other behaviours in early childhood such as hyperactivity leads to anxiety in adolescence). Looking at the interaction of anxiety with other behaviours over time challenged the current theoretical framework surrounding the concept of anxiety and neurodevelopment by incorporating two new factors: complexity (the co-occurence of anxiety with other behavioural difficulties) and time (the context in which these difficulties occur).
In the 4D lab, challenging the current taxonomy in place to study neurodivergent children also involves a rethinking of our methodological approach. In my case, an important caveat of using the traditional diagnostic framework is the exclusion of a significant number of children experiencing anxiety but who have never received a diagnostic label. A way to circumvent this problem is to use ‘data-driven’ methods such as clustering which allow us to group children presenting with similar characteristics (behavioural, cognitive), including children with and without diagnosis (we will explain in detail the alternatives to standard diagnostic-based comparisons in the next two blogs of our series). Another methodological challenge which will help you refine your research question is the question of feasibility: can I really find and/or collect the necessary data to address this question or problem? Will I be able to validate my model and make sure it generalises to ‘unseen’ data?
Community priorities and future interventions
Researchers must finally consider the wider impact of the question being posed. What benefits might come from answering that question? Who will see those benefits? Am I responding to the current needs of a community? Do I want my research to have a direct impact on people’s lives? Or perhaps I am verifying a conceptual hypothesis for the purpose of advancing fundamental understanding of brain and behaviour? There is no right or wrong answer here, but this decision will heavily influence the research questions we pose. Importantly, even when a research study is not intended to address a particular community concern, there is still the potential for it to erode the trust that exist between scientists and the rest of society. For instance, studies involving the recruitment of people must follow a clear pipeline: data sharing policies must be explicitly stated from the very beginning of the recruitment; the message to the study funders must be aligned with the message to the public; finally but not least, the community must be consulted as early as possible to determine the kind of research that would best serve them.
Projects using human-centred designed experiments or user-led citizen science projects are in fact more and more frequent in research and clinical trials (the majority of current NHS digital services in 2021). Such projects offer the opportunity to address questions that matter to the public, drive new insights, embed community priorities, give communities new ways of sourcing and evaluating information, and increase confidence in science.
An important phase in my quest for finding the ‘right’ research question was to double-check that anxiety was an actual concern in the community. After looking at global and national statistics (NHS survey 2017: 18.2% of young people (5 to 19 yo) with special educational needs have an anxiety disorder vs 5.4% with no special needs; 20 to 30% of children without any diagnosis display anxiety symptoms), I needed to have direct contact with ‘real’ people. I contacted a few charities helping children or adults with neurodevelopment disorders or with mental health problems and asked them to share their observations. In the latest survey ran by Autistica and Embracing Complexity which collected answers from more than 500 people with neurodevelopmental disorders (including 65 % of school-aged children), 83% people reported having difficulties with managing anxiety/worry/stress. After difficulty concentrating, anxiety was the second most common barrier encountered by neurodivergent people. It seemed I was on the right track.
Such questions also have clear potential for developing interventions. In my case, we can imagine that exploring the existence of subgroups of children with anxiety developing co-occurring behavioural difficulties such as conduct problems or difficulty forming peer relationships may assist in tailoring intervention measures to make them more effective.
Science and community: a false dichotomy
It can happen that research projects do not have an obvious link to the daily concerns of the community in the ‘here and now’. When researchers are interested in identifying which genes are responsible for a particular symptom or whether the connectivity strength between certain brain areas is associated with a group of children presenting with certain cognitive characteristics, it can be difficult to imagine how we can translate such knowledge into interventions. However, a true dichotomy between ‘scientific purism’ that seeks to understand the processes underlying human behaviour on one end of the scale and a broad community-focused approach based on immediate needs at the other never really occurs.
Understanding the causes of neurodivergence could be of greatest benefit to the community in the long run. In general, knowledge leads to a world which protects against the spread of myths and misinformation, ultimately leading to more stigmatisation and pain. We all remember the sad period of mother-blaming which posited that the cause of autism was a lack of maternal warmth (the so-called ‘refrigerator mum theory’) in the late 1970s. This myth caused enormous pain and suffering among families and still has lasting effects today, with parents of neurodivergent children reporting a huge amount of pressure ‘to be child-saving heroes, expected and encouraged to do anything and everything in pursuit of normalcy, from special diets to special schools, from medications to therapeutic toys’ (Mitzi Waltz). Long-range, expensive projects, teasing out the genetic and environmental factors that contribute to complex conditions like autism are fundamental to debunk such myths.
However, they should never replace or monopolize research funding which should equally value smaller-scale projects intended to understand how to build a world suited to the needs and special abilities of neurodivergent minds. Neurodiversity activism in autism is a pioneer in the new era of ‘Nothing about us without us’ and has led to the establishment of organisations such as the Academic Autistic Spectrum Partnership in Research and Education (AASPIRE) which collaborates with self-advocates to set their agenda for research. Embracing Complexity extends this principle to other neurodivergent people such as dyslexic or people with ADHD by bringing charities, researchers, social enterprises and professional organisations together to identify issues particularly relevant to neurodivergent people and action changes more efficiently and more effectively.
What about my research question?
Keeping all of these elements, exchanging with my colleagues and mentors, I finally reached the conclusion that looking at anxiety in isolation and ‘statically’ was too reductive. I needed to study it along with other behavioural difficulties and across several timepoints. My original broad question ‘how does anxiety impact learning in neurodevelopmental disorders’ led to a range of more specific questions: ‘what are the most common difficulties co-occurring with anxiety? What are the risk factors predicting the transitions from a group of anxious children presenting with a specific co-occurring difficulty (such as difficulty concentrating) to another group of anxious children presenting with another co-occurring difficulty (such as conduct problems) across childhood and adolescence?’.
Finding the right question to ask is a long process and as described above, it typically brings you to unexpected places. The role of a researcher is thus to stay flexible enough to allow new questions to emerge, necessitating curiosity, open-mindedness and critical thinking, often simultaneously.
Great, the research question is now set! What constitutes the next step when conducting a transdiagnostic study in the 4D lab? Surely finding the design that best matches the purpose of the research question starts with this fundamental inquiry: who exactly are you going to study?
Stay tuned! The next article will focus on the different options researchers conducting a transdiagnostic study have when choosing their population sample.