Title of your PhD: Neurobiological mechanisms of hallucinations in schizophrenia
Research group(s): John Suckling and Graham Murray
Supervisor: Professor John Suckling and co-supervised by Dr Graham Murray
Advisor: Professor Jon Simons (Department of Psychology)
- Can you give us a short background into what your PhD/MPhil was about?
Hallucinations involve perceptions of stimuli that do not exist in the physical world, and are experienced transdiagnostically, cross-culturally, and in all sensory modalities. They are common in people with schizophrenia, presenting in 60-80% of patients. Despite over 20 years of active neuroimaging research on hallucinations, the neural systems supporting these experiences remain disputed. My PhD investigated the neurobiology of hallucinations, integrating research across structural and functional magnetic resonance imaging (MRI) to elucidate how hallucinations, chiefly in the context of schizophrenia, are supported by the brain.
There is longstanding evidence that schizophrenia pathology has roots in brain development during foetal life, and more recent evidence that this holds for hallucinations in specific: hallucinations in adults with schizophrenia are related to alterations in brain folding patterns – indices of neurodevelopment. I began my research by conducting a meta-analysis and systematic review of the structural brain basis of hallucinations across diagnoses, finding distinct neuroanatomical organizations for hallucinations in schizophrenia spectrum disorders compared to Parkinson’s disease. Focusing on schizophrenia, I studied two independent datasets of patients with schizophrenia who underwent clinical assessment and 3T MRI from the United Kingdom and Shanghai, China, stratified into those with and without hallucinations, and healthy controls from Shanghai. As sulcal patterns derived from structural MRI provide a proxy in adulthood for early brain development, I assessed sulcal length and depth of the paracingulate and superior temporal sulci, using a novel semi-automated method. To investigate how specific sulcal metrics relate to global neurodevelopmental coordination, I used structural covariance networks of the local gyrification index to assess the covariance within brain regions corresponding to salience and auditory networks. Hypothesizing structure-function relationships, I analyzed resting-state functional MRI data from the same datasets.
- How would you sum up your main findings?
Broadly, my thesis shows that MRI indices of brain development in the second to third trimesters of gestation (sulcal morphology) are associated to whether people with early episode schizophrenia experience hallucinations. This is interesting to me because this link between brain folding and hallucinations suggests that processes governing foetal brain development may have long-term and potent influences on cognition, mental health, and the way we experience the world as adults.
Breaking this down to smaller pieces, my findings showed that: 1. There are different ways that brain structure is associated to hallucinations in different disorders. 2. Sulcal metrics can be measured from MRI using semi-automated and manual methods and may offer an adulthood proxy for early brain development. 3. Specific metrics of brain folding – the length of the paracingulate sulcus and depth of the superior temporal sulcus – are associated with hallucinations in adulthood. 4. Increased covariance of brain folding in regions corresponding to the salience and auditory networks is associated with hallucinations in adulthood. 5. Functional connectivity is associated with the interaction of sulcal alterations and hallucination occurrence, indicating it may be involved in the pathophysiology of hallucinations.
My main findings have been published in EClinicalMedicine DOI: https://doi.org/10.1016/j.eclinm.2019.01.012 and Translational Psychiatry DOI: https://doi.org/10.1038/s41398-020-01075-y.
- What made you want to do a PhD?
Mostly, it was the desire to keep learning. I’ve been interested in the brain and mind – especially in relation to psychiatric and neurological illness – since adolescence, and this interest deepened when I studied Neuroscience at university. I had a number of really positive research experiences at McGill University, the Douglas Mental Health University Institute, and the Montreal Neurological Institute, largely due to incredibly supportive mentors. A PhD seemed like a good route to continue learning about topics I was researching. I also thought that pursuing a PhD would double as a great opportunity to live in a different country (my birth country being Canada) for a few years and experience different ways of living.
- What was your best day during your PhD?
Although there are rarely “Aha!” moments in Psychiatry and Neuroscience in the same way that there seems to be in other fields, there are still moments while conducting original research that lead to insights, and it feels exciting to find patterns, make connections, learn new things, and ask questions. It can also be extremely rewarding to engage in conversations about your research. I think that some of the best days I’ve had during my PhD are when I’ve presented or shared my work with others, be it an academic audience or simply friends and family. Doing a PhD can sometimes feel isolating or that your research is too niche, but it is important to remember how your work contributes to a larger picture, and – at least in the field of Psychiatry – how it may contribute to improving people’s mental health and wellbeing.
- What was your worst day during your PhD?
In the process of transferring a project (at the time, a good chunk of my PhD research) I had done in RStudio to GitHub in an attempt at more reproducible research practices, I accidentally deleted all code, data and analyses for that project. Thankfully I frequently backup my work and didn’t lose anything!
- Do you have any words of advice to future PhD/MPhil students in Psychiatry?
I’ve learned many lessons over the course of my PhD for which I’m grateful. Everyone will face unique challenges, but to rattle off some of the things I’ve learned: Maintain balance. Doing a PhD can feel all-consuming at times, but I’ve learned it’s important to my wellbeing to nourish my other interests (for me, rock climbing, partner acrobatics, and drawing, to name a few) and my relationships with equal energy that I put into my PhD. Begin learning and practicing good research habits from day 1, including organization, time-management, and reproducibility. An PhD/MPhil will be a huge endeavor involving many strands of research and data, be kind to “future you”! Everything takes longer than expected. There will be highs and lows. If you are in the lows, don’t feel shy to ask for help – other people have been there too. If you are in the highs, celebrate those achievements, no matter how small.
- What do you hope to do next?
I was recently awarded the Angharad Dodds John Bursary in Mental Health and Neuropsychiatry 2021, an award that will enable me to continue research from my PhD during the 2021/2022 academic year. I will be working as a post-doctoral researcher in the Department of Psychiatry with Professor John Suckling and Dr Graham Murray. I’m currently leading a public engagement project exploring the lived experience of hallucinations through art making. A component of this project has recently been published in Cognitive Neuropsychiatry: DOI: 10.1080/13546805.2021.1993807