Targeting medial prefrontal cortex brain networks implicated in hallucinations
John Grace Scholarship 2019: Department of Psychology, University of Cambridge
Supervisor: Professor Jon Simons, Professor in Cognitive Neuroscience
Summary. Hallucinations are a hallmark positive symptom of schizophrenia, in which people experience auditory or visual sensations that are not real. Such phenomena may reflect difficulty discriminating information perceived in the external world from information that is imagined. Previous structural and functional neuroimaging work in our laboratory has linked this discrimination difficulty with the medial prefrontal cortex (mPFC). Building on these findings, the proposed PhD project will involve the use of advanced structural and functional neuroimaging techniques to investigate specific mPFC brain morphology variations in people with schizophrenia. Furthermore, as schizophrenia is likely associated with disrupted neural connectivity, it is essential to examine changes in connectivity between cortical regions involved in processing sensory representations and mPFC-supported decision-making processes. Based on these experiments, the objective will be to target mPFC using real-time functional MRI neurofeedback. In this technique, individuals in an MRI scanner learn to modulate neural activity within a particular brain area, using the visual feedback of real-time information relating to the strength of the haemodynamic BOLD response. Building on pilot data already collected, we will explore the feasibility of boosting activity in the mPFC and improving the likelihood of successfully discriminating internally- from externally-generated information, which could reduce the incidence of misattributing imagined experiences as hallucinations. This approach will have the potential to impact people with schizophrenia by informing the development of therapeutic approaches aimed at ameliorating these debilitating sensory and mnemonic distortions, improving everyday functioning for such individuals.
Student: Samantha Mitchell
Hi, I’m Samantha and I’m due to start my PhD in Psychology at the University of Cambridge in October 2021.
I recently completed an MSc in Neuroimaging: Methods and Applications at the Cardiff University Brain Research Imaging Centre (CUBRIC). My MSc dissertation examined the efficacy of combining two methods aimed at improving the quality of resting-state fMRI acquisitions of the human spinal cord. I presented a poster summarising the findings of this research project at the British Neuroscience Association 2021 Festival of Neuroscience.
Prior to this, I graduated from Cardiff University with a BSc in Psychology with a Professional Placement. I spent my placement year in Dublin working as a research assistant at the Trinity College Institute of Neuroscience, conducting research using EEG and tDCS to investigate working memory and perceptual decision-making.
My research interests centre around schizophrenia and I am particularly interested in the neurocognitive basis of hallucinations. I am fascinated by how our brain generates our perception of the world and how this can differ from reality, especially in individuals who experience hallucinations. I am keen to take advantage of the ongoing technological advances in neuroimaging to further our understanding of schizophrenia and hallucinations and aid the development of alternative, non-invasive interventions.
I I am excited to start this project under the supervision of Professor Jon Simons and I would like to express my gratitude to Mental Health Research UK for making this opportunity possible.
Start Date: October 2021
Scientific Goal: Targeting medial prefrontal cortex brain networks implicated in hallucinations.
Progress Report Year 2, 2023
The goal of my PhD is to explore the neurocognitive basis of hallucinations in schizophrenia; primarily investigating the relationship between hallucinations, reality monitoring, and the structural and functional neural mechanisms involved.
This year my work has primarily focused on the paracingulate sulcus (PCS), which is a fold within the medial prefrontal cortex that can vary quite considerably in its morphology. Studies in adults have shown that differences in the length of the PCS are associated with reality monitoring ability and the likelihood that patients experience hallucinations. One of the aims of my PhD is to explore whether the relationship between PCS morphology, reality monitoring and hallucinations can be observed earlier in life, during adolescence.
In order to achieve this research aim, I began my second year by becoming proficient with using a software platform called ‘BrainVISA’ to identify and measure the length of the PCS from 3D visualisations of MRI scans. During this learning process, I noticed some difficulties with reliable PCS identification due to the great variability in the fold’s presence and morphology. I therefore worked with a collaborator to develop an updated protocol which aims to allow researchers to identify and measure the PCS more accurately and reliably. We started by spending time inspecting typical and atypical sulcation patterns within the medial prefrontal cortex. The process made it clear that identifying other less-variable sulci in the medial prefrontal cortex (e.g., the cingulate sulcus) aids the subsequent identification of the PCS. The protocol therefore provides clear guidelines on the expected location, trajectory, and morphology of sulci in the medial prefrontal cortex and outlines the order in which sulci should be identified.
We have conducted a validation study using the protocol, which showed that we can achieve high agreement between experimenters in PCS measurements. Once we make the protocol publicly available, we hope it will be useful for other researchers in this area. During my third year, I will use this protocol to investigate the relationship between PCS morphology, reality monitoring and psychosis in adolescent datasets.
During the year I also supervised three undergraduate dissertation students as they implemented the new protocol to investigate novel research questions around the morphology of the PCS and different cognitive abilities. Supervising dissertation students is a rewarding process; the students enjoyed their projects and wrote interesting dissertations, and it was useful to see the protocol being used by individuals who were new to the field and who were able to provide valuable feedback for its development.
In addition to my work on the PCS protocol, I have continued to work on optimising the parameters of the modality-specific reality monitoring task I developed last year and I will soon start large-scale data collection.
In June, I presented my work at the Emmanuel College (University of Cambridge) Annual Graduate Symposium. I summarised my work from the first two years of my PhD and outlined my future research plans. The symposium was a very interesting day full of multi-disciplinary talks and I was honoured that my talk was voted as the second-best presentation of the day.
I also attended a symposium on reality monitoring hosted by Nadine Dijkstra at UCL. This was a great opportunity to hear about the fascinating and innovative research being conducted by researchers in the field.
Progress report year 1, 2022
The aim of my PhD is to investigate the neurocognitive basis of hallucinations in schizophrenia, with a particular focus on reality monitoring and the role of the medial prefrontal cortex.
Reality monitoring is the ability to discriminate between information that is internally generated (e.g. imagined) from information that is externally generated. Evidence suggests that, in schizophrenia, hallucinations may arise due to a deficit in this reality monitoring ability. For example, in cases of auditory-verbal hallucinations, it is thought that inner speech may be incorrectly perceived to have an external source, so individuals hallucinate that the voices are occurring in the outside world.
I began the year by designing, coding, and piloting a new online cognitive task which allows for direct comparisons between visual and auditory reality monitoring performance. This task will enable us to investigate whether hallucinations of a certain modality (e.g. visual) are primarily associated with reality monitoring deficits in the same modality or whether different hallucination types are associated with a modality-general reality monitoring deficit.
Throughout the year I completed various courses in statistics and coding, and I have attended many insightful seminars. To continue my development, I have recently enrolled in the ‘Cognitive Neuroscience Skills Training In Cambridge’ (COGNESTIC) course which will provide intensive training in neuroimaging techniques and analysis. Expanding my skills and knowledge in this area will allow me to achieve my PhD goals by enabling me to conduct research into the role of the medial prefrontal cortex in relation to hallucination symptomology and reality monitoring performance.
A particularly rewarding element of my first year was co-supervising undergraduate students as they conducted data collection for their final year dissertations. This process developed my skills in mentoring, problem solving, organisation and the communication of complex topics. I look forward to supervising more dissertation students in the future.
For the next part of my PhD, I will be utilising large datasets to examine whether the documented association between psychosis, reality monitoring and structural differences within the medial prefrontal cortex can be detected in adolescence. This will expand our understanding of the manifestation of psychosis and may allow us to explore the potential predictive validity of such measures as markers of subsequent psychosis development.
I feel very fortunate to be completing my PhD within a friendly and supportive lab environment and I would like to thank my supervisors, Professor Jon Simons and Dr Jane Garrison, for their continued support and guidance. I have been able to start exciting and valuable collaborations with fellow researchers and I am looking forward to continuing my research over the next few years.