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Project title: Investigating the role of a medial prefrontal-hippocampal network in the formation of abnormal associations in schizophrenia
Project Description
The Institute of Mental Health at University College London (UCL) is seeking an outstanding, highly motivated and enthusiastic candidate for this PhD studentship. The student will be supervised by Dr Rick Adams (MRC Skills Development Fellow in the Department of Computer Science; primary supervisor) and Prof Neil Burgess (Professor of Cognitive and Computational Neuroscience in the Institute of Cognitive Neuroscience and Wellcome Principal Research Fellow; secondary supervisor).
The full-time PhD studentship is funded by the Institute of Mental Health for three years from October 2019 – see below for funding details. The student will be based mainly in the Institute of Cognitive Neuroscience with magnetoencephalography (MEG) scanning taking place at the Wellcome Centre for Human Neuroimaging, UCL.
Applications via CV and cover letter should be sent to n.monowari@ucl.ac.uk no later than 5pm on Monday 22nd April. Interviews will take place at the end of April.
Project Background
Schizophrenia – characterised by delusions, hallucinations, and motivational and cognitive impairments – has long been hypothesized to be a disorder of structural or functional brain connectivity. ‘Dysconnectivity’ between the left medial temporal lobe (mTL), especially the hippocampus, and prefrontal cortex is heavily implicated in the disorder. A direct hippocampal-mPFC projection is heavily involved in functions relevant to schizophrenia, e.g. working memory and associative memory, planning and decision-making, and contextual regulation of fear. Both Scz and their unaffected relatives are substantially impaired at spatial working memory and associative memory tasks.
Hippocampal-mPFC coupling is strongest in the θ band (~2-4 Hz to ~7-12 Hz). Two recent (genetic and environmental) rodent models of schizophrenia have shown impaired hippocampal-mPFC θ coupling (Sigurdsson et al., 2010, Nature; Dickerson et al., 2010, J Neurosci). Dr Adams and Prof Burgess have recently shown that hippocampal-mPFC θ coupling in schizophrenia is impaired during retrieval of object-location associations, and that this coupling correlates with performance on this spatial memory task.
However, it is not straightforward to make a conceptual link from spatial memory tasks to delusional beliefs. Abnormal associations in delusions are best modelled using an associative memory task. This task contains two elements that are highly relevant to schizophrenia:
i) It measures ‘indirect associations’ e.g. learning A-B and B-C associations, and thereby recalling an A-C association. Indirect associations (in healthy subjects) also correlate with hippocampal-mPFC theta coupling (Backus et al., 2016, Curr Biol). Dr Adams has collected pilot data showing that subjects with schizophrenia are substantially impaired at these associations (Hedge’s g=1.2).
ii) It also measures ‘false alarms’, or false positive inferences. Our pilot data shows schizophrenia subjects have increased false alarms in this task (Hedge’s g=1.0). The electrophysiological correlates of false alarms – a model for delusional inferences – are unknown, however.
We will investigate the neural mechanisms behind these abnormalities of associative inference, by examining brain-behaviour relationships in an associative inference task performed in MEG. We will also use computational (neural network) models to show how biological abnormalities (e.g. interneuron dysfunction) can cause these abnormal inferences.
Key Requirements
Master’s qualification (or to have completed their Master’s by September 2019) in an appropriate discipline (medicine, neuroscience, engineering or physics) or a 2:1 or equivalent in a first degree in a similar discipline. Computational skills are very useful but not essential. All applicants are required to have excellent written and verbal communication skills. They should also be willing to work collaboratively in multi-disciplinary and multi-professional teams. A commitment to mental health research is essential, and a specific research interest in schizophrenia and/or MEG would be desirable.
Further Details
If you have any queries about this studentship, please contact:
Funding Notes
The studentships include home fees, a student stipend and research costs for each of the three years of the award. The funding is for a full-time PhD. Funding of clinical salaries will not be possible. Students must be eligible to pay fees at the UK/EU rate. Please see UCL’s guidance for prospective students (View Website) or contact Access and Admissions in Student and Registry Services for further information.
The 2019/20 funding is as follows:
Stipend: £17,280
Home Fees: £5,161
Research Costs: £1,200
Yearly increases subject to review by the UCL Finance Committee.