IMPACT: Indirect measures of supragranular layer cortical thickness

Lead Supervisor
Dr Kelly Diederen
Lecturer in Psychosis Studies
Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London
kelly.diederen@kcl.ac.uk

Co-supervisor
Dr Tom Spencer
Clinical Senior Lecturer in Early Intervention Honorary Consultant Psychiatrist OASIS Lewisham and OASIS Croydon Education co-Lead
Division of Academic Psychiatry Department of Psychosis Studies Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King’s College London
tom.spencer@kcl.ac.uk

Project Details

Subtle alterations within the laminar structure of the neocortex have been postulated to give rise to schizophrenia spectrum disorders (Guarnieri et al., 2018). Specifically, schizophrenia has been associated with supragranular layer variance (Harrison, 1999), including but not limited to; loss of small interneurons (Benes et al., 1991), layer II depreciation of calbindin cell density (Chance, Walker and Crow, 2005), and supragranular thinning in the dorsolateral prefrontal cortex (DLPFC/BA46; Selemon, Rajkowska and Goldman-Rakic, 1998). Empirical evidence of morphological markers within the laminar structure has, however, been limited by the absence of required sensitivity from conventional MRI methods in quantifying brain anatomy. This has largely restricted study of neocortical alterations to post-mortem analysis.

To bypass the current limits of spatial resolution within MRI, a novel analysis technique has recently been developed to investigate a proxy of lamina specific morphological changes in vivo (Wagstyl et al., 2016). This technique focuses on the structural deviations between the infragranular layer (V and VI) and the supragranular layer (I-III).

The proxy developed by Wagstyl and colleagues (2016) consists of four surrogate markers of supragranular-layer specific thinning, which they investigated in 46 schizophrenia patients. Across these four markers they found that, consistent with post-mortem studies, cortical thickness deficits in schizophrenia may be specific to the supragranular layer, providing additional insight into the underlying neuropathological mechanisms. However, these results require replication across different populations and diagnoses to make robust conclusions on the validity of these four novel morphological markers.

The aim of this PhD is to utilise this novel method to determine whether schizophrenia and (psychometric) schizotypy are characterised by supragranular-layer specific thinning, using existing data. We furthermore aim to determine whether these deficits are specific for schizophrenia, rather than reflecting general psychopathology, by comparing MRI scans of people with schizophrenia, bipolar disorder and ADHD. Finally, we will test whether supragranular-layer specific thinning may give rise to schizophrenia-spectrum disorders via its detrimental effects on cognitive function. It is hypothesised that thinning in the supragranular layers will be related to schizophrenia, and psychometric schizotypy, and to a lesser extent to bipolar disorder and ADHD, and that the strength of this association is mediated by cognitive function.

Year 1:
Learning Freesurfer preprocessing and analyses, including the proxy-measures of supragranular thinning, under supervision of Dr Diederen and Spencer who have already successfully employed these analyses
Training in general academic skills (e.g., conference presentations, literature review and writing scientific manuscripts) as well as specific analyses and coding skills (e.g., R and Python, prediction modelling, machine-learning)
Write the upgrade report and preparing for the upgrade viva
There is also the possibility to identify additional datasets and analytical techniques for the student to work on

Year 2:
Data analyses
Presenting at a conference (e.g., the annual meeting of the Schizophrenia International Research Society)
Preparing manuscripts for submission

Year 3:
Submitting manuscripts
Presenting at a conference (e.g., the annual meeting of the Organisation for Human Brain Mapping)
Dissertation writing
Exploring future career steps/ applying for postdoctoral fellowships

Datasets

ENIGMA consortium for Schizotypy research. The supervisors are part of this consortium which includes over 30 research groups and datasets which have sMRI scans, measures of schizotypy (and in some cases schizophrenia), and in many cases cognition. No additional ethical information is required. All scans have already been pre-processed in Freesurfer, allowing for data analyses to start immediately. 

UCLA Consortium for Neuropsychiatric Phenomics: healthy individuals (130 subjects) and individuals with neuropsychiatric disorders including schizophrenia (50 subjects), bipolar disorder (49 subjects), and attention deficit/hyperactivity disorder (43 subjects). In addition to sMRI scans, this dataset includes an extensive set of clinical assessments, personality questionnaires and cognitive data. All scans have already been pre-processed in Freesurfer, allowing for data analyses to start immediately. The dataset is shared through the OpenfMRI project, which provides automatic and immediate ethical approval to work on the data. For details, please see: POLDRACK, Russell A., et al. A phenome-wide examination of neural and cognitive function. Scientific data, 2016, 3.1: 1-12.)

Keywords

Brain imaging, MRI, schizophrenia, psychosis, psychiatry