2012 – 2015 Research Assistant
Multi-modal imaging and its application in schizophrenia
Professor Peter Morris
Schizophrenia is a seriously debilitating mental disorder characterised by disorder of thought processes and emotional responsiveness.
Research indicates that, despite the large and complex array of symptoms exhibited by patients, there is a core abnormality that underpins the disease. The human brain is split into multiple functionally specific regions (e.g. responsible for vision, memory etc.) and integral to healthy human brain function is communication (connectivity) between those regions. In schizophrenia connectivity is thought to be disturbed, and this underlies all of the observed symptoms.
Connectivity in the human brain is mediated by electrical impulses that travel between brain areas. Those impulses are controlled by a number of different chemicals known as neurotransmitters. Brain function is therefore dependent on a delicate balance of electrochemical interactions. Gaining insight into this electrochemical balance is difficult and has, to date, largely been achieved through highly invasive procedures in animals. However animal experiments are greatly limited in utility since, in an animal, it is impossible to recreate the complex set of symptoms that are observed in the human condition. For this reason, development of non-invasive techniques to measure electrochemical brain function is highly desirable.
EEG/MEG and MRS are different technologies that measure non-invasively the internal workings of the human brain. MEG uses magnetic fields, induced by brain currents, to measure electrical activity, while EEG measures electrical activity directly. MRS uses the chemical specificity of magnetic resonance to measure neurotransmitter concentration. In Nottingham, we have pioneered new techniques for measuring connectivity using EEG/MEG. Furthermore, using our Ultra High Field MR system (the only one in the UK) we have made novel measurements of the key neurotransmitters thought to be altered in schizophrenia (such measurements are not possible on ‘standard’ lower field systems). These new methodological breakthroughs present us with a unique opportunity to investigate the central question in schizophrenia – how and why is connectivity disturbed?
A large body of evidence indicates that the biological, psychological and social factors that combine to produce mental disorders such as schizophrenia involve subtle disturbances of the coordination of electrical and chemical activity in the brain circuits that support thinking and feeling. Corresponding brain circuits exist in animals, but their function has only limited similarity to that in humans. Nonetheless, on account of the inaccessibility of the human brain, examination of the subtle details of the electrical and chemical events in these circuits is difficult.
Hence, many different animal ‘models’ that mimic some features characteristic of schizophrenia have been developed. Some of these models entail disruption of the development of connections in brain circuits by procedures such as rearing the animal in isolation from its mother or other cage-mates. Other models entail administering a chemical agent, either into the abdominal cavity or directly into the brain, at an early stage in the animal’s life to produce developmental disturbances similar to the disturbances of brain development that precede schizophrenia. Yet other approaches involve administering drugs to adult animals to produce biochemical disturbances similar to those that occur during the human illness.