An investigation of the link between cortical inhibition, neural oscillations and psychophysics in schizophrenia

Doctoral thesis English OPEN
Whitlow, Laura
  • Subject: R1

Schizophrenia is a highly complex psychiatric disorder with a lifetime risk of approximately 0.4-0.7%. Alterations in the major inhibitory neurotransmitter GABA have been identified in the brains of those with schizophrenia. Studies examining the nature of these differences have given variable results depending on the type of patient group, medication and the brain region where in vivo MRS GABA was measured. Chapter 5 of this thesis utilises the noninvasive imaging tool magnetic resonance spectroscopy (MRS) to investigate differences in GABA levels in two distinct areas of the brain of those with schizophrenia, whilst adjusting for important potential confounds such as antipsychotic medication dosage. GABA is also of interest due to its link with synchronised oscillatory activity, primarily gamma activity that is implicated in connectivity between different brain regions as well as cognitive functioning, thus demonstrating its potential relevance to schizophrenia research. Chapter 6 investigates differences in gamma activity between those with schizophrenia and controls induced by a static stimulus and a moving radial stimulus, both known to induce strong visual gamma responses, using magnetoencephalography (MEG) imaging methods. Because GABA and gamma measures are robust for visual cortex measures, we used visual psychophysics tasks thought to be dependent on inhibitory processes - orientation discrimination and the tilt illusion, to see if there is a behavioural deficit in schizophrenia and if this also relates to changes in GABA and gamma measures. Chapters 3 and 4 set out to validate the psychophysics and to establish whether they were appropriate paradigms for the patient group for which they were intended. Chapter 7 brings together the imaging and psychophysics to see if a relationship exists between them in both the patient and control groups.
  • References (180)
    180 references, page 1 of 18

    Clifford, C. W., & Harris, J. A. (2005). Contextual modulation outside of awareness. Current biology, 15(6), 574-578.

    Colgin, L. L., Denninger, T., Fyhn, M., Hafting, T., Bonnevie, T., Jensen, O., ... & Moser, E. I. (2009). Frequency of gamma oscillations routes flow of information in the hippocampus. Nature, 462(7271), 353-357.

    Coppola, D. M., White, L. E., Fitzpatrick, D., & Purves, D. (1998). Unequal representation of cardinal and oblique contours in ferret visual cortex. Proceedings of the National Academy of Sciences, 95(5), 2621-2623.

    Cousijn, H., Haegens, S., Wallis, G., Near, J., Stokes, M. G., Harrison, P. J., & Nobre, A. C. (2014). Resting GABA and glutamate concentrations do not predict visual gamma frequency or amplitude. Proceedings of the National Academy of Sciences, 111(25), 9301-9306.

    Crayton, J. W., Meltzer, H. Y., & Goode, D. J. (1968). The dopamine hypothesis of schizophrenia: focus on the dopamine receptor. pathology, 18, 518-531.

    Crook, J. M., Kisvárday, Z. F., & Eysel, U. T. (1998). Evidence for a contribution of lateral inhibition to orientation tuning and direction selectivity in cat visual cortex: reversible inactivation of functionally characterized sites combined with neuroanatomical tracing techniques. European Journal of Neuroscience, 10(6), 2056-2075.

    Curley, A. A., Arion, D., Volk, D. W., Asafu-Adjei, J. K., Sampson, A. R., Fish, K. N., & Lewis, D. A. (2011). Cortical deficits of glutamic acid decarboxylase 67 expression in schizophrenia: clinical, protein, and cell type-specific features. American Journal of Psychiatry, 168(9), 921-929.

    Dakin, S., Carlin, P., & Hemsley, D. (2005). Weak suppression of visual context in chronic schizophrenia. Current Biology, 15(20), 822-824.

    De Valois, R. L., Yund, E. W., & Hepler, N. (1982). The orientation and direction selectivity of cells in macaque visual cortex. Vision research, 22(5), 531-544.

    Dickinson, A., Bruyns‐ Haylett, M., Jones, M., & Milne, E. (2015). Increased peak gamma frequency in individuals with higher levels of autistic traits. European Journal of Neuroscience, 41(8), 1095-1101.

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