Sensory perceptual paradigms as a window into brain health and disease: In vivo assays of cortical plasticity and excitation-inhibition balance

Abstract

Establishing a detailed understanding of cortical function in human health and disease requires accurate, useful, and direct measures that can be administered in vivo, and recorded non-invasively. Using electroencephalography (EEG) and paradigms designed to perturb sensory processing, the aim of this thesis was to investigate both the cortical excitationinhibition balance, and neuroplasticity in two different contexts: health and disease. The first context in health, assessed the effect of hormone changes over the course of the menstrual cycle. Visually induced gamma oscillation frequency was increased in the mid-luteal compared to the follicular phase, indicative of changes in cortical excitation-inhibition balance. Dynamic causal modelling (DCM) revealed associated changes in the underlying synaptic microcircuitry. In addition, a predictive coding index of short-term plasticity and a Hebbian index of long-term plasticity were independently assessed using the roving mismatch negativity (Garrido, Kilner, Kiebel, et al., 2009), and visual long-term potentiation paradigms respectively (Teyler et al., 2005). DCM and event-related potential results suggest specific modification of predictive coding in the mid-luteal compared to the follicular phase, indicating reduced efficiency in sensory change detection. The second context, in disease, investigated changes in patients with treatment-resistant depression following a sub-anaesthetic dose of ketamine. Of our sample, 62.5% of participants experienced a rapid antidepressant response. EEG recordings took place 4-5 hours postinfusion when depressive symptom changes are first emerging. Ketamine did not significantly affect visually induced gamma oscillations, or the underlying microcircuitry. However, across both the predictive coding and Hebbian learning paradigms, post-ketamine enhancements were seen in the plasticity-induced modulation of the paradigm’s respective ERP components. From the DCM of deviance detection, a relationship was also found between the antidepressant response and forward connectivity from primary auditory cortex to inferior temporal gyrus. Repetition suppression did not change with ketamine. This thesis exemplifies the utility of EEG measures of sensory processing in establishing accurate and detailed in vivo assays of human cortical function. Using both observed data features and computational modelling, the thesis demonstrates changes in both neural plasticity, and the excitation-inhibition balance over the healthy menstrual cycle, and in the antidepressant response in treatment-resistant depression.