Interaction between cortical state, dopaminergic modulation, attention and decision making

Abstract

Cortical activity reveals spontaneous fluctuations that are not solely determined by external inputs, but reflect changes to the underlying excitability of neurons, referred to as cortical state. These fluctuations are partly linked to fluctuations in arousal, whereby they influence sensory processing as well as behavioural performance. During active versus inactive states, the cortex is more desynchronised and displays suppressed low-frequency and increased high-frequency activity, as well as lower correlations in population spiking activity. Selective attention facilitates the prioritisation of task-relevant sensory inputs over those which are irrelevant. When attention is directed towards the receptive field of the recorded neuronal population, firing rates increase and, interestingly, this area of the cortex desynchronises in a comparable manner to that observed during cortical state fluctuations. Because of these similarities, it has been suggested that cortical state and selective attention might rely on related underlying circuit mechanisms. In this thesis, I investigated cortical state changes across different spatiotemporal scales and across species, using pupil diameter as an across-species proxy for neuromodulatory controlled central arousal state. In the first chapter, I describe how global, arousal-mediated state fluctuations influence specific behavioural and electro-encephalographic (EEG) signatures of perceptual decision-making in human subjects. Arousal strongly affects behaviour and task-related activity across the brain, including in visual, association, and motor cortex. In the second chapter, I described how top down covert attention affects neuronal signatures of cortical state within sensory areas and their coordination between visual areas in Macaque monkeys. Using a Hidden Markov Model (HMM), I classified periods of vigorous (On) and faint (Off) population spiking activity. These periods were coordinated in a top-down manner across brain areas along the visual hierarchy during selective attention and this coordination was furthermore predictive of behavioural performance. Finally, in the third study, I tested how the local effects of attention induced cortical state changes within a single area are influenced by iontophoretic administration of dopaminergic drugs. Dopamine strongly affects neural activity in parietal cortex, with specific modulations of activity related to attentional processing. These results highlight the strong influences of cortical state and attention on neural activity and behaviour, as well as the crucial role of the interaction between these two functions. They furthermore shed light on the neural mechanisms that underlie cortical state fluctuations, top-down attention and perceptual decision making, from small scale modulations of single neuron firing rates, to the way activity within and across brain areas is coordinated and finally to the way they influence behavioural performance