Zhao, S; (2018) The Role of The Locus Coeruleus Noradrenergic System in Tracking the Statistics of Rapid Sound Sequences. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The sensory world is full of uncertainty; most perception-relevant statistics are highly dynamic, featuring frequently-changing patterns. Rapid adaptation to the everchanging world requires brain sensitivity to environmental changes and resetting of functional neural networks as needed. Norepinephrine (NE) is proposed to mediate this process by initiating functional resetting (Dayan and Yu, 2006; Sara and Bouret, 2012) via the Locus Coeruleus (LC)-NE system. This doctoral thesis employs pupil diameter measurements – a reliable indicator of NE neural activity in the LC (Aston-Jones and Cohen, 2005; Joshi et al. 2016). Human participants listened to sequences of adjoined 50ms tone-pips (adapted from Barascud et al., 2016) containing transitions from random to regular frequency patterns and vice-versa. Participants were instructed to detect occasionally inserted silent gaps, ensuring attention to the auditory stream, not the transition itself. Although both transitions (regular-to-random and random-to-regular) are clearly detectable behaviourally and evoke strong MEG (Barascud et al., 2016), only violations of regularity (prediction errors) appear to elicit pupil responses. Noteworthily, this response is driven by pattern changes and not merely deviant detection. However, stimuli containing pattern emergences (precision increase) evoke no measurable pupil response; this is not due to pre-transition pupillary saturation, as transitions from random patterns to repeating single tones (random-to-repeating) evoke transient pupil dilation. Only when subjects actively reported changes in button-press did random-to-regular transitions evoke pupil dilations. Investigating the effect of task on evoked pupil responses found no response if subjects were not continuously tracking the sequences, e.g. with attention directed to visual or tactile stimuli. Multiple self-replications of these findings provide robust evidence that NE release acts as an automatic switch, resetting the brain’s internal model of the sensory environment and demonstrating that the unexpected uncertainty signalling process operates over much faster timescales than previously known, implicating NE in the fundamental bases of perception.

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