| Summary: | Gap-induced pre-pulse inhibition of the acoustic startle (GPIAS) is a behavioural test for tinnitus in animals. It relies on a short gap in a continuous background noise which provides a cue to the loud startling stimulus which follows. As a result, gap conditions demonstrate an inhibition of the response to the startling stimulus compared to no-gap conditions. The disrupting effect of tinnitus on the normal GPIAS has been shown in a number of species, including in humans. Such disruption was originally thought to be caused by tinnitus ‘filling in’ the gap, but recent studies have challenged this explanation. Preliminary work in humans measuring the eye blink reflex showed gap detection deficits in tinnitus subjects, but the underlying mechanisms of this effect are unclear. The eye blink response has a relatively long latency (>40ms) and therefore is not a simple primary reflex, nor is it specifically related to the auditory system. In small rodents the acoustic startle is measured by the whole body response involving axial muscles but in larger animals like the guinea pig this response habituates very quickly. Thus here a variation of the GPIAS method is used in which the acoustic startle is measured in guinea pigs using the simple pinna reflex. This reflex has been used to provide evidence of tinnitus in guinea pigs and postulated that it might be possible to use a similar method to obtain objective evidence of tinnitus in humans. The post-auricular muscle reflex (PAMR) is the human analogue of the pinna reflex and may represent a metric for an objective tinnitus test. The PAMR is a short-latency (15-18ms) response that involves only two or three synapses in the brainstem and provides a much tighter link between auditory input and motor output than the eye blink reflex. However, gap-induced pre-pulse inhibition (PPI) of the PAMR has not previously been demonstrated. This question is one of the main objectives examined in this thesis, using measures taken in guinea pigs and in humans, with and without tinnitus. The work reports two feasibility experiments and two-hypothesis testing studies in which I have sought to optimise the stimulus parameters for maximising the magnitude of the PAMR, and reflects on the challenges of working at the first translational gap developing adequate animal models of human hearing-related problems.
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