Development of a novel startle response task in Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD), an X-linked childhood-onset muscular dystrophy caused by loss of the protein dystrophin, can be associated with neurodevelopmental, emotional and behavioural problems. A DMD mouse model also displays a neuropsychiatric phenotype, including increased startle responses to threat which normalise when dystrophin is restored in the brain.We hypothesised that startle responses may also be increased in humans with DMD, which would have potential translational therapeutic implications. To investigate this, we first designed a novel discrimination fear-conditioning task and tested it in six healthy volunteers, followed by male DMD (n=11) and Control (n=9) participants aged 7-12 years. The aims of this methodological task development study were to: i) confirm the task efficacy; ii) optimise data processing procedures; iii) determine the most appropriate outcome measures.In the task, two neutral visual stimuli were presented: one ‘safe’ cue presented alone; one ‘threat’ cue paired with a threat stimulus (aversive noise) to enable conditioning of physiological startle responses (skin conductance response, SCR, and heart rate). Outcomes were the unconditioned physiological startle responses to the initial threat, and retention of conditioned responses in the absence of the threat stimulus.We present the protocol development and optimisation of data processing methods based on empirical data. We found that the task was effective in producing significantly higher physiological startle SCR in reinforced ‘threat’ trials compared to ‘safe’ trials (P<.001). Different data extraction methods were compared and optimised, and the optimal sampling window was derived empirically. SCR amplitude was the most effective physiological outcome measure when compared to SCR area and change in heart rate, with the best profile on data processing, the least variance, successful conditioned response retention (P=.01) and reliability assessment in test-retest analysis (rho=.86). The definition of this novel outcome will allow us to study this response in a DMD population.

Fear of self-annihilation and existential uncertainty as predictors of worldview defense: Comparing terror management and uncertainty theories

Terror management theory (TMT) proposes that thoughts of death trigger a concern about self-annihilation that motivates the defense of cultural worldviews. In contrast, uncertainty theorists propose that thoughts of death trigger feelings of uncertainty that motivate worldview defense. University students (N = 414) completed measures of the chronic fear of self-annihilation and existential uncertainty as well as the need for closure. They then evaluated either a meaning threat stimulus or a control stimulus. Consistent with TMT, participants with a high fear of self-annihilation and a high need for closure showed the greatest dislike of the meaning threat stimulus, even after controlling for their existential uncertainty. Contrary to the uncertainty perspective, fear of existential uncertainty showed no significant effects.

The Effect of a Supra-Normal Threat Stimulus On the Growth Rates and Dominance Relationships of Pairs of Male and Female Golden Hamsters

Weanling male and female golden hamsters were caged in matched-weight pairs on removal from their mothers. There were pairs of littermates and non-littermates of each sex. One partner of each pair was dyed on the chest with a black commercial hair-dye. Over 20 days, dyed animals of both sexes had a significantly higher growth rate than their untreated partners. In observations carried out between days 10-20 of the test period, dyed animals were found to be aggressively dominant over their untreated partners, and showed more aggressive behaviour. It is suggested that the growth of untreated animals was inhibited as a "stress" response either to the presence of the supra-normal threat stimulus, or to the aggressive relationship which resulted from it.