Increased prepulse inhibition of the acoustic startle response is associated with better strategy formation and execution times in healthy males.

Prepulse inhibition (PPI) refers to the attenuation of the amplitude of the startle reflex in response to sudden intense stimuli (pulse) if preceded by a weaker sensory stimulus (prepulse). PPI reflects the ability to filter out irrelevant information in the early stages of processing so that attention can be directed to more salient environmental features. Inhibition at this early stage of information processing appears modulated by the prefrontal cortex in a "top-down" fashion and this may account for the normal inter-individual variability in PPI and in cognitive performance. PPI data were calculated from 82 healthy male subjects who were also tested in problem solving (Stockings of Cambridge; SoC), spatial working memory (SWM) and 5-choice reaction time (RT) tests from the Cambridge Neuropsychological Test Automated Battery. Correlations between PPI scores and cognitive test variables were examined. In addition PPI scores were divided in quartiles which were used as grouping factors in examining cognitive test performance. Compared to individuals in the lowest quartile those in the highest had (a) shorter execution but not reaction times on the 5-choice RT, (b) shorter subsequent but not initial thinking times in the SoC where they also solved more problems correctly with the minimum number of moves, and (c) better strategy but not errors scores in the SWM. Our findings suggest that greater PPI is associated with superior abilities in strategy formation and execution times. We suggest that this is due to more efficient early information processing.

Parametric exploration of the fear-inhibited light reflex.

The effect of various parameters on the mediation of the fear-inhibited light reflex was examined. The light reflexes of 16 healthy men were measured across four light probe intensities, either in the presence of white noise alone or when the white noise was associated with the threat of either an electric shock or an acoustic sound blast. The white noise alone did not affect the light reflex amplitude. Both types of threat were subjectively anxiogenic and inhibited the light reflex across all light probe intensities, the threat of shock being more potent than the threat of sound blast. Importantly, the effect of either type of threat on the light reflex amplitude was found to increase with increasing light probe intensity, suggesting that brighter light probes may become more relevant motivationally in the threat condition, thus attracting greater allocation of attentional/cognitive resources.

Effects of peripheral sympathetic blockade with dapiprazole on the fear-inhibited light reflex.

Fear (e.g. associated with the threat of an electric shock) causes an increase in initial pupil diameter (IPD) and a decrease in the amplitude of the light reflex response. There is evidence for dissociation between the two responses to threat: only the reduction in light reflex response amplitude is sensitive to the anxiolytic drug diazepam. We examined the effects of peripheral sympathetic blockade with the alpha(1)-adrenoceptor antagonist dapiprazole on both responses to threat on the basis of the hypothesis that only the response of the IPD will be affected, whereas the response of the light reflex will remain unaffected. Twelve healthy volunteers (Experiment 1) and eight healthy volunteers with smaller pupils (Experiment 2) participated in one experimental session. Dapiprazole 0.5% (two drops of 20 microl, three times) was instilled in the subjects' right or left eye while the contralateral eye was treated with placebo eye drops (artificial tear, two drops of 20 microl, three times) according to a single-blind balanced design. Pupil diameter was monitored by infrared binocular television pupillometry. At the point of maximum dapiprazole-evoked miosis, the light reflex was elicited three times in each of three Safe blocks (no possibility of electric shock), alternating with three Threat blocks (possibility of electric shock). At the end of each Safe and Threat block, subjects rated their mood and feelings on the Visual Analogue Scales. In Experiment 1, dapiprazole caused significant miosis. Threat increased subjectively rated anxiety and inhibited the light reflex. The inhibition of the light reflex was unaffected by dapiprazole. The threat-induced increase in IPD was also unaffected by dapiprazole, probably due to a ceiling effect curtailing the threat-induced increase in IPD. In the smaller pupil group in Experiment 2, where the possible contribution of a ceiling effect was minimized, dapiprazole suppressed the threat-induced increase in IPD. The inhibition of the light reflex by threat is likely to reflect central parasympathetic inhibition and is unlikely to involve the peripheral sympathetic innervation of the iris. The threat-induced increase in IPD is likely to reflect mainly central sympathetic excitation. The different central autonomic mechanisms underlying the two pupillary responses to threat may explain the dissociation between the separate effects of threat on IPD and light reflex amplitude.