| Abstract |
The dynamic light reflex is a homeostatic parasympathetic reflex and consists of a brisk and transient contraction of the smooth iris sphincter muscle in response to rapid increments in light flux to the retina, thus reflecting the amount of light captured by the eye. The light reflex is a primitive, cross-species automatic/reflexive response, not primarily influenced by intentional control, and is mediated by a well defined, subcortical mesencephalon-based, simple neural circuit. Important synapses include the retinal ganglion cells, the olivary pretectal nucleus, the parasympathetic Edinger-Westphal nucleus, the ciliary ganglion and the sphincter iris muscle. Bitsios et al showed for the first time in 1996 that the amplitude of the pupillary light reflex is reduced when the light probe is presented after a warning cue (e.g. a tone) that has been previously verbally associated with an aversive electric shock. These changes in pupillary activity are accompanied by increases in subjective alertness and anxiety and, importantly, light reflex amplitude was shown to correlate negatively with subjective anxiety. This phenomenon was termed "fear-inhibited light reflex" and the threat-induced decrease in light reflex amplitude was proposed as a potential laboratory model for human anxiety. The fear-inhibited light reflex, in common with the fear-potentiated startle reflex, is sensitive to the anxiolytic drug diazepam in a dose-dependent manner, suggesting that a common mechanism may mediate the effect of threat in both cases. Based on the abundant evidence on the amygdala being the critical structure mediating fear responses, including the fear-potentiated startle reflex in rodents and in humans during verbally instructed threat cues, Bitsios et al have argued that this structure, through its connections to the locus coeruleus, drives established direct locus coeruleus and/or direct hypothalamic inhibitory projections to the Edinger-Westphal nucleus (the motor centre of the reflex), thus inhibiting the light reflex during threat of shock (Bitsios et al., 1996, 1998a, 1998b, 1999). An interesting feature of this paradigm is the threat-induced increase in pupil diameter that precedes the threat-induced reduction in light reflex amplitude. Previous studies by Bitsios et al have shown that a) the two measures do not covary and have different habituation rates, b) only the threat-induced reduction in light reflex amplitude correlates with subjective anxiety c) only light reflex amplitude is sensitive to the effects of the anxiolytic diazepam and d) only IPD is sensitive to the alerting effects of a non salient stimulus or and easy mental task. In experiment 1 we provided the neurobiological basis for the dissociation between the threat-induced decrease in light reflex amplitude and the threat-induced increase in pupil diameter. The inhibition of the light reflex by threat was unaffected by peripheral sympathetic blockade while the threat-induced increase in IPD was suppressed when care was taken to avoid the confounding influence of a ceiling effect. Therefore, we showed that 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. Moreover, 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. In experiment 2 we showed that (a) the CS per se does not modify the light reflex (b) the fear-stimulus modality is not important for the inhibition of the light reflex as long as the possibility of stimulus occurrence is an adequately threatening prospect for the subjects, (c) the magnitude of the light reflex amplitude can be a function of the amount of threat posed by a fear-stimulus. The amount of threat may vary between different types of fear stimuli for a given subject, whereas inhibition of the light reflex appears to be sensitive to threat in a "dose-dependent" manner and, (d) the manifest effect of fear on light reflex amplitude increases with increasing light intensity. The last result (d) which shows that the effect of threat on light reflex amplitude is light intensity-dependent, may have important methodological implications in future research involving the fear-inhibited light reflex, as it favors a choice of bright probes for obtaining a larger manifest effect of threat. This observation has also important theoretical implications. It suggests that during anxious anticipatory processing, the more intense light probes become more motivationally relevant (i.e. more aversive), thus multiplying the allocation of attentional resources compared to the weaker probes. This interpretation is consistent with the assumption that the threat-induced reduction in light reflex amplitude reflects fear, although it requires the addition of an intermediate attentional/cognitive component. In study 3 we generated a novel protocol for the study of the time course of anticipatory anxiety and the built up of worry rather than the acute anxiety generated with the hitherto acute threat protocols. This new protocol is more pertinent to the study of generalized anxiety rather than panic. This protocol revealed that the light reflex amplitude closely follows the time-course of anticipatory anxiety. The light reflex amplitude becomes shortest at the time when the shock is imminent and rapidly returns to normal levels at threat offset. On the contrary, IPD followed a very different pattern; It was greater at the beginning of every threat and safe condition quickly habituating thereafter. The possibility that this finding reflects the sensitivity of IPD to contextual changes is an intriguing one. If this is the case, then the fear-inhibited light reflex tested with this protocol can help to simultaneously assess a subjects' responsivity to contextual changes and his/her time-course of anticipatory anxiety.
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