Pharmacological strategies and suicidal outcomes in borderline personality disorder: observational synthesis.

Alongside the outer retinal rod and cone photoreceptors, the mammalian retina expresses a third class of photopigment, known as melanopsin, in a subclass of retinal ganglion cells, rendering these cells intrinsically photosensitive. These intrinsically photosensitive retinal ganglion cells (ipRGCs) integrate extrinsic rod and cone input with the intrinsic melanopsin-mediated response to light to send a composite signal to downstream brain areas. Melanopsin contributes to subconscious responses to ambient light such as circadian entrainment and the pupillary light reflex. However, across mammalian species, ipRGCs also target the lateral geniculate nucleus (LGN) of the thalamus, the relay station for input to the visual cortex and for visual perception. Efforts to understand the significance of the melanopsin contribution to thalamocortical vision for human perception are complicated by the paucity of methods to selectively modulate melanopsin activity. One approach has been to adopt the method of silent substitution, in which the differential response between two spectra matched for cone, but not for melanopsin excitation (i.e., metamers), is used to assess the contribution of melanopsin to visually evoked responses to light. Such metameric stimuli have been shown to have different effectiveness for eliciting pupillary constriction and other unconscious light responses. Several studies have reported the impact of such selective modulation in melanopsin activation on aspects of human conscious vision. The most widely reported percept induced by stimuli providing selective modulation of melanopsin is a change in apparent brightness. This fits also with experiments in mice in which melanopsin knockout can be employed as an additional control. As melanopsin is far from the only photoreceptive mechanism responsible for brightness discrimination, an important question is under what circumstances a melanopsin brightness percept is a useful addition to that provided by cones (luminance). This question has been addressed most extensively in electrophysiological recordings of ipRGCs and their central targets in non-human mammals. The most reliable distinction between the contribution of melanopsin versus rod/cone signals to the activity of these neurons is revealed by a light step lasting several seconds. During the plateau portion of these light steps, maintained excitation relies disproportionately on melanopsin. The significance of this property has not been directly assessed for human vision. In human vision, stabilized images fade into the background (a phenomenon known as Troxler fading), indicating that just as the amplitude of electrophysiological responses mediated by cones dissipates under continuous illumination, so too does perception. It follows that one prediction of the contribution of melanopsin to electrophysiological activity is that it could contribute to counteracting Troxler fading. Here, we set out to test this prediction.