Abstract
Rationale
The benzodiazepine lorazepam enhances the potential for inhibitory γ-aminobutyric acid (GABAA) synapses in the cortex to stabilize postsynaptic, excitatory activity by synchronizing discharge rates at frequencies of around 40 Hz. Treatment with lorazepam also affects contour integration processes, suggesting that GABAA-mediated synchronization plays a role in visuospatial organization. This conclusion is supported by other physiological studies that link visual feature integration with neuronal synchronization.
Objectives
One experiment was conducted to assess variations in dynamic figural priming as a result of lorazepam administration.
Methods
Observers were presented a modified version of a figural priming paradigm designed to investigate the effects of dynamic synchronization on visual feature integration. The priming paradigm consisted of premask crosses presented in a square arrangement within the same phase of a multiphase premask matrix oscillating at 40 Hz. Observers responded to a subsequently presented target square. The modification consisted of line elements presented at various distances relative to the unspecified extension of the lines making up the premask crosses. It was expected that priming effects would be enhanced for lines terminating close to the unspecified extension but only following administration of lorazepam.
Results
As anticipated, priming was enhanced substantially when the premask crosses flickered around static lines that terminated adjacent to the unspecified extension between the premask crosses. This effect was maximal following treatment with lorazepam.
Conclusions
This finding supports the idea that GABAA-enhanced inhibitory synchronization mediates continuity coding during early visual processing.
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Notes
Diazepam was chosen as a control for lorazepam in this experiment because although both drugs have equisedative effects, as measured subjectively and objectively, and equivalent effects on explicit memory (see, e.g., Legrand et al. 1995; Sellal et al. 1992; Vidailhet et al. 1994), they have been shown to differ in their effects on visual perception. In particular, lorazepam, but not diazepam, has been shown to specifically facilitate the detection of a discontinuity between collinear contours (Beckers et al. 2001; Giersch 1999, 2001), resulting in the impaired integration of local visual information into global configurations (Giersch et al. 1997; Giersch and Lorenceau 1999). Diazepam and lorazepam have also been shown to differ with respect to the identification of fragmented pictures (Legrand et al. 1995; Vidailhet et al. 1994; Wagemans et al. 1998), perceptual priming effects (Legrand et al. 1995; Vidailhet et al. 1994; Sellal et al. 1992), the detection of discontinuities in lines (Beckers et al. 2001), and in their effects on masking and vernier offset detection (Giersch and Herzog 2004). The reason why both drugs differ in these effects has still to be determined. On the one hand, there is evidence to suggest that diazepam and lorazepam may affect different subtypes of GABAA receptors (Mohler et al. 2002), but other more parsimonious explanations should also be considered, in particular the different influence of the two drugs on the dynamics of neural activity: while diazepam lowers the firing frequency of individual neurons in a similar fashion to lorazepam unlike lorazepam, it appears to have little influence on the generation of synchrony (Faulkner et al. 1998; Whittington et al. 1996). This characteristic tends to suggest that perceptual performance may be affected by lorazepam as a direct result of its effects upon the patterns of neural synchronization that have been found to emerge between neurons in the dynamic binding of visual features (i.e., Gray et al. 1989; Eckhorn et al. 1988; for review, see Singer 1999).
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Acknowledgements
This research was supported by INSERM, the University Hospital of Strasbourg, and deutsche Forschungsgemeinschaft project grant EL 248/1-1. We would like to thank Dr. M. Welsch for medical examination of the healthy volunteers.
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Elliott, M.A., Giersch, A. & Seifert, D. Some facilitatory effects of lorazepam on dynamic visual binding. Psychopharmacology 184, 229–238 (2006). https://doi.org/10.1007/s00213-005-0242-x
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DOI: https://doi.org/10.1007/s00213-005-0242-x