( A ) Delayed recognition for words presented at maximum concentration shown as change (mean + SE) from baseline. The vertical dotted line at 0 ms indicates the time of stimulus presentation. ( B – F ) Grand average waveforms for ERPs to target (thick line) and nontarget (thin line) tones for the Cz electrode are shown. Effect of the study drugs on memory ( A ) and auditory event-related potentials (ERPs B – F ) at maximum concentration. The maximal peak amplitudes for N2 are larger ( i.e. , more negative) in the groups receiving sedative drugs (mean ± SD:−1.6 ± 4.0 μV for placebo vs. −3.8 ± 2.1 μV for midazolam, −3.9 ± 5.6 μV for propofol, −2.4 ± 3.0 μV for thiopental, and −3.7 ± 5.1 μV for fentanyl).įig. As the P3 waveform disappears, the P2 and N2 components may become more visible. The ERP waveforms are now very similar between target and nontarget tones.
Both N2 and P3 to target tones are reduced in amplitude. The P3 is followed by the negative slow wave (NSW). The N2 is of smaller amplitude (more positive) for the target tones than for the nontargets, as is usually the case, being partially occluded by the large positive wave (P3), which follows at around 300 ms for the target tones only. PLAC = placebo OND = ondansetron FENT = fentanyl THP = thiopental MDZ = midazolam PROP = propofol. 20As before, the memory effect was measured by the ability of volunteers to recognize words previously presented at different target drug concentrations at the end of the study day. 19In the current analysis we chose to use another, possibly more objective measure of sedation, the logarithm of the reaction time (logRT) to an auditory stimulus in a go–no-go class of task. Although the previously used Norris visual analog scale is an accepted method of assessing sedation, it is by necessity subjective. 18to relate auditory ERP components to either memory or sedative effects by means of the predictive probability parameter (P k). 7–9To explore this effect, we used the method of Smith et al. Although the ERPs were obtained using a go–no-go attention task, which does not specifically target memory processes, there is evidence that some memory processes are engaged and that various ERP components from this paradigm index memory function. We hypothesized that this difference is a result of the specific effects of midazolam or propofol on memory versus sedation. The late components of the ERP are visibly affected to a larger extent by midazolam and propofol when compared with thiopental or fentanyl ( fig.
15Few investigations of the memory effects of drug are conducted with the ability to differentiate sedative from amnesic effects while participants are still responsive. 14Consequences of this fact include the current perception of some, for example, that propofol has few or no amnesic properties independent of its hypnotic effects. If a drug is given to induce unresponsiveness (hypnosis), no explicit memory can be formed. The sedation-independent effect of a drug on memory is often not appreciated. 13used these properties of the ERP to dissociate the memory versus sedative effects of lorazepam, diphenhydramine, and scopolamine. 10,11This provides a neuroanatomic basis for the concept that drug effects on memory and sedation are specific. 9As with memory processes, these ERP components may be localized to certain neuroanatomic structures. 7–9This finding can be interpreted as the central nervous system (CNS) attending more to distinct aspects of the stimuli and remembering these in preference to other, less distinctive stimuli. In general, a larger P3 is associated with subsequent remembering. 7In particular, the P3, the longest and most studied ERP component in relation to memory processes, has been repeatedly shown to relate to subsequent memory. 1,2There is evidence that separate neuroanatomic regions mediate arousal or attention versus memory processes in humans who have not received any drug, 3–6and these processes can be indexed by specific components of event-related potentials (ERPs). THE sedative and amnesic effects of sedative–hypnotic drugs are closely related, as sedation itself produces impairment in memory performance, and both effects vary in the same direction as serum concentration changes.
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