Effects On Memory In Dexmedetomidine-induced Sedation:A Study Using A Process Dissociation Procedure And Functional Magnetic Resonance Imaging

BackgroundDexmedetomidine is a highly selective a2-adrenoceptor agonist,which produces corresponding pharmacological effects by acting on a2-adrenoceptors in the central and peripheral nervous systems.It has been widely used as an adjunct to clinical sedation and general anesthesia,even for children’s non-invasive examination or preoperative sedation,which is safe and reliable.However,the effect of dexmedetomidine on memory and its mechanism are still unclear.Human memory can be divided into explicit memory and implicit memory.The past experience that can be consciously retrieved is called Explicit memory.If it can not be consciously retrieved,but the past experience can affect the current thinking and behavior,it is called Implicit memory.Most evidence supports that the implicit and explicit forms of memory depend on different memory systems,which are linked to different areas of the brain.Explicit and implicit memory can be quantified separately by the process dissociation procedure(PDP).In recent years,PDP has been widely introduced into the research of anesthesia and cognitive science.Functional magnetic resonance imaging(fMRI)is a brain imaging method that can show the regional and temporal changes of brain metabolism in real time.These metabolic changes may be task-induced changes in cognitive status or the result of spontaneous activity processes in the resting brain.Because of its high spatial resolution and good clinical applicability,fMRI has been applied to explore the effects of anesthetics on brain functional activities and their regulatory mechanisms in recent years,but there are few fMRI studies on dexmedetomidine.In the present study,we quantified the memory ability before and after sedation with dexmedetomidine by using the process dissociation procedure combined with word stem completion method,and preliminarily explored the brain activation areas in the auditory word memory task before and after sedation by using fMRI,and studied the dynamic changes of brain functional networks during this process by using a novel fMRI dynamic brain functional network analysis index.We hope not only to understand the effects of dexmedetomidine on explicit and implicit memory formation from the real clinical environment,but also to explore the regulation mechanism of dexmedetomidine on memory from the perspective of brain functional imaging.Experiment 1:Effects of different sedation depths of dexmedetomidine on explicit and implicit memory in patients with regional anesthesiaObjective:The effects of dexmedetomidine on memory during surgery are unknown.The purpose of this study was to investigate the effects of dexmedetomidine sedation on explicit and implicit memory in surgical patients by using the process dissociation procedure.Methods:Forty patients aged 18-50 years with ASA physical status scores of Ⅰ or Ⅱunderwent elective regional anaesthesia and were randomly divided into ’mild sedation’(bispectral index,60-80)and ’ deep sedation’(bispectral index,40-60)groups.Conscious auditory verbal learning was presented to patients before dexmedetomidine administration.Dexmedetomidine was then administered for 10 minutes at a loading dose of 0.5 μg/kg for the mild sedation group and 1.0 μg/kg for the deep sedation group.A continuous dexmedetomidine infusion of 0.5 μg/kg/h was then administered.When a stable target sedation depth was achieved,the patients were subjected to sedative auditory verbal learning.Upon completing the learning process,drug administration was terminated.The Observer’s Assessment of Alertness/Sedation Scale was carried out on both groups both before and after sedation and the scores were assessed.Four hours after the termination of drug administration,inclusion and exclusion tests were performed.Finally,the implicit memory and explicit memory scores of the two groups were calculated using the process dissociation procedure.Results:The median scores of explicit memory and implicit memory of the two groups were higher than 0 in the awake state,and there were significant differences compared with 0(P<0.05),indicating that the formation of explicit memory and implicit memory was detected.There was no significant difference between the two groups in explicit and implicit memory scores and 0(P>0.05)under sedation,indicating that there was no explicit and implicit memory formation in both light and deep sedation groups.Conclusion:Dexmedetomidine can inhibit the formation of explicit memory under both mild and deep sedation.More work is required in order to understand implicit memory formation under dexmedetomidine sedation.Experiment 2:Effects of dexmedetomidine sedation on auditory memory and related MRI brain functional imagingObjective:Dexmedetomidine is commonly used for clinical sedation and general anesthesia.We conducted an auditory-verbal process dissociation procedure to delineate explicit and implicit memory under dexmedetomidine sedation in the clinical setting and functional magnetic resonance imaging environment and to reveal brain activity associated with this effect.Methods:8 participants(5 males)received dexmedetomidine mild sedation(BIS 6080)in an MRI scanner,two randomly selected word lists were played and subjects were scanned before and under dexmedetomidine sedation.Imaging data of auditory stimulus effects,differences between conscious states,and memory-related changes were analyzed.Results:The brain regions activated by the memory task included the bilateral middle temporal gyrus,superior temporal gyrus,inferior frontal gyrus,and adjacent insula(P<0.05,alphasim corrected).BOLD activation was significantly reduced by dexmedetomidine in the left middle temporal gyrus,inferior frontal gyrus,and right superior temporal gyrus compared with the awake state(P<0.05,alphasim corrected).Conclusion:Dexmedetomidine sedation significantly inhibited the activation of the left middle temporal gyrus,inferior frontal gyrus,and right superior temporal gyrus when comparing to awake state.The responsiveness of the temporal lobe impaired but was preserved under mild sedation,which is an important functional imaging evidence for the arousable feature of dexmedetomidine.Experiment 3:Objective:This study was designed to explore the neurological effects of dexmedetomidine induced sedation on memory using functional stability,a wholebrain voxel dynamic functional connectivity approach.Methods:A total of 16 participants(10 males)underwent fMRI examinations related to auditory memory tasks while awake and under dexmedetomidine sedation.Explicit and implicit memory tests were performed 4 hours after withdrawal of dexmedetomidine.A single sample Wilcoxon symbolic rank test was used to determine the formation of explicit and implicit memory in the two states.Functional stability was calculated and voxel comparisons were made between wakefulness and sedation.The relationship between functional stability and memory performance was also evaluated.Results:On the wakefulness baseline test,explicit and implicit memory scores were significantly different from zero(P<0.05).Explicit and implicit memory scores did not differ significantly from zero on the sedative tests.Functional stability was reduced in the medial prefrontal cortex,left angular gyrus,and right hippocampus during mild sedation compared to baseline wakefulness(P<0.05,GRF-corrected),while the left superior temporal gyrus showed higher functional stability(P<0.05,GRF-corrected).No significant correlation was observed between functional stability and memory test scores.Conclusion:The distribution and pattern of functional stability changes during sedation indicate that dexmedetomidine regulates functional structure from a dynamic perspective.Our findings provide new insights into the dynamic network of brain functions underlying human consciousness and memory.