Effects Of Ketamine On Functional Brain Activation Induced By Mechanical Stimuli Elucidated By FMRI

Effects of Ketamine on Functional Brain Activation Induced by Mechanical Stimuli Elucidated by fMRIObjectiveUsing functional magnetic resonance imaging at 3.0 T,to investigate the brain regions related to the effects of ketamine on mechanical stimuli.Methods13 healthy male volunteers were enrolled in this study.Ketamine was administrated by target controlled infusion system in pilot study.Von Frey filaments of 100g,300g were used as mechanical stimuli to the center of the left foot at the plasma concentration of 0,100,200ng/ml,pain VAS scores and the psychedelic effect were evaluated.FMRI examinations were taken 1 week after pilot study as the following sequences:structure imaging and 2×functional imaging(stimulus sequence 100g,300g + ketamine sequence).stimulus sequence = 6×(20s on+20s off),this sequence was repeated after ketamine sequence.The monitoring data were recorded during the scanning.FMRI data processing is carried out with the SPM2 and Metlab 7.01 software package.Results1.Areas inhibited by ketamine under vFFs stimulus were:100g vonfrey:no inhibited effect was seen at 100ng/ml;middle frontal gyrus(1), temporal lobe(1),postcentral gyrus,anterior cerebellum lobe(r),thalamus(r) were inhibited at 200ng/ml.300g vonfrey:posterior cerebellum lobe,corpus callosum were inhibited at 100ng/ml;no more region was inhibited at 200ng/ml.2.Areas activated by ketamine under vFFs stimulus were: 100g vonfrey:precentralgyrus(r),postcentralgyrus,superior temporal gyms, inferior parietal lobule,anterior cerebellum lobe,insular lobe were activated at 100ng/ml;frontal lobe(1),temporal lobe(1),occipital lobe(r) were activated at 200ng/ml.300g vonfrey:cingulate gyrus,middle frontal gyrus(r),inferior parietal lobule, occipital lobe,posterior cerebellum lobe(1) were actevated at 100ng/ml;frontal lobe, temporal lobe,occipital lobe,anterior cerebellum lobe,posterior cerebellum lobe, ACC,hippocampus,thalamus,corpus callosum,brain stem(r) were activated at 200ng/ml.3.Areas processing pain intensity affected by ketamine under vFFs stimulus were:Areas inhibited by ketamine were:inferior frontal gyrus(1),temporal gyrus, postcentral gyrus,occipital lobe,cerebellum lobe,insular lobe(r) at 100ng/ml;frontal lobe,corpus callosum(r) at 200ng/ml.Areas activared by ketamine were:temporal lobe(r) at 100ng/ml;frontal lobe(r), temporal lobe,inferior parietal lobule(1),occipital lobe,precentral gyrus(r) at 200ng/ml.ConclusionLight mechanical stimuli activate the ipsilateral brain region while strong mechanical stimuli activate the contralateral brain regions which may participate in the modulation of pain intensity;ketamine can both activates and inhibites the pain related brain region activity at the same time,activative effect was the primary effect; the cingulate gyrus,insula lobe,brain stem,thalamus were target region of ketamine; ketamine acts both on the ipsilateral and the contralateral side of pain related brain region,especialy on the contralateral side.Ketamine shows inhibitory effect at 100ng/ml,but activating effect at 200ng/ml on the pain intensity process. Effect of analgesic dose of ketamine on memory:Process dissociation procedure and functional magnetic resonance imaging studyObjectives To quantitatively investigate the effect of ketamine on explicit and implicit memory and to explore the possible target brain areas associated with the memory processing and the action of ketamine through combined use of PDP and BOLD-fMRI 3.0T.Methods 7 volunteers were enrolled in this study.On their first visit,volunteers were given a ketamine infusion to test the tolerance of ketamine and to familiarize the volunteers with the method of auditory stimulus.The second visit was a scanning session.Each volunteer was given the first auditory stimulus before sedation.Then they received the second auditory stimulus after the target level of sedation had been reached.Imaging response was measured in 4 different time: before and during the first auditory stimulus,ketamine infusion and during the second auditory stimulus accompanied with continuous ketamine infusion.4 h later,the inclusion test and exclusion test were performed outside the scanner.The process dissociation procedure combined with word stem completion was used to estimate the scores of explicit and implicit memory.Results There are no significant differences between awake and ketamine infusion state in explicit memory scores and Implicit memory scores(P>0.05);the superior temporal gyrus,middle temporal gyrus,inferior temporal gyrus,ACC, insula are significantly activated during auditory stimulus;ketamine inhibites the activation of ACC but activates the lentiform nucleus.Conclusions Analgesic dose of ketamine inhibited the activation of ACC, activatesd the activation of lentiform nucleus,but no change of memory score was found through PDP.No damage of the memory maybe due to the low concentration of ketamine. Effect of Midazolam on memory:Process dissociation procedure and functional magnetic resonance imaging studyObjectives To quantitatively investigate the effect of midazolam on explicit and implicit memory and to explore the possible target brain areas associated with the memory processing and the action of midazolam through combined use of PDP and BOLD-fMRI 3.0T.Methods 12 volunteers were equally divided into 2 groups according to the Modified Observer's Assessment of Alertness/Sedation Score:M3,level 3 and M1, level 1.On their first visit,volunteers were given a midazolam infusion to individually predict the needed plasma concentration of each volunteer,to test for tolerance of midazolam sedation and to familiarize the volunteers with the method of auditory stimulus and sedation scoring.The second visit was a scanning session. Each volunteers were given the first auditory stimulus before sedation.Then they received the second auditory stimulus after the target level of sedation had been reached.Imaging response was measured in 4 different time:before and during the first auditory stimulus,midazoalm sedation and during the second auditory stimulus accompanied with continuous midazolam sedation.2 h later,the inclusion test and exclusion test were performed outside the scanner.The process dissociation procedure combined with word stem completion was used to estimate the scores of explicit and implicit memory.Results There are no significant differences between explicit memory scores and zero(P>0.05) in 2 groups.Implicit memory scores were statistically greater than zero(P<0.05) during midazolam sedation in M3 but not in M1.The superior temporal gyms,middle temporal gyrus,,temporal fusiform gyrus and insula lobe are significantly activated during auditory stimulus.Midazolam in M3 did not change the activation og memory related brain region.Midazolam in M1 inhibit all the activated brain areas,while activate the middle frontal gyrus.However compared M1 with M3,no significant activated brain areas are found.Conclusions Midazolam does not impair the implicit memory until the depth of sedation increases to the level 1 of MOAA/S score according to PDP.The superior temporal gyrus,insula lobe and middle frontal gyrus may be the target areas of midazolam in brain and they might be more closely related to the memory processing.