| Abstract: |
INTRODUCTION Midazolam and propofol in sedative doses decrease rCBF in discrete brain regions. Decreases in rCBF greater with high than low dose propofol were identified and compared with previous results from midazolam.(1) To assess the ability of rCBF changes to detect neuronal activity during deep propofol sedation, the rCBF response to increasing word stimulation rate (2) was determined in 1 subject. METHODS After IRB approval and informed consent, 11 right-handed volunteers (4F, 6M, ages 21-36) underwent PET scanning before and during propofol administration in a single session. rCBF images (approximately 5 mm resolution)were obtained using H215O during rest (unstimulated eyes closed), an auditory word memory task, and nonsense word presentation before and after propofol at target concentrations of 600 (n=5,low) or 900 (n=5,high)ng/ml. Subjects were drowsy to very sleepy, but arousable with drug. Words at rates of 0,10,40 words/min were presented to one subject before and after propofol, 2000 ng/ml, which induced unresponsiveness. rCBF images were analyzed with SPM99 (uncorrected p<0.001) using a multigroup with conditions design. rCBF increases in learning versus baseline were identified. Regions where rCBF decreased more with propofol in high than low dose in the rest condition was performed. The adjusted rCBF at a local maxima voxel in auditory and non-auditory cortices in Subject 11 was plotted. RESULTS. The memory decrement was 59+-10% for low versus 85+-3% for high groups. Activation in auditory cortex was present in all drug conditions. The increasing rCBF response with word rate during propofol was similar to baseline, and not present in other brain regions tested. Interaction analysis (Figure, reported maxima Z>4.5) revealed dose related decreases in rCBF in superior, inferior and middle frontal gyri (Brodmann's Areas 6,9,45) and inferior parietal lobule and supramarginal gyrs (BAs 39,40). These prefrontal regions are within 2 cm of rCBF increases associated with the word memory task, and dose related interactions in subjects receiving midazolam.(1) Prefrontal and parietal regions are close (2-3 cm) to those activated during verbal and auditory working memory tasks(3,4). CONCLUSIONS. Midazolam and propofol decrease rCBF in a dose-related fashion in prefrontal and parietal areas associated with verbal and auditory working memory.(3,4) We postulate that the amnesic effects of these drugs may in part be mediated by specific actions on components of working memory located in prefrontal and parietal brain regions. Propofol in increasing doses inhibits perception of tactile stimulation evident by changes in rCBF.(5) At doses up to 2000 ng/ml propofol does not interefere with rCBF response to auditory stimulation. Thus, local coupling of blood flow and neuronal metabolism is preserved, and may indicate continued auditory perception at these doses. |
