| Abstract: |
Introduction : Learning during "adequate" anesthesia seems related to depth of anesthesia. (1) As the incidence of learning is low, it is difficult to determine at what depth of anesthesia learning would not occur. A complex cognitive operation, such as encoding, would require sensory perception of auditory stimuli. We measured sensory perception of auditory stimuli using the quantitative rCBF response to increasing word rate (2) at sedative (S) and hypnotic (UR) levels of propofol (PRP) or thiopental (THP) effect. Methods: Following informed consent, 10 right-handed male volunteer subjects (33.5 +- 10.4 yrs, 74.5 +- 8.4 kg) received THP (n=4) or PRP (n=6) intravenously using Stanpump (S. Shafer; http://anesthesia.stanford.edu/pkpd). Step-wise target concentrations were at S (THP 4 and PRP 1.2 ug/ml) and UR (THP 7-9 and PRP 2.5-3 ug/ml) effects, UR being unresponsiveness to voice or mild stimulation. BISTM was monitored using a standard montage (1050 monitor, Aspect Medical Systems, Natick, MA). Three quantitative PET scans (GE Advance) were obtained at 0, 20 and 40 words per minute, counterbalanced in baseline, S and UR conditions (total of 9 scans; 10 mCi radiotracer/scan; arterial time-activity curve). CoVariation of rCBF with word rate was identified by SPM99 analysis, at a voxel-level p<0.001, and a ROI mask was created using all conditions. Individual mean rCBF responses in the ROIs were obtained using MarsBar (http://www.mrc-cbu.cam.ac.uk/Imaging/marsbar.html). 3 subjects with decreasing rCBF responses with word rate during UR (non-responders) were analyzed separately as above. Results: CoVariation of rCBF with word rate in baseline and S conditions was maximal in superior temporal gyri (max T=6.14(L), 5.23(R)). rCBF response to word rate was significantly less during UR by condition interaction analysis. During UR, BISTM was lower in the 3 non-responders (68.4 +- 3.4 vs. 72.2 +- 6.1, p<0.04). In the 3 non-responders, peak CoVariation of rCBF occurred more medially and posteriorly, with larger rCBF values on the right. Excluding non-responders, CoVariation of rCBF in UR subjects occurs on the left (T=3.18). At sedative concentrations CoVariation of rCBF was larger in extent than at baseline (L 4452 vs. 2875 voxels at baseline, R 4542 vs. 3360 voxels at baseline) Conclusions: A biphasic dose effect of auditory sensory processing is present with increasing anesthetic drug effect. At S concentrations sensory processing may be disinhibited and recruit a larger neuronal population. Word stimuli, or anticipation of these, produce larger rCBF values on the left. At higher doses, auditory rCBF response is depressed and more localized, with non-response occurring in regions slightly outside peak response regions. This rCBF response may define a depth of anesthesia where no memory formation is possible. |
