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Clinical Science  |   March 2006
Cortical Processing of Complex Auditory Stimuli during Alterations of Consciousness with the General Anesthetic Propofol
Author Affiliations & Notes
  • Gilles Plourde, M.D., M.Sc.
    *
  • Pascal Belin, Ph.D.
  • Daniel Chartrand, M.D., Ph.D.
  • Pierre Fiset, M.D.
  • Steven B. Backman, M.D., Ph.D.
  • Guoming Xie, M.D.
    §
  • Robert J. Zatorre, Ph.D.
  • * Professor, ‡ Associate Professor, Department of Anesthesia, ∥ Professor, Department of Neurology and Neurosurgery, § Ph.D. Student, Departments of Anesthesia and Neurology and Neurosurgery, McGill University. † Postdoctoral Student, Department of Neurology and Neurosurgery, McGill University. Current position: Department of Psychology, University of Glasgow, Glasgow, United Kingdom.
Article Information
Clinical Science / Central and Peripheral Nervous Systems / Pharmacology
Clinical Science   |   March 2006
Cortical Processing of Complex Auditory Stimuli during Alterations of Consciousness with the General Anesthetic Propofol
Anesthesiology 3 2006, Vol.104, 448-457. doi:
Anesthesiology 3 2006, Vol.104, 448-457. doi:
AUDITORY perception is obviously disrupted by general anesthetics, but it is unclear at what stage the disturbances occur. This report investigates the extent of auditory cortical activations during general anesthesia with propofol and whether specialized cortical areas remain capable of distinguishing different classes of complex stimuli.
The persistence of component Pa of the auditory middle latency evoked response during general anesthesia1 suggests that processing of clicks or tone bursts persists in the primary auditory cortex (Heschl gyrus [HG]), in agreement with animal studies.2 Animal studies indicate, however, that responses in secondary cortical areas occur much less reliably and only during light anesthesia.3,4 The human N1 auditory evoked potential originates from the secondary auditory cortex5 and is abolished during general anesthesia with isoflurane or thiopental.6,7 The sensitivity of higher-order auditory cortical areas to anesthetics is consistent with the influential hypothesis8 that anesthesia results from impairment of conduction through polysynaptic pathways.9 
However, there is controversy about the N1 during propofol anesthesia: Two studies reported its persistence,10,11 and one study reported its absence.12 These studies also revealed conflicting results about the mismatch negativity13 as evidence of a differential response to pitch.
Using blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI), Van et al.  14 found with one subject that activation of the primary auditory cortex by tone bursts (1,000 Hz) persisted during sevoflurane anesthesia. Kerssens et al.  15 examined the effect of sevoflurane on BOLD activation induced by auditory words. They reported decreased activation during 1.0% end-tidal sevoflurane and no residual activation at 2% end-tidal. Heinke et al.  16 reported that speech-related BOLD fMRI activations were attenuated during propofol sedation and completely abolished during anesthesia (unconsciousness). Dueck et al.  17 recently found that BOLD fMRI activations induced by music were attenuated during propofol sedation. They did not study anesthesia.
However, these studies have important limitations. First, the degree of specificity for complex processing remains unknown because only one type of stimulus was used, allowing only comparison with silence. Therefore, although a response may be observed during sedation or anesthesia, it is unclear whether this response is an attenuated but otherwise typical response or whether it represents residual activity no longer specific for the complex stimulus. Furthermore, no study used noise-mitigation strategies for fMRI, raising the possibility that auditory cortex response was partly saturated by the loud noise from the scanner.18 In particular, this is a problem in concluding that anesthesia leads to an abolition of auditory cortex responsiveness, because a weak BOLD signal would likely be undetectable if auditory cortex responses were already near maximum because of the noise.
The goal of the current study was to reassess the response of the anesthetized human brain to complex auditory stimuli using BOLD fMRI with noise-mitigation strategies (sparse sampling and clustered volume acquisition).19,20 We addressed two questions: (1) How do activation patterns in auditory cortex change as a function of different levels of anesthesia? (2) Do cortical responses continue to distinguish between different classes of stimuli? To address the second question, we used words (compared with scrambled words) and human nonspeech vocal sounds (compared with environmental sounds) because these stimuli produce selective BOLD cortical activations21,22 that are believed to directly reflect the neural activity elicited by these stimuli.23 
Materials and Methods
Subjects and Design
The study was approved by the Montreal Neurologic Institute Research Ethics Committee (Montreal, Quebec, Canada), and subjects gave written informed consent. Seven healthy, right-handed native English speakers aged 20–35 yr (mean, 26 yr) (four men) were tested after a comprehensive medical evaluation. To assess memory performance without anesthesia, a second group of seven nonanesthetized subjects aged 21–36 yr (mean, 31 yr) (three men) were exposed the same stimuli (recorded on a CD and including scanner noise) with the same timing.
Imaging data were recorded during a single session (lasting approximately 4 h) comprising four successive conditions: awake baseline, sedation (blood propofol concentration of 0.6 μg/ml), anesthesia (subjects unconscious; propofol concentration of 4.6 μg/ml), and recovery (45 min after end of propofol infusion). Data acquisition during each period lasted approximately 25 min. Unconsciousness was defined as failure to respond to verbal commands.
Anesthesia
Subjects were under the care of two anesthesiologists. Testing was started in the morning after an overnight fast. A cannula was placed in a forearm vein for drug administration. A cannula was placed in the left radial artery for blood pressure monitoring and for blood sampling. Monitoring included pulse oximetry, intraarterial blood pressure, and on-line concentration of oxygen and carbon dioxide in inspired and expired gas. Subjects breathed spontaneously and received supplemental oxygen (5 l/min) by facemask during baseline, sedation, and recovery. During anesthesia, a laryngeal mask airway and Bain anesthesia circuit (oxygen; 8 l/min) were used to ensure patency of the airway and to assist breathing.
Propofol was infused with a Harvard Apparatus 22 pump (Harvard Apparatus, Holliston, MA) controlled by a laptop computer running Stanpump software (May 11, 1996 version).1The pump and computer were placed away from the scanner behind a shielded wall with a small opening for the propofol tubing. The software combines boluses and an infusion with an exponentially declining rate to achieve the desired effect site drug concentration. The dosage and rate of infusion were based on the pharmacokinetic parameters obtained in a group of subjects similar to ours.24 Arterial blood samples were taken immediately before and after scanning in each condition for subsequent determination of the concentration of propofol and for blood gas analysis. The assay was conducted by Fance Varin, Ph.D. (Faculté de Pharmacie, Université de Montréal, Montreal, Quebec, Canada), using high-performance liquid chromatography.25 The mean of the two values was used.
After placement of anesthesia-related devices and earphones, the subject was comfortably placed on the fMRI stretcher, with eyes closed. After acquisition of the baseline data, the propofol infusion was started, aiming for an effect site concentration of 1.0 μg/ml to produce sedation. When the predicted effect site concentration reached the target, we waited 5 min before acquiring imaging data to allow more complete equilibration. After acquisition of sedation data, the stretcher was slid out of the scanner to allow access to the subject's head. The target concentration of propofol was increased to 6–8 μg/ml for insertion of the laryngeal mask airway. The concentration of propofol was reduced by 0.5-μg increments to the lowest concentration allowing tolerance of the laryngeal mask airway. At this concentration, subjects were unconscious (i.e.  , resting immobile with eyes closed and unresponsive to verbal commands). The fMRI stretcher was then slid back into the scanner for acquisition of anesthesia data. After acquisition of anesthesia data, the propofol infusion was stopped, and the fMRI stretcher was again removed from the scanner. After the return of consciousness and removal of the laryngeal mask airway, the stretcher was once again slid in the scanner for acquisition of recovery data (45 min after termination of propofol infusion).
Stimuli and Task
Subjects were instructed to close their eyes, to listen to the sounds, and to memorize the words. The auditory stimuli were digitized (16-bit, 22,050-Hz sampling rate) with CoolEditPro (Syntrillium software; Haslingden, Lancs, United Kingdom). They were arranged in 10-s blocks (fig. 1) containing only one type of stimuli and were delivered binaurally at mean intensity of 88- to 90-dB sound pressure level with imaging-compatible electrostatic headphones (Koss Corporation, Milwaukee, WI). Word stimuli  consisted of common English words pronounced by a single speaker. Four lists of 10 words were used, one for each condition, with the order counterbalanced across subjects. Each 10-s block corresponded to one word repeated 6 times. There were 20 word blocks per condition, each block played twice. Each word was thus heard 12 times. Scrambled word stimuli  were obtained by scrambling the word stimuli in the frequency domain to eliminate intelligibility while preserving the overall stimulus energy.21 The scrambled words were ordered and presented as above. Vocal sounds  consisted of human nonspeech vocalizations such as laughs, cries, moans, and sighs.21 Four lists of 10 vocal sounds were used, one for each condition and counterbalanced across subjects. Each 10-s block corresponded to different exemplars. Nonvocal sounds  consisted of environmental noises (wind, rain, cars, and so forth) and musical sounds. Mode of presentation was the same as for vocal sounds. The 10-s auditory blocks were presented in a randomized order with a 10-s silence interblock interval. Memory for words was tested with forced-choice recognition (paper-and-pencil four-choice test) after 22–26 h.2
Fig. 1. Functional magnetic resonance imaging (MRI) protocol. Each period comprised 128 trials of different stimulus types including interposed silence (  top row  ). Each trial lasted 10 s for presentation of six stimuli (stim) of the same category with a fixed 1.5-s interval between onsets or of silence. The  hatched rectangle  stands for functional MRI image acquisition. Scr = scrambled. 
Fig. 1. Functional magnetic resonance imaging (MRI) protocol. Each period comprised 128 trials of different stimulus types including interposed silence (  top row  ). Each trial lasted 10 s for presentation of six stimuli (stim) of the same category with a fixed 1.5-s interval between onsets or of silence. The  hatched rectangle  stands for functional MRI image acquisition. Scr = scrambled. 
Fig. 1. Functional magnetic resonance imaging (MRI) protocol. Each period comprised 128 trials of different stimulus types including interposed silence (  top row  ). Each trial lasted 10 s for presentation of six stimuli (stim) of the same category with a fixed 1.5-s interval between onsets or of silence. The  hatched rectangle  stands for functional MRI image acquisition. Scr = scrambled. 
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Image Acquisition
Scanning was performed on a 1.5-T Siemens Vision Imager (Siemens Canada, Montreal, Quebec, Canada). High-resolution T1 images were obtained after each entry into the scanner for coregistration with functional series. One series of 128 functional images was acquired for each condition (gradient-echo, TE [time echo]= 50 ms, TR [time repetition]= 10 s, head coil, matrix size: 64 × 64, voxel size: 4 × 4 × 5 mm3, 10 slices parallel to the sylvian fissure) for a scanning time of 21 min 40 s each. The long interacquisition interval (TR) ensures low signal contamination by scanner noise.19,20 
Image Analysis
Blood oxygenation level dependent signal images were spatially smoothed (6-mm gaussian kernel), corrected for motion artifacts and nonlinearity, and transformed into standard stereotaxic space26 with in-house software.27 3Statistical maps were obtained using Fmristat.28 4For global searches (all sounds–silence), the t values for significance at the P  < 0.05, P  < 0.01, P  < 0.001, and P  < 0.0001 levels were 4.5, 4.8, 5.2, and 5.7 after correction for multiple comparisons. For searches restricted to auditory cortical areas, we report all foci with t values of 3.2 or greater (P  < 0.01, uncorrected). To track signal changes between periods, the magnitude of BOLD signal was sampled from the effect size maps in 5-mm radius spherical volumes of interest (VOIs) centered on local maxima of t value. In the case of the vocal–nonvocal and word–scrambled words contrasts, we used peak activations derived from the recovery phase, because these were the most robust and had similar locations to the peak activations during baseline. To determine the brain activation sites linked to later recognition performance, we ran a whole-brain voxel-wise covariation analysis using recognition scores as input variable.
Statistics
Differences between periods for clinical parameters and VOI measures were evaluated with analyses of variances for repeated measures (Geisser-Greenhouse corrected) and Tukey honest significance test. For the memory results, a second factor (group) was included in the analysis of variance. One-sample t  tests were used to determine whether the VOI measures differed form zero. Procedures were performed with Statistica 4.1 for Macintosh (Statsoft, Tulsa, OK).
Results
Anesthesia Clinical Parameters
Systolic blood pressure was significantly (P  < 0.01) lower during anesthesia and recovery compared with baseline. The concentration of propofol during sedation and recovery did not differ significantly (P  > 0.20; table 1).
Table 1. Clinical Parameters 
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Table 1. Clinical Parameters 
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Memory for Words
The recognition scores during baseline and recovery were significantly (P  < 0.001) higher than during sedation and anesthesia, where performance was at chance level (25%; fig. 2). Recognition during baseline was also significantly (P  < 0.02) higher than during recovery. The control group of nonanesthetized subjects showed a score of greater than 90% for all periods, with no significant differences between periods. The control group had a significantly (P  < 0.001) higher recognition score than the anesthetized group for all periods except baseline (not significant; P  = 0.62).
Fig. 2. Recognition memory. Number of items recognized for anesthetized and control subjects exposed to the same stimuli under similar conditions. Data are mean ± SE. Chance level denoted by  dashed line  .ANES = anesthesia; BASE = baseline; RECO = recovery; SEDA = sedation. 
Fig. 2. Recognition memory. Number of items recognized for anesthetized and control subjects exposed to the same stimuli under similar conditions. Data are mean ± SE. Chance level denoted by  dashed line  .ANES = anesthesia; BASE = baseline; RECO = recovery; SEDA = sedation. 
Fig. 2. Recognition memory. Number of items recognized for anesthetized and control subjects exposed to the same stimuli under similar conditions. Data are mean ± SE. Chance level denoted by  dashed line  .ANES = anesthesia; BASE = baseline; RECO = recovery; SEDA = sedation. 
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All Sounds Combined versus  Silence
Robust (t ≥ 5.7; P  < 0.0001) bilateral activations in HG and planum temporale (PT) were present during all periods, including anesthesia. VOI measures from individual subjects showed, however, that HG and PT activations decreased significantly (P  < 0.05) during sedation and anesthesia compared with baseline and recovery (table 2and fig. 3).
Table 2. All Sounds–Silence 
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Table 2. All Sounds–Silence 
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Table 2. (  Continued  ) 
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Table 2. (  Continued  ) 
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Fig. 3. Group average responses for all sounds–silence. Activation t maps overlaid over average anatomical image in standard stereotaxic space. The  right side  of the images corresponds to the subjects' right side.  Line diagrams  show mean ± SE of signal magnitude (difference in effect size between the two conditions,  i.e.  , sound  vs.  silence) in volume of interest centered on selected voxels (x, y, z coordinates indicated above graph). The y and z values on the  far right  are the Talairach coordinates of the slices; t values are revealed by  color scale  ;values above upper limit are shown in  white  .ANES = anesthesia; BASE = baseline; BOLD = blood oxygen dependent level; HG = Heschl gyrus; PT = planum temporale; RECO = recovery; SEDA = sedation. 
Fig. 3. Group average responses for all sounds–silence. Activation t maps overlaid over average anatomical image in standard stereotaxic space. The  right side  of the images corresponds to the subjects' right side.  Line diagrams  show mean ± SE of signal magnitude (difference in effect size between the two conditions,  i.e.  , sound  vs.  silence) in volume of interest centered on selected voxels (x, y, z coordinates indicated above graph). The y and z values on the  far right  are the Talairach coordinates of the slices; t values are revealed by  color scale  ;values above upper limit are shown in  white  .ANES = anesthesia; BASE = baseline; BOLD = blood oxygen dependent level; HG = Heschl gyrus; PT = planum temporale; RECO = recovery; SEDA = sedation. 
Fig. 3. Group average responses for all sounds–silence. Activation t maps overlaid over average anatomical image in standard stereotaxic space. The  right side  of the images corresponds to the subjects' right side.  Line diagrams  show mean ± SE of signal magnitude (difference in effect size between the two conditions,  i.e.  , sound  vs.  silence) in volume of interest centered on selected voxels (x, y, z coordinates indicated above graph). The y and z values on the  far right  are the Talairach coordinates of the slices; t values are revealed by  color scale  ;values above upper limit are shown in  white  .ANES = anesthesia; BASE = baseline; BOLD = blood oxygen dependent level; HG = Heschl gyrus; PT = planum temporale; RECO = recovery; SEDA = sedation. 
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During sedation, significant (t ≤−6.5; P  < 0.0001) negative activations (i.e.  , silence associated with more activity than sounds) occurred in both lentiform nuclei (x =−22, y = 4, z =−7, and x = 20, y = 6, z =−4; fig. not shown).
Words versus  Scrambled Words
This contrast yielded significant (P  < 0.01, uncorrected) activations during baseline in the left PT and superior temporal sulcus (table 3and fig. 4). During sedation and anesthesia, no activations yielded a t value of 3.2 or above in auditory areas. During recovery, significant activations were present bilaterally in the HG and PT as well as in the superior temporal gyrus and sulcus (3.2 ≤ t ≤ 7.4; P  < 0.01). The VOIs showed no residual activity during anesthesia (one-sample t  tests, P  ≥ 0.2).
Table 3. Words–Scrambled Words 
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Table 3. Words–Scrambled Words 
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Fig. 4. Group average responses for words–scrambled words during recovery. Activation t maps overlaid over average anatomical image in standard stereotaxic space. The  right side  of the images corresponds to the subjects' right side.  Line diagrams  show mean ± SE of signal magnitude in volume of interest centered on selected voxels (x, y, z coordinates indicated above graph). The y and z values in  white  are the Talairach coordinates of the slices; t values are revealed by  color scale  . The  dashed yellow line  shows the section plane of the other view. ANES = anesthesia; BASE = baseline; BOLD = blood oxygen dependent level; PT = planum temporale; RECO = recovery; SEDA = sedation; STS = superior temporal sulcus. 
Fig. 4. Group average responses for words–scrambled words during recovery. Activation t maps overlaid over average anatomical image in standard stereotaxic space. The  right side  of the images corresponds to the subjects' right side.  Line diagrams  show mean ± SE of signal magnitude in volume of interest centered on selected voxels (x, y, z coordinates indicated above graph). The y and z values in  white  are the Talairach coordinates of the slices; t values are revealed by  color scale  . The  dashed yellow line  shows the section plane of the other view. ANES = anesthesia; BASE = baseline; BOLD = blood oxygen dependent level; PT = planum temporale; RECO = recovery; SEDA = sedation; STS = superior temporal sulcus. 
Fig. 4. Group average responses for words–scrambled words during recovery. Activation t maps overlaid over average anatomical image in standard stereotaxic space. The  right side  of the images corresponds to the subjects' right side.  Line diagrams  show mean ± SE of signal magnitude in volume of interest centered on selected voxels (x, y, z coordinates indicated above graph). The y and z values in  white  are the Talairach coordinates of the slices; t values are revealed by  color scale  . The  dashed yellow line  shows the section plane of the other view. ANES = anesthesia; BASE = baseline; BOLD = blood oxygen dependent level; PT = planum temporale; RECO = recovery; SEDA = sedation; STS = superior temporal sulcus. 
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However, during anesthesia, there was a significant negative activation (i.e.  , scrambled words eliciting more activity than the normal words) in the right (t =−4.6; P  < 0.01, two-tailed) and left PT (t =−3.7; P  = 0.01, two-tailed; fig. 5).
Fig. 5. Group average responses for words–scrambled words during anesthesia showing bilateral negative activations in PT. Activation t maps overlaid over average anatomical image in standard stereotaxic space. The  right side  of the images corresponds to the subjects' right side.  Line diagrams  show mean ± SE of signal magnitude in volume of interest centered on selected voxels (x, y, z coordinates indicated above graph). The y and z values in  white  are the Talairach coordinates of the slices; t values are revealed by  color scale  , which is inverted with  blue  corresponding to highest significance. The  dashed yellow line  shows the section plane of the other view. ANES = anesthesia; BASE = baseline; BOLD = blood oxygen dependent level; PT = planum temporale; RECO = recovery; SEDA = sedation. 
Fig. 5. Group average responses for words–scrambled words during anesthesia showing bilateral negative activations in PT. Activation t maps overlaid over average anatomical image in standard stereotaxic space. The  right side  of the images corresponds to the subjects' right side.  Line diagrams  show mean ± SE of signal magnitude in volume of interest centered on selected voxels (x, y, z coordinates indicated above graph). The y and z values in  white  are the Talairach coordinates of the slices; t values are revealed by  color scale  , which is inverted with  blue  corresponding to highest significance. The  dashed yellow line  shows the section plane of the other view. ANES = anesthesia; BASE = baseline; BOLD = blood oxygen dependent level; PT = planum temporale; RECO = recovery; SEDA = sedation. 
Fig. 5. Group average responses for words–scrambled words during anesthesia showing bilateral negative activations in PT. Activation t maps overlaid over average anatomical image in standard stereotaxic space. The  right side  of the images corresponds to the subjects' right side.  Line diagrams  show mean ± SE of signal magnitude in volume of interest centered on selected voxels (x, y, z coordinates indicated above graph). The y and z values in  white  are the Talairach coordinates of the slices; t values are revealed by  color scale  , which is inverted with  blue  corresponding to highest significance. The  dashed yellow line  shows the section plane of the other view. ANES = anesthesia; BASE = baseline; BOLD = blood oxygen dependent level; PT = planum temporale; RECO = recovery; SEDA = sedation. 
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Vocal versus  Nonvocal Sounds
This contrast yielded significant (P  < 0.01 uncorrected) activations during baseline in the PT and bilaterally. During sedation, significant (t = 3.2; P  < 0.01) activations persisted bilaterally in the superior temporal sulcus. These activations did not persist during anesthesia. During recovery, there were significant bilateral activations (3.2 ≤ t ≤ 6.0; P  < 0.01) in the PT and upper bank of the superior temporal sulcus as expected (table 4and fig. 6). The VOIs showed no residual activity during anesthesia (one-sample t  tests, P  ≥ 0.2).
Table 4. Vocal–Nonvocal Sounds 
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Table 4. Vocal–Nonvocal Sounds 
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Fig. 6. Group average responses for vocal–nonvocal sounds during recovery. Activation t maps overlaid over average anatomical image in standard stereotaxic space. The  right side  of the images corresponds to the subjects' right side.  Line diagrams  show mean ± SE of signal magnitude in volume of interest centered on selected voxels (x, y, z coordinates indicated above graph). The y and z values in  white  are the Talairach coordinates of the slices; t values are revealed by  color scale  . The  dashed yellow line  shows the section plane of the other view. ANES = anesthesia; BASE = baseline; BOLD = blood oxygen dependent level; PT = planum temporale; RECO = recovery; SEDA = sedation; STS = superior temporal sulcus. 
Fig. 6. Group average responses for vocal–nonvocal sounds during recovery. Activation t maps overlaid over average anatomical image in standard stereotaxic space. The  right side  of the images corresponds to the subjects' right side.  Line diagrams  show mean ± SE of signal magnitude in volume of interest centered on selected voxels (x, y, z coordinates indicated above graph). The y and z values in  white  are the Talairach coordinates of the slices; t values are revealed by  color scale  . The  dashed yellow line  shows the section plane of the other view. ANES = anesthesia; BASE = baseline; BOLD = blood oxygen dependent level; PT = planum temporale; RECO = recovery; SEDA = sedation; STS = superior temporal sulcus. 
Fig. 6. Group average responses for vocal–nonvocal sounds during recovery. Activation t maps overlaid over average anatomical image in standard stereotaxic space. The  right side  of the images corresponds to the subjects' right side.  Line diagrams  show mean ± SE of signal magnitude in volume of interest centered on selected voxels (x, y, z coordinates indicated above graph). The y and z values in  white  are the Talairach coordinates of the slices; t values are revealed by  color scale  . The  dashed yellow line  shows the section plane of the other view. ANES = anesthesia; BASE = baseline; BOLD = blood oxygen dependent level; PT = planum temporale; RECO = recovery; SEDA = sedation; STS = superior temporal sulcus. 
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Recovery versus  Baseline
Because the t maps for the above three contrasts unexpectedly showed greater activation during recovery than baseline, we obtained additional t maps to directly compare recovery with baseline. The results revealed numerous areas, mainly in the temporal cortices, where activation was greater (3.3 ≤ t ≤ 7.8; P  < 0.01) during recovery (table 5).
Table 5. Recovery–Baseline 
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Table 5. Recovery–Baseline 
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Correlation with Recognition Performance
There was a significant (t ≥ 4.6; P  < 0.01, corrected) correlation between recognition performance and activation in the right and left PTs across all four conditions, indicating that higher BOLD signal in this region was associated with better recognition (fig. 7).
Fig. 7. Group average response showing correlation t map for all sounds–silence as function of recognition memory performance. Activation t maps overlaid over average anatomical image in standard stereotaxic space. The  right side  of the images corresponds to the subjects' right side. The y and z values in  white  are the Talairach coordinates of the slices; t values are revealed by  color scale  . The  dashed yellow line  shows the section plane of the other view. 
Fig. 7. Group average response showing correlation t map for all sounds–silence as function of recognition memory performance. Activation t maps overlaid over average anatomical image in standard stereotaxic space. The  right side  of the images corresponds to the subjects' right side. The y and z values in  white  are the Talairach coordinates of the slices; t values are revealed by  color scale  . The  dashed yellow line  shows the section plane of the other view. 
Fig. 7. Group average response showing correlation t map for all sounds–silence as function of recognition memory performance. Activation t maps overlaid over average anatomical image in standard stereotaxic space. The  right side  of the images corresponds to the subjects' right side. The y and z values in  white  are the Talairach coordinates of the slices; t values are revealed by  color scale  . The  dashed yellow line  shows the section plane of the other view. 
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Discussion
The first significant finding of this study is that propofol reduced but did not abolish BOLD auditory cortical activation. Both primary and secondary auditory cortex remained clearly responsive to auditory stimulation during anesthesia, but with a reduction in magnitude of 42% (HG) and 50% (PT) (fig. 3). These observations show that the state of complete oblivion produced by propofol does not require complete suppression of neural activity in secondary cortical areas.
Our results contrast with those of Heinke et al.  ,16 who did not observe any speech-related activation during general anesthesia with propofol. Their negative finding is perhaps accounted for by a reduction of the dynamic range of the fMRI signal caused by noise from the scanner.18,29 Our results are similar to those of Kerssens et al.  ,15 who reported residual BOLD activations in response to words during 1.0% end-tidal sevoflurane.
The second significant finding is that higher-level processing for speech and voice is abolished during anesthesia. The mean BOLD signal amplitude during anesthesia for speech-specific (fig. 4) and voice-specific (fig. 6) activations was near zero. Cortical areas outside of primary and adjacent regions in the PT, which normally respond in a specific fashion to words22,30 and voices,21 did not discriminate between the target and control stimuli during anesthesia. These results indicate that mainly nonspecific cortical activity remains during anesthesia. Similarly, Pack et al.  31 observed that single neurons in the middle temporal visual cortical area of macaque monkeys lose the ability to integrate conflicting local motion signals during anesthesia with isoflurane, despite intact directional tuning characteristics.
The observation that scrambled words produced more  activation that normal words in the PT bilaterally during anesthesia (fig. 5) was unexpected. This finding contrasts with the vast neuroimaging literature32 that has identified cortical areas that consistently show greater activation after language-specific stimuli than after appropriate control stimuli. The larger activation produced by scrambled words during anesthesia shows, however, that the anesthetized brain may respond differentially but atypically to complex stimuli depending on their structure. Therefore, the absence of cognitive processing that is the hallmark of general anesthesia does not require the complete suppression of differentiated activity in cortical association areas.
The absence of clear speech-specific activations during sedation does not rule out the possibility that residual activity was present. The preserved ability of the subjects to follow verbal commands provides evidence of speech processing during sedation. The lack of significant speech-related activation can be attributed to low signal-to-noise resulting from propofol-induced reduction of signal strength, interference by clinical monitoring devices, and possibly increased motion artifacts. Another factor that may have reduced signal strength is the presentation of only one word (repeated six times) within each block, a strategy that we adopted to facilitate memorization. Blocks made of six different words would have yielded greater activations. On the other hand, the fact that a significant but atypical response to the scrambled words was detected during the fully anesthetized state (fig. 5) suggests that neither insufficient sampling nor movement artifact was a factor during anesthesia, strengthening our conclusion that the normal specificity of auditory cortex to speech and voice is abolished during propofol anesthesia.
Can the absence of speech-specific activations (and explicit memory) during the sedation period be explained by the subject's having fallen asleep? We believe that this explanation is unlikely. First, it is difficult to fall asleep in the cramped and noisy scanner environment. Second, the subjects were closely monitored, and at no time did we have the impression that they were asleep or that we had awakened them. Third, when the subject arrives for testing, we routinely inquire about personal events in the preceding 24 h, including duration and quality of sleep. No subject reported sleep problems. Fourth, natural sleep alone does not abolish auditory activation by complex stimuli.33,34 
What are the mechanisms by which propofol interferes with higher-level analysis? Potentiation of the γ-aminobutyric acid type A receptor is the most plausible mechanism of action for propofol and other general anesthetics.35 Anesthesia is associated with decreased spontaneous activity in the primary auditory cortex with a predominance of narrowly frequency-tuned units that reveal tonotopy more clearly than in awake animals.2,36 Anesthetics seem to reinforce inhibitory mechanisms, thereby decreasing spontaneous activity and suppressing evoked activity of neurons that are synaptically distant from direct thalamic input.2 Therefore, anesthetics could potentiate γ-aminobutyric acid–mediated inhibition at multiple levels of the ascending auditory pathways,37 including the auditory thalamus and cortex.2,38,39 This model would be consistent with our observations.
A third significant finding is that the area most highly correlated with recognition memory was the left PT (fig. 7), although a bilateral effect was observed. This finding is consistent with the role of left perisylvian cortex in speech processing and suggests that successful recognition memory was largely accounted for by the degree to which the stimuli were processed by specialized speech decoding mechanisms at the time of presentation. Because this process was abolished during anesthesia, as indexed by low or absent BOLD signal, later recognition was impossible. The residual activation in primary regions during anesthesia was evidently insufficient to support formation of any memory traces.
The absence of explicit memory during sedation is surprising because we would have predicted a recognition rate near 50% based on the propofol concentration.40 It is of course possible that implicit memory was present and that our recognition procedure was insufficient to demonstrate it. However, a forced-choice task was used, and responses were indistinguishable from chance, suggesting that little if any memory trace remained. The absence of recognition during sedation may be explained by differences in experimental conditions during encoding (number of words, number of repetitions, depth of processing) or the retention phase (subsequent exposure to two other lists of words and to hypnotic concentration of propofol). Based on the current data, this amnesic effect would seem to be linked to the disruption of perceptual processes, rather than encoding or consolidation processes.
A fourth significant finding is that the activation levels during recovery were much higher than during sedation despite similar propofol concentrations (table 1). We think that the most likely explanation is acute tolerance to propofol, a phenomenon that has also been reported with rats.41,42 Therefore, the level of BOLD signal activity would seem to constitute a better index of conscious processing than blood concentration of anesthetic agent.
Czisch et al.  33 reported that non–rapid eye movement sleep reduces but does not abolish BOLD activations induced in the auditory cortices by complex auditory stimuli (tape recordings of Mark Twain novels), a finding that resembles our observations. By contrast, Portas et al.  34 observed no change in auditory cortical activation during non–rapid eye movement sleep using pure tones and the subject's first name. However, they observed reduced activations during sleep in the thalamus and cortical areas, including the prefrontal and left parietal cortex. Auditory stimulation (95-dB clicks) activated bilateral primary, but not associative, auditory cortices in neurovegetative patients,43 suggesting that the neurovegetative state is associated with a more severe disruption of sensory processing than anesthesia with propofol.
Finally, the current findings serve to illuminate the neural changes associated with pharmacologic alterations of consciousness in humans. The data indicate that one prominent characteristic of loss of consciousness induced by propofol is that specialized, higher-order processing areas that normally respond differentially to certain classes of stimuli no longer do so. Instead, a generalized but attenuated response in primary and adjacent regions persists, as well as a paradoxical response to scrambled words. These data therefore indicate that although not all cortical responses are abolished in the unconscious state, the highly differentiated neural processes whose outcome leads to conscious perception either are deprived of their normal input or are unable to perform their normal computations. The outcome, then, is that the normal pathways for processing that eventually lead to formation of percepts are not operative, which in turn contributes to what we experience as a loss of consciousness. Whether similar events occur with other anesthetic drugs deserves inquiry.
The authors thank Louise Ullyatt, R.N. (Department of Anesthesia, McGill University, Montreal, Quebec, Canada), and Chantale Porlier (EEG Technician, Department of Anesthesia, McGill University), for assistance with subject recruitment, anesthetic care, and testing; Bruce Pike, Ph.D. (Director), André Cormier (Chief Radiology Technician), and the staff of the McConnell Brain Imaging Center, McGill University, for help and support; Marc Bouffard (Research Assistant, Department of Neurology and Neurosurgery, McGill University) for help with data analysis; and the staff of the Anesthesia Recovery Room for care provided to the subjects.
References
Heier T, Steen PA: Assessment of anaesthesia depth (review article). Acta Anaesthesiol Scand 1996; 40:1087–100Heier, T Steen, PA
deRibaupierre F: Acoustical information processing in the auditory thalamus and cerebral cortex, The Central Auditory System. Edited by Ehret G, Romand R. New York, Oxford University Press, 1997, pp 317–97deRibaupierre, F Ehret G, Romand R New York Oxford University Press
Ehret E: The auditory cortex. J Comp Physiol A 1997; 181:547–57Ehret, E
Eggermont JJ: Representation of spectral and temporal sound features in three cortical fields of the cat: Similarities outweigh differences. J Neurophysiol 1998; 80:2743–64Eggermont, JJ
Picton TW, Alain C, Woods DL, John MS, Scherg M, Valdes-Sosa P, Bosch-Bayard J, Trujillo NJ: Intracerebral sources of human auditory-evoked potentials. Audiol Neurootol 1999; 4:64–79Picton, TW Alain, C Woods, DL John, MS Scherg, M Valdes-Sosa, P Bosch-Bayard, J Trujillo, NJ
Plourde G, Picton TW: Long-latency auditory evoked potentials during general anesthesia: N1 and P3 components. Anesth Analg 1991; 72:342–50Plourde, G Picton, TW
Howard MA, Volkov IO, Mirsky R, Garell PC, Noh MD, Granner M, Damasio H, Steinschneider M, Reale RA, Hind JE, Brugge JF: Auditory cortex on the human posterior superior temporal gyrus. J Comp Neurol 2000; 416:79–92Howard, MA Volkov, IO Mirsky, R Garell, PC Noh, MD Granner, M Damasio, H Steinschneider, M Reale, RA Hind, JE Brugge, JF
French JD, Verzeano M, Magoun HW: A neural basis of the anesthetic state. Arch Neurol Psychiatr 1953; 69:519–29French, JD Verzeano, M Magoun, HW
Clark DL, Rosner BS: Neurophysiologic effects of general anesthetics: I. The electroencephalogram and sensory evoked responses in man (review article). Anesthesiology 1973; 38:564–82Clark, DL Rosner, BS
Ypparila H, Karhu J, Westeren-Punnonen S, Musialowicz T, Partanen J: Evidence of auditory processing during postoperative propofol sedation. Clin Neurophysiol 2002; 113:1357–64Ypparila, H Karhu, J Westeren-Punnonen, S Musialowicz, T Partanen, J
van Hooff JC, de Beer NA, Brunia CH, Cluitmans PJ, Korsten HH: Event-related potential measures of information processing during general anesthesia. Electroencephalogr Clin Neurophysiol 1997; 103:268–81van Hooff, JC de Beer, NA Brunia, CH Cluitmans, PJ Korsten, HH
Simpson TP, Manara AR, Kane NM, Barton RL, Rowlands CA, Butler SR: Effect of propofol anaesthesia on the event-related potential mismatch negativity and the auditory-evoked potential N1. Br J Anaesth 2002; 89:382–8Simpson, TP Manara, AR Kane, NM Barton, RL Rowlands, CA Butler, SR
Naatanen R: The perception of speech sounds by the human brain as reflected by the mismatch negativity (MMN) and its magnetic equivalent (MMNm). Psychophysiology 2001; 38:1–21Naatanen, R
Van HT, Fraysse B, Berry I, Berges C, Deguine O, Honegger A, Sevely A, Ibarrola D: Functional magnetic resonance imaging may avoid misdiagnosis of cochleovestibular nerve aplasia in congenital deafness. Am J Otol 2000; 21:663–70Van, HT Fraysse, B Berry, I Berges, C Deguine, O Honegger, A Sevely, A Ibarrola, D
Kerssens C, Hamann S, Peltier S, Hu XP, Byas-Smith MG, Sebel PS: Attenuated brain response to auditory word stimulation with sevoflurane: A functional magnetic resonance imaging study in humans. Anesthesiology 2005; 103:11–9Kerssens, C Hamann, S Peltier, S Hu, XP Byas-Smith, MG Sebel, PS
Heinke W, Fiebach CJ, Schwarzbauer C, Meyer M, Olthoff D, Alter K: Sequential effects of propofol on functional brain activation induced by auditory language processing: An event-related functional magnetic resonance imaging study. Br J Anaesth 2004; 92:641–50Heinke, W Fiebach, CJ Schwarzbauer, C Meyer, M Olthoff, D Alter, K
Dueck MH, Petzke F, Gerbershagen HJ, Paul M, Hesselmann V, Girnus R, Krug B, Sorger B, Goebel R, Lehrke R, Sturm V, Boerner U: Propofol attenuates responses of the auditory cortex to acoustic stimulation in a dose-dependent manner: A FMRI study. Acta Anaesthesiol Scand 2005; 49:784–91Dueck, MH Petzke, F Gerbershagen, HJ Paul, M Hesselmann, V Girnus, R Krug, B Sorger, B Goebel, R Lehrke, R Sturm, V Boerner, U
Shah N, Steinhoff S, Mirzazade S, Zafiris O, Grosse-Ruyken M-L, Jancke L, Zilles K: The effect of sequence repeat time on auditory cortex stimulation during phonetic discrimination. Neuroimage 2000; 12:100–8Shah, N Steinhoff, S Mirzazade, S Zafiris, O Grosse-Ruyken, ML Jancke, L Zilles, K
Belin P, Zatorre RJ, Hoge R, Evans AC, Pike B: Event-related fMRI of the auditory cortex. Neuroimage 1999; 10:417–29Belin, P Zatorre, RJ Hoge, R Evans, AC Pike, B
Hall DA, Haggard MP, Akeroyd MA, Palmer AR, Summerfield AQ, Elliott MR, Gurney EM, Bowtell RW: “Sparse” temporal sampling in auditory fMRI. Hum Brain Mapp 1999; 7:213–23Hall, DA Haggard, MP Akeroyd, MA Palmer, AR Summerfield, AQ Elliott, MR Gurney, EM Bowtell, RW
Belin P, Zatorre RJ, Lafaille P, Ahad P, Pike B: Voice-selective areas in human auditory cortex. Nature 2000; 403:309–12Belin, P Zatorre, RJ Lafaille, P Ahad, P Pike, B
Binder JR, Frost JA, Hammeke TA, Bellgowan PSF, Springer JA, Kaufman JN, Possing ET: Human temporal lobe activation by speech and nonspeech sounds. Cereb Cortex 2000; 10:512–28Binder, JR Frost, JA Hammeke, TA Bellgowan, PSF Springer, JA Kaufman, JN Possing, ET
Logothetis NK: The underpinnings of the BOLD functional magnetic resonance imaging signal. J Neurosci 2003; 23:3963–71Logothetis, NK
Tackley RM, Lewis GTR, Prys-Roberts C, Boaden RW, Dixon J, Harvey JT: Computer controlled infusion of propofol. Br J Anaesth 1989; 62:46–53Tackley, RM Lewis, GTR Prys-Roberts, C Boaden, RW Dixon, J Harvey, JT
Plummer GF: Improved method for the determination of propofol in blood by HPLC with fluorescence detection. J Chromatogr 1987; 421:171–6Plummer, GF
Talairach J, Tournoux P: Co-planar Stereotactic Atlas of the Human Brain. New York, Thieme, 1988Talairach, J Tournoux, P New York Thieme
Collins DL, Neelin P, Peters TM, Evans AC: Automatic 3D intersubject registration of MR volumetric data in standardized Talairach space. J Comput Assist Tomogr 1994; 18:192–205Collins, DL Neelin, P Peters, TM Evans, AC
Worsley KJ, Liao CH, Aston J, Petre V, Duncan GH, Morales F, Evans AC: A general statistical analysis for fMRI data. Neuroimage 2002; 15:1–15Worsley, KJ Liao, CH Aston, J Petre, V Duncan, GH Morales, F Evans, AC
Talavage TM, Edmister WB, Ledden PJ, Weisskoff RM: Quantitative assessment of auditory cortex responses induced by imager acoustic noise. Hum Brain Mapp 1999; 7:79–88Talavage, TM Edmister, WB Ledden, PJ Weisskoff, RM
Zatorre RJ, Evans AC, Meyer E, Gjedde A: Lateralization of phonetic and pitch discrimination in speech processing. Science 1992; 256:846–9Zatorre, RJ Evans, AC Meyer, E Gjedde, A
Pack CC, Berezovskii VK, Born RT: Dynamic properties of neurons in cortical area MT in alert and anaesthetized macaque monkeys. Nature 2001; 414:905–8Pack, CC Berezovskii, VK Born, RT
Demonet JF, Thierry G, Cardebat D: Renewal of the neurophysiology of language: functional neuroimaging. Physiol Rev 2005; 85:49–95Demonet, JF Thierry, G Cardebat, D
Czisch M, Wetter TC, Kaufmann C, Pollmacher T, Holsboer F, Auer DP: Altered processing of acoustic stimuli during sleep: Reduced auditory activation and visual deactivation detected by a combined fMRI/EEG study. Neuroimage 2002; 16:251–8Czisch, M Wetter, TC Kaufmann, C Pollmacher, T Holsboer, F Auer, DP
Portas CM, Krakow K, Allen P, Josephs O, Armony JL, Frith CD: Auditory processing across the sleep-wake cycle: simultaneous EEG and fMRI monitoring in humans. Neuron 2000; 28:991–9Portas, CM Krakow, K Allen, P Josephs, O Armony, JL Frith, CD
Franks NP, Lieb WR: Molecular and cellular mechanisms of general anaesthesia. Nature 1994; 367:607–14Franks, NP Lieb, WR
Gaese BH, Ostwald J: Anesthesia changes frequency tuning of neurons in the rat primary auditory cortex. J Neurophysiol 2001; 86:1062–6Gaese, BH Ostwald, J
Ehret G, Romand R: The Central Auditory System. New York, Oxford University Press, 1997, pp 3–96Ehret, G Romand, R New York Oxford University Press
Hefti BJ, Smith PH: Anatomy, physiology and synaptic responses of rat layer V auditory cortical cells and effects of intracellular GABAAblockade. J Neurophysiol 2000; 83:2626–38Hefti, BJ Smith, PH
Kaur S, Lazar R, Metherate R: Intracortical pathways determine breadth of subthreshold frequency receptive fields in primary auditory cortex. J Neurophysiol 2004; 91:2551–67Kaur, S Lazar, R Metherate, R
Veselis RA, Reinsel RA, Feshchenko VA, Wronski M: The comparative amnestic effects of midazolam, propofol, thiopental, and fentanyl at equisedative concentrations. Anesthesiology 1997; 87:749–64Veselis, RA Reinsel, RA Feshchenko, VA Wronski, M
Ihmsen H, Tzabazis A, Schywalsky M, Schwilden H: Propofol in rats: Testing for nonlinear pharmacokinetics and modelling acute tolerance to EEG effects. Eur J Anaesthesiol 2002; 19:177–88Ihmsen, H Tzabazis, A Schywalsky, M Schwilden, H
Larsson JE, Wahlstrom G: Age-dependent development of acute tolerance to propofol and its distribution in a pharmacokinetic compartment-independent rat model. Acta Anaesthesiol Scand 1996; 40:734–40Larsson, JE Wahlstrom, G
Laureys S, Faymonville M-E, Degueldre C, Del Fiore G, Damas P, Lambermont B, Janssens N, Aerts J, Franck G, Luxen A, Moonen G, Lamy M, Maquet P: Auditory processing in the vegetative state. Brain 2000; 123:1589–601Laureys, S Faymonville, ME Degueldre, C Del Fiore, G Damas, P Lambermont, B Janssens, N Aerts, J Franck, G Luxen, A Moonen, G Lamy, M Maquet, P
Fig. 1. Functional magnetic resonance imaging (MRI) protocol. Each period comprised 128 trials of different stimulus types including interposed silence (  top row  ). Each trial lasted 10 s for presentation of six stimuli (stim) of the same category with a fixed 1.5-s interval between onsets or of silence. The  hatched rectangle  stands for functional MRI image acquisition. Scr = scrambled. 
Fig. 1. Functional magnetic resonance imaging (MRI) protocol. Each period comprised 128 trials of different stimulus types including interposed silence (  top row  ). Each trial lasted 10 s for presentation of six stimuli (stim) of the same category with a fixed 1.5-s interval between onsets or of silence. The  hatched rectangle  stands for functional MRI image acquisition. Scr = scrambled. 
Fig. 1. Functional magnetic resonance imaging (MRI) protocol. Each period comprised 128 trials of different stimulus types including interposed silence (  top row  ). Each trial lasted 10 s for presentation of six stimuli (stim) of the same category with a fixed 1.5-s interval between onsets or of silence. The  hatched rectangle  stands for functional MRI image acquisition. Scr = scrambled. 
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Fig. 2. Recognition memory. Number of items recognized for anesthetized and control subjects exposed to the same stimuli under similar conditions. Data are mean ± SE. Chance level denoted by  dashed line  .ANES = anesthesia; BASE = baseline; RECO = recovery; SEDA = sedation. 
Fig. 2. Recognition memory. Number of items recognized for anesthetized and control subjects exposed to the same stimuli under similar conditions. Data are mean ± SE. Chance level denoted by  dashed line  .ANES = anesthesia; BASE = baseline; RECO = recovery; SEDA = sedation. 
Fig. 2. Recognition memory. Number of items recognized for anesthetized and control subjects exposed to the same stimuli under similar conditions. Data are mean ± SE. Chance level denoted by  dashed line  .ANES = anesthesia; BASE = baseline; RECO = recovery; SEDA = sedation. 
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Fig. 3. Group average responses for all sounds–silence. Activation t maps overlaid over average anatomical image in standard stereotaxic space. The  right side  of the images corresponds to the subjects' right side.  Line diagrams  show mean ± SE of signal magnitude (difference in effect size between the two conditions,  i.e.  , sound  vs.  silence) in volume of interest centered on selected voxels (x, y, z coordinates indicated above graph). The y and z values on the  far right  are the Talairach coordinates of the slices; t values are revealed by  color scale  ;values above upper limit are shown in  white  .ANES = anesthesia; BASE = baseline; BOLD = blood oxygen dependent level; HG = Heschl gyrus; PT = planum temporale; RECO = recovery; SEDA = sedation. 
Fig. 3. Group average responses for all sounds–silence. Activation t maps overlaid over average anatomical image in standard stereotaxic space. The  right side  of the images corresponds to the subjects' right side.  Line diagrams  show mean ± SE of signal magnitude (difference in effect size between the two conditions,  i.e.  , sound  vs.  silence) in volume of interest centered on selected voxels (x, y, z coordinates indicated above graph). The y and z values on the  far right  are the Talairach coordinates of the slices; t values are revealed by  color scale  ;values above upper limit are shown in  white  .ANES = anesthesia; BASE = baseline; BOLD = blood oxygen dependent level; HG = Heschl gyrus; PT = planum temporale; RECO = recovery; SEDA = sedation. 
Fig. 3. Group average responses for all sounds–silence. Activation t maps overlaid over average anatomical image in standard stereotaxic space. The  right side  of the images corresponds to the subjects' right side.  Line diagrams  show mean ± SE of signal magnitude (difference in effect size between the two conditions,  i.e.  , sound  vs.  silence) in volume of interest centered on selected voxels (x, y, z coordinates indicated above graph). The y and z values on the  far right  are the Talairach coordinates of the slices; t values are revealed by  color scale  ;values above upper limit are shown in  white  .ANES = anesthesia; BASE = baseline; BOLD = blood oxygen dependent level; HG = Heschl gyrus; PT = planum temporale; RECO = recovery; SEDA = sedation. 
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Fig. 4. Group average responses for words–scrambled words during recovery. Activation t maps overlaid over average anatomical image in standard stereotaxic space. The  right side  of the images corresponds to the subjects' right side.  Line diagrams  show mean ± SE of signal magnitude in volume of interest centered on selected voxels (x, y, z coordinates indicated above graph). The y and z values in  white  are the Talairach coordinates of the slices; t values are revealed by  color scale  . The  dashed yellow line  shows the section plane of the other view. ANES = anesthesia; BASE = baseline; BOLD = blood oxygen dependent level; PT = planum temporale; RECO = recovery; SEDA = sedation; STS = superior temporal sulcus. 
Fig. 4. Group average responses for words–scrambled words during recovery. Activation t maps overlaid over average anatomical image in standard stereotaxic space. The  right side  of the images corresponds to the subjects' right side.  Line diagrams  show mean ± SE of signal magnitude in volume of interest centered on selected voxels (x, y, z coordinates indicated above graph). The y and z values in  white  are the Talairach coordinates of the slices; t values are revealed by  color scale  . The  dashed yellow line  shows the section plane of the other view. ANES = anesthesia; BASE = baseline; BOLD = blood oxygen dependent level; PT = planum temporale; RECO = recovery; SEDA = sedation; STS = superior temporal sulcus. 
Fig. 4. Group average responses for words–scrambled words during recovery. Activation t maps overlaid over average anatomical image in standard stereotaxic space. The  right side  of the images corresponds to the subjects' right side.  Line diagrams  show mean ± SE of signal magnitude in volume of interest centered on selected voxels (x, y, z coordinates indicated above graph). The y and z values in  white  are the Talairach coordinates of the slices; t values are revealed by  color scale  . The  dashed yellow line  shows the section plane of the other view. ANES = anesthesia; BASE = baseline; BOLD = blood oxygen dependent level; PT = planum temporale; RECO = recovery; SEDA = sedation; STS = superior temporal sulcus. 
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Fig. 5. Group average responses for words–scrambled words during anesthesia showing bilateral negative activations in PT. Activation t maps overlaid over average anatomical image in standard stereotaxic space. The  right side  of the images corresponds to the subjects' right side.  Line diagrams  show mean ± SE of signal magnitude in volume of interest centered on selected voxels (x, y, z coordinates indicated above graph). The y and z values in  white  are the Talairach coordinates of the slices; t values are revealed by  color scale  , which is inverted with  blue  corresponding to highest significance. The  dashed yellow line  shows the section plane of the other view. ANES = anesthesia; BASE = baseline; BOLD = blood oxygen dependent level; PT = planum temporale; RECO = recovery; SEDA = sedation. 
Fig. 5. Group average responses for words–scrambled words during anesthesia showing bilateral negative activations in PT. Activation t maps overlaid over average anatomical image in standard stereotaxic space. The  right side  of the images corresponds to the subjects' right side.  Line diagrams  show mean ± SE of signal magnitude in volume of interest centered on selected voxels (x, y, z coordinates indicated above graph). The y and z values in  white  are the Talairach coordinates of the slices; t values are revealed by  color scale  , which is inverted with  blue  corresponding to highest significance. The  dashed yellow line  shows the section plane of the other view. ANES = anesthesia; BASE = baseline; BOLD = blood oxygen dependent level; PT = planum temporale; RECO = recovery; SEDA = sedation. 
Fig. 5. Group average responses for words–scrambled words during anesthesia showing bilateral negative activations in PT. Activation t maps overlaid over average anatomical image in standard stereotaxic space. The  right side  of the images corresponds to the subjects' right side.  Line diagrams  show mean ± SE of signal magnitude in volume of interest centered on selected voxels (x, y, z coordinates indicated above graph). The y and z values in  white  are the Talairach coordinates of the slices; t values are revealed by  color scale  , which is inverted with  blue  corresponding to highest significance. The  dashed yellow line  shows the section plane of the other view. ANES = anesthesia; BASE = baseline; BOLD = blood oxygen dependent level; PT = planum temporale; RECO = recovery; SEDA = sedation. 
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Fig. 6. Group average responses for vocal–nonvocal sounds during recovery. Activation t maps overlaid over average anatomical image in standard stereotaxic space. The  right side  of the images corresponds to the subjects' right side.  Line diagrams  show mean ± SE of signal magnitude in volume of interest centered on selected voxels (x, y, z coordinates indicated above graph). The y and z values in  white  are the Talairach coordinates of the slices; t values are revealed by  color scale  . The  dashed yellow line  shows the section plane of the other view. ANES = anesthesia; BASE = baseline; BOLD = blood oxygen dependent level; PT = planum temporale; RECO = recovery; SEDA = sedation; STS = superior temporal sulcus. 
Fig. 6. Group average responses for vocal–nonvocal sounds during recovery. Activation t maps overlaid over average anatomical image in standard stereotaxic space. The  right side  of the images corresponds to the subjects' right side.  Line diagrams  show mean ± SE of signal magnitude in volume of interest centered on selected voxels (x, y, z coordinates indicated above graph). The y and z values in  white  are the Talairach coordinates of the slices; t values are revealed by  color scale  . The  dashed yellow line  shows the section plane of the other view. ANES = anesthesia; BASE = baseline; BOLD = blood oxygen dependent level; PT = planum temporale; RECO = recovery; SEDA = sedation; STS = superior temporal sulcus. 
Fig. 6. Group average responses for vocal–nonvocal sounds during recovery. Activation t maps overlaid over average anatomical image in standard stereotaxic space. The  right side  of the images corresponds to the subjects' right side.  Line diagrams  show mean ± SE of signal magnitude in volume of interest centered on selected voxels (x, y, z coordinates indicated above graph). The y and z values in  white  are the Talairach coordinates of the slices; t values are revealed by  color scale  . The  dashed yellow line  shows the section plane of the other view. ANES = anesthesia; BASE = baseline; BOLD = blood oxygen dependent level; PT = planum temporale; RECO = recovery; SEDA = sedation; STS = superior temporal sulcus. 
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Fig. 7. Group average response showing correlation t map for all sounds–silence as function of recognition memory performance. Activation t maps overlaid over average anatomical image in standard stereotaxic space. The  right side  of the images corresponds to the subjects' right side. The y and z values in  white  are the Talairach coordinates of the slices; t values are revealed by  color scale  . The  dashed yellow line  shows the section plane of the other view. 
Fig. 7. Group average response showing correlation t map for all sounds–silence as function of recognition memory performance. Activation t maps overlaid over average anatomical image in standard stereotaxic space. The  right side  of the images corresponds to the subjects' right side. The y and z values in  white  are the Talairach coordinates of the slices; t values are revealed by  color scale  . The  dashed yellow line  shows the section plane of the other view. 
Fig. 7. Group average response showing correlation t map for all sounds–silence as function of recognition memory performance. Activation t maps overlaid over average anatomical image in standard stereotaxic space. The  right side  of the images corresponds to the subjects' right side. The y and z values in  white  are the Talairach coordinates of the slices; t values are revealed by  color scale  . The  dashed yellow line  shows the section plane of the other view. 
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Table 1. Clinical Parameters 
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Table 1. Clinical Parameters 
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Table 2. All Sounds–Silence 
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Table 2. All Sounds–Silence 
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Table 2. (  Continued  ) 
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Table 2. (  Continued  ) 
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Table 3. Words–Scrambled Words 
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Table 3. Words–Scrambled Words 
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Table 4. Vocal–Nonvocal Sounds 
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Table 4. Vocal–Nonvocal Sounds 
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Table 5. Recovery–Baseline 
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Table 5. Recovery–Baseline 
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