Article Figures & Data
Figures
- Figure 1.
Conscious responsiveness schematic. Sensory input results in purposeful behavioral output only when all aspects of conscious information processing (A, conscious state; B, awareness and comprehension of the stimulus) and motor readiness (C, will and intention to respond; D, ability to respond) are functional. Arrows represent signal processing in different consciousness states: 1, all stimuli blocked from reaching consciousness (deep anesthesia or brain death); 2, dreaming during sleep or anesthesia, surrounding stimuli may (but not necessarily) (slashed arrow) influence dream content; 3, deficient will to act (e.g., anterior cingulate lesion) (Crick, 1994); 4, inability to respond regardless of total awareness (e.g., awareness during anesthesia); 5, commands lead to purposeful responses (normal waking consciousness).
- Figure 2.
Neural correlates associated with the ROC during constant dose dexmedetomidine anesthesia. a, LV1 design score pattern showing changes associated with the temporary return of consciousness (p < 0.0001). b, PLS singular image (positive salience; top, sagittal; bottom, axial) of LV1 (p < 0.001) projected on SPM-8 glass brain template. c, Sagittal (top) and axial (bottom) sections showing cingulate (i), thalamus (ii), inferior parietal cortex (iii), and brainstem activations. d, Cortical renderings showing parietal (iii) and frontal activations. e, Voxel intensity plots (mean ± SE) showing how i, ii, and iii follow LV1 pattern.
- Figure 3.
Consciousness-related functional connectivity differences of the right parietal cortex during constant dose dexmedetomidine anesthesia. The parietal region (x = 52, y= −52, z = 46) is functionally connected with cingulate (x = −4, y = 36, z = 20) and other ventral forebrain regions when conscious. a, Projections (top, sagittal; bottom, axial; PLS analysis results projected on SPM-8 glass brain template) showing regions significantly more correlated with the seed voxel (black dot) during consciousness. b, Renderings reveal cortical areas more connected when conscious. c, Sagittal (top) and axial (bottom) sections showing effects in cingulate, hypothalamus, and basal forebrain. d, Correlation plot showing state-related functional connectivity changes between parietal (left circle) and cingulate (right circle) activity. Linear regressions, conscious (red); unconscious (blue).
- Figure 4.
Neural correlates associated with the return of consciousness following propofol anesthesia. a, LV2 design score pattern shows changes primarily associating with ROC (p < 0.03). b, PLS singular image (positive salience; top, sagittal; bottom, axial) showing the regions associated with LV2 (p < 0.001) projected on SPM-8 glass brain template. c, Sagittal (top) and axial (bottom) sections showing activation in the ACC (i), thalamus (ii), and the brainstem (iii). d, Cortical renderings showing minimal occipital, parietal, and frontal activations at this threshold. e, Region-specific voxel intensity plots showing how i, ii, and iii follow the overall pattern of LV2 (mean ± SE).
- Figure 5.
Neural correlates associated with the return of consciousness (groups combined). a, LV2 design score pattern shows changes primarily associated with ROC (p < 0.0001). b, PLS singular image (positive salience; top, sagittal; bottom, axial) showing regions associated with LV2 (p < 0.001) projected on SPM-8 glass brain template. c, Sagittal (top) and axial (bottom) sections showing activation in the ACC (i), thalamus (ii), and the brainstem (iii) locus ceruleus/parabrachial area. d, Cortical renderings showing no activations at this threshold. e, Region-specific voxel intensity plots showing how i, ii, and iii follow the overall pattern of LV2 (mean ± SE). Abbreviations as in Figure 4.
- Figure 6.
State-related activity suppressions that follow the anesthetic dose (groups combined). a, LV1 design score pattern across the four conditions (p < 0.0001). b, PLS singular image (positive salience; top, sagittal; bottom, axial) showing regions associated with LV1 (p < 0.001) projected on SPM-8 glass brain template. c, Sagittal (top) and axial (bottom) sections showing suppression in the posterior cingulate (i), thalamus (ii), inferior parietal (iii), and frontal cortices, precuneus, and brainstem. Light blue, p < 0.001; dark blue, p < 0.0005. d, Cortical renderings showing frontal, parietal (iii) and temporal suppression. e, Voxel intensity plots (mean ± SE) showing how i, ii, and iii follow LV1 pattern. Abbreviations as in Figure 4.
Tables
- Table 1.
Calculated (with STANPUMP software) and measured drug concentrations in plasma during the neuroimaging sessions
Drug Sed LOC ROC LOC-2 Calculated Measured Calculated Measured Calculated Measured Calculated Measured Dexmedetomidine (ng/ml) 1.7 ± 0.4 2.3 ± 0.7 2.1 ± 0.6 3.2 ± 1.3 2.1 ± 0.6 3.0 ± 1.1 2.1 ± 0.7 2.8 ± 1.1 Propofol (μg/ml) 1.6 ± 0.5 1.3 ± 0.5 2.2 ± 0.6 1.8 ± 0.6 1.6 ± 0.5 0.6 ± 0.4 NA NA Sed, sedation; LOC, loss of consciousness; ROC, return of consciousness; LOC-2, second loss of consciousness (dexmedetomidine only); NA = not applicable. Data as mean ± SD.
- Table 2.
The neural correlates of the return of consciousness during constant level dexmedetomidine revealed by PLS
Brain regions Brodmann area MNI coordinates (in mm) x, y,z Cluster size (voxels) BSR p value Latent Variable 1 Positive salience—shown in Figure 2 L superior frontal gyrus 8/9/10/11 −20, 62, 20 793 17.26 <0.0001 R anterior prefrontal 10/11 36, 62, −24 834 16.0008 <0.0001 Cerebellum 0, −78, −42 8102 15.2835 <0.0001 Superior frontal gyrus 8/9/10/11 14, 70, 26 231 13.6909 <0.0001 Thalamus 10/24 −4, −14, 14 1429 10.2229 <0.0001 R superior temporal sulcus 39 68, −68, 22 219 10.0856 <0.0001 L inferior frontal gyrus 13/46/47 −36, 16, −16 850 10.0765 <0.0001 R inferior parietal 39/40 56, −68, 50 538 8.8778 <0.0001 R medial frontal gyrus 8/9 6, 36, 34 1204 7.9879 <0.0001 L superior temporal gyrus 38 −36, 14, −66 112 7.4662 <0.0001 R middle frontal gyrus 6/8/9 40, 28, 44 121 7.2273 <0.0001 Brainstem/pons 8, −36, −32 836 7.1674 <0.0001 R middle frontal gyrus 6/8/9 32, 62, 24 155 6.7936 <0.0001 R inferior frontal gyrus 13/46/47 44, 34, −14 645 6.611 <0.0001 L inferior parietal 39/40 −54, −62, 38 183 6.5215 <0.0001 L orbital gyrus 11 −14, 56, −56 890 6.5092 <0.0001 Anterior cingulate 24/32 −14, 48, −6 239 6.2658 <0.0001 R orbital gyrus 11 16, 58, −66 219 5.8429 <0.0001 L inferior frontal gyrus 13/46/47 −30, 38, −32 115 5.6669 <0.0001 L supramarginal gyrus 40 −72, −52, 28 115 5.6521 <0.0001 Negative salience L parahippocampal gyrus 20/35/36 −30, −36, −16 6488 −22.0599 <0.0001 R lingual gyrus 17/19 18, −44, −6 9395 −18.9551 <0.0001 R angular gyrus 39 34, −62, 36 2176 −18.1224 <0.0001 L inferior parietal 39/40 −36, −42, 42 2122 −14.0804 <0.0001 R middle frontal gyrus 6/8/9 46, 4, 40 1674 −13.5639 <0.0001 L postcentral gyrus 2/3/4 −12, −40, 68 1306 −6.3560 <0.0001 L lingual gyrus 17/19 −12, −92, −2 143 −4.3952 <0.0001 Corresponding clusters are shown in Figure 2. MNI, Montreal Neurological Institute; BSR, Bootstrap ratio.
- Table 3.
Right inferior parietal cortex functional connectivity changes associated with the changing state of consciousness during constant level dexmedetomidine revealed by PLS
Brain regions Brodmann area MNI coordinates (in mm) x,y,z Cluster size (voxels) BSR p value Positive correlations—shown in Figure 3 R precuneus/superior posterior parietal 7 14, −80, 56 220 4.3339 <0.0001 R anterior cingulate/medial frontal/caudate 10/24/32 10, 18, −4 3326 4.2181 <0.0001 R inferior frontal gyrus 13/46/47 52, 40, 12 207 3.5084 0.0005 R inferior temporal gyrus 20 66, −22, −22 266 3.4935 0.0005 R inferior frontal gyrus 13/46/47 24, 16, −22 333 3.4 0.0007 R middle temporal gyrus 21/37/39 46, 12, −40 106 3.3091 0.0009 R inferior occipital gyrus 52, −80, −12 106 3.2705 0.0011 Pons 10, −32, −36 124 3.1521 0.0016 Insula 13 42, 20, 10 667 3.1009 0.0019 R inferior parietal 39/40 58, −46, 52 125 3.0594 0.0022 R superior frontal gyrus 8/9/10/11 28, 44, 46 189 2.816 0.0049 R supramarginal gyrus 40 66, −48, 28 126 2.7575 0.0058 Putamen −28, 14, 2 197 2.7574 0.0058 Negative correlations R middle frontal gyrus 6/8/9 22, −12, 64 5092 −6.0758 <0.0001 L postcentral gyrus 2/3/4 −52, −18, 54 1325 −4.5581 <0.0001 R lingual gyrus 17/19 22, −104, −14 210 −3.969 0.0001 R precuneus 7 18, −52, 62 173 −3.3259 0.0009 Corresponding clusters are shown in Figure 3.
- Table 4.
The regional changes associated with the return of consciousness and the loss of consciousness observed in the combined analysis of dexmedetomidine and propofol revealed by PLS
Brain regions Brodmann area MNI coordinates (in mm) x,y,z Cluster size (voxels) BSR p value Latent variable 2 Positive salience—shown in Figure 5 Anterior cingulate/caudate/thalamus 10/24 12, 24, 16 10341 10.5547 <0.0001 R cerebellum 16, −52, −58 2694 6.0852 <0.0001 L cerebellum −12, −64, −46 669 5.0053 <0.0001 Pons 2, −12, −40 167 4.6936 <0.0001 Thalamus 10/24 26, −32, 6 123 4.0715 <0.0001 Negative salience R parahippocampal gyrus 20/35/36 24, −8, −28 5591 −16.6896 <0.0001 L parahippocampal gyrus 20/35/36 −28, −34, −18 6551 −11.0476 <0.0001 R postcentral gyrus 2/3/4 58, −20, 24 4541 −6.4574 <0.0001 R inferior parietal 39/40 42, −46, 48 270 −5.7562 <0.0001 R cuneus 17/18 6, −106, −4 462 −5.7045 <0.0001 L precentral gyrus 4/6/9 −38, 2, 36, 202 −4.6472 <0.0001 L middle temporal gyrus 21/37/39 −58, −62, −6 324 −4.6033 <0.0001 L cerebellum/culmen −4, 44, −28 123 −4.1926 <0.0001 Latent variable 1 Positive salience—shown in Figure 6 R inferior parietal/precuneus 39/40/7 52, −54, 48 9744 12.8661 <0.0001 L inferior parietal/angular gyrus 39 −48, −72, 36 4560 12.5331 <0.0001 R middle temporal gyrus 21/37/39 76, −28, −16 920 9.552 <0.0001 R cerebellum 32, −78, −50 3353 9.4273 <0.0001 L orbital gyrus 10/47 −14, 36, −28 19859 8.3257 <0.0001 L cerebellum −36, −78, −46 4329 6.8598 <0.0001 Thalamus/medial dorsal nucleus 10/24 8, −14, 0 2642 6.8006 <0.0001 R superior frontal gyrus 8/9/10/11 14, 36, 54 687 5.9129 <0.0001 Brainstem 4, −24, −50 103 5.9054 <0.0001 Negative salience R superior temporal gyrus 38 40, −46, 14 54536 −19.4447 <0.0001 Corresponding clusters are shown in Figures 5 and 6.
