Disruption of thalamic functional connectivity is a neural correlate of dexmedetomidine-induced unconsciousness
- Massachusetts General Hospital, Harvard Medical School, United States
- MGH/MIT/HMS Athinoula A Martinos Center for Biomedical Imaging, United States
- Brigham and Women's Hospital, Harvard Medical School, United States
- Massachusetts General Hospital, United States
- Massachusetts Institute of Technology, United States
Figures
Figure 1
Schematic of dexmedetomidine signaling illustrating similarities to the mechanism proposed for the generation of non-rapid eye movement II sleep.
Dexmedetomidine binds to α2 receptors on neurons emanating from the locus ceruleus to inhibit NE release in the POA. The disinhibited POA reduces arousal by means of GABA- and galanin-mediated …
Figure 2 with 1 supplement
CMRglc and rCBF are decreased in both the default mode and the frontal–parietal network brain regions during unconsciousness.
(A) Study outline of healthy volunteers recruited to undergo both baseline and dexmedetomidine-induced unconsciousness PET brain imaging in a random order. (B) Group wise (n = 10) …
Figure 2—figure supplement 1
PET SUV changes during unconsciousness.
(A) Group wise (n = 10) Dexmedetomidine-induced unconsciousness vs baseline changes in SUV (PET) displayed on the MNI152 standard volume highlighting that only SUV decreases were notable during …
Figure 3 with 1 supplement
Changes in the default mode and the bilateral frontal parietal networks during unconsciousness.
(A) The DMN extracted from BOLD signals during the awake (n = 16) and unconscious states (n = 16) and displayed on the MNI152 standard volume. (B) A comparison the DMN network during the unconscious …
Figure 3—figure supplement 1
SUV, CMRglc, rCBF changes during unconsciousness and the relationship to the DMN and bilateral FCNs.
(A) Surface projection of the voxelwise, cluster corrected analysis illustrating overlapping decreases in CMRglc (n = 10) and rCBF (n = 17) in regions corresponding to the DMN, and the bilateral …
Figure 4
Seed based functional connectivity analysis of the brain region with overlapping changes in CMRglc, rCBF, and functional connectivity.
(A) Brain wide representation of regions connected to the thalamic seed during the awake and unconscious states (n = 16). A comparison of thalamic seed functional connectivity during the unconscious …
Figure 5 with 1 supplement
Cortical increase in rCBF is not evident during the recovery of consciousness.
(A) Cluster corrected (n = 10) rCBF comparison of the recovery state vs the unconsciousness state displayed on the MNI152 standard volume highlighting no change in rCBF at recovery. (B) Uncorrected …
Figure 5—figure supplement 1
Cortical decrease in rCBF persists during the recovery of consciousness.
Statistically significant rCBF clusters from Figure 1D were extracted and intersected with the Harvard–Oxford cortical and subcortical map arbitrarily thresholded at 30. Subjects were aligned to …
Figure 6
Functional connectivity changes observed during recovery of consciousness.
(A) The DMN extracted from BOLD signals obtained during the recovery state (n = 15) displayed on the MNI152 standard volume. (B) A comparison the DMN network during the recovery vs the awake state …
Author response image 1
Tables
Table 1
CMRglc, awake vs dex-induced unconsciousness
| MNI coordinate (mm) | ||||||
|---|---|---|---|---|---|---|
| Label | Z-stat | x | y | z | cluster size (# voxels) | cluster p-value |
| awake > dex-induced unconsciousness | ||||||
| R middle/inferior frontal gyrus | 4.35 | 52 | 42 | 4 | 17919 | 2.95E-12 |
| R medial orbital gyrus | 4.22 | 24 | 38 | −16 | ||
| L inferior frontal gyrus | 4.02 | −52 | 36 | 10 | ||
| L superior frontal gyrus, medial part | 4 | −6 | 20 | 40 | ||
| L middle frontal gyrus | 3.94 | −42 | 18 | 38 | ||
| L middle frontal gyrus | 3.86 | −34 | 8 | 66 | ||
| R middle frontopolar gyrus | 3.79 | −30 | 58 | 2 | ||
| L lateral orbital gyrus | 3.58 | −46 | 28 | −12 | ||
| L medial orbital gyrus | 3.56 | −26 | 32 | −22 | ||
| R middle frontal gyrus | 3.55 | 48 | 20 | 44 | ||
| R superior frontal gyrus | 3.48 | 26 | 2 | 56 | ||
| R inferior frontal gyrus, pars opercularis | 3.37 | 54 | 16 | 4 | ||
| L inferior frontal gyrus, pars opercularis | 3.36 | −46 | 20 | 0 | ||
| L superior frontal gyrus, medial part (2) | 3.33 | −4 | 42 | 22 | ||
| inferior rostral gyrus | 3.15 | 0 | 48 | −10 | ||
| R anterior insula | 2.82 | 40 | 22 | 0 | ||
| L Posterior Cingulate Gyrus | 5.56 | −4 | −24 | 38 | 5443 | 2.85E-05 |
| L precuneus | 4.27 | −12 | −64 | 22 | ||
| R precuneus | 3.86 | 12 | −60 | 28 | ||
| L supramarginal gyrus | 4.58 | −40 | −46 | 42 | 2861 | 0.0029 |
| L angular gyrus | 3.76 | −48 | −68 | 34 | ||
| R supramarginal gyrus | 4.59 | 44 | −46 | 48 | 2214 | 0.0112 |
| R angular gyrus | 4 | 34 | −62 | 44 | ||
| R thalamus | 4.52 | 12 | −20 | 4 | 1610 | 0.0444 |
| L thalamus | 3.89 | −14 | −26 | 4 | ||
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CMRglc, cerebral metabolic rate of glucose; Dex, dexmedetomidine; L, left; MNI, Montreal Neurological Institute; R, right.
Table 2
rCBF, awake vs unconscious
| MNI coordinate (mm) | ||||||
|---|---|---|---|---|---|---|
| Label | Z-stat | x | y | z | cluster size (# voxels) | cluster p-value |
| awake > unconscious | ||||||
| L thalamus | 5.36 | −10 | −14 | 12 | 10876 | 4.20E-11 |
| L midbrain | 5.2 | 8 | −32 | −10 | ||
| L posterior cingulate cortex | 5.14 | −2 | −46 | 28 | ||
| R thalamus | 5.03 | 8 | −12 | 10 | ||
| R midbrain | 4.44 | −6 | −36 | −12 | ||
| L precuneus | 4.44 | −2 | −70 | 32 | ||
| R precuneus | 4.3 | 8 | −76 | 42 | ||
| R intracalcarine cortex | 4.2 | 4 | −84 | 4 | ||
| L intracalcarine cortex | 4.18 | −2 | −82 | 2 | ||
| R hippocampus | 4.17 | 30 | −34 | −4 | ||
| L supramarginal gyrus/intraparietal sulcus | 4.03 | −34 | −50 | 44 | ||
| L hippocampus | 3.09 | −26 | −22 | −12 | ||
| R frontopolar cortex | 4.71 | −24 | 64 | 2 | 1773 | 0.00463 |
| L frontopolar cortex | 4.32 | 20 | 62 | −6 | ||
| L middle frontal gyrus | 3.77 | −22 | 38 | 28 | ||
| R inferior frontal gyrus, orbital part | 2.88 | 50 | 40 | −14 | ||
| L dorsal anterior cingulate cortex | 3.93 | 10 | 38 | 22 | 1262 | 0.0227 |
| R dorsal anterior cingulate cortex | 3.75 | −10 | 38 | 20 | ||
| L subgenual anterior cingulate cortex | 3.3 | −2 | 24 | −10 | ||
| R pregenual anterior cingulate cortex | 3.21 | 6 | 42 | −6 | ||
| unconscious > awake | ||||||
| n.s. | ||||||
-
L, left; MNI, Montreal Neurological Institute; n.s, not significant; R, right.
Table 3
DMN
| MNI coordinate (mm) | ||||||
|---|---|---|---|---|---|---|
| Label | Z-stat | x | y | z | cluster size (# voxels) | cluster p-value |
| awake > unconscious | ||||||
| R thalamus | 4.04 | 2 | −14 | 8 | 438 | 0.00193 |
| L thalamus | 3.9 | −4 | −14 | 8 | ||
| L cerebellum (Crus II) | 3.93 | −44 | −64 | −44 | 270 | 0.0429 |
| unconscious > awake | ||||||
| R inferior frontal gyrus, pars opercularis | 3.83 | 56 | 12 | 20 | 399 | 0.00381 |
| R inferior frontal gyrus, pars triangularis | 3.35 | 54 | 32 | 10 | ||
| L putamen | 3.47 | −24 | 6 | −8 | 382 | 0.00517 |
| L insula | 3.43 | −36 | −10 | −4 | ||
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DMN, Default Mode Network; L, left; MNI, Montreal Neurological Institute; R, right.
Table 4
rFCN
| MNI coordinate (mm) | ||||||
|---|---|---|---|---|---|---|
| Label | Z-stat | x | y | z | cluster size (# voxels) | cluster p-value |
| awake > unconscious | ||||||
| L cerebellum (Crus II) | 3.99 | −36 | −70 | −40 | 472 | 0.000724 |
| L cerebellum (VIIb) | 3.83 | −34 | −62 | −50 | ||
| L cerebellum (VI) | 3.28 | −28 | −62 | −32 | ||
| unconscious > awake | ||||||
| R cerebellum (VI) | 4.02 | 12 | −68 | −28 | 693 | 1.97E-05 |
| R cerebellum (Crus II) | 3.67 | 26 | −78 | −42 | ||
| R cerebellum (Crus I) | 3.24 | 20 | −74 | −24 | ||
| R precuneus | 2.99 | 26 | −60 | 18 | 519 | 0.000323 |
| R parietal operculum | 4.1 | 58 | −12 | 12 | 516 | 0.00034 |
| R insula | 3.23 | 44 | −4 | 0 | ||
| R cerebellum (Crus I) | 4.28 | 44 | −56 | −32 | 292 | 0.0212 |
| R fusiform gyrus | 3.59 | 30 | −42 | −20 | ||
| L angular gyrus | 3.72 | −38 | −86 | 20 | 272 | 0.0319 |
| L angular gyrus | 3.56 | −48 | −78 | 30 | ||
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L, left; MNI, Montreal Neurological Institute; R, right; rFCN, right Frontoparietal Control Network.
Table 5
lFCN
| MNI coordinate (mm) | ||||||
|---|---|---|---|---|---|---|
| Label | Z-stat | x | y | z | cluster size (# voxels) | cluster p-value |
| awake > unconscious | ||||||
| R cerebellum (Crus II) | 4.24 | 38 | −74 | −50 | 1223 | 5.33E-09 |
| R cerebellum (VIIb) | 4.1 | 38 | −56 | −50 | ||
| R cerebellum (VI) | 4.08 | 28 | −62 | −32 | ||
| R intracalcarine cortex | 3.58 | 4 | −86 | −2 | ||
| L middle frontal gyrus | 3.89 | −32 | 12 | 54 | 490 | 0.000341 |
| L superior frontal gyrus, medial part | 3.52 | −4 | 32 | 46 | ||
| unconscious > awake | ||||||
| n.s. | ||||||
-
L, left; lFCN, left Frontoparietal Control Network; MNI, Montreal Neurological Institute; n.s, not significant; R, right.
Table 6
Thalamic seed
| MNI coordinate (mm) | ||||||
|---|---|---|---|---|---|---|
| Label | Z-stat | x | y | z | cluster size (# voxels) | cluster p-value |
| awake > unconscious | ||||||
| R thalamus | 5.33 | 12 | −12 | 8 | 3445 | 4.05E-16 |
| L posterior cingulate cortex | 4.95 | −6 | −36 | 30 | ||
| R posterior cingulate cortex | 4.73 | 6 | −28 | 34 | ||
| L thalamus | 4.48 | −16 | −10 | 10 | ||
| R caudate nucleus | 3.44 | 12 | 10 | 18 | ||
| L globus pallidus | 3.44 | −12 | 2 | −2 | ||
| L precuneus | 4.03 | −6 | −56 | 36 | 1230 | 1.79E-07 |
| R precuneus | 3.71 | 12 | −60 | 36 | ||
| R angular gyrus | 4.07 | 36 | −60 | 50 | 1094 | 9.54E-07 |
| R supramarginal gyrus | 3.67 | 48 | −48 | 36 | ||
| R cerebellum (crus II) | 4.07 | 8 | −76 | −30 | 906 | 8.76E-06 |
| R cerebellum (crus I) | 3.84 | 22 | −88 | −22 | ||
| R intracalcarine cortex | 3.75 | 2 | −100 | 4 | ||
| L cerebellum (crus I) | 3.14 | −20 | −84 | −28 | ||
| L supramarginal gyrus | 4.6 | −38 | −52 | 42 | 831 | 2.21E-05 |
| L angular gyrus | 3.43 | −32 | −76 | 48 | ||
| unconscious > awake | ||||||
| L inferior frontal gyrus, pars opercularis | 4.21 | −56 | 14 | 8 | 1458 | 1.80E-08 |
| L superior temporal gyrus | 4.2 | −62 | −10 | 4 | ||
| L middle temporal gyrus | 4.04 | −50 | −2 | −22 | ||
| L insula | 3.55 | −38 | 4 | −6 | ||
| R paracentral lobule | 3.77 | 4 | −32 | 58 | 963 | 4.41E-06 |
| L paracentral lobule | 3.64 | −10 | −38 | 58 | ||
| R superior frontal gyrus, lateral part | 3.44 | 14 | −6 | 56 | ||
| R precentral gyrus | 3.23 | 14 | −20 | 66 | ||
| L postcentral gyrus | 3.2 | −16 | −44 | 72 | ||
| R superior frontal gyrus, medial part | 2.86 | 10 | 2 | 50 | ||
| R postcentral gyrus | 2.72 | 16 | −38 | 70 | ||
| R superior temporal gyrus | 5 | 48 | −42 | 10 | 868 | 1.39E-05 |
| R middle temporal gyrus | 4.53 | 44 | −28 | −6 | ||
| R precentral gyrus | 3.51 | 54 | −2 | 46 | ||
| L postcentral gyrus | 4.03 | −62 | −8 | 36 | 453 | 0.00401 |
| L precentral gyrus | 3.77 | −60 | −4 | 36 | ||
| L superior temporal gyrus | 3.97 | −66 | −44 | 10 | 340 | 0.0244 |
-
L, left; MNI, Montreal Neurological Institute; R, right.
Table 7
Recovery
| MNI coordinate (mm) | ||||||
|---|---|---|---|---|---|---|
| Label | Z-stat | x | y | z | cluster size (# voxels) | cluster p-value |
| DMN, recovery > unconscious | ||||||
| R thalamus | 3.3 | 2 | −8 | 4 | 78 | 0.0345 |
| L thalamus | 3 | −4 | −4 | 8 | ||
| DMN, unconscious > recovery | ||||||
| n.s. | ||||||
| rFCN, recovery > unconscious | ||||||
| n.s. | ||||||
| rFCN, unconscious > recovery | ||||||
| R cerebellum (VI) | 3.92 | 14 | −70 | −28 | 246 | 0.00172 |
| R cerebellum (Crus I) | 3.81 | 22 | −76 | −28 | ||
| R cerebellum (Crus II) | 3.06 | 24 | −80 | −38 | ||
| lFCN, recovery > unconscious | ||||||
| R cerebellum (VI) | 3.58 | 12 | −66 | −30 | 118 | 0.012 |
| R cerebellum (Crus I) | 3.29 | 38 | −58 | −32 | 93 | 0.0232 |
| R cerebellum (Crus II) | 3.05 | 32 | −64 | −42 | ||
| lFCN, unconscious > recovery | ||||||
| n.s. | ||||||
| Thalamic seed, recovery > unconscious | ||||||
| posterior cingulate cortex | 3.53 | 0 | −40 | 22 | 367 | 0.00367 |
| L thalamus | 3.49 | −10 | −22 | 12 | 348 | 0.00471 |
| L putamen | 2.51 | −14 | 4 | 2 | ||
| Thalamic seed, unconscious > recovery | ||||||
| n.s. | ||||||
-
DMN, default mode network; L, left; lFCN, left Frontoparietal Control Network; MNI, Montreal Neurological Institute; n.s, not significant; R, right; rFCN, right Frontoparietal Control Network.
