Supplementary Material S3 Further Seed Regions

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1 Supplementary Material S3 Further Seed Regions Figure I. Changes in connectivity with the right anterior insular cortex. (A) wake > mild sedation, showing a reduction in connectivity between the anterior insular cortex and posterior external control network-associated regions; (B) wake >, showing decreased connectivity between anterior insular cortex and thalamus, salience network, and external control network-associated regions; (C) > mild sedation, with a reduction of connectivity between anterior insular cortex and salience network and thalamus. p < 0.001, see Supplementary Material S4 for whole brain and small volume corrections.

2 Figure II. Changes in connectivity with the thalamus. (A) wake > mild sedation, showing a decrease in connectivity between thalamus and cerebellum; (B) wake >, showing a decrease in thalamus- connectivity, and between thalamus and salience (insulae and anterior cingulate cortex) and external control network-associated regions (inferior parietal lobules); (C) > mild sedation, showing an increase in connectivity between medial thalamus and posterior thalamus, as well as to the secondary visual cortex. p < 0.001, see Supplementary Material S4 for whole brain and small volume corrections.

3 Figure III. Changes in connectivity with the mesencephalon. (A) wake > mild sedation, showing a reduction in connectivity between mesencephalon and and anterior cingulate cortex; (B) wake >, showing a reduced connectivity with posterior cingulate cortex/, medial prefrontal cortex, and temporoparietal areas; (C) mild sedation >, showing a connectivity reduction between mesencephalon and posterior cingulate cortex/, temporoparietal areas, and anterior cingulate cortex. p < 0.001, see Supplementary Material S4 for whole brain and small volume corrections.

4 Figure IV. Changes in connectivity with the pons. (A) wake > mild sedation, showing a decrease in connectivity between pons and thalamus and anterior cingulate cortex/supplementary motor area; (B) wake >, showing a decrease in connectivity between pons and superior frontal gyri, supplementary motor area and thalamus, and between pons and posterior cingulate cortex; (C) > mild sedation, showing an increase in connectivity between pons and the inferior temporal cortex. p < 0.001, see Supplementary Material S4 for whole brain and small volume corrections.

5 Figure V. Changes in connectivity with the hippocampus. (A) wake > mild sedation, showing a reduction in connectivity between hippocampus and posterior cingulate cortex/ and secondary visual cortex; (B) wake >, showing a reduced connectivity between hippocampus and posterior cingulate cortex/; (C) > mild sedation, showing a reduction in connectivity between hippocampus and inferior parietal lobule. p < 0.001, see Supplementary Material S4 for whole brain and small volume corrections.

6 Accompanying Figures I to V of Supplementary Material S3 Image Seed region Contrast Coordinates (x, y, z) Name of connected structure p-values whole brain FWE cluster corrected ( * ) or small volume FWE cluster corrected I A I B I C Right anterior insular cortex Right anterior insular cortex Right anterior insular cortex Wake > mild sedation 3, 49, 52 Precuneus , 37, 49 Secondary sensorimotor 0.018* area 54, 34, 28 Inferior parietal lobule < 0.001* 45, 31, 13 Inferior parietal lobule , 31, 10 Primary auditory cortex , 25, 13 Primary auditory cortex Wake > Mild sedation > 9, 52, 49 Precuneus , 34, 13 Insula , 31, 10 Primary auditory cortex , 31, 22 Inferior parietal lobule , 28, 19 Inferior parietal lobule < 0.001* 3, 10, 13 Thalamus , 10, 10 Thalamus , 4, 4 Superior temporal gyrus/ 0.029* Wernicke s area 6, 2, 43 Pre-/supplementary motor < area 30, 11, 7 Inferior frontal gyrus pars 0.012* orbitalis 9, 17, 34 Anterior cingulate gyrus < 0.001* 33, 20, 4 Inferior frontal cortex , 26, 7 Medial prefrontal cortex ventral 3, 32, 19 Frontal cortex , 44, 16 Frontal cortex , 44, 16 Frontal cortex < 0.001* 42, 52, 40 Inferior parietal lobule 0.009* 3, 7, 13 Thalamus , 4, 7 Thalamus < , 2, 10 Inferior frontal gyrus pars < 0.001* orbitalis 39, 8, 4 Inferior frontal gyrus pars orbitalis 6, 5, 40 Pre-/supplementary motor < area 12, 20, 28 Anterior cingulate cortex < , 20, 1 Inferior frontal cortex < , 20, 28 Frontal cortex < 0.001* 24, 47, 19 Frontal cortex , 50, 16 Frontal cortex , 26, 10 Medial prefrontal cortex ventral 39, 44, 19 Middle frontal gyrus < 0.001* II A Medial thalamus Wake > mild sedation 3, 55, 20 Cerebellum , 37, 26 Posterior cingulate gyrus 0.001* II B Medial thalamus Wake > 3, 55, 20 Cerebellum , 55, 31 Posterior cingulate cortex/ , 55, 46 Inferior parietal lobule , 52, 40 Inferior parietal lobule 0.002* 63, 37, 37 Inferior parietal lobule < 0.001* 6, 19, 31 Posterior cingulate gyrus < 0.001* 6, 32, 25 Anterior cingulate gyrus < 0.001* 42, 41, 10 Middle frontal gyrus < 0.001* (continued)

7 Image Seed region Contrast Supplementary Material S3. (Continued) Coordinates (x, y, z) Name of connected structure p-values whole brain FWE cluster corrected ( * ) or small volume FWE cluster corrected II C Medial thalamus Unconsciousness > mild sedation 0, 44, 4 Medial prefrontal cortex ventral 3, 44, 7 Medial prefrontal cortex anterior 42, 47, 7 Anterior middle frontal gyrus < 0.001* 12, 85, 28 Secondary visual cortex , 16, 13 Posterior thalamus III A Mesencephalon Wake > mild sedation 3, 61, 55 Precuneus , 40, 28 Posterior cingulate cortex , 19, 2 Mesencephalon III B Mesencephalon Wake > 6, 41, 2 Anterior cingulate cortex , 52, 31 Posterior cingulate cortex/ , 49, 43 Inferior parietal cortex , 55, 49 Inferior parietal cortex III C Mesencephalon Mild sedation > IV A IV B IV C Pontine tegmental area Pontine tegmental area Pontine tegmental area 33, 49, 52 Inferior parietal cortex , 52, 37 Posterior cingulate cortex/ Wake > mild sedation 3, 13, 7 Thalamus , 23, 49 Anterior cingulate cortex/ supplementary motor area 24, 50, 31 Superior frontal gyrus , 50, 37 Superior frontal gyrus Wake > Unconsciousness > mild sedation 3, 67, 49 Precuneus , 37, 22 Posterior cingulate cortex 0.003* 3, 13, 7 Thalamus , 23, 49 Supplementary motor area , 50, 31 Superior frontal gyrus , 50, 37 Superior frontal gyrus 0.023* 51, 34, 8 Parahippocampal gyrus V A Hippocampus Wake > mild sedation 15, 88, 2 Primary visual cortex < 0.001* 0, 76, 7 Secondary visual cortex , 49, 28 Posterior cingulate cortex/ V B Hippocampus Wake > 6, 55, 25 Posterior cingulate cortex/ , 16, 13 Thalamus V C Hippocampus Mild sedation > 42, 55, 46 Inferior parietal lobule 0.038

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