Returning from oblivion: imaging the neural core of consciousness

Abstract

One of the greatest challenges of modern neuroscience is to discover the neural mechanisms of consciousness and to explain how they produce the conscious state. We sought the underlying neural substrate of human consciousness by manipulating the level of consciousness in volunteers with anesthetic agents and visualizing the resultant changes in brain activity using regional cerebral blood flow imaging with positron emission tomography. Study design and methodology were chosen to dissociate the state-related changes in consciousness from the effects of the anesthetic drugs. We found the emergence of consciousness, as assessed with a motor response to a spoken command, to be associated with the activation of a core network involving subcortical and limbic regions that become functionally coupled with parts of frontal and inferior parietal cortices upon awakening from unconsciousness. The neural core of consciousness thus involves forebrain arousal acting to link motor intentions originating in posterior sensory integration regions with motor action control arising in more anterior brain regions. These findings reveal the clearest picture yet of the minimal neural correlates required for a conscious state to emerge.

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.