Wakefulness and loss of awareness: brain and brainstem interaction in the vegetative state

Abstract

Objective: The ascending reticular activating system (ARAS) modulates circadian wakefulness, which is preserved in a persistent vegetative state (PVS). Its metabolism is preserved. Impairment of metabolism in the polymodal associative cortices (i.e., precuneus) is characteristic of PVS where awareness is abolished. Because the interaction of these 2 structures allows conscious sensory perception, our hypothesis was that an impaired functional connectivity between them participates in the loss of conscious perception.

Methods: (15)O-radiolabeled water PET measurement of regional cerebral blood flow (rCBF) was performed at rest and during a proprioceptive stimulation. Ten patients in PVS and 10 controls were compared in a cross-sectional study. The functional connectivity from the primary sensorimotor cortex (S1M1) and the ARAS in both groups was also investigated.

Results: Compared with controls, patients showed significantly less rCBF in posterior medial cortices (precuneus) and higher rCBF in ARAS at rest. During stimulation, bilateral Brodmann area 40 was less activated and not functionally correlated to S1M1 in PVS as it was in controls. Precuneus showed a lesser degree of deactivation in patients. Finally, ARAS whose activity was functionally correlated to that of the precuneus in controls was not in PVS.

Conclusions: Global neuronal workspace theory predicts that damage to long-distance white matter tracts should impair access to conscious perception. During persistent vegetative state, we identified a hypermetabolism in the ascending reticular activating system (ARAS) and impaired functional connectivity between the ARAS and the precuneus. This result emphasizes the functional link between cortices and brainstem in the genesis of perceptual awareness and strengthens the hypothesis that consciousness is based on a widespread neural network.

Figure 1 Comparison of regional cerebral blood flow at rest between controls and patients in persistent vegetative state Two-sample t test, family-wise error corrected p < 0.05; images are displayed at a noncorrected threshold p < 0.001.

Figure 2 Plot of the regression of neural activity in ascending reticular activating system and in precuneus F values, corrected p < 0.05 in controls (full circles: slope, r = 0.58, p < 0.0001) and in patients in persistent vegetative state (PVS) (open circles: slope, r = 0.08, p = not significant). During PVS, an impaired functional connectivity was found between the ascending reticular activating system and precuneus (difference between slopes F = 16.3, p < 0.0001). rCBF = regional cerebral blood flow.

Figure 3 Brain regions that showed less decrease in activity during stimulation in persistent vegetative state than in controls Interaction (rest vs finger movement) × (patients vs controls) (images are displayed at a noncorrected threshold p < 0.005; small volume correction applied on precuneus, family-wise error corrected p < 0.05).

Figure 4 Plot of the regression of neural activity in contralateral S1M1 and bilateral BA 40 Both control (full circles) and persistent vegetative state (PVS; open circles) groups are shown (F values, corrected p < 0.05). (A) During PVS, primary sensorimotor cortex (S1M1; Brodmann area [BA] 1–4) showed no functional correlation with ipsilateral parietal cortex (BA 40) (control slope: r = 0.62, p < 0.0001; patients in PVS slope: r = 0.12, p = not significant; difference between slopes: F = 16.4, p < 0.0001) and (B) contralateral BA 40 (controls slope: r = 0.71, p < 0.0001; patients in PVS slope: r = 0.40, p < 0.005; difference between slopes: F = 27, p < 0.0001). rCBF = regional cerebral blood flow.