Perception of pain in the minimally conscious state with PET activation: an observational study

Summary Background Patients in a minimally conscious state (MCS) show restricted self or environment awareness but are unable to communicate consistently and reliably. Therefore, better understanding of cerebral noxious processing in these patients is of clinical, therapeutic, and ethical relevance. Methods We studied brain activation induced by bilateral electrical stimulation of the median nerve in five patients in MCS (aged 18–74 years) compared with 15 controls (19–64 years) and 15 patients (19–75 years) in a persistent vegetative state (PVS) with 15O-radiolabelled water PET. By way of psychophysiological interaction analysis, we also investigated the functional connectivity of the primary somatosensory cortex (S1) in patients and controls. Patients in MCS were scanned 57 (SD 33) days after admission, and patients in PVS 36 (9) days after admission. Stimulation intensities were 8•6 (SD 6•7) mA in patients in MCS, 7•4 (5•9) mA in controls, and 14•2 (8•7) mA in patients in PVS. Significant results were thresholded at p values of less than 0•05 and corrected for multiple comparisons. Findings In patients in MCS and in controls, noxious stimulation activated the thalamus, S1, and the secondary somatosensory or insular, frontoparietal, and anterior cingulate cortices (known as the pain matrix). No area was less activated in the patients in MCS than in the controls. All areas of the cortical pain matrix showed greater activation in patients in MCS than in those in PVS. Finally, in contrast with patients in PVS, those in MCS had preserved functional connectivity between S1 and a widespread cortical network that includes the frontoparietal associative cortices. Interpretation Cerebral correlates of pain processing are found in a similar network in controls and patients in MCS but are much more widespread than in patients in PVS. These findings might be objective evidence of a potential pain perception capacity in patients in MCS, which supports the idea that these patients need analgesic treatment. Funding FNRS; Reine Elisabeth Medical Foundation; University of Liège; European Commission; James S McDonnell Foundation; Mind Science Foundation; Concerted Research Action; Fondation Léon Frédéricq.