Measures of metabolism and complexity in the brain of patients with disorders of consciousness

Abstract

Background: Making an accurate diagnosis in patients with disorders of consciousness remains challenging. ¹⁸F-fluorodeoxyglucose (FDG)-PET has been validated as a diagnostic tool in this population, and allows identifying unresponsive patients with a capacity for consciousness. In parallel, the perturbational complexity index (PCI), a new measure based on the analysis of the electroencephalographic response to transcranial magnetic stimulation, has also been suggested as a tool to distinguish between unconscious and conscious states. The aim of the study was to cross-validate FDG-PET and PCI, and to identify signs of consciousness in otherwise unresponsive patients.

Methods: We jointly applied the Coma Recovery Scale-Revised, FDG-PET and PCI to assess 24 patients with non-acute disorders of consciousness or locked-in syndrome (13 male; 19-54 years old; 12 traumatic; 9 unresponsive wakefulness syndrome, 11 minimally conscious state; 2 emergence from the minimally conscious state, and 2 locked-in syndrome).

Results: FDG-PET and PCI provided congruent results in 22 patients, regardless of their behavioural diagnosis. Notably, FDG-PET and PCI revealed preserved metabolic rates and high complexity levels in four patients who were behaviourally unresponsive.

Conclusion: We propose that jointly measuring the metabolic activity and the electrophysiological complexity of cortical circuits is a useful complement to the diagnosis and stratification of patients with disorders of consciousness.

Keywords: Brain injury; CRS-R, Coma Recovery Scale-Revised; DOC, disorders of consciousness; Disorders of consciousness; EMCS, emergence from the minimally conscious state; Electroencephalography; FDG, 18F-fluorodeoxyglucose; LIS, locked-in syndrome; MCS*, non-behavioural minimally conscious state; MCS, minimally conscious state; PCI, perturbational complexity index; Positron emission tomography; SPM, statistical parametric mapping; TMS–EEG, transcranial magnetic stimulation coupled with high-density EEG; Transcranial magnetic stimulation; UWS, unresponsive wakefulness syndrome; Unresponsive wakefulness syndrome minimally conscious state; fMRI, functional MRI.

Fig. 1

Typical results of the active fMRI paradigm in a healthy control and in an MCS* patient. Functional MRI activation of the supplementary motor area (yellow) and of the parahippocampal gyrus (blue-green) after motor imagery and spatial imagery tasks, respectively, in healthy subjects (A). Subject UWS1 shows significant activation in the supplementary motor area (yellow) after the motor imagery task, similar to the one found in healthy subjects.

Fig. 2

Typical behavioural, PCI, and FDG–PET results in an UWS, MCS*, MCS and LIS patients. Top row illustrates the behavioural subscores of each assessment with the black line representing the threshold for MCS. The second row illustrates the areas on the left hemisphere in which FDG–PET finds significantly impaired (blue) or preserved (red) metabolism compared to 39 controls (p < 0.05). The third raw illustrates the TMS evoked potential traces at the cortical level, which are later used to compute PCI. Note that while behaviourally, UWS and MCS* are alike, the MCS*'s TMS evoked potentials and FDG–PET patterns are more similar to those observed in MCS and LIS patients. FDG–PET images were created by merging the impaired and preserved metabolism maps from SPM8. UWS: unresponsive wakefulness syndrome, MCS*: non-behavioural minimally conscious state, MCS: minimally conscious state, Aud. Vis. Mot. Oro. Com. Aro. are the six CRS-R subscales, A: anterior, P: posterior.

Fig. 3

Behavioural, PCI, and FDG–PET results in the patients with incongruent results. Top row illustrates the behavioural subscores of each assessment with the black line representing the threshold for MCS. The second row illustrates the areas in which FDG–PET finds significantly decreased (blue) or preserved (red) metabolism compared to 39 controls (p < 0.05). The third raw illustrates the TMS evoked potential traces at the cortical level, which are later used to compute the PCI. Despite being behaviourally unresponsive on all evaluations, and with a PCI < 0.31, patient UWS5's FDG–PET shows metabolism preservation of a large part of his right hemisphere. Patient MCS11 has some preserved metabolism in the fronto-parietal network, and is MCS− based on one visual pursuit, but the PCI remained < 0.31. FDG–PET images were created by merging the impaired and preserved metabolism maps from SPM8. UWS: unresponsive wakefulness syndrome, MCS*: non-behavioural minimally conscious state, MCS: minimally conscious state, Aud. Vis. Mot. Oro. Com. Aro. are the six CRS-R subscales, A: anterior, P: posterior, L: left, R: right.

Fig. 4

Proposed screening algorithm. Patients with unidentified DOC should be first assessed using validated standardized behavioural scale, such as the CRS-R. If no signs of consciousness can be detected, potential for consciousness can be identified using ¹⁸FDG-PET. In case this exam shows at least partial preservation of the fronto-parietal network metabolism, TMS-EEG could be used to detect the presence of covert consciousness. This would be the case if the PCI was above the distribution found in unconsciousness (> 0.31).