Electrophysiological correlates of thalamocortical function in acute severe traumatic brain injury

Abstract

Few reliable biomarkers of consciousness exist for patients with acute severe brain injury. Tools assaying the neural networks that modulate consciousness may allow for tracking of recovery. The mesocircuit model, and its instantiation as the ABCD framework, classifies resting-state EEG power spectral densities into categories reflecting widely separated levels of thalamocortical network function and correlates with outcome in post-cardiac arrest coma. We applied the ABCD framework to acute severe traumatic brain injury and tested four hypotheses: 1) EEG channel-level ABCD classifications are spatially heterogeneous and temporally variable; 2) ABCD classifications improve longitudinally, commensurate with the degree of behavioural recovery; 3) ABCD classifications correlate with behavioural level of consciousness; and 4) the Coma Recovery Scale-Revised arousal facilitation protocol improves EEG dynamics along the ABCD scale. In this longitudinal cohort study, we enrolled 20 patients with acute severe traumatic brain injury requiring intensive care and 16 healthy controls. Through visual inspection, channel-level spectra from resting-state EEG were classified based on spectral peaks within frequency bands defined by the ABCD framework: A = no peaks above delta (<4 Hz) range (complete thalamocortical disruption); B = theta (4-8 Hz) peak (severe thalamocortical disruption); C = theta and beta (13-24 Hz) peaks (moderate thalamocortical disruption); or D = alpha (8-13 Hz) and beta peaks (normal thalamocortical function). We assessed behavioural level of consciousness with the Coma Recovery Scale-Revised or neurological examination and, in 12 patients, performed repeat EEG and behavioural assessments at ≥6-months post-injury. Acutely, 95% of patients demonstrated D signals in at least one channel but exhibited heterogeneity in the proportion of different channel-level ABCD classifications (mean percent D signals: 37%, range: 0-90%). By contrast, healthy participants and patients at follow-up predominantly demonstrated signals corresponding to intact thalamocortical network function (mean percent D signals: 94%). In patients studied acutely, ABCD classifications improved after the Coma Recovery Scale-Revised arousal facilitation protocol (P<0.05), providing electrophysiological evidence for the effectiveness of this commonly performed technique. ABCD classification did not correspond with behavioural level of consciousness acutely, where patients demonstrated substantial within-session temporal variability in ABCD classifications. However, ABCD classification distinguished patients with and without command-following in the subacute-to-chronic phase of recovery (P<0.01). Patients also demonstrated significant longitudinal improvement in EEG dynamics along the ABCD scale (median change in D signals: 37%, P<0.05). These findings support the use of the ABCD framework to characterize channel-level EEG dynamics and track fluctuations in functional thalamocortical network integrity in spatial detail.

Conventional and Investigational Approaches Leveraging Clinical EEG for Prognosis in Acute Disorders of Consciousness

“…86 Acute ABCD classification has also been demonstrated to correlate with outcome and likelihood of in-hospital mortality in aneurysmal SAH. 87 Specifically, patients with acute EEG classified as “A” or “B” had significantly higher likelihood of in-hospital mortality and poor outcome at follow-up (median: 4 months), defined as modified Rankin scale (mRS) score 4 to 6, as compared with patients with acute EEG classified as “C” or “D.” The ABCD framework has also been applied to TBI, 88 89 90 but a definitive association with outcome has not yet been demonstrated.…”

Behavioral Assessment of Patients with Disorders of Consciousness

“…• Increase arousal before performing evaluations (e.g., with the CRS-R Arousal Facilitation Protocol 83 ).…”

“…The Nociception Coma Scale and its revised version were specifically developed to assess pain perception in patients with VS/UWS and MCS. 46 Additional scales that complement the CRS-R but focus specifically on language assessment 47 and swallowing 48 • Increase arousal before performing evaluations (e.g., with the CRS-R Arousal Facilitation Protocol 83 ). • Optimize positioning to promote arousal (e.g., wakefulness may improve when sitting up vs. laying down).…”