EEG power spectra and subcortical pathology in chronic disorders of consciousness

Abstract

Objective:To determine (i) the association between long-term impairment of consciousness after severe brain injury, spontaneous brain oscillations, and underlying subcortical damage, and (ii) whether such data can be used to aid patient diagnosis, a process known to be susceptible to high rates of error.Methods: Cross-sectional observational sample of 116 patients with an acquired disorder of consciousness secondary to brain injury, collected prospectively at a tertiary center between 2011 and 2013. Multimodal analyses relating clinical measures of impairment, electroencephalographic measures of spontaneous brain activity, and magnetic resonance imaging data of subcortical atrophy were conducted in 2018.Results: Systematic associations were found between electroencephalographic power spectra and subcortical damage. Specifically, the ratio of beta-to-delta relative power was negatively associated with greater atrophy in regions of the bilateral thalamus and globus pallidus (both left > right) previously shown to be preferentially atrophied in chronic disorders of consciousness. Power spectrum total density was also negatively associated with widespread atrophy in regions of the left globus pallidus, right caudate, and in brainstem. Furthermore, we showed that the combination of behavioral, encephalographic, and imaging data in an analytic framework can be employed to aid behavioral diagnosis.Interpretation: These results associate, for the first time, electroencephalographic presentation, as detected with routine clinical techniquesthus grounding them in the underlying brain pathology of disorders of consciousnessand demonstrate how multimodal combination of clinical, electroencephalographic, and imaging data can be employed in potentially mitigating the high rates of misdiagnosis typical of patients in this cohort.

Cortical and thalamic connections of the human globus pallidus: Implications for disorders of consciousness

“…Furthermore, in as much as frontal cortices play a key role in forebrain arousal regulation (Schiff, 2008), the present data suggest that the model might be incomplete without the inclusion of direct connections linking the external segment of the GP and prefrontal cortex. Under this extended mesocircuit model, deficits in behavioral arousal (Lutkenhoff et al, 2015) and slowing of EEG rhythms (Lutkenhoff et al, 2020b) would map onto the GPe-cortical axis, in parallel to the results in animal models (Qiu et al, 2010). Similarly, this extended model would allow interpreting the finding of direct pallido-frontal effective connectivity being modulated by loss and recovery of consciousness (Crone et al, 2017) in healthy volunteers.…”

“…Given the structural nature of our methodology, the functional role of direct GPe-PFC and GPe-thalamic pathways, in humans and DOC patients in particular, has to remain speculative. Nonetheless, the reviewed findings across animal models (Qiu et al, 2010 , 2016a , b ; Yuan et al, 2017 ), healthy volunteers (Crone et al, 2017 ), and Parkinson's disease (Trenkwalder, 1998 ; Albers et al, 2017 ; Castillo et al, 2020 ) and DOC patients (Lutkenhoff et al, 2015 , 2020a , b ) suggest an involvement in the regulation of electrocortical and behavioral arousal.…”

“…Intriguingly, recent work has also shown an association between the degree of atrophy in the globus pallidus, and its lateral aspect in particular, and neurobehavioral (Lutkenhoff et al, 2015) and neurophysiological (Lutkenhoff et al, 2020b) biomarkers of impairment in DOC, in line with the results reported in the rodent model (Qiu et al, 2010). Furthermore, GPe atrophy in a cohort of DOC patients was also found to be the only region correlated (inversely) with a well-validated quantitative measure associated with a state of conscious awareness (i.e., the perturbational complexity index) (Lutkenhoff et al, 2020a).…”

Brain Activity Characteristics of Patients With Disorders of Consciousness in the EEG Resting State Paradigm: A Review

“…The power of faster oscillations is significantly reduced in patients with DoC (Coleman et al, 2005 ; Babiloni et al, 2009 ; Chennu et al, 2014 ; Naro et al, 2018 ; Stefan et al, 2018 ). In the case of patients with UWS, in comparison with those with MCS, brain activity is dominated by the low oscillation of the δ band (Lehembre et al, 2012a ; Höller et al, 2014 ; Sitt et al, 2014 ; Naro et al, 2016 , 2018 ; Piarulli et al, 2016 ; Stefan et al, 2018 ; Lutkenhoff et al, 2019 ) (refer to Figure 2 ). A significant increase in the δ band in patients with UWS in comparison with MCS and healthy controls was observed mainly in frontal areas (Lehembre et al, 2012a ; Naro et al, 2016 ).…”