Recovering Consciousness after Coma
INSTITUTE: UCLA, Department of Psychology
PROJECT LEADERS: Martin Monti, Evan Lutkenhoff, Marina Weiler, Joel Frohlich, Daniel Toker
PROJECT DURATION: 3 years
LAB WEBSITE: Monti Lab
This project addresses the neural correlates of consciousness in the context of patients who suffer a severe brain injury leading to a state of post-injury unconsciousness or decreased consciousness such as Coma, the Vegetative State, and the Minimally Conscious State. In particular, this project takes advantage of multimodal fusion techniques and advanced analysis of MR data to assess anatomical and functional signatures associated with impairments of consciousness and its recovery.
Overall, this work has led to two central outcomes. First, we have uncovered a strong association between post-injury atrophy in deep brain nuclei and multiple signatures of consciousness impairment. Atrophy in the thalamus, for example, is associated with clinical indicators of depth of the impairment and electrophysiological features (e.g., slowing of brain rhythms measured with electroencephalography). Atrophy in other deep brain nuclei, such as the globus pallidus, is associated with clinical measures of behavioral arousal and measures of the brain’s ability to support complex network dynamics (Figure 1). Second, we find a relationship between some of these anatomical and functional traits and recovery from post-injury unconsciousness. For example, we find the re-emergence of faster electroencephalographic rhythms to track the recovery of consciousness over time and to be predictive of subsequent atrophy in deep brain nuclei as well as degree of recovery at six months.
To transition this work from observational to a more mechanistic understanding, our most recent work has started leveraging the idea that the state of consciousness requires the brain’s electrodynamics to operate near a critical point known as edge-of-chaos. Indeed, our initial results show a relationship between recovery of consciousness after Coma and decrease of the distance between observed brain rhythms and the critical point (Figure 2).
Ultimately, this project aims at bridging the gap – in the clinical context – between behavior-based assessments of a patient’s level of conscious and the underlying functional and anatomical pathologies.
Figure 1. Depiction of thalamic and subcortical atrophy (colored areas) proportional to (i) clinical measures of depth of impairment in acule (left) and chronic (middle) DOC patients and (il) the slowing of electrophysiological rhythms (right). [Adapted from Lutkenhoff et al., 2015; 2020a; 2020b, respectively]
Figure 2. Relationship between state of consciousness and low-frequency criticality in DOC (red/blue circles), GABA anesthesia (brown asterisks) and generalized seizures (plus sign). (A) States of unconsciousness are associated with greater distance from criticality. (B) Association between a measure of signal complexity (Lempel-Ziv complexity) and state of consciousness. (C) Correlation between the measure of complexity shown in 8 and proximity to criticality shown in A. (D) In 4 DOC patients, low-frequency oscillations are systematically closer to criticality when the patient was conscious as opposed to when they were unconscious. [From Toker et al., 2022]
Broader Impact:
One the one hand, this project informs the science of consciousness by mapping the relationship between loss and recovery of consciousness and specific aspect of brain function and anatomy. On the other hand, these findings can find application, in the clinical context, by providing biomarkers that can be used to monitor patients, their progression over time (including changes after neurorestorative interventions).
Publications:
Toker, D., Pappas, I., Lendner, J. D., Frohlich, J., Mateos, D. M., Muthukumaraswamy, S., ... & D’Esposito, M. (2022). Consciousness is supported by near-critical slow cortical electrodynamics. Proceedings of the National Academy of Sciences, 119(7), e2024455119.
Frohlich, J., Crone, J. S., Johnson, M. A., Lutkenhoff, E. S., Spivak, N. M., Dell'Italia, J., ... & Monti, M. M. (2021). Neural oscillations track recovery of consciousness in acute traumatic brain injury patients. Human Brain Mapping.
Lutkenhoff, E. S., Johnson, M. A., Casarotto, S., Massimini, M., & Monti, M. M. (2020). Subcortical atrophy correlates with the perturbational complexity index in patients with disorders of consciousness. Brain Stimulation, 13(5), 1426-1435.
Lutkenhoff, E. S., Wright, M. J., Shrestha, V., Real, C., McArthur, D. L., Buitrago-Blanco, M., ... & Monti, M. M. (2020). The subcortical basis of outcome and cognitive impairment in TBI: A longitudinal cohort study. Neurology, 95(17), e2398-e2408.
Lutkenhoff, E. S., Nigri, A., Sebastiano, D. R., Sattin, D., Visani, E., Rosazza, C., ... & Monti, M. M. (2020). EEG power spectra and subcortical pathology in chronic disorders of consciousness. Psychological Medicine, 1-10.
Crone, J. S., Lutkenhoff, E. S., Vespa, P. M., & Monti, M. M. (2020). A systematic investigation of the association between network dynamics in the human brain and the state of consciousness. Neuroscience of consciousness, 2020(1), niaa008.
Dell'Italia, J., Johnson, M. A., Vespa, P. M., & Monti, M. M. (2020). Accounting for Changing Structure in Functional Network Analysis of TBI Patients. Frontiers in Systems Neuroscience, 14, 42.
Schnakers, C., Lutkenhoff, E. S., Bio, B. J., McArthur, D. L., Vespa, P. M., & Monti, M. M. (2019). Acute EEG spectra characteristics predict thalamic atrophy after severe TBI. Journal of Neurology, Neurosurgery & Psychiatry, 90(5), 617-619.
Luppi, A. I., Cain, J., Spindler, L. R., Górska, U. J., Toker, D., Hudson, A. E., ... & Boly, M. (2021). Mechanisms Underlying Disorders of Consciousness: Bridging Gaps to Move Toward an Integrated Translational Science. Neurocritical Care, 35(1), 37-54.