Validation of TMS-EEG Responses with Functional MRI and EEG in Patients with Disorders of Consciousness

INSTITUTE: Massachusetts General Hospital/Neurology

PROJECT LEADER: Brian L. Edlow, M.D.

PROJECT DURATION: 2019-2022

LAB WEBSITE: Coma Recovery Lab

The current gold standard to assess consciousness in patients with traumatic brain injuries and affected by disorders of consciousness (DOC) is a behavioral bedside examination, named Coma Recovery Scale-Revised (CRS-R). This assessment is crucial in distinguishing between vegetative state and minimally conscious state patients but can lead to the misclassification of consciousness due to possible patient motor, sensory, or language deficits. 

Recently, transcranial magnetic stimulation coupled with electroencephalography (TMS-EEG) has been demonstrated to be a promising tool to detect consciousness in patients with DOC. TMS-EEG can directly and non-invasively probe the brain to assess the capability of the thalamocortical system to sustain consciousness, bypassing motor and sensory pathways. A novel metric called perturbational complexity index (PCI) has been developed based on the quantification of the EEG responses to TMS and has been shown to have an unprecedented high sensitivity for bedside identification of patients who are conscious. TMS-EEG may also identify those who retain covert consciousness (patients who are conscious but are unable to respond and are misclassified with the CRS-R).

Here we aim to test whether patients whose PCI measurements suggest a higher level of consciousness than their behavioral examination will also show evidence of covert consciousness by means of command-following on an fMRI- or EEG-based motor imagery task. We ask the patients to imagine performing a task, such as opening and closing a hand, and we test whether the brain purposefully responds to these tasks.

To detect signs of consciousness in patients with DOC, we perform multimodal assessments that include behavioral evaluation with the CRS-R, task-based fMRI and EEG, and TMS-EEG.

Broader Impact:

Diagnostic uncertainties and the high cost of life-sustaining therapy are the source of intense burden on caregivers and patients’ families. 

There is thus an urgent need for a new technique that could be routinely used to reliably detect covert consciousness in brain-injured patients who cannot communicate.

TMS-EEG is an advanced diagnostic test that can improve detection of covert consciousness in patients with DOC. 

Publications:

• S. Sarasso,et al., Local sleep-like cortical reactivity in the awake brain after focal injury. Brain 143, 3672–3684 (2020).

• S. Casarotto, et al., The rt-TEP tool: Real-time visualization of TMS-evoked potentials to maximize cortical activation and minimize artifacts. J Neurosci Methods 370, 3672–3684 (2022). 

• S. Russo, et al., TAAC - TMS Adaptable Auditory Control: a universal tool to mask TMS click. . J Neurosci Methods 370, 209491 (2022). 

• Y. G. Bodien, et al., Diagnosing level of consciousness: The limits of the Glasgow Coma Scale total score. Journal of Neurotrauma 38, 3295-3305 (2021).

• B.L. Edlow, J. Claassen, N.D. Schiff, D.M. Greer, Recovery from disorders of consciousness: Mechanisms, prognosis and emerging therapies. Nature Reviews Neurology 17, 135-156 (2021).

• D. Fischer, B.L. Edlow, J.T. Giacino, D.M. Greer Neuroprognostication: A conceptual framework. Nature Reviews Neurology, https://doi.org/10.1038/s41582-022-00644-7 (2022).

• M.J. Young, Y.G. Bodien, B.L. Edlow, Ethical considerations in clinical trials for disorders of consciousness. Brain Sciences 12, 211 (2022).