Low-Intensity Focused Ultrasound Pulsation (LIFUP) in Disorders of Consciousness (DoC): Brainstem, Posterior Thalamic and Parathalamic Nuclei
This project tests the hypothesis that applying low-intensity focused ultrasound pulsation (LIFUP) stimulation to the brainstem.of patients increases their behavioral responsiveness.
To test the hypothesis, we will use a Transcranial Magnetic Stimulation-Electroencephalogram device before and after treatment with LIFUP in DoC cases to determine changes in Perturbational Complexity Index (PCI)—a metric that has been demonstrated to distinguish conscious from unconscious states. Patients will also complete a neurological assessment including the Coma Recovery Scale-Revised before and after the LIFUP sonification as a behavior measure.
To determine the most effective neuroanatomic target for LIFUP stimulation, this project aims to identify fMRI-based biomarkers of brain network connectivity, which will be used to guide LIFUP simulation on individual patients. This project is studying the subcortical functional connectivity of the default mode network, which is well established as contributing to human consciousness. A group analysis has been started with the high-quality high-resolution 7T resting-state fMRI dataset from the Human Connectome Project. This team is now transitioning to 3T clinical scans at the individual level to inform the selection of therapeutic targets.
Broader Impact:
Subcortical activating systems in the brainstem, thalamus, basal ganglia and basal forebrain play a crucial role in supporting consciousness. Damage or inactivation of these systems can result in a coma, vegetative state, or minimally conscious state. However, we expect that these subcortical activating systems contribute to consciousness not directly, by contributing specific contents, but rather indirectly, by enabling the normal functioning of the cerebral cortex. Hence, it is important to test the enabling role of subcortical activating systems using LIFUP sonification in patients with disorders of consciousness.
Publications:
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).
J. Li, et al., Mapping the subcortical connectivity of the human default mode network. NeuroImage, 245, 118758 (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).
B.L. Edlow, et al., Personalized connectome mapping to guide targeted therapy and promote recovery of consciousness in the intensive care unit. Neurocritical care 33, 364-375 (2020).
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).