Developing and Disseminating a Reliable Index to Detect Consciousness at the Patient’s Bedside
INSTITUTION: University of Milan, Italy
PROJECT LEADERS:
PI: Marcello Massimini, MD PhD
CO-PI: Simone Sarasso PhD, Mario Rosanova MD, PhD, Silvia Casarotto PhD
PROJECT DURATION: 3 years
Detecting consciousness in unresponsive patients represents a major scientific challenge with obvious and profound ethical implications. The fundamental aim of this project is to develop and disseminate effective brain-based measures of consciousness that can be applied at the bedside of patients.
Based on the combination of Transcranial Magnetic Stimulation (TMS) and electroencephalography (EEG), we formerly devised a practical index of consciousness (the Perturbational Complexity Index, or PCI) which quantifies the complexity of the spatiotemporal brain activation in response to a direct perturbation. With an extensive empirical effort, we demonstrated that PCI shows an unprecedented accuracy in discriminating consciousness irrespective of responsiveness across a variety of conditions—including sleep, anesthesia, dreaming, and disorders of consciousness. Further, we showed that adapted and simplified methods for PCI calculation can be applied across different scales and models, thus generalizing the original observations obtained in humans. The empirical evidence produced by these works were central in the context of a recent trend in the literature linking practical measures of brain complexity to early theoretical principles and offering interesting vistas on scientific and ethical open questions.
In parallel, key practical progresses were made towards the implementation and dissemination of tools and protocols to simplify, standardize, and generalize brain complexity measures (i.e. PCI) in routine clinical settings. A first step in this direction is represented by the ongoing multi-centric study for the collection of a common dataset across different universities supported by The Tiny Blue Dot Foundation.
Broader Impact:
Developing and disseminating a reliable brain-based measure of consciousness will impact the way consciousness is assessed in hospitals and rehabilitation centers worldwide. This work will open a much wider spectrum of possibilities in our capacity to understand, manipulate and expand human experience.
Publications:
A. Arena, R. Comolatti, S. Thon, A. G. Casali,J. F. Storm, General anesthesia disrupts complex cortical dynamics in response to intracranial electrical stimulation in rats. eNeuro, 8, https://doi.org/10.1523/ENEURO.0343-20.2021 (2021).
T. Bayne, A.K. Seth, , M. Massimini, Are there islands of awareness? Trends in Neurosciences 43, 6–16 (2020).I. Colombi, T. Nieus, M. Massimini, M. Chiappalone, Spontaneous and perturbational complexity in cortical cultures. Brain Sciences 11, 1453 (2021).
A. Comanducci, et al., Clinical and advanced neurophysiology in the prognostic and diagnostic evaluation of disorders of consciousness: Review of an IFCN-endorsed expert group. Clinical Neurophysiology 131, 2736–2765 (2020).R. Comolatti, et al., A fast and general method to empirically estimate the complexity of brain responses to transcranial and intracranial stimulations. Brain Stimulation 12, 1280–1289 (2019).
M. D’Andola, et al. Bistability, causality, and complexity in cortical networks: An in vitro perturbational study. Cerebral Cortex 28, 2233–2242 (2018).
A. Lavazza, M. Massimini, Cerebral organoids: Ethical issues and consciousness assessment. Journal of Medical Ethics 44, 606–610 (2018).
M. Massimini, S. Sarasso, S. Casarotto, M. Rosanova, Measures of differentiation and integration: One step closer to consciousness. Behavioral and Brain Sciences 45, e54.
S. Sarasso, , et al., Consciousness and complexity: A consilience of evidence. Neuroscience of Consciousness, https://doi.org/10.1093/nc/niab023 (2021).