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Colombo, M. A.

Publications and source records attributed to Colombo, M. A..

5 recordsLinked to original sources

Critical dynamics in spontaneous EEG predict perturbational complexity in disorders of consciousness with measurable evoked responses

Identifying which severely brain-injured patients retain the capacity for consciousness remains a major challenge in neurocritical care. The perturbational complexity index (PCI) provides a reliable assessment of consciousness capacity, but its reliance on transcranial magnetic stimulation and EEG (TMS-EEG) limits bedside scalability. PCI and brain criticality capture complementary dimensions of brain dynamics: PCI quantifies the complexity of the brains evoked response to perturbation, whereas criticality characterizes the intrinsic organization of spontaneous activity. Here, we tested whether resting-state EEG signatures of criticality predict PCImax in disorders of consciousness, extending prior findings from anesthesia to severe brain injury. In 26 patients with vascular, traumatic, or anoxic brain injury, multivariate criticality related features did not generalize PCImax prediction across the full heterogeneous cohort. However, criticality features predicted PCImax when analyses were restricted to non-anoxic patients and when restricting analyses to patients with non-zero PCImax values. These findings suggest that spontaneous criticality measures index the brains intrinsic dynamical regime that supports complex perturbational responses, while their correspondence with PCImax depends on whether the injured brain retains sufficient capacity to sustain large-scale evoked responses. Together, our results extend the relationship between resting-state criticality and evoked perturbational complexity to disorders of consciousness and support the development of stratified EEG measures in severe brain injury.

neuroscience↗

Thermodynamics of consciousness: A non-invasive perturbational framework

The quest for reliable and objective measures of consciousness is critical in basic and clinical neuroscience. Across species, the Perturbational Complexity Index (PCI) has emerged as a robust empirical marker by directly perturbing the brain, yet its underlying principles of physics are not fully understood. Here, we bridge this gap by introducing a non-invasive framework based on generative whole-brain models of non-equilibrium brain dynamics. Using these models, we identified violations of the Fluctuation-Dissipation Theorem (FDT) in humans and rodents across wakefulness, anesthesia, and disorders of consciousness. Mirroring the patterns observed with PCI, we found decreased FDT violations in unresponsive disorders of consciousness and anesthesia compared to conscious conditions. This reveals a close link between PCI and non-equilibrium dynamics in spontaneous brain signals, grounding PCI in fundamental principles of physics. Overall, this framework offers new complementary, non-invasive, model-based avenues for understanding the nature of consciousness and for developing objective tools to assess its loss and recovery in health and disease. It also provides a principled foundation for discovering novel strategies to restore consciousness.

neuroscience↗

Slow waves generation and propagation in a model of brain lesions

Slow waves (SWs), the hallmark of non-rapid eye movement (NREM) sleep, reflect the periodic occurrence of transient silent periods in cortical neurons (Down states). During NREM, SWs and Down states physiologically disrupt large-scale network interactions. Since early EEG studies, SWs have also been observed in awake patients after brain injury. Emerging evidence indicates that these intrusions of sleep-like activity interfere with ongoing network activity and contribute to motor and cognitive deficits; yet, the mechanisms governing the generation and spread of post-lesional SWs remain unclear. Here, we extend a neural mass model of EEG to capture transitions between wake-like and sleep-like dynamics and embed it in connectome-based networks with virtual lesions. This model supports that local disfacilitation, topology-dependent propagation, and synchrony-dependent amplification throughout the connectome are sufficient to produce post-lesional SWs. These mechanisms reproduce the spatial gradients of post-lesional SWs seen in patients and identify actionable targets for neuromodulation and rehabilitation.

neuroscience↗

Hemispherotomy: a cortical island of sleep-like activity in awake humans

Hemispherotomy is a neurosurgical procedure for treating refractory epilepsy, which entails disconnecting a significant portion of the cortex, potentially encompassing an entire hemisphere, from its cortical and subcortical connections. While this intervention prevents the spread of seizures, it raises important questions. Given the complete isolation from sensory-motor pathways, it remains unclear whether the disconnected cortex retains any form of inaccessible awareness. More broadly, the activity patterns that large portions of the deafferented cortex can sustain in awake humans remain poorly understood. We address these questions by exploring for the first time the electrophysiological state of the isolated cortex before and after surgery in ten awake pediatric patients. Post-surgery, the isolated cortex exhibited prominent slow oscillations (<2 Hz) and a broad-band shift in power spectral density from high to low frequencies. This resulted in a marked decrease of the spectral exponent, a validated consciousness marker, indicating broad-band slowing characteristic of unconscious states. When compared with a reference pediatric sample across the sleep-wake cycle, the spectral exponent of the contralateral cortex aligned with wakefulness, whereas that of the isolated cortex was consistent with deep NREM sleep. However, spindles did not emerge in the isolated cortex due to the lack of subcortical inputs, constituting a fundamental difference from physiological sleep. These findings demonstrate a unihemispheric sleep-like state during wakefulness, challenging the possibility that hemispherotomy might lead to inaccessible "islands of awareness." Moreover, the persistence of sleep-like patterns years after disconnection provides unique insights into the electrophysiological effects of disconnections in the human brain.

neuroscience↗

Criticality of resting-state EEG predicts perturbational complexity and level of consciousness during anesthesia

1Consciousness has been proposed to be supported by electrophysiological patterns poised at criticality, a dynamical regime which exhibits adaptive computational properties, maximally complex patterns and divergent sensitivity to perturbation. Here, we investigated dynamical properties of the resting-state electroencephalogram of healthy subjects undergoing general anesthesia with propofol, xenon or ketamine. We then studied the relation of these dynamic properties with the perturbational complexity index (PCI), which has shown remarkably high sensitivity in detecting consciousness independent of behavior. All participants were unresponsive under anesthesia, while consciousness was retained only during ketamine anesthesia (in the form of vivid dreams)., enabling an experimental dissociation between unresponsiveness and unconsciousness. We estimated (i) avalanche criticality, (ii) chaoticity, and (iii) criticality-related measures, and found that states of unconsciousness were characterized by a distancing from both the edge of activity propagation and the edge of chaos. We were then able to predict individual subjects PCI (i.e., PCImax) with a mean absolute error below 7%. Our results establish a firm link between the PCI and criticality and provide further evidence for the role of criticality in the emergence of consciousness. 2 Significance StatementComplexity has long been of interest in consciousness science and had a fundamental impact on many of todays theories of consciousness. The perturbational complexity index (PCI) uses the complexity of the brains response to cortical perturbations to quantify the presence of consciousness. We propose criticality as a unifying framework underlying maximal complexity and sensitivity to perturbation in the conscious brain. We demonstrate that criticality measures derived from resting-state electroencephalography can distinguish conscious from unconscious states, using propofol, xenon and ketamine anesthesia, and from these measures we were able to predict the PCI with a mean error below 7%. Our results support the hypothesis that critical brain dynamics are implicated in the emergence of consciousness and may provide new directions for the assessment of consciousness.

neuroscience↗