Marcello Massimini

Marcello Massimini
University of Milan | UNIMI · Department of Biomedical and Clinical Sciences "Luigi Sacco"

MD, PhD

About

229
Publications
459,385
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22,960
Citations
Additional affiliations
January 2009 - present
University of Liège
January 2004 - December 2011
University of Wisconsin–Madison
January 2001 - December 2002
Université Laval

Publications

Publications (229)
Article
Full-text available
Objective Validating objective, brain‐based indices of consciousness in behaviorally unresponsive patients represents a challenge due to the impossibility of obtaining independent evidence through subjective reports. Here we address this problem by first validating a promising metric of consciousness—the Perturbational Complexity Index (PCI)—in a b...
Article
Full-text available
A common endpoint of general anesthetics is behavioral unresponsiveness [1], which is commonly associated with loss of consciousness. However, subjects can become disconnected from the environment while still having conscious experiences, as demonstrated by sleep states associated with dreaming [2]. Among anesthetics, ketamine is remarkable [3] in...
Article
Full-text available
During non-rapid eye movement (NREM) sleep (stage N3), when consciousness fades, cortico-cortical interactions are impaired while neurons are still active and reactive. Why is this? We compared cortico-cortical evoked-potentials recorded during wakefulness and NREM by means of time-frequency analysis and phase-locking measures in 8 epileptic patien...
Article
Full-text available
One challenging aspect of the clinical assessment of brain-injured, unresponsive patients is the lack of an objective measure of consciousness that is independent of the subject's ability to interact with the external environment. Theoretical considerations suggest that consciousness depends on the brain's ability to support complex activity patter...
Article
Full-text available
Patients surviving severe brain injury may regain consciousness without recovering their ability to understand, move and communicate. Recently, electrophysiological and neuroimaging approaches, employing simple sensory stimulations or verbal commands, have proven useful in detecting higher order processing and, in some cases, in establishing some d...
Preprint
Signatures of consciousness are found in spectral and temporal properties of neuronal activity. Among these, spatiotemporal complexity after a perturbation has recently emerged as a robust metric to infer levels of consciousness. Perturbation paradigms remain, however, difficult to perform routinely. To discover alternative paradigms and metrics we...
Preprint
Signatures of consciousness are found in spectral and temporal properties of neuronal activity. Among these, spatiotemporal complexity after a perturbation has recently emerged as a robust metric to infer levels of consciousness. Perturbation paradigms remain, however, difficult to perform routinely. To discover alternative paradigms and metrics we...
Article
Full-text available
By connecting old and recent notions, different spatial scales, and research domains, we introduce a novel framework on the consequences of brain injury focusing on a key role of slow waves. We argue that the long-standing finding of EEG slow waves after brain injury reflects the intrusion of sleep-like cortical dynamics during wakefulness; we illu...
Preprint
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Hemispherotomy is a surgical procedure that disconnects a large portion of the cerebral cortex from cortical and subcortical inputs in patients with severe refractory epilepsy. Whether the disconnected cortex - inaccessible to behavioral assessment - supports consciousness remains unknown. Functional MRI studies have indicated preserved resting-sta...
Preprint
Background: Acute ischemia triggers a number of cellular mechanisms not only leading to excitotoxic cell death but also to enhanced neuroplasticity, facilitating neuronal reorganization and functional recovery. Objective: Identifying their critical distinction and transferring these cellular mechanisms to neurophysiological correlates adaptable to...
Preprint
Introduction Recent studies have shown that, following brain injury, sleep-like cortical dynamics intrude into wakefulness, potentially contributing to brain network disruption and behavioral deficits. Aim We employ TMS in combination with EEG to detect these dynamics and assess their impact on brain networks and clinical evolution in awake stroke...
Article
The analysis of spontaneous electroencephalogram (EEG) is a cornerstone in the assessment of patients with disorders of consciousness (DoC). Although preserved EEG patterns are highly suggestive of consciousness even in unresponsive patients, moderately or severely abnormal patterns are difficult to interpret. Indeed, growing evidence shows that co...
Article
Mismatch negativity (MMN) and P3b are well known for their clinical utility. There exists no gold standard, however, for acquiring them as EEG markers of consciousness in clinical settings. This may explain why the within‐individual sensitivity of MMN/P3b paradigms is often quite poor and why seemingly identical EEG markers can behave differently a...
Preprint
How is conscious experience related to material brain processes? A variety of theories aiming to answer this age-old question have emerged from the recent surge in consciousness research, and some are now hotly debated. While most researchers have so far focused on the development and validation of their preferred theory in relative isolation, this...
Preprint
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Cortical stimulation with single electrical or magnetic pulses is a popular technique in clinical practice and research. However, we still do not understand the extent to which non-cortical circuits contribute to the associated evoked potentials (EPs). Here we optogenetically dissect the underlying circuit in mice, demonstrating that the late compo...
Article
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Brain complexity relies on the integrity of structural and functional brain networks, where specialized areas synergistically cooperate on a large scale. Local alterations within these areas can lead to widespread consequences, leading to a reduction in overall network complexity. Investigating the mechanisms governing this occurrence and exploring...
Article
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This scientific commentary refers to ‘Functional hub disruption emphasizes consciousness recovery in severe traumatic brain injury’, by Oujamaa et al. (https://doi.org/10.1093/braincomms/fcad319)
Preprint
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Significant advances in the scientific investigation of the neurobiology of consciousness have been slow to be translated into clinical settings, limited by factors of conceptual (e.g., what is consciousness?), methodological (e.g., how to identify reliable indicators of consciousness?), and technical (e.g., how to improve sensitivity and specifici...
Article
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Background: Cortical excitability is higher in unconsciousness than in wakefulness, but it is unclear how this relates to anaesthesia. We investigated cortical excitability in response to dexmedetomidine, the effects of which are not fully known. Methods: We recorded transcranial magnetic stimulation (TMS) and EEG in frontal and parietal cortex...
Article
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Background: The cyclical brain disorder of sensory processing accompanying migraine phases lacks an explanatory unified theory. Methods: We searched Pubmed for non-invasive neurophysiological studies on migraine and related conditions using transcranial magnetic stimulation, electroencephalography, visual and somatosensory evoked potentials. We...
Article
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Human studies employing intracerebral and transcranial perturbations suggest that the input-output properties of cortical circuits are dramatically affected during sleep in healthy subjects as well as in awake patients with multifocal and focal brain injury. In all these conditions, cortical circuits react to direct stimulation with an initial acti...
Article
During development, the brain undergoes radical structural and functional changes following a posterior-to-anterior gradient, associated with profound changes of cortical electrical activity during both wakefulness and sleep. However, a systematic assessment of the developmental effects on aperiodic EEG activity maturation across vigilance states i...
Article
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How can an intentional movement be distinguished from the same movement done nonintentionally? How can this distinction be drawn without asking the subject, or in patients who are unable to communicate? Here we address these questions, by focusing on blinking. This is one of the most frequent spontaneous actions in our daily life, but it can also b...
Preprint
Full-text available
Mismatch negativity (MMN) and P3b are well known for their clinical utility. There exists no gold standard, however, to acquire these markers. This may explain why the within-individual sensitivity of MMN/P3b is often quite poor and why seemingly identical markers can behave differently across studies. Here we compare two traditional paradigms for...
Preprint
Full-text available
Neural bases of consciousness have been explored through many different paradigms and the notion of complexity emerged as a unifying framework to characterize conscious experience. To date, the perturbational complexity index (PCI), rooted on information theory, shows high performance in assessing consciousness. However, the mechanisms underpinning...
Article
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Focal epileptic seizures are characterized by abnormal neuronal discharges that can spread to other cortical areas and interfere with brain activity, thereby altering the patient's experience and behavior. The origin of these pathological neuronal discharges encompasses various mechanisms that converge toward similar clinical manifestations. Recent...
Presentation
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Conscious and unconscious states are characterized by differences in whole brain dynamics as well as differences in the microscale of single neurons. The awake brain generates high-frequency, asynchronous neuronal activity, corresponding to sustained but irregular firing patterns of single neurons, defined as Asynchronous Irregular (AI). On the con...
Article
Early reemergence of consciousness predicts long-term functional recovery for patients with severe brain injury. However, tools to reliably detect consciousness in the intensive care unit are lacking. Transcranial magnetic stimulation electroencephalography has the potential to detect consciousness in the intensive care unit, predict recovery, and...
Article
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Neurophysiological markers can overcome the limitations of behavioural assessments of Disorders of Consciousness (DoC). EEG alpha power emerged as a promising marker for DoC, although long-standing literature reported alpha power being sustained during anesthetic-induced unconsciousness, and reduced during dreaming and hallucinations. We hypothesiz...
Preprint
The analysis of spontaneous EEG is a cornerstone in the assessment of patients with disorders of consciousness (DoC). Alterations in specific frequency bands have been reported, including a predominance of delta power in vegetative state/unresponsive wakefulness syndrome (VS/UWS) patients in contrast with a predominance of alpha activity in minimal...
Article
The review provides a comprehensive update (previous report: Chen R, Cros D, Curra A, Di Lazzaro V, Lefaucheur JP, Magistris MR, et al. The clinical diagnostic utility of transcranial magnetic stimulation: report of an IFCN committee. Clin Neurophysiol 2008;119(3):504-32) on clinical diagnostic utility of transcranial magnetic stimulation (TMS) in...
Preprint
Full-text available
The clinical assessment of patients with disorders of consciousness (DoC) relies on the observation of behavioral responses to standardized sensory stimulation. However, several medical comorbidities may directly impair the production of reproducible and appropriate responses, thus reducing the sensitivity of behavior-based diagnoses. One of these...
Preprint
Full-text available
The clinical assessment of patients with disorders of consciousness (DoC) relies on the observation of behavioral responses to standardized sensory stimulation. However, several medical comorbidities may directly impair the production of reproducible and appropriate responses, thus reducing the sensitivity of behavior-based diagnoses. One of these...
Preprint
Full-text available
Human studies employing intracerebral and transcranial perturbations suggest that the input-output properties of cortical circuits are dramatically affected during sleep in healthy subjects as well as in awake patients with multifocal and focal brain injury. In all these conditions, cortical circuits react to direct stimulation with an initial acti...
Article
Background Cortico-cortical evoked potentials (CCEPs) recorded by stereo-electroencephalography (SEEG) are a valuable tool to investigate brain reactivity and effective connectivity. However, invasive recordings are spatially sparse since they depend on clinical needs. This sparsity hampers systematic comparisons across-subjects, the detection of t...
Article
Interpreting empirical measures of integration and differentiation as indices of cortical performance and memory consolidation during wakefulness rather than consciousness per se is inconsistent with the literature. Recent studies show that these theory-inspired measures can dissociate from such processes and reliably index the brain's capacity for...
Article
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Objective Quantitative Electroencephalography (qEEG) can capture changes in brain activity following stroke. qEEG metrics traditionally focus on oscillatory activity, however recent findings highlight the importance of aperiodic (power-law) structure in characterizing pathological brain states. We assessed neurophysiological alterations and recove...
Article
Full-text available
Consciousness can be defined by two components: arousal (wakefulness) and awareness (subjective experience). However, neurophysiological consciousness metrics able to disentangle between these components have not been reported. Here, we propose an explainable consciousness indicator (ECI) using deep learning to disentangle the components of conscio...
Article
Background Coupling transcranial magnetic stimulation with electroencephalography (TMS-EEG) allows recording the EEG response to a direct, non-invasive cortical perturbation. However, obtaining a genuine TMS-evoked EEG potential requires controlling for several confounds, among which a main source is represented by the auditory evoked potentials (A...
Article
Full-text available
Dissociated cortical neurons in vitro display spontaneously synchronized, low-frequency firing patterns, which can resemble the slow wave oscillations characterizing sleep in vivo. Experiments in humans, rodents, and cortical slices have shown that awakening or the administration of activating neuromodulators decrease slow waves, while increasing t...
Preprint
Full-text available
Background The impact of transcranial magnetic stimulation (TMS) on cortical neurons is currently hard to predict based on a priori biophysical and anatomical knowledge alone. This problem can hamper the reliability and reproducibility of protocols aimed at measuring electroencephalographic (EEG) responses to TMS. New Method We introduce and releas...
Preprint
Full-text available
Background Coupling transcranial magnetic stimulation with electroencephalography (TMS-EEG) allows recording the EEG response to a direct, non-invasive cortical perturbation. However, obtaining a genuine TMS-evoked EEG potential requires controlling for several confounds, among which a main source is represented by the auditory evoked potentials (A...
Article
Full-text available
Over the last years, a surge of empirical studies converged on complexity-related measures as reliable markers of consciousness across many different conditions, such as sleep, anesthesia, hallucinatory states, coma, and related disorders. Most of these measures were independently proposed by researchers endorsing disparate frameworks and employing...
Preprint
Full-text available
Background Quantitative EEG (qEEG) can capture changes in brain activity that follow a stroke. Accordingly, EEG metrics could be used to monitor patients’ state and recovery. Although qEEG metrics traditionally focus on oscillatory activity, recent findings highlight the importance of aperiodic (power-law) structure in characterizing pathological b...
Article
Full-text available
Aim In order to successfully detect, classify, prognosticate, and develop targeted therapies for patients with disorders of consciousness (DOC), it is crucial to improve our mechanistic understanding of how severe brain injuries result in these disorders. Methods To address this need, the Curing Coma Campaign convened a Mechanisms Sub-Group of the...
Preprint
Full-text available
Background Cortical excitability changes across conscious states, being higher in unconsciousness compared to normal wakefulness. Anaesthesia offers controlled manipulation to investigate conscious processes and underlying brain dynamics. Among commonly used anaesthetic agents, dexmedetomidine (DEX) effects are not completely known. In this study,...
Article
Full-text available
Focal cortical lesions are known to result in large-scale functional alterations involving distant areas; however, little is known about the electrophysiological mechanisms underlying these network effects. Here, we addressed this issue by analysing the short and long distance intracranial effects of controlled structural lesions in humans. The cha...
Article
Full-text available
The functional consequences of focal brain injury are thought to be contingent on neuronal alterations extending beyond the area of structural damage. This phenomenon, also known as diaschisis, has clinical and metabolic correlates but lacks a clear electrophysiological counterpart, except for the long-standing evidence of a relative EEG slowing ov...
Chapter
Developing biomarkers for psychiatric disorders represents a major challenge. Indeed, the identification of dependable brain-based measures, such as those derived from electrophysiological techniques, would represent a key step toward better profiling of patients with major psychiatric disorders. A principled neurophysiological approach would also...
Article
Full-text available
The analysis of spontaneous EEG activity and evoked potentials is a cornerstone of the instrumental evaluation of patients with disorders of consciousness (DoC). The past few years have witnessed an unprecedented surge in EEG-related research applied to the prediction and detection of recovery of consciousness after severe brain injury, opening up...
Article
Full-text available
Background The complexity of neurophysiological brain responses to direct cortical stimulation, referred to as the perturbational complexity index (PCI), has been shown able to discriminate between consciousness and unconsciousness in patients surviving severe brain injury as well as several other conditions (e.g., wake, dreamless sleep, sleep and...
Article
Full-text available
Precisely localizing the sources of brain activity as recorded by EEG is a fundamental procedure and a major challenge for both research and clinical practice. Even though many methods and algorithms have been proposed, their relative advantages and limitations are still not well established. Moreover, these methods involve tuning multiple paramete...
Preprint
Full-text available
Precisely localizing the sources of brain activity as recorded by EEG is a fundamental procedure and a major challenge for both research and clinical practice. Even though many methods and algorithms have been proposed, their relative advantages and limitations are still not well established. Moreover, these methods involve tuning multiple paramete...
Preprint
Full-text available
Background: The perturbational complexity index (PCI) is a useful measure of consciousness that combines transcranial magnetic stimulation (TMS) with electroencephalography (EEG). However, the PCI has not been assessed for reliability between sessions nor is there a clear best stimulation target to acquire a PCI. Objective/Hypothesis: We assessed t...
Preprint
Full-text available
The functional consequences of brain injury are known to depend on neuronal alterations extending beyond the area of structural damage. Although a lateralized EEG slowing over the injured hemisphere was known since the early days of clinical neurophysiology, its electrophysiological mechanisms were not systematically investigated. In parallel, basi...
Article
Introduction Peripheral as well as direct cortical stimulations have been classically used to probe the reactivity of thalamocortical circuits across brain states, showing consistent state-dependent modifications. Methods Here we aim at directly comparing state-dependent changes across the wake/sleep cycle of the electroencephalographic (EEG) resp...
Article
Background Direct cortical perturbations had been used to study state-dependent changes in thalamocortical network. TMS combined with EEG has demonstrated consistent modifications among wakefulness, NREM sleep, and anesthesia; furthermore, these measurements resulted useful in the diagnosis and pathophysiological stratification of patients with dis...
Article
Background: The Perturbational Complexity Index (PCI) was recently introduced to assess the capacity of thalamocortical circuits to engage in complex patterns of causal interactions. While showing high accuracy in detecting consciousness in brain-injured patients, PCI depends on elaborate experimental setups and offline processing, and has restric...
Article
Full-text available
Despite the absence of responsiveness during anesthesia, conscious experience may persist. However, reliable, easily acquirable and interpretable neurophysiological markers of the presence of consciousness in unresponsive states are still missing. A promising marker is based on the decay-rate of the power spectral density (PSD) of the resting EEG....
Article
Background and objective: Knowing whether a subject is conscious or not is a current challenge with a deep potential clinical impact. Recent theoretical considerations suggest that consciousness is linked to the complexity of distributed interactions within the corticothalamic system. The fractal dimension (FD) is a quantitative parameter that has...