Integrating Cross-species And Cross-modal Approaches To Identify And Modulate States Of Consciousness
Chair(s): Jitka Annen (-Ghent university, department of data analysis (BE) -University of Liège, Coma Science Group (BE))
Abstract
This symposium unites cross-species, cross-modal research to investigate brain states linked to consciousness, aiming to pinpoint neural correlates and ultimately enhance treatments for disorders of consciousness (DoC).
Across species, perturbations of consciousness have been consistently associated with changes in the dynamical regime of brain activity and connectivity. We explore recent insights into brain-state origins and mechanisms in humans and non-human animals (macaques, marmosets, mice, and hamsters) during physiological, pharmacological, and pathological consciousness disruptions—such as sleep, anesthesia, DoC, epilepsy, torpor, and psychedelics. This research combines functional MRI for spatial insights with electrophysiology for layer- and frequency-specific resolution. To highlight translational potential, we discuss direct comparisons of brain dynamics from the same modality (functional MRI) and same perturbation (anaesthesia) across human, macaque, marmoset and mouse.
We also delve into pharmacological (amantadine, zolpidem) and brain stimulation (transcranial direct current stimulation, deep brain stimulation) methods to restore consciousness and associated brain states. We provide evidence of subjective experiences triggered by intracranial stimulation in human patients and the reversal of anesthesia effects in macaques via deep-brain stimulation. We argue that limited success in current therapeutic approaches for DoC patients might stem from insufficiently targeted brain-state interventions.
Finally, we integrate these diverse findings into a coherent mechanistic account, using whole-brain biophysical modelling based on species-specific structural connectivity and gene expression. We propose that an integrated framework might help identify consistent neural mechanisms related to consciousness, and advance the scientific study of consciousness and lead to the development of better-targeted therapies for patients suffering from DoC.
Rationale on symposium's general scientific interest
The neurobiological mechanisms that support consciousness and may permit its restoration in clinical populations remain poorly understood - leaving a pressing unmet scientific and clinical need. The neural-behavioural manifestations of sleep and pharmacology resemble DoC and are highly phylogenetically conserved, offering potential for studying consciousness in species that are more amenable to invasive experimental manipulations, and translating the resulting insights back to humans.
Our symposium distills experimental and computational evidence about bi-directional causal manipulations of brain and consciousness across species. These mechanistic insights about the structural and neuromodulatory determinants of brain activity will be relevant for scientific and medical audiences alike.
Rationale on complementarity of talks
Our talks offer synergy across multiple dimensions. First, by studying diverse species: humans (for subjective reports), rodents (for invasive manipulation), and non-human primates (for translational insights). Second, we explore varied perturbations, including human brain injuries (with clinical relevance), natural sleep, and controlled pharmacological interventions like anesthesia and psychedelics. Third, we combine broad functional MRI coverage with electrophysiology's layer- and frequency-specific insights. Integrating focal intracranial and deep-brain stimulation with whole-brain interventions allows us to link local and global aspects of consciousness. Finally, computational models deepen our causal understanding. This integrative approach advances neuromodulation targets and clarifies consciousness mechanisms across species.
Rationale on timeliness/importance
The science of consciousness is advancing rapidly with new tools for recording, model organisms, and causal interventions revealing neural mechanisms underlying conscious states. Yet, treatments for disorders of consciousness (DoC) remain limited. Research on brain states and consciousness is often disconnected from brain stimulation approaches. This symposium unites findings across species using advanced brain recording and stimulation techniques, offering insights into consciousness correlates and treatment possibilities for DoC. We demonstrate how modulating specific neural targets impacts consciousness, supported by computational models and detailed connectivity maps of human and macaque brains, enabling meaningful predictions of brain perturbation effects.
Rationale on panel inclusivity
Our panelists come from diverse countries across three continents, with most trained and working outside their home countries. The group is gender-balanced and spans academic ranks, from postdoc to full professor. Expertise spans species—from humans and clinical patients (DL, AIL, JA) to non-human primates and mammals (MJR, AIL, VV)—and techniques, including MRI (AIL, DL, JA), transcriptomics (AIL), electrophysiology (MJR, DL), and pharmacology (AIL, MJR, VV). Disciplines include circuit and systems neuroscience (MJR, VV), clinical neuroscience (AIL, DL, JA), philosophy, cognitive science (AIL, MJR, JA, DL), and engineering (AIL), enriching our perspectives on consciousness research.
Presentations of the Symposium
Causal Evidence About Brain Function and Consciousness From Direct Electrical Stimulation in the Human Brain
Dian Lyu
-Stanford University, Department of Neurology and Neurological Sciences, School of Medicine (USA) -Stanford University, Laboratory of Behavioral and Cognitive Neuroscience (USA)
Neuroimaging studies have repeatedly demonstrated functional architectures in the human brain related to consciousness states and contents. Despite this promise, a significant bottleneck in these studies and the resulting theories lies in the lack of causal evidence. In this context, direct electrical stimulation provides crucial insights into the causal mapping between the brain and the mind.
In this talk, I will present an “unconventional” study paradigm for investigating the neural substrate of consciousness through invasive techniques (i.e., intracranial electroencephalography and electrical brain stimulation) in a clinical cohort of highly functional epileptic patients. The causal evidence from direct electrical stimulation comes from two aspects: first, the subjective feelings elicited by perturbations at a focal brain site (using a 50 Hz functional mapping stimulation protocol); and second, the causal connectivity between brain sites established via a 0.5 Hz single-pulse stimulation protocol.
The talk will be organized into two parts. In the first part, I will overview the various perceptual, motor, and cognitive effects elicited by stimulation in different brain regions. Particularly, I will highlight our recent finding on the anterior precuneus, which elicited self-dissociative symptoms. In the second part, I will introduce repeated single-pulse electrical stimulation and its utility in mapping causal electrophysiological connectivity across the brain. By stimulating and recording from approximately 4,500 electrode contacts across 27 participants, we have mapped corticocortical, corticothalamic, and thalamocortical connections, which may inform future studies on system control and whole-brain modeling.
Central Thalamic Deep Brain Stimulation to Exert Bidirectional Control of Consciousness
Michelle Redinbaugh
-University of Wisconsin-Madison, Department of Psychology (USA) -Stanford University, Department of of Biology (USA)
Research suggests consciousness depends on complex cortico-cortical communication. However, the relative importance of anterior, posterior, and subcortical regions, as well as feedforward and feedback pathways remains contested. The central lateral thalamus, with projections to both frontal and parietal cortex has the potential to influence communication in these pathways, and thus, consciousness. Indeed, case studies and animal research suggest that central thalamic deep brain stimulation (DBS) leads to improvements in disorders of consciousness (DOC). However, parallel lines of research link similar treatments to DOC such as absence epilepsy. To test the bidirectional role of the central thalamus in consciousness, we performed thalamic DBS in macaque monkeys during general anesthesia and natural wakefulness. Frequency-specific DBS proved effective, increasing consciousness in anesthetized animals and causing vacancy in wakeful animals. To identify pathway specific signatures of consciousness, we performed simultaneous multielectrode recordings from frontal, parietal, striatal and thalamic regions in macaque monkeys across natural (resting wakefulness and sleep) and manipulated (propofol and isoflurane general anesthesia and DBS conditions) states of consciousness. Our results show that conscious states strongly associate with complex information in parieto-striato-thalamic circuits. Anesthesia disrupts consciousness by reducing frequency-specific communication in specific feedforward, feedback, and intracolumnar pathways. Thalamic DBS restores network connectivity by reactivating deep cortical neurons and permitting functional cortico-cortical communication. High and low-frequency thalamic DBS instead disrupts consciousness by isolating network components in a dominant low-frequency regime. These results further our understanding about the neural mechanisms of consciousness and suggest specific thalamic neuromodulation may prove an effective treatment for DOC.
Elucidating Mechanisms and Functions of “Default” Brain States: From Torpor to Psychedelics
Vladyslav Vyazovskiy
-University of Oxford, Department of Physiology, Anatomy and Genetics -University of Oxford, Kavli Institute for Nanoscience Discovery
Typically, brain states are classified into wake, non-rapid eye movement sleep, and rapid eye movement sleep, which are distinguished by the EEG and underlying neural activity. In addition to these three fundamental global states of arousal, there is a variety of mixed or entirely distinct states where features of waking and sleep coexist. For example, sleep-like slow waves have been observed in awake animals after sleep deprivation, in patients with stroke or brain injury, during anaesthesia, coma, or in an immature brain during early ontogeny, which led to the concept of a “default state”, where the brain always gravitates to in the absence of stimulation or an excitatory input.
Here I will discuss brain activity and dynamics during non-ordinary brain states occurring during deep hypometabolism (torpor) and after treatment with psychedelics in laboratory mice and hamsters. During torpor, EEG resembles deep sedation or anaesthesia, but the state is easily reversible, and paradoxically the cortical responses to sensory stimulation are enhanced. In contrast, psychedelics, such as psilocin or 5-MeO DMT lead to an acute induction of a dissociated state of arousal, characterised by prominent sleep-like slow waves in the cortex and marked pupil dilation in behaviourally awake, moving animals. I conclude that dissociated brain states combining features of waking and sleep may fundamentally underpin the well-known features of altered states of consciousness, such as disconnection or dream-like hallucinations. Elucidating the neurobiological mechanisms of non-ordinary brain states is essential for making progress in management and treatment of consciousness disorders.
Systematic Phenotyping of Mammalian Brain Dynamics Reveals an Evolutionarily Conserved Dynamical Regime of Anaesthesia
Luppi Andrea
-University of Cambridge Department of Engineering (UK) -University of Oxford Department of Psychiatry (UK) -Montreal Neurological Institute, McGill University (Canada)
Systematically and reversibly perturbing brain function with anaesthesia while recording neural activity provides a unique opportunity to understand how local dynamics mediate the link between neurobiological organisation and consciousness.
Here I will discuss recent work searching for a shared mechanism whereby diverse anaesthetics change the dynamical regime of the mammalian brain to induce unconsciousness. We applied massive temporal feature extraction to generate more than 6000 dynamical features that comprehensively characterise local neural activity from functional MRI signals in humans, macaques, marmosets, and mice, comparing wakefulness against a wide range of anaesthetics. We identified an evolutionarily conserved dynamical profile of anaesthesia. Brain activity under anaesthesia remains more localised both spatially and temporally. This is consistent with work showing that under anaesthesia, both spontaneous and stimulus-evoked activity remains localised and fails to propagate globally.
I will show that spatial transcriptomics across humans, macaques, and mice indicates that this shared dynamical regime of anaesthesia is underpinned by a phylogenetically conserved axis of gene expression pertaining to regulation of arousal and sleep-wake cycles. The dynamical signature of anaesthesia is reversed upon spontaneous awakening in humans, and upon re-awakening induced by deep-brain stimulation of the central thalamus in macaques, demonstrating that it is amenable to bi-directional control by pharmacology and local stimulation. Finally, I will show that we can reproduce or reverse the dynamical regime of the anaesthetised brain in silico with a biophysical computational model based on structural connectivity, providing mechanistic insights into its origins and indicating avenues for potential therapeutic intervention.
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