Yonatan Sanz Perl

University Pompeu Fabra | UPF

Severely brain-injured patients may enter a spectrum of conditions collectively known as disorders of consciousness (DoC). This spectrum includes clinical categories such as unresponsive wakefulness syndrome or minimally conscious state, where the behavioral assessment of consciousness can often be deceptive. To bridge this dissociation, neuroimagi...

Psilocybin has been shown to induce fast and sustained improvements in mental well-being across various populations, yet its long-term mechanisms of action are not fully understood. Initial evidence suggests that longitudinal functional and structural brain changes implicate fronto-striatal-thalamic (FST) circuitry, a broad system involved in goal-...

Adaptive cognition relies on cooperation across anatomically distributed brain circuits. However, specialised neural systems are also in constant competition for limited processing resources. How does the brain's network architecture enable it to balance these cooperative and competitive tendencies? Here we use computational whole-brain modelling t...

Resting-state functional magnetic resonance imaging evolves through a repertoire of functional connectivity patterns which might reflect ongoing cognition, as well as the contents of conscious awareness. We investigated whether the dynamic exploration of these states can provide robust and generalizable markers for the state of consciousness in hum...

Neuroimaging studies have identified significant age-related disruptions in whole-brain dynamics, yet the influence of women's reproductive stages and associated hormonal shifts remains underexplored. This study leverages resting-state fMRI data from the Human Connectome Project in Aging to examine brain dynamics through five reproductive stages: r...

Disorders of consciousness (DoC) represent a challenging and complex group of neurological conditions characterised by profound disturbances in consciousness. The current range of treatments for DoC is limited. This has sparked growing interest in developing new treatments, including the use of psychedelic drugs. Nevertheless, clinical investigatio...

INTRODUCTION Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline. Although traditional methods have provided insights into brain dynamics in AD, they have limitations in capturing non-equilibrium dynamics across disease stages. Recent studies suggest that dynamic functional connectivity in resting...

Depression is a multifactorial clinical syndrome with a low pharmacological treatment response rate. Therefore, identifying predictors of treatment response capable of providing the basis for future developments of individualized therapies is crucial. Here, we applied model-free and model-based measures of whole-brain turbulent dynamics in resting-...

The study of disorders of consciousness (DoC) is very complex because patients are suffering from a wide variety of lesions, affected brain mechanisms, different symptom severity and are unable to communicate. Combining neuroimaging data and mathematical modeling can help us quantify and better describe some of these alterations. This study's goal...

The multidimensional nature of schizophrenia requires a comprehensive exploration of the functional and structural brain networks. While prior research has provided valuable insights into these aspects, our study goes a step further to investigate the reconfiguration of the hierarchy of brain dynamics, which can help understand how brain regions in...

Disorders of consciousness (DoC), including the unresponsive wakefulness syndrome (UWS) and the minimally conscious state (MCS), have limited treatment options. Recent research suggests that psychedelic drugs, known for their complexity-enhancing properties, could be promising treatments for DoC. This study uses whole-brain computational models to...

Effective interventions for neuropsychiatric disorders may work by rebalancing the brain’s functional hierarchical organization. Here we directly investigated the effects of two different serotonergic pharmacological interventions on functional brain hierarchy in major depressive disorder in a two-arm double-blind phase II randomized controlled tri...

Different whole-brain computational models have been recently developed to investigate hypotheses related to brain mechanisms. Among these, the Dynamic Mean Field (DMF) model is particularly attractive, combining a biophysically realistic model that is scaled up via a mean-field approach and multimodal imaging data. However, an important barrier to...

Computational whole-brain models describe the resting activity of each brain region based on a local model, inter-regional functional interactions, and a structural connectome that specifies the strength of inter-regional connections. Strokes damage the healthy structural connectome that forms the backbone of these models and produce large alterati...

The brain needs to perform time-critical computations to ensure survival. A potential solution lies in the non-local, distributed computation at the whole-brain level made possible by criticality and amplified by the rare long-range connections found in the brain's unique anatomical structure. This non-locality can be captured by the mathematical s...

As a response to the environment and internal signals, brain networks reorganize on a sub-second scale. To capture this reorganization in patients with disorders of consciousness and understand their residual brain activity, we investigated the dynamics of electroencephalography (EEG) microstates. We analyze EEG microstate markers to quantify the p...

A fundamental challenge in neuroscience is accurately defining brain states and predicting how and where to perturb the brain to force a transition. Here, we investigated resting-state fMRI data of patients suffering from disorders of consciousness (DoC) after coma (minimally conscious and unresponsive wakefulness states) and healthy controls. We a...

Background The hypothesis of decreased neural inhibition in dementia has been sparsely studied in functional magnetic resonance imaging (fMRI) data across patients with different dementia subtypes, and the role of social and demographic heterogeneities on this hypothesis remains to be addressed. Methods We inferred regional inhibition by fitting a...

The brain is able to sustain many different states as shown by the daily natural transitions between wakefulness and sleep. Yet, the underlying complex dynamics of these brain states are essentially in non-equilibrium. Here, we develop a thermodynamical formalism based on the off-equilibrium extension of the fluctuation-dissipation theorem (FDT) to...

The transition towards the brain state induced by psychedelic drugs is frequently neglected in favor of a static description of their acute effects. We used a time-dependent whole-brain model to reproduce large-scale brain dynamics measured with fMRI from 15 volunteers under 20 mg of bolus intravenous N,N-Dimethyltryptamine (DMT), a short-lasting p...

Brain signal irreversibility has been shown to be a promising approach to study neural dynamics. Nevertheless, the relation with cortical hierarchy and the influence of different electrophysiological features is not completely understood. In this study, we recorded local field potentials (LFPs) during spontaneous behavior, including awake and sleep...

Disorders of consciousness (DoC) are a challenging and complex group of neurological conditions characterised by absent or impaired awareness. The current range of therapeutic options for DoC patients is limited, offering few non-invasive pharmacological alternatives. This situation has sprung a growing interest in the development of novel treatmen...

The brain is a nonequilibrium system whose dynamics change in different brain states, such as wakefulness and deep sleep. Thermodynamics provides the tools for revealing these nonequilibrium dynamics. We used violations of the fluctuation-dissipation theorem to describe the hierarchy of nonequilibrium dynamics associated with different brain states...

Resting-state functional magnetic resonance imaging evolves through a repertoire of functional connectivity patterns which might reflect ongoing cognition, as well as the contents of conscious awareness. We investigated whether the dynamic exploration of these states can provide robust and generalizable markers for the state of consciousness in hum...

The revolutionary discovery of resting state networks radically shifted the focus from the role of local regions in cognitive tasks to the ongoing spontaneous dynamics in global networks. Yet, there is a growing realisation that these resting state networks could be a bit like the shadow tracings in Plato's famous cave, perhaps mere epiphenomena of...

Large-scale brain networks reveal structural connections as well as functional synchronization between distinct regions of the brain. The latter, referred to as functional connectivity (FC), can be derived from neuroimaging techniques such as functional magnetic resonance imaging (fMRI). FC studies have shown that brain networks are severely disrup...

Brain signal irreversibility has been shown to be a promising approach to study neural dynamics. Nevertheless, the relation with cortical hierarchy and the influence of different electrophysiological features is not completely understood. In this study, we recorded local field potentials (LFPs) during spontaneous behavior, including awake and sleep...

A fundamental challenge in neuroscience is accurately defining brain states and predicting how and where to perturb the brain to force a transition. The ability to promote a transition from one brain state to another by externally driven stimulation could significantly impact rehabilitation and treatments for patients suffering from complex brain i...

Surviving and thriving in a complex world require intricate balancing of higher order brain functions with essential survival-related behaviours. Exactly how this is achieved is not fully understood but a large body of work has shown that different regions in the prefrontal cortex (PFC) play key roles for diverse cognitive and emotional tasks inclu...

Brain states are frequently represented using a unidimensional scale measuring the richness of subjective experience (level of consciousness). This description assumes a mapping between the high-dimensional space of whole-brain configurations and the trajectories of brain states associated with changes in consciousness, yet this mapping and its pro...

One of the potential and promising adjuvant therapies for Alzheimer’s disease is that of non-invasive transcranial neurostimulation to potentiate cognitive training interventions. Conceptually, this is achieved by driving brain dynamics towards an optimal state for an effective facilitation of cognitive training interventions. However, current neur...

Psychedelic drugs, including lysergic acid diethylamide (LSD) and other agonists of the serotonin 2A receptor (5HT2A‑R), induce drastic changes in subjective experience, and provide a unique opportunity to study the neurobiological basis of consciousness. One of the most notable neurophysiological signatures of psychedelics, increased entropy in sp...

Fast, efficient information transfer is essential for the brain to ensure survival. As recently shown in functional magnetic resonance imaging with high spatial resolution, turbulence appears to offer a fundamental way to facilitate energy and information transfer across spatiotemporal scales in brain dynamics. However, given that this imaging moda...

Life is a constant battle against equilibrium. From the cellular level to the macroscopic scale, living organisms as dissipative systems require the violation of their detailed balance, i.e. metabolic enzymatic reactions, in order to survive. We present a framework based on temporal asymmetry as a measure of non-equilibrium. By means of statistical...

The brain is a non-equilibrium system whose dynamics change in different brain states, such as wakefulness and deep sleep. Thermodynamics provides the tools for revealing these non-equilibrium dynamics. We used violations of the fluctuation-dissipation theorem to describe the hierarchy of non-equilibrium dynamics associated with different brain sta...

The treatment of neurodegenerative diseases is hindered by lack of interventions capable of steering multimodal whole-brain dynamics towards patterns indicative of preserved brain health. To address this problem, we combined deep learning with a model capable of reproducing whole-brain functional connectivity in patients diagnosed with Alzheimer's...

Identifying the functional specialization of the brain has moved from using cognitive tasks and resting state to using ecological relevant, naturalistic movies. We leveraged a large-scale neuroimaging dataset to directly investigate the hierarchical reorganization of functional brain activity when watching naturalistic films compared to performing...

Large variability exists across brain regions in health and disease, considering their cellular and molecular composition, connectivity and function. Large-scale whole-brain models comprising coupled brain regions provide insights into the underlying dynamics that shape complex patterns of spontaneous brain activity. In particular, biophysically gr...

Comprehensive integration of structural and functional connectivity data is required to model brain functions accurately. While resources for studying the structural connectivity of non-human primate brains already exist, their integration with functional connectivity data has remained unavailable. Here we present a comprehensive resource that inte...

Significant advances in non-linear dynamics and computational modeling have opened up the possibility of studying how whole-brain dynamics may be impacted by brain injury. Importantly, by looking at the local level of synchronization, it is possible to obtain a comprehensive characterization of the spatiotemporal patterns affected at different spat...

Human behavior and cognitive function correlate with complex patterns of spatio-temporal brain dynamics, which can be simulated using computational models with different degrees of biophysical realism. We used a data-driven optimization algorithm to determine and classify the types of local dynamics that enable the reproduction of different observa...

Despite decades of research, there is still a lack of understanding of the role and generating mechanisms of the ubiquitous fluctuations and oscillations found in recordings of brain dynamics. Here, we used whole-brain computational models capable of presenting different dynamical regimes to reproduce empirical data’s turbulence level. We showed th...

Brain states are frequently represented using a unidimensional scale measuring the richness of subjective experience (level of consciousness). This description assumes a mapping between the high-dimensional space of whole-brain configurations and the trajectories of brain states associated with changes in consciousness, yet this mapping and its pro...

The treatment of neurodegenerative diseases is hindered by lack of interventions capable of steering multimodal whole-brain dynamics towards patterns indicative of preserved brain health. To address this problem, we combined deep learning with a model capable of reproducing whole-brain functional connectivity in patients diagnosed with Alzheimer's...

The self-organising global dynamics underlying brain states emerge from complex recursive nonlinear interactions between interconnected brain regions. Until now, most efforts of capturing the causal mechanistic generating principles have supposed underlying stationarity, being unable to describe the non-stationarity of brain dynamics, i.e. time-dep...

Human behavior and cognitive function correlate with complex patterns of spatio-temporal brain dynamics, which can be simulated using computational models with different degrees of biophysical realism. We used a data-driven optimization algorithm to determine and classify the types of local dynamics that enable the reproduction of different observa...

Finding precise signatures of different brain states is a central, unsolved question in neuroscience. We reformulated the problem to quantify the ‘inside out’ balance of intrinsic and extrinsic brain dynamics in brain states. The difference in brain state can be described as differences in the detailed causal interactions found in the underlying in...

Dissipative systems evolve in the preferred temporal direction indicated by the thermodynamic arrow of time. The fundamental nature of this temporal asymmetry led us to hypothesize its presence in the neural activity evoked by conscious perception of the physical world, and thus its covariance with the level of conscious awareness. We implemented a...

Different whole-brain models constrained by neuroimaging data have been developed during the last years to investigate causal hypotheses related to brain mechanisms. Among these, the Dynamic Mean Field (DMF) model is a particularly attractive model, combining a biophysically realistic single-neuron model that is scaled up via a mean-field approach...

Psychedelic drugs show promise as safe and effective treatments for neuropsychiatric disorders, yet their mechanisms of action are not fully understood. A fundamental hypothesis is that psychedelics work by dose-dependently changing the functional hierarchy of brain dynamics, but it is unclear whether different psychedelics act similarly. Here, we...

Brain dynamics have recently been shown to be modulated by rhythmic changes in female sex hormone concentrations across an entire menstrual cycle. However, many questions remain regarding the specific differences in information processing across spacetime between the two main follicular and luteal phases in the menstrual cycle. Using a novel turbul...

How the brain constructs gender identity is largely unknown, but some neural differences have recently been discovered. Here, we used an intrinsic-ignition framework to investigate if gender identity changes the propagation of the neural activity across the whole-brain network and within resting-state networks. Studying 29 transmen and 17 transwome...

Understanding the brain changes occurring during aging can provide new insights for developing treatments that alleviate or reverse cognitive decline. Neurostimulation techniques have emerged as potential treatments for brain disorders and to improve cognitive functions. Nevertheless, given the ethical restrictions of neurostimulation approaches, i...

The self-organising global dynamics underlying brain states emerge from complex recursive nonlinear interactions between interconnected brain regions. Until now, all efforts of capturing the causal mechanistic generating principles have proven elusive, since they have been unable to describe the non-stationarity of brain dynamics, i.e. time-depende...

The self-organising global dynamics underlying brain states emerge from complex recursive nonlinear interactions between interconnected brain regions. Until now, all efforts of capturing the causal mechanistic generating principles have proven elusive, since they have been unable to describe the non-stationarity of brain dynamics, i.e. time-depende...

Even though the fundamental laws of physics are the same when the direction of time is inverted, dissipative systems evolve in the preferred temporal direction indicated by the thermodynamic arrow of time. The fundamental nature of this temporal asymmetry led us to hypothesize its presence in the neural activity evoked by conscious perception of th...

N,N-Dimethyltryptamine (DMT) is a classic psychedelic capable of inducing short-lasting but profound changes in consciousness. As with other psychedelics, the experience induced by DMT strongly depends upon contextual factors, yet the neurobiological determinants of this variability remain unknown. The present study investigated changes in neural o...

Recently, significant advances have been made by identifying the levels of synchronicity of the underlying dynamics of a given brain state. This research has demonstrated that unconscious dynamics tend to be more synchronous than those found in conscious states, which are more asynchronous. Here we go beyond this dichotomy to demonstrate that the d...

Going beyond previous research, we use strength-dependent perturbation to obtain a deeper understanding of the mechanisms underlying the emergence of large-scale brain activity. Despite decades of research, we still have a shallow understanding of the role and generating mechanisms of the ubiquitous fluctuations and oscillations found in recordings...

Even though the fundamental laws of physics are the same when the direction of time is inverted, dissipative systems evolve in the preferred temporal direction indicated by the thermodynamic arrow of time. The fundamental nature of this temporal asymmetry led us to hypothesize its presence in the neural activity evoked by conscious perception of th...