Adrián Ponce-Alvarez

Modèles probabilistes pour l'étude de la variabilité dans l'activité de neurones individuels et d'ensembles de neurones: Une des caractéristiques les plus singulières de l’activité corticale est son degré élevé de variabilité. Ma thèse dedoctorat s’est focalisée sur l’étude de (i) l’irrégularité des intervalles entre potentiels d’action (PAs)successivement émis par un neurone, et (ii) la variabilité dans l’évolution temporelle de l’activité d’un ensemblede neurones. Premièrement, j’ai étudié l’irrégularité des neurones enregistrés dans le cortex moteur de singesmacaques performant une tâche d’estimation du temps et de préparation à l’action. J’ai montré que l’irrégularitén’est pas un paramètre libre de l’activité neuronale, contrairement au taux de PAs, mais est déterminée par lescontraintes structurelles des réseaux neuronaux. Deuxièmement, j’ai utilisé le modèle de Markov caché (MMC)pour analyser l’activité d’ensembles de neurones enregistrés dans plusieurs aires corticales, sensorielles etmotrices, de singes exécutant une tâche de discrimination tactile. J’ai montré que les processus sensoriels etdécisionnels sont distribués dans plusieurs aires corticales. Les résultats suggèrent que l’action et la décision surlaquelle elle est basée sont reliées par une cascade d’évènements non stationnaires et stochastiques. Finalement,j’ai utilisé le MMC pour caractériser l’activité spontanée d’un ensemble de neurones du cortex préfrontal d’unrat. Les résultats montrèrent que l’alternance entre les états UP et DOWN est un processus stochastique etdynamique. La variabilité apparaît donc aussi bien pendant l’activité spontanée que pendant le comportementactif et semble être contrainte par des facteurs structurels qui, à leur tour, contraignent le mode d’opération desréseaux neuronaux.

A central challenge in neuroscience is to understand how the brain flexibly balances local and distributed information processing to support diverse cognitive and conscious states. We hypothesize that a key signature of this balance is the presence of memory effects, which arise when a brain region's future activity depends not only on its current state, but also on past information fed back from the wider network. Here we introduce the FDTest, a method for assessing local memory effects in multidimensional systems by measuring violations of a generalized Fluctuation-dissipation theorem (FDT). We first apply this framework to whole-brain models fitted to human neuroimaging data, showing that the brain's memory structure reflects its underlying connectivity. We then extend the analysis to individualized models of subjects during wakefulness and deep sleep. Memory effects are consistently stronger in wakefulness, indicating richer inter-regional dependencies and more integrated dynamics. These findings establish local memory as a dynamical marker of brain state and position the FDTest as a principled tool for probing the hidden structure of neural dynamics in both models and experiments.

SUMMARY: Neuronal avalanches are sequences of neural activations exhibiting scale-invariant statistics, indicative of critical dynamics. Theoretical studies proposed that the balance between excitation (E) and inhibition (I), along with neuromodulation, are key factors influencing this critical behavior. Here, we performed in-vivo studies to investigate the role of E and I neurons in generating neuronal avalanches in the optic tectum of zebrafish larvae. For this, we used double-transgenic zebrafish larvae expressing cell-type-specific fluorescent proteins and GCaMP6f, combined with immunostaining and selective-plane illumination microscopy to monitor spontaneous neuronal activity and neurotransmitter identity. We found that neural activity approached criticality at balanced and slightly excitatory-dominated E-I ratios but became disordered when E-I ratios were imbalanced. A stochastic network model operating at a critical point, where excitation and inhibition couplings are balanced and balanced amplification drives network avalanches, successfully reproduced the observed statistics of neuronal avalanches and their dependence on E-I ratio fluctuations.

The brain's activity fluctuations have different temporal scales across the brain regions, with associative regions displaying slower timescales than sensory areas. This hierarchy of timescales has been shown to correlate with both structural brain connectivity and intrinsic regional properties. Here, using publicly available human resting-state fMRI and dMRI data, it was found that, while more structurally connected brain regions presented activity fluctuations with longer timescales, their activity fluctuations presented lower variance. The opposite relationships between the structural connectivity and the variance and temporal scales of resting-state fluctuations, respectively, were not trivially explained by simple network propagation principles. To understand these structure–function relationships, two commonly used whole-brain models were studied, namely, the Hopf and Wilson–Cowan models. These models use the brain's connectome to couple local nodes (representing brain regions) displaying noise-driven oscillations. The models show that the variance and temporal scales of activity fluctuations can oppositely relate to connectivity within specific parameter regions, even when all nodes have the same intrinsic dynamics—but also when intrinsic dynamics are constrained by the myelinization-related macroscopic gradient. These results show that, setting aside intrinsic regional differences, connectivity and network state are sufficient to explain the regional differences in fluctuations’ scales. State dependence supports the vision that structure–function relationships can serve as biomarkers of altered brain states. Finally, the results indicate that the hierarchies of timescales and variances reflect a balance between stability and responsivity, with greater and faster responsiveness at the network periphery, while the network core ensures overall system robustness.

Whole-brain models have proven to be useful to understand the emergence of collective activity among neural populations or brain regions. These models combine connectivity matrices, or connectomes, with local node dynamics, noise, and, eventually, transmission delays. Multiple choices for the local dynamics have been proposed. Among them, nonlinear oscillators corresponding to a supercritical Hopf bifurcation have been used to link brain connectivity and collective phase and amplitude dynamics in different brain states. Here, we studied the linear fluctuations of this model to estimate its stationary statistics, i.e., the instantaneous and lagged covariances and the power spectral densities. This linear approximation—that holds in the case of heterogeneous parameters and time-delays—allows analytical estimation of the statistics and it can be used for fast parameter explorations to study changes in brain state, changes in brain activity due to alterations in structural connectivity, and modulations of parameter due to non-equilibrium dynamics.

Whole-brain models have proven to be useful to understand the emergence of collective activity among neural populations or brain regions. These models combine connectivity matrices, or connectomes, with local node dynamics, noise, and, eventually, transmission delays. Multiple choices for the local dynamics have been proposed. Among them, nonlinear oscillators corresponding to a supercritical Hopf bifurcation have been used to link brain connectivity and collective phase and amplitude dynamics in different brain states. Here, we studied the linear fluctuations of this model to estimate its stationary statistics, i.e., the instantaneous and lagged covariances and the power spectral densities. This linear approximation ⸺that holds in the case of heterogeneous parameters and time-delays⸺ allows analytical estimation of the statistics and it can be used for fast parameter explorations to study changes in brain state, changes in brain activity due to alterations in structural connectivity, and modulations of parameter due to non-equilibrium dynamics.

Scale invariance is a characteristic of neural activity. How this property emerges from neural interactions remains a fundamental question. Here, we studied the relation between scale-invariant brain dynamics and structural connectivity by analyzing human resting-state (rs-) fMRI signals, together with diffusion MRI (dMRI) connectivity and its approximation as an exponentially decaying function of the distance between brain regions. We analyzed the rs-fMRI dynamics using functional connectivity and a recently proposed phenomenological renormalization group (PRG) method that tracks the change of collective activity after successive coarse-graining at different scales. We found that brain dynamics display power-law correlations and power-law scaling as a function of PRG coarse-graining based on functional or structural connectivity. Moreover, we modeled the brain activity using a network of spins interacting through large-scale connectivity and presenting a phase transition between ordered and disordered phases. Within this simple model, we found that the observed scaling features were likely to emerge from critical dynamics and connections exponentially decaying with distance. In conclusion, our study tests the PRG method using large-scale brain activity and theoretical models and suggests that scaling of rs-fMRI activity relates to criticality.

A topic of growing interest in computational neuroscience is the discovery of fundamental principles underlying global dynamics and the self-organization of the brain. In particular, the notion that the brain operates near criticality has gained considerable support, and recent work has shown that the dynamics of different brain states may be modeled by pairwise maximum entropy Ising models at various distances from a phase transition, i.e., from criticality. Here we aim to characterize two brain states (psychedelics-induced and placebo) as captured by functional magnetic resonance imaging (fMRI), with features derived from the Ising spin model formalism (system temperature, critical point, susceptibility) and from algorithmic complexity. We hypothesized, along the lines of the entropic brain hypothesis, that psychedelics drive brain dynamics into a more disordered state at a higher Ising temperature and increased complexity. We analyze resting state blood-oxygen-level-dependent (BOLD) fMRI data collected in an earlier study from fifteen subjects in a control condition (placebo) and during ingestion of lysergic acid diethylamide (LSD). Working with the automated anatomical labeling (AAL) brain parcellation, we first create “archetype” Ising models representative of the entire dataset (global) and of the data in each condition. Remarkably, we find that such archetypes exhibit a strong correlation with an average structural connectome template obtained from dMRI (r = 0.6). We compare the archetypes from the two conditions and find that the Ising connectivity in the LSD condition is lower than in the placebo one, especially in homotopic links (interhemispheric connectivity), reflecting a significant decrease of homotopic functional connectivity in the LSD condition. The global archetype is then personalized for each individual and condition by adjusting the system temperature. The resulting temperatures are all near but above the critical point of the model in the paramagnetic (disordered) phase. The individualized Ising temperatures are higher in the LSD condition than in the placebo condition (p = 9 × 10⁻⁵). Next, we estimate the Lempel-Ziv-Welch (LZW) complexity of the binarized BOLD data and the synthetic data generated with the individualized model using the Metropolis algorithm for each participant and condition. The LZW complexity computed from experimental data reveals a weak statistical relationship with condition (p = 0.04 one-tailed Wilcoxon test) and none with Ising temperature (r(13) = 0.13, p = 0.65), presumably because of the limited length of the BOLD time series. Similarly, we explore complexity using the block decomposition method (BDM), a more advanced method for estimating algorithmic complexity. The BDM complexity of the experimental data displays a significant correlation with Ising temperature (r(13) = 0.56, p = 0.03) and a weak but significant correlation with condition (p = 0.04, one-tailed Wilcoxon test). This study suggests that the effects of LSD increase the complexity of brain dynamics by loosening interhemispheric connectivity—especially homotopic links. In agreement with earlier work using the Ising formalism with BOLD data, we find the brain state in the placebo condition is already above the critical point, with LSD resulting in a shift further away from criticality into a more disordered state.

Spontaneous brain activity changes across states of consciousness. A particular consciousness-mediated configuration is the anticorrelations between the default mode network and other brain regions. What this antagonistic organization implies about consciousness to date remains inconclusive. In this Perspective Article, we propose that anticorrelations are the physiological expression of the concept of segregation, namely the brain’s capacity to show selectivity in the way areas will be functionally connected. We postulate that this effect is mediated by the process of neural inhibition, by regulating global and local inhibitory activity. While recognizing that this effect can also result from other mechanisms, neural inhibition helps the understanding of how network metastability is affected after disrupting local and global neural balance. In combination with relevant theories of consciousness, we suggest that anticorrelations are a physiological prior that can work as a marker of preserved consciousness. We predict that if the brain is not in a state to host anticorrelations, then most likely the individual does not entertain subjective experience. We believe that this link between anticorrelations and the underlying physiology will help not only to comprehend how consciousness happens, but also conceptualize effective interventions for treating consciousness disorders in which anticorrelations seem particularly affected.