Frontiers in Systems Neuroscience
Latest Publications

Previous studies have demonstrated that the brain has an intrinsic resistance to changes in arousal state. This resistance is most easily measured at the population level in the setting of general anesthesia and has been termed neural inertia. To date, no study has attempted to determine neural inertia in individuals. We hypothesize that individuals with markedly increased or decreased neural inertia might be at increased risk for complications related to state transitions, from awareness under anesthesia, to delayed emergence or confusion/impairment after emergence. Hence, an improved theoretical and practical understanding of neural inertia may have the potential to identify individuals at increased risk for these complications. This study was designed to explicitly measure neural inertia in individuals and empirically test the stochastic model of neural inertia using spectral analysis of the murine EEG. EEG was measured after induction of and emergence from isoflurane administered near the EC50 dose for loss of righting in genetically inbred mice on a timescale that minimizes pharmacokinetic confounds. Neural inertia was assessed by employing classifiers constructed using linear discriminant or supervised machine learning methods to determine if features of EEG spectra reliably demonstrate path dependence at steady-state anesthesia. We also report the existence of neural inertia at the individual level, as well as the population level, and that neural inertia decreases over time, providing direct empirical evidence supporting the predictions of the stochastic model of neural inertia.

The performance of working memory can be improved by the corresponding high-value vs. low-value rewards consciously or unconsciously. However, whether conscious and unconscious monetary rewards boosting the performance of working memory is regulated by the difficulty level of working memory task is unknown. In this study, a novel paradigm that consists of a reward-priming procedure and N-back task with differing levels of difficulty was designed to inspect this complex process. In particular, both high-value and low-value coins were presented consciously or unconsciously as the reward cues, followed by the N-back task, during which electroencephalogram signals were recorded. It was discovered that the high-value reward elicited larger event-related potential (ERP) component P3 along the parietal area (reflecting the working memory load) as compared to the low-value reward for the less difficult 1-back task, no matter whether the reward was unconsciously or consciously presented. In contrast, this is not the case for the more difficult 2-back task, in which the difference in P3 amplitude between the high-value and low-value rewards was not significant for the unconscious reward case, yet manifested significance for the conscious reward processing. Interestingly, the results of the behavioral analysis also exhibited very similar patterns as ERP patterns. Therefore, this study demonstrated that the difficulty level of a task can modulate the influence of unconscious reward on the performance of working memory.

Neural signatures of working memory (WM) have been reported in numerous brain areas, suggesting a distributed neural substrate for memory maintenance. In the current manuscript we provide an updated review of the literature focusing on intracranial neurophysiological recordings during WM in primates. Such signatures of WM include changes in firing rate or local oscillatory power within an area, along with measures of coordinated activity between areas based on synchronization between oscillations. In comparing the ability of various neural signatures in any brain area to predict behavioral performance, we observe that synchrony between areas is more frequently and robustly correlated with WM performance than any of the within-area neural signatures. We further review the evidence for alteration of inter-areal synchrony in brain disorders, consistent with an important role for such synchrony during behavior. Additionally, results of causal studies indicate that manipulating synchrony across areas is especially effective at influencing WM task performance. Each of these lines of research supports the critical role of inter-areal synchrony in WM. Finally, we propose a framework for interactions between prefrontal and sensory areas during WM, incorporating a range of experimental findings and offering an explanation for the observed link between intra-areal measures and WM performance.

Being able to correctly predict the future and to adjust own actions accordingly can offer a great survival advantage. In fact, this could be the main reason why brains evolved. Consciousness, the most mysterious feature of brain activity, also seems to be related to predicting the future and detecting surprise: a mismatch between actual and predicted situation. Similarly at a single neuron level, predicting future activity and adapting synaptic inputs accordingly was shown to be the best strategy to maximize the metabolic energy for a neuron. Following on these ideas, here we examined if surprise minimization by single neurons could be a basis for consciousness. First, we showed in simulations that as a neural network learns a new task, then the surprise within neurons (defined as the difference between actual and expected activity) changes similarly to the consciousness of skills in humans. Moreover, implementing adaptation of neuronal activity to minimize surprise at fast time scales (tens of milliseconds) resulted in improved network performance. This improvement is likely because adapting activity based on the internal predictive model allows each neuron to make a more “educated” response to stimuli. Based on those results, we propose that the neuronal predictive adaptation to minimize surprise could be a basic building block of conscious processing. Such adaptation allows neurons to exchange information about own predictions and thus to build more complex predictive models. To be precise, we provide an equation to quantify consciousness as the amount of surprise minus the size of the adaptation error. Since neuronal adaptation can be studied experimentally, this can allow testing directly our hypothesis. Specifically, we postulate that any substance affecting neuronal adaptation will also affect consciousness. Interestingly, our predictive adaptation hypothesis is consistent with multiple ideas presented previously in diverse theories of consciousness, such as global workspace theory, integrated information, attention schema theory, and predictive processing framework. In summary, we present a theoretical, computational, and experimental support for the hypothesis that neuronal adaptation is a possible biological mechanism of conscious processing, and we discuss how this could provide a step toward a unified theory of consciousness.

Cognitive processes involve precisely coordinated neuronal communications between multiple cerebral cortical structures in a task specific manner. Rich new evidence now implicates the cerebellum in cognitive functions. There is general agreement that cerebellar cognitive function involves interactions between the cerebellum and cerebral cortical association areas. Traditional views assume reciprocal interactions between one cerebellar and one cerebral cortical site, via closed-loop connections. We offer evidence supporting a new perspective that assigns the cerebellum the role of a coordinator of communication. We propose that the cerebellum participates in cognitive function by modulating the coherence of neuronal oscillations to optimize communications between multiple cortical structures in a task specific manner.

Maintaining a balance between excitatory and inhibitory activity is an essential feature of neural networks of the neocortex. In the face of perturbations in the levels of excitation to cortical neurons, synapses adjust to maintain excitatory-inhibitory (EI) balance. In this review, we summarize research on this EI homeostasis in the neocortex, using stroke as our case study, and in particular the loss of excitation to distant cortical regions after focal lesions. Widespread changes following a localized lesion, a phenomenon known as diaschisis, are not only related to excitability, but also observed with respect to functional connectivity. Here, we highlight the main findings regarding the evolution of excitability and functional cortical networks during the process of post-stroke recovery, and how both are related to functional recovery. We show that cortical reorganization at a global scale can be explained from the perspective of EI homeostasis. Indeed, recovery of functional networks is paralleled by increases in excitability across the cortex. These adaptive changes likely result from plasticity mechanisms such as synaptic scaling and are linked to EI homeostasis, providing a possible target for future therapeutic strategies in the process of rehabilitation. In addition, we address the difficulty of simultaneously studying these multiscale processes by presenting recent advances in large-scale modeling of the human cortex in the contexts of stroke and EI homeostasis, suggesting computational modeling as a powerful tool to tie the meso- and macro-scale processes of recovery in stroke patients.

Aims: Therapy with kinesthetic illusion of segmental body part induced by visual stimulation (KINVIS) may allow the treatment of severe upper limb motor deficits in post-stroke patients. Herein, we investigated: (1) whether the effects of KINVIS therapy with therapeutic exercise (TherEx) on motor functions were induced through improved spasticity, (2) the relationship between resting-state functional connectivity (rs-FC) and motor functions before therapy, and (3) the baseline characteristics of rs-FC in patients with the possibility of improving their motor functions.Methods: Using data from a previous clinical trial, three path analyses in structural equation modeling were performed: (1) a mediation model in which the indirect effects of the KINVIS therapy with TherEx on motor functions through spasticity were drawn, (2) a multiple regression model with pre-test data in which spurious correlations between rs-FC and motor functions were controlled, and (3) a multiple regression model with motor function score improvements between pre- and post-test in which the pre-test rs-FC associated with motor function improvements was explored.Results: The mediation model illustrated that although KINVIS therapy with TherEx did not directly improve motor function, it improved spasticity, which led to ameliorated motor functions. The multiple regression model with pre-test data suggested that rs-FC of bilateral parietal regions is associated with finger motor functions, and that rs-FC of unaffected parietal and premotor areas is involved in shoulder/elbow motor functions. Moreover, the multiple regression model with motor function score improvements suggested that the weaker the rs-FC of bilateral parietal regions or that of the supramarginal gyrus in an affected hemisphere and the cerebellar vermis, the greater the improvement in finger motor function.Conclusion: The effects of KINVIS therapy with TherEx on upper limb motor function may be mediated by spasticity. The rs-FC, especially that of bilateral parietal regions, might reflect potentials to improve post-stroke impairments in using KINVIS therapy with TherEx.

In the last decade, burst suppression has been increasingly studied by many to examine whether it is a mechanism leading to postoperative cognitive impairment. Despite a lack of consensus across trials, the current state of research suggests that electroencephalogram (EEG) burst suppression, duration and EEG emergence trajectory may predict postoperative delirium (POD). A mini literature review regarding evidence about burst suppression impact and susceptibilities was conducted, resulting in conflicting studies. Primarily, studies have used different algorithm values to replace visual burst suppression examination, although many studies have since emerged showing that algorithms underestimate burst suppression duration. As these methods may not be interchangeable with visual analysis of raw data, it is a potential factor for the current heterogeneity between data. Even though additional research trials incorporating the use of raw EEG data are necessary, the data currently show that monitoring with commercial intraoperative EEG machines that use EEG indices to estimate burst suppression may help physicians identify burst suppression and guide anesthetic titration during surgery. These modifications in anesthetics could lead to preventing unfavorable outcomes. Furthermore, some studies suggest that brain age, baseline impairment, and certain medications are risk factors for burst suppression and postoperative delirium. These patient characteristics, in conjunction with intraoperative EEG monitoring, could be used for individualized patient care. Future studies on the feasibility of raw EEG monitoring, new technologies for anesthetic monitoring and titration, and patient-associated risk factors are crucial to our continued understanding of burst suppression and postoperative delirium.

It is still elusive to explain the emergence of behavior and understanding based on its neural mechanisms. One renowned proposal is the Free Energy Principle (FEP), which uses an information-theoretic framework derived from thermodynamic considerations to describe how behavior and understanding emerge. FEP starts from a whole-organism approach, based on mental states and phenomena, mapping them into the neuronal substrate. An alternative approach, the Energy Homeostasis Principle (EHP), initiates a similar explanatory effort but starts from single-neuron phenomena and builds up to whole-organism behavior and understanding. In this work, we further develop the EHP as a distinct but complementary vision to FEP and try to explain how behavior and understanding would emerge from the local requirements of the neurons. Based on EHP and a strict naturalist approach that sees living beings as physical and deterministic systems, we explain scenarios where learning would emerge without the need for volition or goals. Given these starting points, we state several considerations of how we see the nervous system, particularly the role of the function, purpose, and conception of goal-oriented behavior. We problematize these conceptions, giving an alternative teleology-free framework in which behavior and, ultimately, understanding would still emerge. We reinterpret neural processing by explaining basic learning scenarios up to simple anticipatory behavior. Finally, we end the article with an evolutionary perspective of how this non-goal-oriented behavior appeared. We acknowledge that our proposal, in its current form, is still far from explaining the emergence of understanding. Nonetheless, we set the ground for an alternative neuron-based framework to ultimately explain understanding.