Sensory signals during active versus passive movement

Our sensory systems are simultaneously activated as the result of our own actions and changes in the external world. The ability to distinguish self-generated sensory events from those that arise externally is thus essential for perceptual stability and accurate motor control. Recently, progress has been made towards understanding how this distinction is made. It has been proposed that an internal prediction of the consequences of our actions is compared to the actual sensory input to cancel the resultant self-generated activation. Evidence in support of this hypothesis has been obtained for early stages of sensory processing in the vestibular, visual and somatosensory systems. These findings have implications for the sensory-motor transformations that are needed to guide behavior.     

Dysregulation of neural calcium signaling in Alzheimer disease,bipolar disorder and schizophrenia

Neurons have highly developed Ca²⁺ signaling systems responsible for regulating a large number of neural functions such as the control of brain rhythms, information processing and the changes in synaptic plasticity that underpin learning and memory. The tonic excitatory drive, which is activated by the ascending arousal system, is particularly important for processes such as sensory perception, cognition and consciousness. The Ca²⁺ signaling pathway is a key component of this arousal system that regulates the neuronal excitability responsible for controlling the neural brain rhythms required for information processing and cognition. Dysregulation of the Ca²⁺ signaling pathway responsible for many of these neuronal processes has been implicated in the development of some of the major neural diseases in man such as Alzheimer disease, bipolar disorder and schizophrenia. Various treatments, which are known to act by reducing the activity of Ca²⁺ signaling, have proved successful in alleviating the symptoms of some of these neural diseases.     

Estrogens and cognition: Friends or foes?: An evaluation of the opposing effects of estrogens on learning and memory

This article is part of a Special Issue “Estradiol and cognition”.Estrogens are becoming well known for their robust enhancement on cognition particularly for learning and memory that relies upon functioning of the hippocampus and related neural systems. What is also emerging is that estrogen modulation of cognition is not uniform, at times enhancing yet at other times impairing learning. This review explores the bidirectional effects of estrogens on learning from a multiple memory systems view, focusing on the hippocampus and striatum, whereby modulation by estrogens sorts according to task attributes and neural systems engaged during cognition. We highlight our findings showing that the ability to solve hippocampus-sensitive tasks typically improves under relatively high estrogen status while the ability to solve striatum-sensitive tasks degrades with estrogen exposures. Though constrained by dose and timing of exposure, these opposing enhancements and impairments of cognition can be observed following treatments with different estrogenic compounds including the hormone estradiol, the isoflavone genistein found in soybeans, and agonists that are selective for specific estrogen receptors, suggesting that activation of a single receptor type is sufficient to produce the observed shifts in learning strategies. Using this multi-dimensional framework will allow us to extend our thinking of the relationship between estrogens and cognition to other brain regions and cognitive functions.     

Visualizing spatiotemporal dynamics of multicellular cell-cycle progression

The cell-cycle transition from G1 to S phase has been difficult to visualize. We have harnessed antiphase oscillating proteins that mark cell-cycle transitions in order to develop genetically encoded fluorescent probes for this purpose. These probes effectively label individual G1 phase nuclei red and those in S/G2/M phases green. We were able to generate cultured cells and transgenic mice constitutively expressing the cell-cycle probes, in which every cell nucleus exhibits either red or green fluorescence. We performed time-lapse imaging to explore the spatiotemporal patterns of cell-cycle dynamics during the epithelial-mesenchymal transition of cultured cells, the migration and differentiation of neural progenitors in brain slices, and the development of tumors across blood vessels in live mice. These mice and cell lines will serve as model systems permitting unprecedented spatial and temporal resolution to help us better understand how the cell cycle is coordinated with various biological events.     

Evolution of the neural basis of consciousness: a bird-mammal comparison

The main objective of this essay is to validate some of the principal, currently competing, mammalian consciousness-brain theories by comparing these theories with data on both cognitive abilities and brain organization in birds. Our argument is that, given that multiple complex cognitive functions are correlated with presumed consciousness in mammals, this correlation holds for birds as well. Thus, the neuroanatomical features of the forebrain common to both birds and mammals may be those that are crucial to the generation of both complex cognition and consciousness. The general conclusion is that most of the consciousness-brain theories appear to be valid for the avian brain. Even though some specific homologies are unresolved, most of the critical structures presumed necessary for consciousness in mammalian brains have clear homologues in avian brains. Furthermore, considering the fact that the reptile-bird brain transition shows more structural continuity than the stem amniote-mammalian transition, the line drawn at the origin of mammals for consciousness by several of the theorists seems questionable. An equally important point is that consciousness cannot be ruled out in the absence of complex cognition; it may in fact be the case that consciousness is a necessary prerequisite for complex cognition.     

Irregular dynamics in up and down cortical states

Complex coherent dynamics is present in a wide variety of neural systems. A typical example is the voltage transitions between up and down states observed in cortical areas in the brain. In this work, we study this phenomenon via a biologically motivated stochastic model of up and down transitions. The model is constituted by a simple bistable rate dynamics, where the synaptic current is modulated by short-term synaptic processes which introduce stochasticity and temporal correlations. A complete analysis of our model, both with mean-field approaches and numerical simulations, shows the appearance of complex transitions between high (up) and low (down) neural activity states, driven by the synaptic noise, with permanence times in the up state distributed according to a power-law. We show that the experimentally observed large fluctuation in up and down permanence times can be explained as the result of sufficiently noisy dynamical synapses with sufficiently large recovery times. Static synapses cannot account for this behavior, nor can dynamical synapses in the absence of noise.     

Shaping the dynamics of a bidirectional neural interface

Progress in decoding neural signals has enabled the development of interfaces that translate cortical brain activities into commands for operating robotic arms and other devices. The electrical stimulation of sensory areas provides a means to create artificial sensory information about the state of a device. Taken together, neural activity recording and microstimulation techniques allow us to embed a portion of the central nervous system within a closed-loop system, whose behavior emerges from the combined dynamical properties of its neural and artificial components. In this study we asked if it is possible to concurrently regulate this bidirectional brain-machine interaction so as to shape a desired dynamical behavior of the combined system. To this end, we followed a well-known biological pathway. In vertebrates, the communications between brain and limb mechanics are mediated by the spinal cord, which combines brain instructions with sensory information and organizes coordinated patterns of muscle forces driving the limbs along dynamically stable trajectories. We report the creation and testing of the first neural interface that emulates this sensory-motor interaction. The interface organizes a bidirectional communication between sensory and motor areas of the brain of anaesthetized rats and an external dynamical object with programmable properties. The system includes (a) a motor interface decoding signals from a motor cortical area, and (b) a sensory interface encoding the state of the external object into electrical stimuli to a somatosensory area. The interactions between brain activities and the state of the external object generate a family of trajectories converging upon a selected equilibrium point from arbitrary starting locations. Thus, the bidirectional interface establishes the possibility to specify not only a particular movement trajectory but an entire family of motions, which includes the prescribed reactions to unexpected perturbations.     

Viewing brain processes as Critical State Transitions across levels of organization: Neural events in Cognition and Consciousness,and general principles

In this theoretical and speculative essay, I propose that insights into certain aspects of neural system functions can be gained from viewing brain function in terms of the branch of Statistical Mechanics currently referred to as “Modern Critical Theory” [Stanley, H.E., 1987. Introduction to Phase Transitions and Critical Phenomena. Oxford University Press; Marro, J., Dickman, R., 1999. Nonequilibrium Phase Transitions in Lattice Models. Cambridge University Press, Cambridge, UK]. The application of this framework is here explored in two stages: in the first place, its principles are applied to state transitions in global brain dynamics, with benchmarks of Cognitive Neuroscience providing the relevant empirical reference points. The second stage generalizes to suggest in more detail how the same principles could also apply to the relation between other levels of the structural-functional hierarchy of the nervous system and between neural assemblies. In this view, state transitions resulting from the processing at one level are the input to the next, in the image of a ‘bucket brigade’, with the content of each bucket being passed on along the chain, after having undergone a state transition. The unique features of a process of this kind will be discussed and illustrated.     

Thalamic deep brain stimulation paradigm to reduce consciousness: Cortico-striatal dynamics implicated in mechanisms of consciousness

Anesthetic manipulations provide much-needed causal evidence for neural correlates of consciousness, but non-specific drug effects complicate their interpretation. Evidence suggests that thalamic deep brain stimulation (DBS) can either increase or decrease consciousness, depending on the stimulation target and parameters. The putative role of the central lateral thalamus (CL) in consciousness makes it an ideal DBS target to manipulate circuit-level mechanisms in cortico-striato-thalamic (CST) systems, thereby influencing consciousness and related processes. We used multi-microelectrode DBS targeted to CL in macaques while recording from frontal, parietal, and striatal regions. DBS induced episodes of abnormally long, vacant staring with low-frequency oscillations here termed vacant, perturbed consciousness (VPC). DBS modulated VPC likelihood in a frequency-specific manner. VPC events corresponded to decreases in measures of neural complexity (entropy) and integration (Φ*), proposed indices of consciousness, and substantial changes to communication in CST circuits. During VPC, power spectral density and coherence at low frequencies increased across CST circuits, especially in thalamo-parietal and cortico-striatal pathways. Decreased consciousness and neural integration corresponded to shifts in cortico-striatal network configurations that dissociated parietal and subcortical structures. Overall, the features of VPC and implicated networks were similar to those of absence epilepsy. As this same multi-microelectrode DBS method–but at different stimulation frequencies–can also increase consciousness in anesthetized macaques, it can be used to flexibly address questions of consciousness with limited confounds, as well as inform clinical investigations of other consciousness disorders.     

Contributions of electric fish to the understanding of sensory processing by reafferent systems.

Sensory systems must solve the inverse problem of determining environmental events based on patterns of neural activity in the central nervous system that are affected by those environmental events. Different environmental events can give rise to indistinguishable patterns of neural activity, so that there will often, perhaps even always, be multiple solutions to a sensory inverse problem. Imaging strategies and brain organization confine these multiple solutions within a bounded set. Three different active strategies may be employed by animals to constrain the number of solutions to the sensory inverse problem: active generation of the energy (carrier) that stimulates receptors; reorientation of the point of view; and control of signal conditioning before transduction (pre-receptor mechanisms). This paper describes how these strategies are used in sensory-motor systems, using electric fish as a paradigmatic example. Carrier generation and receptor tuning to the carrier improve signal to noise ratio. Receptor tuning to different frequency bands of the carrier spectrum allows a sensory system to evaluate different kinds of carrier modulations and to extract the different features of objects in the environment. Pre-receptor mechanisms condition the signals, optimizing their detection at a foveal region where the sensory resolution is maximum. Active orientation of the sensory surface redirects the fovea to explore in detail the source of interesting signals. Sensory input generated by these active exploration mechanisms ('reafference') has two components: one, necessary, derived from the self-generated actions and another, contingent, consisting of the information obtained from the external world. Extracting environmental information ('exafference') requires that the self generated afference be subtracted from the sensory inflow. Such subtraction is often associated with the generation and storage of expectations about sensory inputs. It can be concluded that an animal's perceptual world and its ability to transform the world are inextricably linked. Understanding sensory systems must, therefore, always require understanding the organization of motor behavior.     

Motor Imagery Learning Modulates Functional Connectivity of Multiple Brain Systems in Resting State

Background

Learning motor skills involves subsequent modulation of resting-state functional connectivity in the sensory-motor system. This idea was mostly derived from the investigations on motor execution learning which mainly recruits the processing of sensory-motor information. Behavioral evidences demonstrated that motor skills in our daily lives could be learned through imagery procedures. However, it remains unclear whether the modulation of resting-state functional connectivity also exists in the sensory-motor system after motor imagery learning.

Methodology/Principal Findings

We performed a fMRI investigation on motor imagery learning from resting state. Based on previous studies, we identified eight sensory and cognitive resting-state networks (RSNs) corresponding to the brain systems and further explored the functional connectivity of these RSNs through the assessments, connectivity and network strengths before and after the two-week consecutive learning. Two intriguing results were revealed: (1) The sensory RSNs, specifically sensory-motor and lateral visual networks exhibited greater connectivity strengths in precuneus and fusiform gyrus after learning; (2) Decreased network strength induced by learning was proved in the default mode network, a cognitive RSN.

Conclusions/Significance

These results indicated that resting-state functional connectivity could be modulated by motor imagery learning in multiple brain systems, and such modulation displayed in the sensory-motor, visual and default brain systems may be associated with the establishment of motor schema and the regulation of introspective thought. These findings further revealed the neural substrates underlying motor skill learning and potentially provided new insights into the therapeutic benefits of motor imagery learning.     

Current state-of-the-art of auditory functional MRI (fMRI) on zebra finches: Technique and scientific achievements

Songbirds provide an excellent model system exhibiting vocal learning associated with an extreme brain plasticity linked to quantifiable behavioral changes. This animal model has thus far been intensively studied using electrophysiological, histological and molecular mapping techniques. However, these approaches do not provide a global view of the brain and/or do not allow repeated measures, which are necessary to establish correlations between alterations in neural substrate and behavior. In contrast, functional Magnetic Resonance Imaging (fMRI) is a non-invasive in vivo technique which allows one (i) to study brain function in the same subject over time, and (ii) to address the entire brain at once. During the last decades, fMRI has become one of the most popular neuroimaging techniques in cognitive neuroscience for the study of brain activity during various tasks ranging from simple sensory-motor to highly cognitive tasks. By alternating various stimulation periods with resting periods during scanning, resting and task-specific regional brain activity can be determined with this technique. Despite its obvious benefits, fMRI has, until now, only been sparsely used to study cognition in non-human species such as songbirds. The Bio-Imaging Lab (University of Antwerp, Belgium) was the first to implement Blood Oxygen Level Dependent (BOLD) fMRI in songbirds – and in particular zebra finches – for the visualization of sound perception and processing in auditory and song control brain regions. The present article provides an overview of the establishment and optimization of this technique in our laboratory and of the resulting scientific findings. The introduction of fMRI in songbirds has opened new research avenues that permit experimental analysis of complex sensorimotor and cognitive processes underlying vocal communication in this animal model.     

Levels of processing during non-conscious perception: a critical review of visual masking

Understanding the extent and limits of non-conscious processing is an important step on the road to a thorough understanding of the cognitive and cerebral correlates of conscious perception. In this article, we present a critical review of research on subliminal perception during masking and other related experimental conditions. Although initially controversial, the possibility that a broad variety of processes can be activated by a non-reportable stimulus is now well established. Behavioural findings of subliminal priming indicate that a masked word or digit can have an influence on perceptual, lexical and semantic levels, while neuroimaging directly visualizes the brain activation that it evokes in several cortical areas. This activation is often attenuated under subliminal presentation conditions compared to consciously reportable conditions, but there are sufficiently many exceptions, in paradigms such as the attentional blink, to indicate that high activation, per se, is not a sufficient condition for conscious access to occur. We conclude by arguing that for a stimulus to reach consciousness, two factors are jointly needed: (i) the input stimulus must have enough strength (which can be prevented by masking) and (ii) it must receive top-down attention (which can be prevented by drawing attention to another stimulus or task). This view leads to a distinction between two types of non-conscious processes, which we call subliminal and preconscious. According to us, maintaining this distinction is essential in order to make sense of the growing neuroimaging data on the neural correlates of consciousness.     

Differential effects of propofol and ketamine on critical brain dynamics

Whether the brain operates at a critical “tipping” point is a long standing scientific question, with evidence from both cellular and systems-scale studies suggesting that the brain does sit in, or near, a critical regime. Neuroimaging studies of humans in altered states of consciousness have prompted the suggestion that maintenance of critical dynamics is necessary for the emergence of consciousness and complex cognition, and that reduced or disorganized consciousness may be associated with deviations from criticality. Unfortunately, many of the cellular-level studies reporting signs of criticality were performed in non-conscious systems (in vitro neuronal cultures) or unconscious animals (e.g. anaesthetized rats). Here we attempted to address this knowledge gap by exploring critical brain dynamics in invasive ECoG recordings from multiple sessions with a single macaque as the animal transitioned from consciousness to unconsciousness under different anaesthetics (ketamine and propofol). We use a previously-validated test of criticality: avalanche dynamics to assess the differences in brain dynamics between normal consciousness and both drug-states. Propofol and ketamine were selected due to their differential effects on consciousness (ketamine, but not propofol, is known to induce an unusual state known as “dissociative anaesthesia”). Our analyses indicate that propofol dramatically restricted the size and duration of avalanches, while ketamine allowed for more awake-like dynamics to persist. In addition, propofol, but not ketamine, triggered a large reduction in the complexity of brain dynamics. All states, however, showed some signs of persistent criticality when testing for exponent relations and universal shape-collapse. Further, maintenance of critical brain dynamics may be important for regulation and control of conscious awareness.     

Reflections on a giant of brain science

Walter J. Freeman was a giant of the field of neuroscience whose visionary work contributed various experimental and theoretical breakthroughs to brain research in the past 60 years. He has pioneered a number of Electroencephalogram and Electrocorticogram tools and approaches that shaped the field, while “Freeman Neurodynamics” is a theoretical concept that is widely known, used, and respected among neuroscientists all over the world. His recent death is a profound loss to neuroscience and biomedical engineering. Many of his revolutionary ideas on brain dynamics have been ahead of their time by decades. We summarize his following groundbreaking achievements: (1) Mass Action in the Nervous System, from microscopic (single cell) recordings, through mesoscopic populations, to large-scale collective brain patterns underlying cognition; (2) Freeman–Kachalsky model of multi-scale, modular brain dynamics; (3) cinematic theory of cognitive dynamics; (4) phase transitions in cortical dynamics modeled with random graphs and quantum field theory; (5) philosophical aspects of intentionality, consciousness, and the unity of brain–mind–body. His work has been admired by many of his neuroscientist colleagues and followers. At the same time, his multidisciplinary approach combining advanced concepts of control theory and the mathematics of nonlinear systems and chaos, poses significant challenges to those who wish to thoroughly understand his message. The goal of this commemorative paper is to review key aspects of Freeman’s neurodynamics and to provide some handles to gain better understanding about Freeman’s extraordinary intellectual achievement.     

Neural dynamics of event segmentation in music: converging evidence for dissociable ventral and dorsal networks

The real world presents our sensory systems with a continuous stream of undifferentiated information. Segmentation of this stream at event boundaries is necessary for object identification and feature extraction. Here, we investigate the neural dynamics of event segmentation in entire musical symphonies under natural listening conditions. We isolated time-dependent sequences of brain responses in a 10 s window surrounding transitions between movements of symphonic works. A strikingly right-lateralized network of brain regions showed peak response during the movement transitions when, paradoxically, there was no physical stimulus. Model-dependent and model-free analysis techniques provided converging evidence for activity in two distinct functional networks at the movement transition: a ventral fronto-temporal network associated with detecting salient events, followed in time by a dorsal fronto-parietal network associated with maintaining attention and updating working memory. Our study provides direct experimental evidence for dissociable and causally linked ventral and dorsal networks during event segmentation of ecologically valid auditory stimuli.     

Interactions of sugars with membranes

Water profoundly affects the stability of biological membranes, and its removal leads to destructive events including fusion and liquid crystalline to gel phase transitions. In heterogeneous mixtures such as those found in biological membranes the phase transitions can lead to increases in permeability and lateral phase separations that often are irreparable. Certain sugars are capable of preventing these deleterious events by inhibiting fusion during drying and by maintaining the lipid in a fluid state in the absence of water. As a result, the increased permeability and lateral phase separations that accompany dehydration are absent. The weight of the evidence suggests strongly that there is a direct interaction between the sugars and lipids in the dry state. Although the evidence is less clear about whether these sugars can interact directly with hydrated bilayers, there are strong suggestions in the literature that sugars free in solution or covalently linked to membrane constituents can also affect the physical properties and presumably the stability of bilayers. Finally, we have far less evidence concerning the mechanism by which they do so, but the same sugars are also capable of preserving the structure and function of both membrane-bound and soluble proteins in the absence of water. We believe these effects may be important in the survival of intact cells and organisms such as seeds in the absence of water. Furthermore, in view of the practical importance of preserving biological structures we suspect that the results described here will ultimately have important applications in biology and medicine.     

Computation and physiology of sensory-motor processing in eye movements

Performance in sensory-motor behaviors guides our understanding of many of the key computational functions of the brain: the representation of sensory information, the translation of sensory signals to commands for movement, and the production of behavior. Eye movement behaviors have become a valuable testing ground for theories of neural computation because the neural circuitry has been well characterized and the mechanical control of the eye is comparatively simple. Here I review recent studies of eye movement behaviors that provide insight into sensory-motor computation at the single neuron and systems levels. They show that errors in sensory estimation dominate eye movement variability and that the motor system functions to reduce the behavioral impact of its own intrinsic noise sources.     

The slow process: A hypothetical cognitive adaptation for distributed cognitive networks

Human cognitive evolution is characterized by two special features that are truly novel in the primate line. The first is the emergence of "mindsharing" cultures that perform cooperative cognitive work, and serve as distributed cognitive networks. The second is the emergence of a brain that is specifically adapted for functioning within those distributed networks, and cannot realize its design potential without them. This paper proposes a hypothetical neural process at the core of this brain adaptation, called the "slow process". It enables the human brain to comprehend social events of much longer duration and complexity than those that characterize primate social life. It runs in the background of human cognitive life, with the faster moving sensorimotor interface running in the foreground. Most mammals can integrate events in the shorter time zone that corresponds to working memory. However, very few can comprehend complex events that extend over several hours (for example, a game or conversation) in what may be called the "intermediate" time zone. Adult humans typically live, plan, and imagine their lives in this time range, which seems to exceed the capabilities of our closest relatives, bonobos and chimpanzees. In summary, human cognition has both an individual and a collective dimension. Individual brains and minds function within cognitive-cultural networks, or CCNs, that store and transmit knowledge. The human brain relies on cultural input even to develop the basic cognitive capacities needed to gain access to that knowledge in the first place. The postulated slow process is a top-down executive capacity that evolved specifically to manage the cultural connection, and handle the cognitive demands imposed by increasingly complex distributed systems.