What blindness can tell us about seeing again: merging neuroplasticity and neuroprostheses

Significant progress has been made in the development of visual neuroprostheses to restore vision in blind individuals. Appropriate delivery of electrical stimulation to intact visual structures can evoke patterned sensations of light in those who have been blind for many years. However, success in developing functional visual prostheses requires an understanding of how to communicate effectively with the visually deprived brain in order to merge what is perceived visually with what is generated electrically.     

Similar neural activity during fear and disgust in the rat basolateral amygdala

Much research has focused on how the amygdala processes individual affects, yet little is known about how multiple types of positive and negative affects are encoded relative to one another at the single-cell level. In particular, it is unclear whether different negative affects, such as fear and disgust, are encoded more similarly than negative and positive affects, such as fear and pleasure. Here we test the hypothesis that the basolateral nucleus of the amygdala (BLA), a region known to be important for learned fear and other affects, encodes affective valence by comparing neuronal activity in the BLA during a conditioned fear stimulus (fear CS) with activity during intraoral delivery of an aversive fluid that induces a disgust response and a rewarding fluid that induces a hedonic response. Consistent with the hypothesis, neuronal activity during the fear CS and aversive fluid infusion, but not during the fear CS and rewarding fluid infusion, was more similar than expected by chance. We also found that the greater similarity in activity during the fear- and disgust-eliciting stimuli was specific to a subpopulation of cells and a limited window of time. Our results suggest that a subpopulation of BLA neurons encodes affective valence during learned fear, and furthermore, within this subpopulation, different negative affects are encoded more similarly than negative and positive affects in a time-specific manner.     

My baby doesn't smell as bad as yours: The plasticity of disgust

Disgust is a powerful behavioral adaptation, which confers the advantage of reducing the risk of pathogen infection. However, there are situations in which disgust at core elicitors (e.g., feces) must be modulated in the service of other goals (e.g., caring for a close kin). In Study 1, mothers of infants completed a self-report questionnaire about their reactions to changing their baby's feces-soiled diaper compared with the diaper of someone else's baby. In Study 2, mothers of infants were presented with a series of trials in which they smelled concealed samples of their own baby's feces-soiled diaper and those of someone else's baby. In addition, labels were used to identify the source of the sample (correctly labeled, mislabeled, or no label). Both studies provide evidence suggesting that mothers regard their own baby's fecal smell as less disgusting than that from someone else's baby. Furthermore, labeling had relatively little influence on this effect, and the effect persisted when social desirability was controlled.     

The feeling of understanding: an exploration with neural models

There exists a dynamic interaction between the world of information and the world of concepts, which is seen as a quintessential byproduct of the cultural evolution of individuals as well as of human communities. The feeling of understanding (FU) is that subjective experience that encompasses all the emotional and intellectual processes we undergo in the process of gathering evidence to achieve an understanding of an event. This experience is part of every person that has dedicated substantial efforts in scientific areas under constant research progress. The FU may have an initial growth followed by a quasi-stable regime and a possible decay when accumulated data exceeds the capacity of an individual to integrate them into an appropriate conceptual scheme. We propose a neural representation of FU based on the postulate that all cognitive activities are mapped onto dynamic neural vectors. Two models are presented that incorporate the mutual interactions among data and concepts. The first one shows how in the short time scale, FU can rise, reach a temporary steady state and subsequently decline. The second model, operating over longer scales of time, shows how a reorganization and compactification of data into global categories initiated by conceptual syntheses can yield random cycles of growth, decline and recovery of FU.     

Sex differences in neural activation to facial expressions denoting contempt and disgust

The facial expression of contempt has been regarded to communicate feelings of moral superiority. Contempt is an emotion that is closely related to disgust, but in contrast to disgust, contempt is inherently interpersonal and hierarchical. The aim of this study was twofold. First, to investigate the hypothesis of preferential amygdala responses to contempt expressions versus disgust. Second, to investigate whether, at a neural level, men would respond stronger to biological signals of interpersonal superiority (e.g., contempt) than women. We performed an experiment using functional magnetic resonance imaging (fMRI), in which participants watched facial expressions of contempt and disgust in addition to neutral expressions. The faces were presented as distractors in an oddball task in which participants had to react to one target face. Facial expressions of contempt and disgust activated a network of brain regions, including prefrontal areas (superior, middle and medial prefrontal gyrus), anterior cingulate, insula, amygdala, parietal cortex, fusiform gyrus, occipital cortex, putamen and thalamus. Contemptuous faces did not elicit stronger amygdala activation than did disgusted expressions. To limit the number of statistical comparisons, we confined our analyses of sex differences to the frontal and temporal lobes. Men displayed stronger brain activation than women to facial expressions of contempt in the medial frontal gyrus, inferior frontal gyrus, and superior temporal gyrus. Conversely, women showed stronger neural responses than men to facial expressions of disgust. In addition, the effect of stimulus sex differed for men versus women. Specifically, women showed stronger responses to male contemptuous faces (as compared to female expressions), in the insula and middle frontal gyrus. Contempt has been conceptualized as signaling perceived moral violations of social hierarchy, whereas disgust would signal violations of physical purity. Thus, our results suggest a neural basis for sex differences in moral sensitivity regarding hierarchy on the one hand and physical purity on the other.     

Language processing: the neural basis of nouns and verbs

A new study of the functional anatomy of noun and verb production suggests an important role for semantic representations in the cortical processing of these two distinct grammatical classes.     

Developmental plasticity in neural circuits controlling birdsong: Sexual differentiation and the neural basis of learning

In many species of passerine songbirds, males learn their song during defined periods of life. Female song in often reduced or absent, as are the brain regions controlling song. Sexual differences in the brain arise because of the action of sex steroids, which trigger the formation of some neural pathways (especially the pathway from the higher vocal center to the robust nucleus) and prevent the atrophy of others in males. These neural changes occur during periods of developmental song learning and can recur during periods of learning in adult birds. The process of learning is correlated with major increases or decreases in the number of neurons in specific neuronal populations, suggesting that the formation or loss of specific neural pathways regulates the ability to learn. Species differences in sexual differentiation and learning allow informative cross-species comparisons of neural structure and behavior. © 1992 John Wiley & Sons, Inc.     

Dissociation between seeing and acting: insights from common marmosets (Callithrix jacchus)

Perception-based measures often reveal much earlier competencies than action-based approaches. We explored this phenomenon generally labeled as “knowledge dissociation” in 28 common marmoset monkeys (Callithrix jacchus) using a paradigm where subjects had to localize a food item dropped down an opaque tube. Experiments 1 and 2 assessed common marmoset monkeys’ gravity bias in an action based version of the tubes task. Experiments 3 and 4 investigated whether marmosets’ performance increases in an action-free task context where they simply look at objects falling down a tube. The results suggest that common marmosets have some intuition of continuity/solidity constraints when tested with perception based measures even though these principles do not appear to guide their search for falling objects.     

Opinion: the neural basis of human moral cognition

Moral cognitive neuroscience is an emerging field of research that focuses on the neural basis of uniquely human forms of social cognition and behaviour. Recent functional imaging and clinical evidence indicates that a remarkably consistent network of brain regions is involved in moral cognition. These findings are fostering new interpretations of social behavioural impairments in patients with brain dysfunction, and require new approaches to enable us to understand the complex links between individuals and society. Here, we propose a cognitive neuroscience view of how cultural and context-dependent knowledge, semantic social knowledge and motivational states can be integrated to explain complex aspects of human moral cognition.     

Developmental plasticity in neural circuits controlling birdsong: sexual differentiation and the neural basis of learning.

In many species of passerine songbirds, males learn their song during defined periods of life. Female song is often reduced or absent, as are the brain regions controlling song. Sexual differences in the brain arise because of the action of sex steroids, which trigger the formation of some neural pathways (especially the pathway from the higher vocal center to the robust nucleus) and prevent the atrophy of others in males. These neural changes occur during periods of developmental song learning and can recur during periods of learning in adult birds. The process of learning is correlated with major increases or decreases in the numbers of neurons in specific neuronal populations, suggesting that the formation or loss of specific neural pathways regulates the ability to learn. Species differences in sexual differentiation and learning allow informative cross-species comparisons of neural structure and behavior.     

PKG and the neural basis for behavioral phenotypes

Cyclic GMP-dependent protein kinase (PKG) has been implicated in the regulation of diverse aspects of vertebrate and insect behavior, yet the mechanisms underlying these effects are poorly understood. In this issue of Neuron, Fujiwara et al. and L'Etoile et al. address the neural basis for PKG function in C. elegans and demonstrate the power of behavioral genetic analysis in simple systems in the elucidation of neuronal signaling mechanisms in vivo.     

Sensorimotor integration in speech processing: computational basis and neural organization

Sensorimotor integration is an active domain of speech research and is characterized by two main ideas, that the auditory system is critically involved in speech production and that the motor system is critically involved in speech perception. Despite the complementarity of these ideas, there is little crosstalk between these literatures. We propose an integrative model of the speech-related "dorsal stream" in which sensorimotor interaction primarily supports speech production, in the form of a state feedback control architecture. A critical component of this control system is forward sensory prediction, which affords a natural mechanism for limited motor influence on perception, as recent perceptual research has suggested. Evidence shows that this influence is modulatory but not necessary for speech perception. The neuroanatomy of the proposed circuit is discussed as well as some probable clinical correlates including conduction aphasia, stuttering, and aspects of schizophrenia.     

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.     

Progress and promise in understanding the genetic basis of common diseases

Susceptibility to common human diseases is influenced by both genetic and environmental factors. The explosive growth of genetic data, and the knowledge that it is generating, are transforming our biological understanding of these diseases. In this review, we describe the technological and analytical advances that have enabled genome-wide association studies to be successful in identifying a large number of genetic variants robustly associated with common disease. We examine the biological insights that these genetic associations are beginning to produce, from functional mechanisms involving individual genes to biological pathways linking associated genes, and the identification of functional annotations, some of which are cell-type-specific, enriched in disease associations. Although most efforts have focused on identifying and interpreting genetic variants that are irrefutably associated with disease, it is increasingly clear that—even at large sample sizes—these represent only the tip of the iceberg of genetic signal, motivating polygenic analyses that consider the effects of genetic variants throughout the genome, including modest effects that are not individually statistically significant. As data from an increasingly large number of diseases and traits are analysed, pleiotropic effects (defined as genetic loci affecting multiple phenotypes) can help integrate our biological understanding. Looking forward, the next generation of population-scale data resources, linking genomic information with health outcomes, will lead to another step-change in our ability to understand, and treat, common diseases.     

The neural basis of catalepsy in the stick insect

The known nonlinearities of the femur-tibia control loop of the stick insect Carausius morosus (enabling the system to produce catalepsy) are already present in the nonspiking interneuron E4: (1) The decay of depolarizations in interneuron E4 following slow elongation movements of the femoral chordotonal organ apodeme could be described by a single exponential function, whereas the decay following faster movements had to be characterized by a double exponential function. (2) Each of the two corresponding time constants was independent of stimulus velocity. (3) The relative contribution of each function to the total amount of depolarization changed with stimulus velocity. (4) The characteristics described in (1)–(3) were also found in the slow extensor tibiae motoneuron. (5) Single electrode voltage clamp studies on interneuron E4 indicated that no voltage dependent membrane properties were involved in the generation of the observed time course of decay. Thus, we can trace back a certain behavior (catalepsy) to the properties of an identified, nonspiking interneuron.Abbrevations FETi fast extensor tibiae motor neuron - FT-joint femur-tibia joint - FT-control loop femur-tibia control loop - SETi slow extensor tibiae motor neuron - R regression coefficient     

Exploring the neural basis of cognitive reserve in aging

The concept of reserve arose from the mismatch between the extent of brain changes or pathology and the clinical manifestations of these brain changes. The cognitive reserve hypothesis posits that individual differences in the flexibility and adaptability of brain networks underlying cognitive function may allow some people to cope better with brain changes than others. Although there is ample epidemiologic evidence for cognitive reserve, the neural substrate of reserve is still a topic of ongoing research. Here we review some representative studies from our group that exemplify possibilities for the neural substrate of reserve including neural reserve, neural compensation, and generalized cognitive reserve networks. We also present a schematic overview of our ongoing research in this area. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.     

Not so divided: the common basis of plant and animal cell division

Plant cells do not have centrioles and their mitosis is frequently likened to the chromosome-based mechanism seen in acentriolar animal cells. However, this is a false analogy. Although plants can use this mechanism, they generally divide by a method that uses bipolar mitotic caps, which is more similar to the canonical centrosome-based method of animals.     

Path integration and the neural basis of the 'cognitive map'

The hippocampal formation can encode relative spatial location, without reference to external cues, by the integration of linear and angular self-motion (path integration). Theoretical studies, in conjunction with recent empirical discoveries, suggest that the medial entorhinal cortex (MEC) might perform some of the essential underlying computations by means of a unique, periodic synaptic matrix that could be self-organized in early development through a simple, symmetry-breaking operation. The scale at which space is represented increases systematically along the dorsoventral axis in both the hippocampus and the MEC, apparently because of systematic variation in the gain of a movement-speed signal. Convergence of spatially periodic input at multiple scales, from so-called grid cells in the entorhinal cortex, might result in non-periodic spatial firing patterns (place fields) in the hippocampus.