The sophisticated function of the central nervous system (CNS) is largely supported by proper interactions between neural cells and blood vessels. Accumulating evidence has demonstrated that neurons and glial cells support the formation of blood vessels, which in turn, act as migratory scaffolds for these cell types. Neural progenitors are also involved in the regulation of blood vessel formation. This mutual interaction between neural cells and blood vessels is elegantly controlled by several chemokines, growth factors, extracellular matrix, and (...) adhesion molecules such as integrins. Recent research has revealed that newly migrating cell types along blood vessels repel other preexisting migrating cell types, causing them to detach from the blood vessels. In this review, we discuss vascular formation and cell migration, particularly during development. Moreover, we discuss how the crosstalk between blood vessels and neurons and glial cells could be related to neurodevelopmental disorders. (shrink)

Fezf1 and Fezf2 are highly conserved transcription factors that were first identified by their specific expression in the anterior neuroepithelium of Xenopus and zebrafish embryos. These proteins share an N‐terminal domain with homology to the canonical engrailed repressor motif and a C‐terminal DNA binding domain containing six C2H2 zinc‐finger repeats. Over a decade of study indicates that the Fez proteins play critical roles during nervous system development in species as diverse as fruit flies and mice. Herein we (...) discuss recent progress in understanding the functions of Fezf1 and Fezf2 in neurogenesis and cell fate specification during mammalian nervous system development. Going forward we believe that efforts should focus on understanding how expression of these factors is precisely regulated, and on identifying target DNA sequences and interacting partners. Such knowledge may reveal the mechanisms by which Fezf1 and Fezf2 accomplish both independent and redundant functions across diverse tissue and cell types. (shrink)

We consider the evidence that RA†, the vitamin A metabolite, is involved in three fundamental aspects of the development of the CNS: (1) the stimulation of axon outgrowth in particular neuronal sub‐types; (2) the migration of the neural crest; and (3) the specification of rostrocaudal position in the developing CNS (forebrain, midbrain, hindbrain, spinal cord). The evidence we discuss involves RA‐induction of neurites in cell cultures and explants of neural tissue; the teratological effects of RA on the embryo's (...) class='Hi'>nervous system; the observation that RA can be detected endogenously in the spinal cord; and the fact that the receptors and binding proteins for RA are expressed in precise domains and neuronal cell types within the nervous system. (shrink)

Large numbers of cells with unique neuronal specificity are generated during development of the central nervous system of animals. Here we discuss the events that generate cell diversity during early development of the ventral nerve cord of different arthropod groups. Neural precursors are generated in a spatial array in the epithelium of each hemisegment over a period of time. Spatial cues within the epithelium are thought to evolve as embryogenesis proceeds. This spatiotemporal information might generate diversity (...) among the neural precursors in all arthropod groups, although the mechanisms regulating the positioning of individual precursors have diverged. However, distinct strategies for the generation of neuronal diversity have evolved in the different arthropod lineages that appear to correlate with specific modes of ontogenesis. We hypothesize that an evolutionary trend towards reduced cell numbers and possibly rapid embryogenesis in insects has culminated in the appearance of stereotyped neuroblast lineages. BioEssays 27:874–883, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

There is increasing evidence that carbohydrate antigens act as cell recognition molecules in the highly organized structure of the nervous system. These carbohydrate antigens may be expressed as glycolipids, glycoproteins or proteoglycans, and in some cases all three forms of these glycoconjugates, expressing identical carbohydrate epitopes, can be detected in a specific brain region. This article summarizes recent studies concerning the expression of glycoconjugates during development of the vertebrate central nervous system. These findings are discussed (...) in association with current models of glycoconjugate function. (shrink)

During embryogenesis, the basic axon scaffold of the nervous system is formed by special axons that pioneer pathways between groups of cells. To find their way, the pioneer growth cones detect specific cues in their extracellular environment. One of these guidance cues is netrin. Observations and experimental manipulations in vertebrates and nematodes have shown that netrin is a bifunctional guidance cue that can simultaneously attract and repel axons. During the formation of this basic axon scaffold in Caenorhabditis elegans, (...) the netrin UNC‐6 is expressed by neuroglia and pioneer neurons, providing hierarchical guidance cues throughout the animal. Each cue has a characteristic role depending on the cell type, its position and the developmental stage. These roles include activities as global, decussation and labeled‐pathway cues. This hierarchical model of UNC‐6 netrin‐mediated guidance suggests a method by which guidance cues can direct formation of basic axon scaffolds in developing nervous systems. (shrink)

It remains a standing problem how and why the first nervous systems evolved. Molecular and genomic information is now rapidly accumulating but the macroscopic organization and functioning of early nervous systems remains unclear. To explore potential evolutionary options, a coordination centered view is discussed that diverges from a standard input–output view on early nervous systems. The scenario involved, the skin brain thesis, stresses the need to coordinate muscle-based motility at a very early stage. This paper addresses how (...) this scenario with its focus on coordination also deals with sensory aspects. It will be argued that the neural structure required to coordinate extensive sheets of contractile tissue for motility provides the starting point for a new multicellular organized form of sensing. Moving a body by muscle contraction provides the basis for a multicellular organization that is sensitive to external surface structure at the scale of the animal body. Instead of thinking about early nervous systems as being connected to the environment merely through input and output, the implication developed here is that early nervous systems provide the foundation for a highly specific animal sensorimotor organization in which neural activity directly reflects bodily and environmental spatiotemporal structure. While the SBT diverges from the input–output view, it is closely linked to and supported by ongoing work on embodied approaches to intelligence to which it adds a new interpretation of animal embodiment and sensorimotor organization. (shrink)

Context: Neurophenomenology is a relatively new field, with scope for novel and informative approaches to empirical questions about what structural parallels there are between neural activity and phenomenal experience. Problem: The overall aim is to present a method for examining possible correlations of neurodynamic and phenodynamic structures within the structurally-coupled work of Alexander Technique practitioners with their pupils. Method: This paper includes the development of an enkinaesthetic explanatory framework, an overview of the salient aspects of the Alexander Technique, and (...) the presentation of an elicitation interview technique as part of a neurophenomenological method. It will propose a way of testing the hypothesis that if, in the effective practice of Alexander Technique, there is a union between the nervous systems of teacher and pupil, it should be visible neurologically and affective phenomenologically, and thus it should be possible to investigate both its neural and phenomenal signatures. Results: The proposed means of testing the hypothesis is to use the elicitation interview technique alongside neural monitoring during the teaching of the Alexander Technique in four paired sets of subjects. Constructivist content: At the heart of this paper is the claim that all activity is co-activity. I make no assumption of an ontological primacy of mental or physical, or explanatory primacy of any methodology. Implications: This has important ramifications for somatic education and therapies, for establishing frameworks of co-engagement and care in health-care situations, and for understanding empathy. (shrink)

The autonomic nervous system is the other division of the human nervous system, which is in charge of most of the automatic processes in the body including heartbeat, digestion, breathing, dilation of the pupils, constriction of pupils, ejaculation, and micturition. This work focuses on the relations and mediators implied in these functions and on the principal regulatory models. Both sympathetic and parasympathetic systems are essential in creating flexibility, and whenever a shift occurs, many health issues may (...) develop as a result. For instance, an ANS activity level too high will cause hypertension or heart issues, while an ANS activity level too low will cause anxiety or panic disorders. The review also discusses the impact of ANS and other new advancements in genetics and genetic makeup regarding stress responsiveness. Even though some people’s genetic predisposes them to certain ANS disorders they can be faced with it due to their lifestyle and stress. Nevertheless, concise information is still scarce about ANS, underlining the importance of further research to evaluate pathogenic genes, and constituent the genetic treatments to enhance the disease's negative outlook. (shrink)

The specification of specific and often unique fates to individual cells as a function of their position within a developing organism is a fundamental process during the development of multicellular organisms. The development of the Drosophila embryonic central nervous system serves as an excellent model system in which to clarify the developmental mechanisms that link pattern formation to cell-type specification. The Drosophila embryonic central nervous system develops from a set of neural stem cells (...) termed neuroblasts. Neuroblasts arise from the ectoderm in an invariant pattern, and each neuroblast acquires a unique fate based on its position within this pattern. Two groups of genes recently have been demonstrated to govern the individual fate specification of neuroblasts. One group, the segment polarity genes, enables neuroblasts that develop in different anteroposterior positions to acquire different fates. The second group, referred to as the columnar genes, ensures that neuroblasts that develop in different dorsoventral domains assume different fates. When integrated, the activities of the segment polarity and columnar genes create a Cartesian coordinate system that bestows unique fates to individual neuroblasts as a function of their position of formation within the ectoderm. BioEssays 1999;21:922–931. © 1999 John Wiley & Sons, Inc. (shrink)

The specification of specific and often unique fates to individual cells as a function of their position within a developing organism is a fundamental process during the development of multicellular organisms. The development of the Drosophila embryonic central nervous system serves as an excellent model system in which to clarify the developmental mechanisms that link pattern formation to cell-type specification. The Drosophila embryonic central nervous system develops from a set of neural stem cells (...) termed neuroblasts. Neuroblasts arise from the ectoderm in an invariant pattern, and each neuroblast acquires a unique fate based on its position within this pattern. Two groups of genes recently have been demonstrated to govern the individual fate specification of neuroblasts. One group, the segment polarity genes, enables neuroblasts that develop in different anteroposterior positions to acquire different fates. The second group, referred to as the columnar genes, ensures that neuroblasts that develop in different dorsoventral domains assume different fates. When integrated, the activities of the segment polarity and columnar genes create a Cartesian coordinate system that bestows unique fates to individual neuroblasts as a function of their position of formation within the ectoderm. BioEssays 1999;21:922–931. © 1999 John Wiley & Sons, Inc. (shrink)

What is the primary function of consciousness in the nervous system? The answer to this question remains enigmatic, not so much because of a lack of relevant data, but because of the lack of a conceptual framework with which to interpret the data. To this end, we have developed Passive Frame Theory, an internally coherent framework that, from an action-based perspective, synthesizes empirically supported hypotheses from diverse fields of investigation. The theory proposes that the primary function of consciousness (...) is well-circumscribed, serving the 'somatic nervous system[. For this system, consciousness serves as a frame that constrains and directs skeletal muscle output, thereby yielding adaptive behavior. The mechanism by which consciousness achieves this is more counterintuitive, passive, and “low level” than the kinds of functions that theorists have previously attributed to consciousness. Passive frame theory begins to illuminate (a) what consciousness contributes to nervous function, (b) how consciousness achieves this function, and (c) the neuroanatomical substrates of conscious processes. Our untraditional, action-based perspective focuses on olfaction instead of on vision and is 'descriptive' (describing the products of nature as they evolved to be) rather than 'normative' (construing processes in terms of how they should function). Passive frame theory begins to isolate the neuroanatomical, cognitive-mechanistic, and representational (e.g., conscious contents) processes associated with consciousness. (shrink)

The controversy of neuroanatomy on the principal structure of the nervous systems, which took place at the end of the nineteenth century, is described. Two groups of scientists are identified: one that favoured the idea of a discrete cellular organization of the nervous tissue, and one that favoured a syncytial organization. These two interpretations arose from different histological techniques that produced conflicting pictures of the organization of the nervous tissue. In an experimental reexamination of the techniques used (...) at the end of the nineteenth century, the present study concerns the impact of these different histological procedures on the controversy about the principle nature of the nervous tissue. This controversy could not be resolved by neuroanatomy itself until the 1950s when electron microscopy was introduced into neurobiology. Thus, in a critical period of the conceptual development of neurosciences, neuroanatomy failed to establish a proper base for an interpretation of the functional morphology of nervous tissues. (shrink)

Enhancer detectors are DNA constructs which, when introduced into a eukaryotic genome, respond to nearby genomic transcriptional regulatory elements by means of a reporter gene, revealing the expression pattern of genes in their vicinity. Recent experiments in Drosophila suggest that enhancer detection is a powerful method to identify genes that are expressed in the nervous system. Since enhancer detectors allow a rapid molecular and genetic characterization of genes in their vicinity, the method will greatly facilitate the study of (...) neural development and behavior. (shrink)

In this article we discuss the molecular signaling mechanisms that coordinate interactions between Schwann cells and the neurons of the peripheral nervous system. Such interactions take place perpetually during development and in adulthood, and are critical for the homeostasis of the peripheral nervous system (PNS). Neurons provide essential signals to control Schwann cell functions, whereas Schwann cells promote neuronal survival and allow efficient transduction of action potentials. Deregulation of neuron–Schwann cell interactions often results in developmental (...) abnormalities and diseases. Recent investigations have shown that during development, neuronally provided signals, such as Neuregulin, Jagged, and Wnt interact to fine‐tune the Schwann cell lineage progression. In adult, the signal exchange between neurons and Schwann cells ensures proper nerve function and regeneration. Identification of the mechanisms of neuron–Schwann cell interactions is therefore essential for our understanding of the development, function and pathology of the peripheral nervous system as a whole. -/- . (shrink)

The development of vertebrate and invertebrate nervous systems requires the production of thousands to millions of uniquely specified neurons from progenitor neural stem cells. A central question focuses on the elucidation of the developmental mechanisms that function within neural stem cell lineages to impart unique identities to neurons. A recent report(1) details the roles that two genes, pdm‐1 and pdm‐2, play within an identified neural stem cell lineage in the Drosophila embryonic central nervous system. The results (...) show that pdm‐1 and pdm‐2 are coexpressed in an identified neural precursor and function redundantly to specify the fate of this cell. As such this report offers an initial view of the genetic programs that create neural diversity. (shrink)

Some neurotropic enteroviruses hijack Trojan horse/raft commensal gut bacteria to render devastating biomimicking cryptic attacks on human/animal hosts. Such virus-microbe interactions manipulate hosts’ gut-brain axes with accompanying infection-cycle-optimizing central nervous system disturbances, including severe neurodevelopmental, neuromotor, and neuropsychiatric conditions. Co-opted bacteria thus indirectly influence host health, development, behavior, and mind as possible “fair-weather-friend” symbionts, switching from commensal to context-dependent pathogen-like strategies benefiting gut-bacteria fitness.

While recent studies have shed some light on the significance of the electrical activity of the nervous system, there has been no adequate explanation for the wave formation or synchronization of this electrical activity. Adrian sums up the problem. “The origin of the 10-a-second rhythm is still uncertain, though the evidence points to some widespread organization, probably involving the central masses as well as the cortex. There are abundant nervous connexions for coordinating the beat, and when the (...) rhythm is well developed it is possible to record impulse discharges in phase with it passing to and fro in the nerve fibers of the white matter below the cortex. But in some areas no impulse could be detected entering or leaving the cell layers, though the potential waves keep more or less in step with those elsewhere. There is no proof that the waves are kept in phase by some means which does not involve nervous signalling, for impulses in axons of small diameter might well be missed, but it is not altogether unlikely that the synchronization is due in part to a direct electrical influence of one group of nerve cells on another. Gerard and Libet have shown that synchronization can occur between the two halves of a frog's brain cut in two and then placed in contact, and more recently Arvanitaki has shown that individual nerve cells may influence one another if they are brought close together in a conducting medium. At all events there are many examples of synchronized rhythmic activity in large collections of nerve-or-muscle cells. In the optic ganglion of the water beetle, for instance, there may be both a slow rhythm when the eye is in darkness and a rapid one when the eye is exposed to a bright light. The change from a slow to a fast rhythm is curiously reminiscent of that in the cerebral cortex when a sensory stimulus abolishes the 10-a-second rhythm and substitutes one at 40–60 a second. Such resemblances in preparations of quite different structures may be quite fortuitous, but they make it difficult to resist the suggestion that the rhythms of the brain may be dependent on the general properties of cell masses rather than on any special anatomical arrangement of them. Whatever its origin, the 10-a-second rhythm of the cortex corresponds to the resting, drowsy, or inattentive state and there is no such uniform pulsation when the brain is alert.”. (shrink)

The first paper in this pair (Bickhard in Axiomathes, 2015) developed a model of the nature of representation and cognition, and argued for a model of the micro-functioning of the brain on the basis of that model. In this sequel paper, starting with part III, this model is extended to address macro-functioning in the CNS. In part IV, I offer a discussion of an approach to brain functioning that has some similarities with, as well as differences from, the model presented (...) here: sometimes called the Predictive Brain approach. (shrink)

Standard semantic information processing models—information in; information processed; information out —lend themselves to standard models of the functioning of the brain in terms, e.g., of threshold-switch neurons connected via classical synapses. That is, in terms of sophisticated descendants of McCulloch and Pitts models. I argue that both the cognition and the brain sides of this framework are incorrect: cognition and thought are not constituted as forms of semantic information processing, and the brain does not function in terms of passive input (...) processing units organized as neural nets. An alternative framework is developed that models cognition and thought not in terms of semantic information processing, and, correspondingly, models brain functional processes also not in terms of semantic information processing. As alternative to such models: I outline a pragmatist oriented, interaction based, model of representation; derive from this model a fundamental framework of constraints on how the brain must function; show that such a framework is in fact found in the brain, and develop the outlines of a broader model of how mental processes can be realized within this alternative framework. Part I of this discussion focuses on some criticisms of standard modeling frameworks for representation and cognition, and outlines an alternative interactivist, pragmatist oriented, model. In part II, the focus is on the fact that the brain does not, in fact, function in accordance with standard passive input processing models—e.g., information processing models. Instead, there are multiple endogenously active processes at multiple spatial and temporal scales across multiple kinds of cells. A micro-functional model that accounts for, and even predicts, these multi-scale phenomena in generating emergent representation and cognition is outlined. That is, I argue that the interactivist model of representation outlined offers constraints on how the brain should function that are in fact empirically found, and, in reverse, that the multifarious details of brain functioning entail the pragmatist representational model—a very strong interrelationship. In the sequel paper, starting with part III, this model is extended to address macro-functioning in the CNS. In part IV, I offer a discussion of an approach to brain functioning that has some similarities with, as well as differences from, the model presented here: sometimes called the predictive brain approach. (shrink)

Chaos theory is a rapidly growing field. As a technical term, chaos refers to deterministic but unpredictable processes being sensitively dependent upon initial conditions. Neurobiological models and experimental results are very complicated and some research groups have tried to pursue the neuronal chaos. Babloyantz's group has studied the fractal dimension (d) of electroencephalograms (EEG) in various physiological and pathological states. From deep sleep (d=4) to full awakening (d>8), a hierarchy of strange attractors paralles the hierarchy of states of consciousness. In (...) epilepsy (petit mal), despite the turbulent aspect of a seizure, the attractor dimension was near to 2. In Creutzfeld-Jacob disease, the regular EEG activity corresponded to an attractor dimension less than the one measured in deep sleep. Is it healthy to be chaotic? An active desynchronisation could be favourable to a physiological system. Rapp's group reported variations of fractal dimension according to particular tasks. During a mental arithmetic task, this dimension increased. In another task, a P300 fractal index decreased when a target was identified. It is clear that the EEG is not representing noise. Its underlying dynamics depends on only a few degrees of freedom despite yet it is difficult to compute accurately the relevant parameters.What is the cognitive role of such a chaotic dynamics? Freeman has studied the olfactory bulb in rabbits and rats for 15 years. Multi-electrode recordings of a few mm2 showed a chaotic hierarchy from deep anaesthesia to alert state. When an animal identified a previously learned odour, the fractal dimension of the dynamics dropped off (near limit cycles). The chaotic activity corresponding to an alert-and-waiting state seems to be a field of all possibilities and a focused activity corresponds to a reduction of the attractor in state space. For a couple of years, Freeman has developed a model of the olfactory bulb-cortex system. The behaviour of the simple model without learning was quite similar to the real behaviour and a model with learning is developed. (shrink)

The neuron doctrine, according to which nerves consist of discontinuous neurons, presented investigators with the challenge of determining what activities occurred between them or between them and muscles. One group of researchers, dubbed the sparks, viewed the electrical current in one neuron as inducing a current in the next neuron or in muscles. For them there was no gap between the activities of neurons or neurons and muscles that required filling with a new type of activity. A competing group, the (...) soups, came to argue for chemicals, subsequently referred to neurotransmitters, as carrying out the activities between neurons or between neurons and muscles. But even for them the conclusion that chemicals performed this activity was only arrived over time. I examine the prolonged period in which proponents of chemical transmission developed their account and challenged the sparks. My goal is to illuminate the epistemic processes that led to the discovery of a new scientific phenomenon—chemical transmission between neurons. (shrink)

Electromagnetic field oscillations produced by the brain are increasingly being viewed as causal drivers of consciousness. Recent research has highlighted the importance of the body’s various endogenous rhythms in organizing these brain-generated fields through various types of entrainment. We expand this approach by examining evidence of extracerebral shared oscillations between the brain and other parts of the body, in both humans and animals. We then examine the degree to which these data support one of General Resonance Theory’s principles: the Slowest (...) Shared Resonance principle, which states that the combination of micro- to macro-consciousness in coupled field systems is a function of the slowest common denominator frequency or resonance. This principle may be utilized to develop a spatiotemporal hierarchy of brain-body shared resonance systems. It is predicted that a system’s SSR decreases with distance between the brain and various resonating structures in the body. The various resonance relationships examined, including between the brain and gastric neurons, brain and sensory organs, and brain and spinal cord, generally match the predicted SSR relationships, empirically supporting this principle of GRT. (shrink)

The brain ventricular system is a series of connected cavities, filled with cerebrospinal fluid (CSF), that forms within the vertebrate central nervous system (CNS). The hollow neural tube is a hallmark of the chordate CNS, and a closed neural tube is essential for normal development. Development and function of the ventricular system is examined, emphasizing three interdigitating components that form a functional system: ventricle walls, CSF fluid properties, and activity of CSF constituent factors. (...) The cellular lining of the ventricle both can produce and is responsive to CSF. Fluid properties and conserved CSF components contribute to normal CNS development. Anomalies of the CSF/ventricular system serve as diagnostics and may cause CNS disorders, further highlighting their importance. This review focuses on the evolution and development of the brain ventricular system, associated function, and connected pathologies. It is geared as an introduction for scholars with little background in the field. (shrink)

Frameworks of emotional development have tended to focus on how environmental factors shape children's emotion understanding. However, individual experiences of emotion represent a complex interplay between both external environmental inputs and internal somatovisceral signaling. Here, we discuss the importance of afferent signals and coordination between central and peripheral mechanisms in affective response processing. We propose that incorporating somatovisceral theories of emotions into frameworks of emotional development can inform how children understand emotions in themselves and others. We highlight promising (...) directions for future research on emotional development incorporating this perspective, namely afferent cardiac processing and interoception, immune activation, physiological synchrony, and social touch. (shrink)

Abstract. The American dream of the “self-made man” is as central to the functioning of our capitalist society as Wall Street and as familiar as the Statue of Liberty. According to this dream, the tired masses have a shot at making it on their own if they have the will power, stamina, and intestinal fortitude to survive and compete. What do we do now that we are faced with scientific evidence that this very strategy is driving society into disconnection, despair, (...) and even poor health? Relational-cultural theory states that growth happens through and toward relationships not toward increased separation and autonomy. Relational-cultural theory describes empathy and mutuality as key components to healthy relationships. This essay will focus on the latest research in the neuroscience of relationships—the development of the capacity to connect within relationships, the systems that help us read and empathize with others, the adaptability and plasticity of the central nervous system, and the destructive nature of isolation. (shrink)

Central sensitization refers to the increased responsiveness of nociceptive neurons in the central nervous system after repeated or sustained peripheral nociceptor activation. It is hypothesized to play a key role in the development of chronic pain. A hallmark of central sensitization is an increased sensitivity to noxious mechanical stimuli extending beyond the injured location, known as secondary hyperalgesia. For its ability to modulate the transmission and the processing of nociceptive inputs, attention could constitute a promising target to (...) prevent central sensitization and the development of chronic pain. It was recently shown that the experimental induction of central sensitization at both forearms of healthy volunteers using bilateral high-frequency electrocutaneous stimulation (HFS), can be modulated by encouraging participants to selectively focus their attention to one arm, to the detriment of the other arm, resulting in a greater secondary hyperalgesia on the attended arm as compared to the unattended one. Given the potential value of the question being addressed, we conducted a preregistered replication study in a well-powered independent sample to assess the robustness of the effect, i.e., the modulatory role of spatial attention on the induction of central sensitization. This hypothesis was tested using a double-blind, within-subject design. Sixty-seven healthy volunteers performed a task that required focusing attention toward one forearm to discriminate innocuous vibrotactile stimuli while HFS was applied on both forearms simultaneously. Our results showed a significant increase in mechanical sensitivity directly and 20 min after HFS. However, in contrast to the previous study, we did not find a significant difference in the development of secondary hyperalgesia between the attended vs. unattended arms. Our results question whether spatial selective attention affects the development of secondary hyperalgesia. Alternatively, the non-replication could be because the bottom-up capture of attention caused by the HFS-mediated sensation was too strong in comparison to the top-down modulation exerted by the attentional task. In other words, the task was not engaging enough and the HFS pulses, including those on the unattended arm, were too salient to allow a selective focus on one arm and modulate nociceptive processing. (shrink)

Current empirical work suggests that early social experiences could have a substantial impact on the areas of the brain responsible for representation of the body. In this context, one aspect of functioning that may be particularly susceptible to social experiences is interoception. Interoceptive functioning has been linked to several areas of the brain which show protracted post-natal development, thus leaving a substantial window of opportunity for environmental input to impact the development of the interoceptive network. We first introduce (...) a biopsychosocial model of interoceptive development. In our proposed model of interoceptive development, attachment related processes are purported to affect the development of interoception by influencing the growth of neural architecture and by modifying functioning of the HPA axis. Further, the idea that patterns of caretaking affect children’s development of interoception is presented. This model explains both normatively developing interoception and accounts for instances in which dysfunctional attachment related processes can lead to either a hypersensitivity or a blunted awareness of bodily cues. Second, we report findings from two existing datasets showing significant relationships between attachment related processes and interoception. In the first study, looking at a sample of healthy young adults (n = 132, 66 males), we assessed self-reported interoceptive awareness and attachment style. We found relationships between aspects of interoception and attachment style such that avoidant individuals reported lower interoceptive functioning across several dimensions (r’s (130) = -.20 to -.26, p’s<.05). More anxious individuals, on the other hand, reported heightened interoceptive across several dimensions (r’s(130)=.18 to.43, p’s <.05). In the second study, we examined the congruence between a person’s self-reported negative emotion and a measure of sympathetic nervous system arousal (SCL). The congruence score was positively associated with parental rejection of negative emotion. These results suggest that parenting style, as reported by the mother, are associated with a child’s ability to coordinate their self-reported emotional and physiological responding across a series of independent assessments, r(108)= -.24, p<.05. In other words, the more maternal reported parental rejection of child negative emotions, the less congruent a child’s self and physiological reports of distress. (shrink)

It was thus the combination of observational and experimental approaches that ultimately led to confirmation of the outgrowth theory. The observational method was essential for defining various possible methods of nerve fiber development. The multicellular, protoplasmic bridge and outgrowth theories were each postulated to explain purely observational evidence. However, the lack of truly suitable equipment and techniques to study the developing nervous system made it impossible to agree on a single theory on this basis alone. The experimental (...) method provided a means of choosing between these theories. Without the preceding observations that had led to the formulation of various hypotheses, however, the experimental approach might not have been so successful, for the power of this method is more of selection than of generation.Therefore it is impossible to weigh separately the contributions of the observational and experimental approaches to the question of nerve fiber development. Both were necessary for the ultimate acceptance of the outgrowth theory. *** DIRECT SUPPORT *** A8402051 00004. (shrink)

Hirschsprung disease and the multiple endocrine neoplasia type 2 syndromes are hereditary disorders related to the abnormal migration, proliferation or survival of neural crest cells and their derivatives. Hirschsprung disease is a frequent disorder of the enteric nervous system, resulting in intestinal obstruction. The multiple endocrine neoplasia type 2 syndromes predispose to cancers of neural crest derivatives. Both diseases are associated with heterozygous mutations in the RET proto‐oncogene. RET encodes a transmembrane receptor tyrosine kinase expressed in neural crest (...) lineages and whose ligand, glial‐cell‐line‐derived neurotrophic factor, has been very recently identified. In vitro expression studies demonstrate that while Hirschsprung disease mutations result in loss of function of the mutant RET tyrosine kinase, multiple endocrine neoplasia type 2 mutations lead to its constitutive activation. Thus, the two ‘faces’ of RET, gain of function and loss of function, each lead to a different syndrome, respectively: multiple endocrine neoplasia type 2, a cancer syndrome, or Hirschsprung disease, a developmental defect. (shrink)

Glial cells play a central role in the development and function of complex nervous systems. Drosophila is an excellent model organism for the study of mechanisms underlying neural development, and recent attention has been focused on the differentiation and function of glial cells. We now have a nearly complete description of glial cell organization in the embryo, which enables a systematic genetic analysis of glial cell development. Most glia arise from neural stem cells that originate in (...) the neurogenic ectoderm. The bifurcation of glial and neuronal fates is under the control of the glial promoting factor glial cells missing. Differentiation is propagated through the regulation of several transcription factors. Genes have been discovered affecting the terminal differentiation of glia, including the promotion glial–neuronal interactions and the formation of the blood–nerve barrier. Other roles of glia are being explored, including their requirement for axon guidance, neuronal survival, and signaling. BioEssays 23:877–887, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

The Myelin Regulator Factor (MYRF) is a master regulator governing myelin formation and maintenance in the central nervous system. The conservation of MYRF across metazoans and its broad tissue expression suggest it has functions extending beyond the well‐established role in myelination. Loss of MYRF results in developmental lethality in both invertebrates and vertebrates, andMYRFhaploinsufficiency in humans causesMYRF‐related Cardiac Urogenital Syndrome, underscoring its importance in animal development; however, these mechanisms are largely unexplored. MYRF, an unconventional transcription factor, begins (...) embedded in the membrane and undergoes intramolecular chaperone mediated trimerization, which triggers self‐cleavage, allowing its N‐terminal segment with an Ig‐fold DNA‐binding domain to enter the nucleus for transcriptional regulation. Recent research suggests developmental regulation of cleavage, yet the mechanisms remain enigmatic. While some parts of MYRF's structure have been elucidated, others remain obscure, leaving questions about how these motifs are linked to its intricate processing and function. (shrink)

A substantial portion of the human genome has been found to consist of simple sequence repeats, including microsatellites and minisatellites. Microsatellites, tandem repeats of 1–6 nucleotides, form the template for dynamic mutations, which involve heritable changes in the lengths of repeat sequences. In recent years, a large number of human disorders have been found to be caused by dynamic mutations, the most common of which are trinucleotide repeat expansion diseases. Dynamic mutations are common to numerous nervous system disorders, (...) including Huntington's disease, various spinocerebellar ataxias, fragile X syndrome, fragile X tremor/ataxia syndrome, Friedreich ataxia and other neurodegenerative disorders. The involvement of dynamic mutations in brain disorders will be reviewed, with a focus on the large group caused by CAG/glutamine repeat expansions. We will also outline a proposed role of tandem repeat polymorphisms (TRPs), with unique ‘digital’ genetic distributions, in modulating brain development and normal function, so as to generate additional mutational diversity upon which natural selection may act. BioEssays 29:525–535, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

This article considers the psychology of meditation and other introverted forms of mystical development from a neo-Piagetian perspective, which has commonalities with biogenetic structuralist and neurotheological approaches. Evidence is found that lines of meditative development unfold through Patañjali’s stages at different rates in an echo of the unfolding of lines of cognitive development through Piaget’s stages at different rates. Similar factors predicting the degree of independence of development apply to both conventional cognitive and meditative contents. As (...) the same brain and the same nervous system are involved in both cognitive developmental psychology and meditation there are likely to be commonalities between conventional psychological and transpersonal development. Neo-Piagetian transpersonal psychology predicts a variable landscape of spiritual development across traditions and individuals, in line with variability in the cultural learning environment. (shrink)

BackgroundThe effect of orgasm on the development and shaping of partner preferences may involve a catalysis of the neurochemical mechanisms of bonding. Therefore, understanding such process is relevant for neuroscience and psychology.MethodsA systematic review was carried out using the terms Orgasm, Sexual Reward, Partner Preference, Pair Bonding, Brain, Learning, Sex, Copulation.ResultsIn humans, concentrations of arousing neurotransmitters and potential bonding neurotransmitters increase during orgasm in the cerebrospinal fluid and the bloodstream. Similarly, studies in animals indicate that those neurotransmitters and others (...) modulate the appetitive and consummatory phases of sexual behavior and reward. This suggests a link between the experience of orgasm/sexual reward and the neurochemical mechanisms of pair bonding. Orgasm/reward functions as an unconditioned stimulus. Some areas in the nervous system function as UCS-dete... (shrink)

Stoffregen & Bardy reject the likelihood that infants are sensitive to the global array, implying that intersensory integration is not possible in early development. We argue that infants are sensitive to unimodal arrays and are able to integrate them through the active participation of their nervous system and that the observed developmental changes are due to experience and brain development.

Pax6 is a transcription factor essential for the development of tissues including the eyes, central nervous system and endocrine glands of vertebrates and invertebrates. It regulates the expression of a broad range of molecules, including transcription factors, cell adhesion and short‐range cell–cell signalling molecules, hormones and structural proteins. It has been implicated in a number of key biological processes including cell proliferation, migration, adhesion and signalling both in normal development and in oncogenesis. The mechanisms by which (...) Pax6 regulates its downstream targets likely involve the use of different splice variants and interactions with multiple proteins, allowing it to generate different effects in different cells. Extrapolation to developmental transcription factors in general suggests that variation in the nature of individual factors is likely to contribute to the emergence of differences between tissues. BioEssays 24:1041–1051, 2002. © 2002 Wiley‐Periodicals, Inc. (shrink)

Helix–loop–helix (HLH) genes encode for transcription factors affecting a whole variety of developmental programs, including neurogenesis. At least seven functional classes (denoted I to VII) of HLH genes exist,1 with subclass members exhibiting homo‐ and heterodimerisation for proper DNA binding and transcriptional regulation of downstream target genes. In the developing nervous system, members of class II, V and VI have been most extensively studied concerning their roles in neural programming. In contrast, the function of class I proteins (such (...) as E12 and E47) is poorly defined and the orthodox view relegates them to general dimerisation duties that are necessary for the activity of the other classes. However, closer scrutiny of the spatiotemporal expression patterns of class I factors, combined with recent biochemical evidence, would suggest that class I proteins possess specific functions during early neural differentiation. This essay supports this possibility, in addition to putting forward the hypothesis that, outside their general dimerisation activity, class I genes have independent roles in regulating neurogenesis. BioEssays 25:709–716, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Multicellular organisms develop on a predictable schedule that depends on both cell‐intrinsic timers and sequential cell‐cell interactions mediated by extracellular signals. The interplay between intracellular timers and extracellular signals is well illustrated by the development of oligodendrocytes, the cells that make the myelin in the vertebrate central nervous system. An intrinsic timing mechanism operates in each oligodendrocyte precursor cell to limit the length of time the cell divides before terminally differentiating. This mechanism consists of two components, a (...) timing component, which depends on the mitogen platelet‐derived growth factor (PDGF) and measures elapsed time, and an effector component, which depends on thyroid hormone and stops cell division and initiates differentiation at the appropriate time. The cell‐cycle inhibitor p27/Kip1 accumulates in the precursor cells as they proliferate and is part of both components of the timer. It seems likely that similar timing mechanisms operate in other cell lineages. BioEssays 22:64–71, 2000. ©2000 John Wiley & Sons, Inc. (shrink)

The Drosophila embryo provides a useful model system to study the mechanisms that lead to pattern and cell diversity in the central nervous system (CNS). The Drosophila CNS, which encompasses the brain and the ventral nerve cord, develops from a bilaterally symmetrical neuroectoderm, which gives rise to neural stem cells, called neuroblasts. The structure of the embryonic ventral nerve cord is relatively simple, consisting of a sequence of repeated segmental units (neuromeres), and the mechanisms controlling the formation (...) and specification of the neuroblasts that form these neuromeres are quite well understood. Owing to the much higher complexity and hidden segmental organization of the brain, our understanding of its development is still rudimentary. Recent investigations on the expression and function of proneural genes, segmentation genes, dorsoventral‐patterning genes and a number of other genes have provided new insight into the principles of neuroblast formation and patterning during embryonic development of the fly brain. Comparisons with the same processes in the trunk help us to understand what makes the brain different from the ventral nerve cord. Several parallels in early brain patterning between the fly and the vertebrate systems have become evident. BioEssays 26:739–751, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

BackgroundGait Analysis of healthy people, imitating pathological conditions while walking, has increased our understanding of biomechanical factors. The influence of the pelvis as a biomechanical constraint during gait is not specifically studied. How could mimicking a pelvic attitude influence the dynamic mechanical interaction of the body segments? We proposed an investigation of the pelvic attitude role on the gait pattern of typically developed people when they mimicked pelvic anteversion and posteroversion.Materials and methodsSeventeen healthy volunteers were enrolled in this study. They (...) simulated a pelvic anteversion and posteroversion during walking, exaggerating these postures as much as possible. 3D gait analysis was conducted using an optoelectronic system with eight cameras and two force plates. The kinematic, kinetic, and spatio-temporal parameters were compared between the three walking conditions.ResultsIn Pelvic Anteversion gait we found: increased hip flexion, increased knee flexion during stance, and reduction of ankle flexion-extension Range of Motion compared with Pelvic Normal gait. In Pelvic Posteroversion gait compared with PN, we found: decreased hip flexion-extension RoM with a tendency to hip extension, decreased knee maximum extension in stance, and increased ankle maximum dorsiflexion in stance.ConclusionThe configuration of PA contains gait similarities and differences when compared with pathologic gait where there is an anteversion as seen in children with Cerebral Palsy or Duchenne Muscular Dystrophy. Similarly, attitudes of PP have been described in patients with Charcot-Marie-Tooth Syndrome or patients who have undergone Pelvic Osteotomy. Understanding the dynamic biomechanical constraints is essential to the assessment of pathological behavior. The central nervous system adapts motor behavior in interaction with body constraints and available resources. (shrink)

Presenilin‐1 (PS1) is thought to regulate cell differentiation and survival by modulating the Notch signaling pathway. Mutations in PS1 have been shown to cause early‐onset inherited forms of Alzheimer's disease (AD) by a gain‐of‐function mechanism that alters proteolytic processing of the amyloid precursor protein (APP) resulting in increased production of neurotoxic forms of amyloid β‐peptide. The present article considers a second pathogenic mode of action of PS1 mutations, a defect in cellular calcium signaling characterized by overfilling of endoplasmic reticulum (ER) (...) calcium stores and altered capacitive calcium entry; this abnormality may impair synaptic plasticity and sensitize neurons to apoptosis and excitotoxicity. The calcium signaling defect has also been documented in lymphocytes, suggesting a contribution of immune dysfunction to the pathogenesis of AD. A better understanding of the calcium signaling defect resulting from PS1 mutations may lead to the development of novel preventative and therapeutic strategies for disorders of the nervous and immune systems. BioEssays 23:733–744, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

Nervous systems are intricately organized on many levels of analysis.The intricate organization invites the development of mathematicalsystems that reflect its logical structure. Particular logical structures and choices of invariants within those structures narrowthe ranges of perceptions that are possible and sensorimotorcoordination that may be selected. As in quantum logic, choicesaffect outcomes.Some of the mathematical tools in use in quantum logic havealready also been used in neurobiology, including the mathematicsof ordered structures and a product like a tensor product. Astheoretical (...) neurobiology is developed on its own foundation, wemay expect a rich dialogue between theoretical neurobiology andquantum logic. (shrink)

Pulmonary ventilation and respiration are considered to be primarily involved in oxygenation of blood for oxygen delivery to cells throughout the body for metabolic purposes. Other pulmonary physiological observations, such as respiratory sinus arrhythmia, Hering Brewer reflex, cardiorespiratory synchronization, and the heart rate variability (HRV) relationship with breathing rhythm, lack complete explanations of physiological/functional significance. The spectrum of waveforms of breathing activity correlate to anxiety, depression, anger, stress, and other positive and negative emotions. Respiratory pattern has been thought not only (...) to be influenced by emotion but to itself influence emotion in a bi-directional relationship between the body and the mind. In order to show how filling in gaps in understanding could lead to certain future developments in mind–body medicine, biofeedback, and personal health monitoring, we review and discuss empirical work and tracings to express the vital role of bodily rhythms in influencing emotion, autonomic nervous system activity, and even general neural activity. Future developments in measurement and psychophysiological understanding of the pattern of breathing in combination with other parameters such as HRV, cardiorespiratory synchronization, and skin conductivity may allow for biometric monitoring systems to one day accurately predict affective state and even affective disorders such as anxiety. Better affective prediction based on recent research when incorporated into personal health monitoring devices could greatly improve public mental health by providing at-home biofeedback for greater understanding of one’s mental state and for mind–body affective treatments such as breathing exercises. (shrink)

Viktor Hamburger was a developmental biologist interested in the ontogenesis of the vertebrate nervous system. A student of Hans Spemann at Freiburg in the 1920s, Hamburger picked up a holistic view of the embryo that precluded him from treating it in a reductionist way; at the same time, he was committed to a materialist and analytical approach that eschewed any form of vitalism or metaphysics. This paper explores how Hamburger walked this thin line between mechanistic reductionism and metaphysical (...) vitalism in light of his work on the factors influencing growth of neurons into limb buds, and the discovery of nerve growth factor, work carried out with Rita Levi-Montalcini and Stanley Cohen. (shrink)

This paper proposes that neurodynamic system theory may be used to connect structural and functional aspects of neural organization. The paper claims that generalized causal dynamic models are proper tools for describing the self-organizing mechanism of the nervous system. In particular, it is pointed out that ontogeny, development, normal performance, learning, and plasticity, can be treated by coherent concepts and formalism. Taking into account the self-referential character of the brain, autopoiesis, endophysics and hermeneutics are offered as (...) elements of a poststructuralist brain (-mind-computer) theory. (shrink)